Acute Changes Research Articles

Lipid Nanoparticle-Mediated Delivery of mRNA Into the Mouse and Human Retina and Other Ocular Tissues.

Lipid nanoparticles (LNPs) show promise in their ability to introduce mRNA to drive protein expression in specific cell types of the mammalian eye. Here, we examined the ability of mRNA encapsulated in LNPs with two distinct formulations to drive gene expression in mouse and human retina and other ocular tissues. We introduced mRNA-carrying LNPs into two biological systems. Intravitreal injections were tested to deliver LNPs into the mouse eye. Human retinal pigment epithelium (RPE) and retinal explants were used to assess mRNA expression in human tissue. We analyzed specificity of expression using histology, immunofluorescence, and imaging. In mice, mRNAs encoding GFP and ciliary neurotrophic factor (CNTF) were specifically expressed by Müller glia and RPE. Acute inflammatory changes measured by microglia distribution (Iba-1) or interleukin-6 (IL-6) expression were not observed 6hours post-injection. Human RPE also expressed high levels of GFP. Human retinal explants expressed GFP in cells with apical and basal processes consistent with Müller glia and in perivascular cells consistent with macrophages. We demonstrated the ability to reliably transfect subpopulations of retinal cells in mouse eye tissues in vivo and in human ocular tissues. Of significance, intravitreal injections were sufficient to transfect the RPE in mice. To our knowledge, we demonstrate delivery of mRNA using LNPs in human ocular tissues for the first time. Ocular gene-replacement therapies using non-viral vector methods are a promising alternative to adeno-associated virus (AAV) vectors. Our studies show that mRNA LNP delivery can be used to transfect retinal cells in both mouse and human tissues without inducing significant inflammation. This methodology could be used to transfect retinal cell lines, tissue explants, mice, or potentially as gene-replacement therapy in a clinical setting in the future.

Climate, weather, and child health: quantifying health co-benefits

Climate change affects human health negatively in a number of complex ways, and children are particularly vulnerable. Quantifying the negative impacts of climate change on health, and identifying locations where children are at greater risk, can aid evidence-based policy making. We combine high-resolution climatic data with a dataset on infant and child mortality, wasting, and stunting, from more than a hundred countries, to estimate the effects of both gradual and acute climate change, focusing on drought and heatwaves, to plausibly attribute changing child health outcomes to historical climate change. Our results suggest a non-linear relationship between temperature and children’s health, adverse effects of increases in acute events, and a strong regional heterogeneity in these impacts. Our findings also highlight the importance of poverty reduction. Greater wealth is associated with better child health outcomes, and partially mitigates the negative impacts of climate change on child health. Finally, using updated warming scenarios, our projections show that there are substantial health co-benefits from achieving low emissions scenarios.

Cardiac autonomic regulation following a 246-km mountain ultra-marathon: An observational study.

Physical exercise requires integrated autonomic and cardiovascular adjustments to maintain homeostasis. We aimed to observe acute posture-related changes in blood pressure, and apply a portable noninvasive monitor to measure the heart index for detecting arrhythmia among elite participants of a 246-km mountain ultra-marathon. Nine experienced ultra-marathoners (8 males and 1 female) participating in the Run Across Taiwan Ultra-marathon in 2018 were enrolled. The runners' Heart Spectrum Blood Pressure Monitor measurements were obtained in the standing and supine positions before and immediately after the race. Their high-sensitivity troponin T and N-terminal proB-type natriuretic peptide levels were analyzed 1 week before and immediately after the event. Heart rate was differed significantly in the immediate postrace assessment compared to the prerace assessment, in both the standing (P = .011; d = 1.19) and supine positions (P = .008; d = 1.35). Postural hypotension occurred in 4 (44.4%) individuals immediately postrace. In 3 out of 9 (33.3%) recruited finishers, the occurrence of premature ventricular complex signals in the standing position was detected; premature ventricular complex signal effect was observed in the supine position postrace in only 1 participant (11.1%). Premature ventricular complex signal was positively correlated with running speed (P = .037). Of the 6 individuals who completed the biochemical tests postrace, 2 (33.3%) had high-sensitivity troponin T and 6 (100%) had N-terminal proB-type natriuretic peptide values above the reference interval. A statistically significant increase was observed in both the high-sensitivity troponin T (P = .028; d = 1.97), and N-terminal proB-type natriuretic peptide (P = .028; d = 2.91) levels postrace compared to prerace. In conclusion, significant alterations in blood pressure and heart rate were observed in the standing position, and postexercise (postural) hypotension occurred among ultra-marathoners. The incidence of premature ventricular complexes was higher after the race than before.

Acute and chronic mammary periprosthetic histological changes of the muscle

Augmentation mammoplasty with subpectoral prosthesis implantation is a frequent performed procedure in plastic surgery for reconstructive and aesthetic purposes. Although prosthesis implantation in a pocket under the major pectoralis muscle has been related to volumetric and functional alterations, there is not much information about the associated short- and long-term histological changes. Therefore, the aim of our study was to describe the acute and chronic histological muscle alterations associated with subpectoral prosthesis implantation. We collected samples from patients with breast tissue expander (<6 months after implantation) and prosthesis (>1 year after implantation) and from patients without implantation as a control group. The samples were processed for assessing their histological, histochemical and immunohistochemical properties. In the control group, no relevant histological findings were identified. Additionally, in the patients with expander, we observed mild augmentation of the internalised nuclei, normal morphology, significant muscle atrophy and fibrosis, whereas in the patients with prosthesis considerable augmentation of internalised nuclei, significant muscle atrophy, fibrosis and alteration of normal muscle morphology were observed. Prosthesis implantation induces histological changes in the periprosthetic striated muscle. Chronic fibrosis and inflammation play key roles in this process, which should be characterised in more detail from the histological and molecular biological perspective.

Hypoxaemic load in sleep apnoea is associated with acute changes in T-wave amplitude.

Obstructive sleep apnoea (OSA) imposes significant stress on the cardiovascular system and the heart. While long-term cardiac effects are understood, the immediate impact of hypoxaemia on the heart's electrophysiology lacks understanding. Our study aims to explore desaturation severity on cardiovascular repolarisation. We retrospectively analysed ECGs from full diagnostic polysomnographies from 492 patients with suspected OSA. The analyses were conducted before, during and after 9137 nocturnal apnoea- or hypopnoea-related desaturations. The mean and sd of T-wave amplitude change from the baseline level to the level during and after desaturations (ΔTamp_mean and ΔTamp_SD) were calculated. To investigate the modulatory effects of desaturation severity, the data were divided into subgroups based on the desaturation duration (Tdes; 10 s≤Tdes<20 s, 20 s≤Tdes<30 s, 30 s≤Tdes<45 s and Tdes≥45 s) and magnitude of blood oxygen saturation drop (change in peripheral oxygen saturation (ΔS pO2 ); 3%≤ΔS pO2 <4.5%, 4.5%≤ΔS pO2 <6%, 6%≤ΔS pO2 <7.5% and ΔS pO2 ≥7.5%) for men and women. Desaturations caused significant (p<0.01) changes in ΔTamp_mean during and after desaturations. In men, the median ΔTamp_mean during and after deep (ΔS pO2 ≥7.5%) desaturations were 21 µV and 24 µV, respectively. In women, the median ΔTamp_mean in deep desaturations was 15 µV during and 21 µV after desaturations. Similarly, the ΔTamp_SD increased during and after deep desaturations. In regression analysis, the desaturation depth was an independent predictor for ventricular repolarisation instability. We found an association between the severity of nocturnal desaturations and cardiac repolarisation instability. These findings hold particular importance, as repolarisation instability has been linked with cardiovascular morbidity and could potentially serve as a trigger for arrhythmias and sudden cardiac death.

The Role of Procalcitonin and Red Cell Distribution Width as Diagnostic and Prognostic Biomarkers in Patients with Sepsis and Septic Shock at Intensive Care Unit

Abstract Background Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Organ dysfunction can be identified as an acute change in total sequential organ failure assessment (SOFA). Septic shock is a subset of sepsis with circulatory and cellular/metabolic dysfunction associated with a higher risk of mortality. Biomarkers can be used in suspected sepsis for identifying or ruling out sepsis, evaluating the severity and assessing the prognosis and evaluating patients’ response to proper treatment. This study is on procalcitonin (PCT) and red cell distribution width (RDW) as diagnostic and prognostic biomarkers in patients with sepsis and septic shock. Objective This study aims to assess the feasibility of PCT and RDW as early diagnostic and prognostic biomarkers in patients with sepsis and septic shock. Methods This is a prospective observational study, in which 100 blood samples of clinically suspected sepsis and septic shock patients’ were included following a convenience sampling technique. PCT and RDW were recorded in day 0, 3, 6, 9 and 12. Results A rise in RDW and PCT levels could serve as early indicators of outcome including mortality. We found that baseline RDW cut-off point &amp;gt; 15.6 with sensitivity of 80.0%, specificity of 85.71% while in day 12 cut-off point &amp;gt; 17.3 with sensitivity of 60.0%, specificity of 100.0%. Accordingly PCT cut-off point &amp;gt; 4.1 with sensitivity of 80.0% and specificity of 94.29% in baseline values. While cut-off point in day 12 was &amp;gt; 0.7 with sensitivity of 80.0%, specificity of 97.0%. Conclusion A significant concurrence was seen between elevated serum PCT and RDW levels with severity and prognosis of sepsis. They were found to be a good predictor of sepsis and low levels rule out an infection.

Engaging Mood Brain Circuits with Psilocybin (EMBRACE): a study protocol for a randomized, placebo-controlled and delayed-start, neuroimaging trial in depression

BackgroundMajor depressive disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin’s acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression.MethodsFifty participants diagnosed with MDD or persistent depressive disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or 25 mg microcrystalline cellulose (MCC) placebo for the first treatment. Three weeks later, those in the control arm will transition to receiving 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level-dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in (1) cerebral blood flow and (2) functional brain activity in networks associated with mood regulation and depression when compared to placebo, along with changes in MADRS score over time compared to placebo. Secondary outcomes include changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline and follow-up to examine relationships with clinical response, and neuroimaging measures.DiscussionThis study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin’s antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response.Trial registrationClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.

990 A Rare Case of Adenomyoma in Gastric Pylorus of a Young Adult Female: A Case Report

Abstract Introduction Gastric adenomyoma is a rare benign tumour which occurs 85% in antrum and 15% in pylorus. Although adenomyomas are benign, diagnosis is difficult as they are commonly found alongside with adenocarcinomas. Case report A 20-year-old previously healthy female presented with epigastric pain, gastric outflow obstruction features and weight loss for 3 months. Initial USS was followed by a CECT which, showed intramural mass lesion with necrotic centre arising from the inferior wall of the pre pyloric area of the stomach with acute inflammatory changes of the adjacent omental fat, giving differential diagnosis of GIST or gastrinoma at pyloric region. Subsequent upper GI endoscopy revealed a protruding pyloric mass without mucosal lesions. Unfortunately, the unavailability of EUS and biopsy posed a diagnostic hurdle. Intraoperatively, a mass intricately adhered to the transverse colon and omentum was discovered, leading to a surgical intervention involving distal gastrectomy, gastrojejunostomy, and jejunojejunostomy. Unexpectedly, histological analysis unveiled adenomyoma at the prepyloric area, characterized by Brunner’s glands, dilated glands, and heterotrophic small intestinal tissue. Discussion This rare manifestation of adenomyoma in the gastric pylorus, particularly in a young adult, highlights the challenges in accurate preoperative diagnosis. The favourable postoperative outcome prompts reflection on the potential role of advanced diagnostic tools, emphasizing the significance of EUS and biopsy in steering clear of extensive surgeries. Conclusions This case report underscores the crucial role of personalized diagnostic methods, especially in cases like ours where a rare adenomyoma mimicking other tumours.

Pathognomic Magnetic Resonance Imaging Findings in a Patient with Acute Mental Status Change

Pathognomic Magnetic Resonance Imaging Findings in a Patient with Acute Mental Status Change

Evaluation of tricuspid valve regurgitation following transvenous rotational mechanical lead extraction.

Transvenous lead extraction (TLE) is potentially complicated by significant tricuspid valve regurgitation increase (TRI). However, there are limited data on the effect of the bidirectional rotational mechanical sheaths on significant TRI. The aim of the present study was to investigate the rate of significant changes in tricuspid regurgitation (TR) severity following mechanical rotational TLE and their outcomes. In 158 patients (mean age 66 ± 16.9 years) undergoing mechanical rotational TLE, acute changes in TR severity were assessed by echocardiography evaluation. A significant acute TRI was defined as an increase of at least one grade with a post-extraction severity at least moderate. A total of 290 leads were extracted (mean implant duration, 93 ± 65 months). Significant TRI was noted in 5.7% of patients, and it was linked to tricuspid valve damage, TLE infection indication, and longer lead implant duration. Univariate predictors of significant TRI included implant duration of all leads [odds ratio (OR) 1.01; 95% confidence interval (CI) 1.003-1.018; P = 0.001] and right ventricular leads (OR 1.01; 95% CI 1.004-1.017; P = 0.002). Severe increase of TR following TLE was an independent predictor of mortality [hazard ratio (HR) 5.20; 95% CI 1.44-18.73; P = 0.012 ] along with severe systolic dysfunction (HR 2.37; 95% CI 1.01-5.20; P = 0.032), and systemic infection (HR 2.28; 95% CI 1.06-4.89; P = 0.035). Significant TRI was detected in 5.7% of patients following transvenous rotational mechanical lead extraction. The duration of lead implantation emerged as the sole predictor of significant TRI. Physicians engaged in TLE should exercise greater vigilance for this potential complication.

Hedging Market Risk with the Index: Experiment Based on Chinese Stock Market

The index can be seen as a reflection of the market. Index futures, also known as stock index futures, are financial derivatives whose value is based on the performance of the whole market. As a consequence, investors can hedge the market risk by longing or shorting some specific value of index futures. Based on the idea, the paper tried to hedge the market risk and have a deeply look into whether it works and what characteristics it has. The paper chooses 10 stocks from those who are the components of the three main Index in China. The results show that with all the hedging strategies, volatility is effectively reduced and the ROI significantly increased during the period with acute value changes. The paper refined the whole experiment by randomly choosing the stocks with python and comparing the stock selection within the industry. The experiment verify the feasibility and the effectiveness of the hedging strategies based on the Index.

The Surgical Method of Craniectomy Differentially Affects Acute Seizures, Brain Deformation and Behavior in a TBI Animal Model.

Traumatic brain injury (TBI) is the leading cause of morbidity and mortality worldwide. Multiple injury models have been developed to study this neurological disorder. One such model is the lateral fluid-percussion injury (LFPI) rodent model. The LFPI model can be generated with different surgical procedures that could affect the injury and be reflected in neurobehavioral dysfunction and acute EEG changes. A craniectomy was performed either with a trephine hand drill or with a trephine electric drill that was centered over the left hemisphere of adult, male Sprague Dawley rats. Sham craniectomy groups were assessed by hand-drilled (ShamHMRI) and electric-drilled (ShamEMRI) to evaluate by MRI. Then, TBI was induced in separate groups (TBIH) and (TBIE) using a fluid-percussion device. Sham-injured rats (ShamH/ShamE) underwent the same surgical procedures as the TBI rats. During the same surgery session, rats were implanted with screw and microwire electrodes positioned in the neocortex and hippocampus and the EEG activity was recorded 24 hours for the first 7 days after TBI for assessing the acute EEG seizure and Gamma Event Coupling (GEC). The electric drilling craniectomy induced greater tissue damage and sensorimotor deficits compared to the hand drill. Analysis of the EEG revealed acute seizures in at least one animal from each group after the procedure. Both TBI and Sham rats from the electric drill groups had a significant greater total number of seizures than the animals that were craniectomized manually (p<0.05). Similarly, EEG functional connectivity was lower in ShamE compared to ShamH rats. These results suggest that electrical versus hand drilling craniectomies produce cortical injury in addition to the LFPI which increases the likelihood for acute post-traumatic seizures. Differences in the surgical approach could be one reason for the variability in the injury that makes it difficult to replicate results between preclinical TBI studies.

Perinatal Cardiac Functional Adaptation in Hypoplastic Left Heart Syndrome: A Longitudinal Analysis

The perinatal transition is characterized by acute changes in cardiac loading. Compared with normal newborn combined cardiac output (CCO), single right ventricular (RV) output of neonates with hypoplastic left heart syndrome (HLHS) is markedly greater. The aim of this study was to examine the mechanisms of cardiac adaptation that facilitate this perinatal transition from late fetal to early neonatal life in HLHS. Prospectively recruited pregnancies complicated by fetal HLHS (n=35) and healthy control subjects (Ctrl; n=17) underwent serial echocardiography in late gestation (38±1weeks) and 6, 24, and 48hours after birth. Cardiac function was assessed using conventional, Doppler tissue, and speckle-tracking echocardiography. Term fetuses with HLHS had RV output comparable with Ctrl CCO via higher stroke volume. Compared with both left ventricular and RV indices of Ctrl, they exhibited globular and dilated right ventricles with reduced relative wall thickness (0.40±0.08 vs 0.49±0.10, P<.01), increased Tei index' (HLHS vs Ctrl left ventricle/Ctrl right ventricle: sphericity index, 0.9±0.25 vs 0.5±0.10/0.6±0.11; RV area index, 28±6 vs 15±3/17±5cm2/m2; Tei index', 0.65±0.11 vs 0.43±0.07/0.45±0.09; P<.0001 for all). Neonates with HLHS generated elevated RV cardiac output compared with Ctrl CCO via higher heart rate and stroke volume, with further RV dilatation, increased longitudinal systolic strain at 48hours (-17±4% vs -14±3%/14±5%) with reduced circumferential and rotational myocardial deformation and altered diastolic function. Neonates with HLHS also demonstrated right atrial enlargement with increased longitudinal strain: 6hours (33±12% vs 26±6%), 24hours (37±15% vs 26± 13%), and 48hours (38±11% vs 24±13%) (P<.0001). Term fetuses with HLHS exhibit altered RV geometry and RV systolic and diastolic functional parameters. After birth, further alterations in these cardiac parameters likely reflect adaptation to acutely altered RV loading from increasing cardiac output and pulmonary artery flow demands.

Altering developmental oxygen exposure influences thermoregulation and flight performance of Manduca sexta.

Endothermic, flying insects are capable of some of the highest recorded metabolic rates. This high aerobic demand is made possible by the insect's tracheal system, which supplies the flight muscles with oxygen. Many studies focus on metabolic responses to acute changes in oxygen to test the limits of the insect flight metabolic system, with some flying insects exhibiting oxygen limitation in flight metabolism. These acute studies do not account for possible changes induced by developmental phenotypic plasticity in response to chronic changes in oxygen levels. The endothermic moth Manduca sexta is a model organism that is easy to raise and exhibits a high thorax temperature during flight (∼40°C). In this study, we examined the effects of developmental oxygen exposure during the larval, pupal and adult stages on the adult moth's aerobic performance. We measured flight critical oxygen partial pressure (Pcrit-), thorax temperature and thermoregulating metabolic rate to understand the extent of developmental plasticity as well as effects of developmental oxygen levels on endothermic capacity. We found that developing in hypoxia (10% oxygen) decreased thermoregulating thorax temperature when compared with moths raised in normoxia or hyperoxia (30% oxygen), when moths were warming up in atmospheres with 21-30% oxygen. In addition, moths raised in hypoxia had lower critical oxygen levels when flying. These results suggest that chronic developmental exposure to hypoxia affects the adult metabolic phenotype and potentially has implications for thermoregulatory and flight behavior.

Impact of optimized transcutaneous auricular vagus nerve stimulation on cardiac autonomic profile in healthy subjects and heart failure patients

Objective. To determine the optimal frequency and site of stimulation for transcutaneous vagus nerve stimulation (tVNS) to induce acute changes in the autonomic profile (heart rate (HR), heart rate variability (HRV)) in healthy subjects (HS) and patients with heart failure (HF). Approach. We designed three single-blind, randomized, cross-over studies: (1) to compare the acute effect of left tVNS at 25 Hz and 10 Hz (n = 29, age 60 ± 7 years), (2) to compare the acute effect of left and right tVNS at the best frequency identified in study 1 (n = 28 age 61 ± 7 years), and (3) to compare the acute effect of the identified optimal stimulation protocol with sham stimulation in HS and HF patients (n = 30, age 59 ± 5 years, and n = 32, age 63 ± 7 years, respectively). Main results. In study 1, left tragus stimulation at 25 Hz was more effective than stimulation at 10 Hz in decreasing HR (−1.0 ± 1.2 bpm, p < 0.001 and −0.5 ± 1.6 bpm, respectively) and inducing vagal effects (significant increase in RMSSD, and HF power). In study 2, the HR reduction was greater with left than right tragus stimulation (−0.9 ± 1.5 bpm, p < 0.01 and −0.3 ± 1.4 bpm, respectively). In study 3 in HS, left tVNS at 25 Hz significantly reduced HR, whereas sham stimulation did not (−1.1 ± 1.2 bpm, p< 0.01 and −0.2 ± 2.9 bpm, respectively). In HF patients, both active and sham stimulation produced negligible effects. Significance. Left tVNS at 25 Hz is effective in acute modulation of cardiovascular autonomic control (HR, HRV) in HS but not in HF patients (NCT05789147).

Arrhythmogenic effects of acute electronic cigarette compared to tobacco cigarette smoking in people living with HIV.

The leading cause of death in people living with HIV (PLWH) is cardiovascular disease, and the high prevalence of tobacco cigarette (TC) smoking is a major contributor. Switching to electronic cigarettes (ECs) has been promoted as a harm reduction strategy. We sought to determine if acute EC compared to TC smoking had less harmful effects on arrhythmogenic risk factors including acute changes in hemodynamics, heart rate variability (HRV), and ventricular repolarization (VR). In PLWH who smoke, changes in hemodynamics, HRV, and VR were compared pre/post acutely using an EC, TC, or puffing on an empty straw on different days in random order, in a crossover study. Thirty-seven PLWH (36 males, mean age 40.5 ± 9.1 years) participated. Plasma nicotine was greater after TC versus EC use (10.12 ± 0.96 vs. 6.18 ± 0.99 ng/mL, respectively, p = 0.004). HR increased significantly, and similarly, after acute EC and TC smoking compared to control. Changes in HRV that confer increased cardiac risk (LF/HF ratio) were significantly smaller after acute EC versus TC use, consistent with a harm reduction effect. In a post-hoc analysis of PLWH with and without positive concurrent recreational drug use as indicated by point of care urine toxicology testing, this differential effect was only seen in PLWH not currently using recreational drugs. Changes in VR were not different among the three exposures. In PLWH who smoke, EC compared to TC smoking resulted in smaller adverse changes in HRV. This differential effect was accompanied by a smaller increase in plasma nicotine, and was negated by concurrent recreational drug use. Additional studies are warranted in this vulnerable population disproportionately affected by tobacco-related health disparities.

Improving acute stroke assessment in non-enhanced computed tomography: automated tool for early ischemic lesion volume detection.

ASPECTs is a widely used marker to identify early stroke signs on non-enhanced computed tomography (NECT), yet it presents interindividual variability and it may be hard to use for non-experts. We introduce an algorithm capable of automatically estimating the NECT volumetric extension of early acute ischemic changes in the 3D space. We compared the power of this marker with ASPECTs evaluated by experienced practitioner in predicting the clinical outcome. We analyzed and processed neuroimaging data of 153 patients admitted with acute ischemic stroke. All patients underwent a NECT at admission and on follow-up. The developed algorithm identifies the early ischemic hypodense region based on an automatic comparison of the gray level in the images of the two hemispheres, assumed to be an approximate mirror image of each other in healthy patients. In the two standard axial slices used to estimate the ASPECTs, the regions identified by the algorithm overlap significantly with those identified by experienced practitioners. However, in many patients, the regions identified automatically extend significantly to other slices. In these cases,the volume marker provides supplementary and independent information.Indeed,theclinical outcome of patients with volume marker = 0 can be distinguished with higher statistical confidence than the outcome of patients with ASPECTs = 10. The volumetric extension and the location of acute ischemic region in the 3D-space, automatically identified by our algorithm, provide data that are mostly in agreement with the ASPECTs value estimated by expert practitioners, and in some cases complementary and independent.

Feasibility Trial Exploring Immune-Related Biomarkers Pertaining to Rapid Immune Surveillance and Cytokine Changes after Consuming a Nutraceutical Supplement Containing Colostrum- and Egg-Based Low-Molecular-Weight Peptides.

Immune protection associated with consuming colostrum-based peptides is effective against bacterial and viral insults. The goal for this study was to document acute changes to immune surveillance and cytokine levels after consuming a single dose of a nutraceutical blend in the absence of an immune challenge. A double-blind, randomized, placebo-controlled, cross-over pilot study involved healthy participants attending two clinic visits. Blood draws were performed pre-consumption and at 1, 2, and 24 h after consuming a blend of bovine colostrum- and hen's egg-based low-molecular-weight peptides (CELMPs) versus a placebo. Immunophenotyping was performed by flow cytometry, and serum cytokines were measured by multiplex cytokine arrays. Consumption of CELMPs triggered increased immune surveillance after 1 h, involving monocytes (p < 0.1), natural killer (NK) cells (p < 0.1), and natural killer T (NKT) cells (p < 0.05). The number of NKT cells expressing the CD25 immunoregulatory marker increased at 1 and 2 h (p < 0.1). Increased serum levels of monocyte chemoattractant protein-1 (MCP-1) was observed at 2 and 24 h (24 h: p < 0.05). Selective reduction in pro-inflammatory cytokines was seen at 1, 2, and 24 h, where the 2-h reduction was highly significant for IL-6, IFN-γ, and IL-13. The rapid, transient increase in immune surveillance, in conjunction with the reduced levels of inflammatory markers, suggests that the CELMP blend of natural peptides provides immune benefits of use in preventive medicine. Further studies are warranted in chronic inflammatory conditions.

Deciphering the pathogenesis of melanized focal changes in the white skeletal muscle of farmed Atlantic salmon (Salmo salar).

Melanized focal changes (MFCs) in the fillet of farmed Atlantic salmon is a major quality concern. The changes are thought to initially appear as acute red focal changes (RFCs) that progress into chronic MFCs. Recent findings have indicated that hypoxia may be important in their development, possibly leading to necrosis affecting not only myocytes but also adipocytes. Thus, the aim of this study was to investigate possible hypoxic conditions in RFCs and the subsequent inflammatory responses and lesions in the adipose tissue in RFCs and MFCs. A collection of RFCs, MFCs and control muscle samples from several groups of farmed salmon was studied. Using immunohistochemistry, we found induction of the hypoxia-inducible factor 1 pathway in RFCs. Histological investigations of RFCs and MFCs revealed different stages of fat necrosis, including necrotic adipocytes, a myospherulosis-like reaction and the formation of pseudocystic spaces. Accumulations of foamy macrophages were detected in MFCs, indicating degradation and phagocytosis of lipids. Using insitu hybridization, we showed the presence of tyrosinase- and tyrosinase-related protein-1-expressing amelanotic cells in RFCs, which in turn became melanized in MFCs. In conclusion, we propose a sequence of events leading to the formation of MFCs, highlighting the pivotal role of adiposity, hypoxia and fat necrosis.

Acute and Chronic Changes in Muscle Androgen Receptor Markers Are Not Associated with Muscle Hypertrophy in Women and Men.

Androgen receptor (AR) expression and signaling has been regarded as a mechanism for regulating muscle hypertrophy. However, little is known about the associations between acute and chronic changes in skeletal muscle total AR, cytoplasmic AR (cAR), nuclear AR (nAR) and AR DNA-binding (AR-DNA) induced by resistance training (RT) and hypertrophy outcomes in women and men. This study aimed to investigate the acute and chronic effects of RT on skeletal muscle total AR, cAR, nAR contents and AR-DNA in women and men. Additionally, we investigated whether these acute and chronic changes in these markers were associated with muscle hypertrophy in both sexes. Nineteen women and 19 men underwent 10 weeks of RT. Muscle biopsies were performed at baseline, 24 h after the first RT session and 96-120 h after the last session. AR, cAR and nAR were analyzed using Western blotting, and AR-DNA using an ELISA-oligonucleotide assay. Fiber cross-sectional area (fCSA) was analyzed through immunohistochemistry and muscle cross-sectional area (mCSA) by ultrasound. At baseline, men demonstrated greater nAR than women. Baseline cAR was significantly associated with type II fCSA hypertrophy in men. Acutely, both sexes decreased AR and cAR, whereas men demonstrated greater decreases in nAR. After 10 weeks of RT, AR and nAR remained unchanged, men demonstrated greater cAR compared to women, and both sexes decreased AR-DNA activity. Acute and chronic changes in AR markers did not correlate with muscle hypertrophy (type I/II fCSA and mCSA) in women or men. Baseline cAR content may influence hypertrophy in men, while neither RT-induced acute nor chronic changes in AR, cAR, nAR, and AR-DNA are associated with muscle hypertrophy in women or men.