Tuning and modeling cheese flavor.

Flavor is a major sensory attribute affecting consumers' preference for cheese products. Differences in cheesemaking change the cheese microenvironment, thereby affecting cheese flavor profiles. A framework for tuning cheese flavor is proposed in this study, which depicts the full picture of flavor development and modulation, from manufacturing and ripening factors through the main biochemical pathways to flavor compounds and flavor notes. Taking semi-hard and hard cheeses as examples, this review describes how cheese flavor profiles are affected by milk type and applied treatment, fat and salt content, microbiota composition and microbial interactions, ripening time, temperature, and environmental humidity, together with packaging method and material. Moreover, these factors are linked to flavor profiles through their effects on proteolysis, the further catabolism of amino acids, and lipolysis. Acids, alcohols, ketones, esters, aldehydes, lactones, and sulfur compounds are key volatiles, which elicit fruity, sweet, rancid, green, creamy, pungent, alcoholic, nutty, fatty, and sweaty flavor notes, contributing to the overall flavor profiles. Additionally, this review demonstrates how data-driven modeling techniques can link these influencing factors to resulting flavor profiles. This is done by providing a comprehensive review on the (i) identification of key factors and flavor compounds, (ii) discrimination of cheeses, and (iii) prediction of flavor notes. Overall, this review provides knowledge tools for cheese flavor modulation and sheds light on using data-driven modeling techniques to aid cheese flavor analysis and flavor prediction.

Unsupervised Pattern Analysis to Differentiate Multiple Sclerosis Phenotypes Using Principal Component Analysis on Various MRI Sequences.

Background: Multiple sclerosis (MS) has two main phenotypes: relapse-remitting MS (RRMS) and progressive MS (PMS), distinguished by disability profiles and treatment response. Differentiating them using conventional MRI is challenging. Objective: This study explores the use of scaled subprofile modelling using principal component analysis (SSM/PCA) on MRI data to distinguish between MS phenotypes. Methods: MRI scans were performed on patients with RRMS (n = 30) and patients with PMS (n = 20), using the standard sequences T1w, T2w, T2w-FLAIR, and the myelin-sensitive sequences magnetisation transfer (MT) ratio (MTR), quantitative MT (qMT), inhomogeneous MT ratio (ihMTR), and quantitative inhomogeneous MT (qihMT). Results: SSM/PCA analysis of qihMT images best differentiated PMS from RRMS, with the highest specificity (87%) and positive predictive value (PPV) (83%), but a lower sensitivity (67%) and negative predictive value (NPV) (72%). Conversely, T1w data analysis showed the highest sensitivity (93%) and NPV (89%), with a lower PPV (67%) and specificity (53%). Phenotype classification agreement between T1w and qihMT was observed in 57% of patients. In the subset with concordant classifications, the sensitivity, specificity, PPV, and NPV were 100%, 88%, 90%, and 100%, respectively. Conclusions: SSM/PCA on MRI data revealed distinctive patterns for MS phenotypes. Optimal discrimination occurred with qihMT and T1w sequences, with qihMT identifying PMS and T1w identifying RRMS. When qihMT and T1w analyses align, MS phenotype prediction improves.

A survey and analysis of peri-operative quality indicators promoted by National Societies of Anaesthesiologists in Europe: The EQUIP project.

BACKGROUND: To capture preventable peri-operative patient harm and guide improvement initiatives, many quality indicators (QIs) have been developed. Several National Anaesthesiologist Societies (NAS) in Europe have implemented quality indicators. To date, the definitions, validity and dissemination of such quality indicators, and their comparability with validated published indicators are unknown. OBJECTIVES: The aim of this study was to identify all quality indicators promoted by NAS in Europe, to assess their characteristics and to compare them with published validated quality indicators. DESIGN: A cross-sectional study with mixed methods analysis. Using a survey questionnaire, representatives of 37 NAS were asked if their society provided quality indicators to their members and, if so, to provide the list, definitions and details of quality indicators. Characteristics of reported quality indicators were analysed. SETTING: The 37 NAS affiliated with the European Society of Anaesthesiology and Intensive Care (ESAIC) at the time. Data collection, translations: March 2018 to February 2020. PARTICIPANTS: Representatives of all 37 NAS completed the survey. MAIN OUTCOME MEASURES: QIs reported by NAS. RESULTS: Only 12 (32%) of the 37 NAS had made a set of quality indicators available to their members. Data collection was mandatory in six (16.2%) of the 37 countries. We identified 163 individual quality indicators, which were most commonly descriptive (60.1%), anaesthesia-specific (50.3%) and related to intra-operative care (21.5%). They often measured structures (41.7%) and aspects of safety (35.6%), appropriateness (20.9%) and prevention (16.6%). Patient-centred care (3.7%) was not well covered. Only 11.7% of QIs corresponded to published validated or well established quality indicator sets. CONCLUSIONS: Few NAS in Europe promoted peri-operative quality indicators. Most of them differed from published sets of validated indicators and were often related to the structural dimension of quality. There is a need to establish a European-wide comprehensive core set of usable and validated quality indicators to monitor the quality of peri-operative care. TRIAL REGISTRATION: No registration.

Radio frequency-only thermal processing of skimmed milk powder: Case study on the influence of RF heating profile on quality and Salmonella Typhimurium inactivation.

Radio frequency (RF) is a dielectric heating technology that allows rapid and volumetric heating of milk powder, outperforming the heating uniformity of conventional powder heating methods. Typically, RF milk powder processing consists of a fast RF heating phase, followed by an oven heating phase in temperatures around 90 °C. This methodology can result in milk powder quality deterioration due to non-uniform temperature distributions and local overheating. Radio frequency-only processes with a more gradual heating rate are alternative solutions to minimise the impact on milk powder quality. This study investigated the effect of the heating rate on the microbial inactivation of Salmonella Typhimurium inoculated in skimmed milk powder, as well as the effect of each process on two quality characteristics, colour and solubility. Overall, a slower heating profile resulted in sufficient inactivation rates of Salmonella in skimmed milk powder, while still providing a high-quality end product. A 4-log reduction was achieved by treating the skimmed milk powder up to 95 °C using a slower, longer heating rate. No statistically significant changes were observed in the solubility of skimmed milk powder and only the harshest treatment to 95 °C led to a slight increase in the yellowness of the skimmed milk powder colour.

Off versus on pump myocardial revascularization in patients with severe asymptomatic carotid stenosis.

BACKGROUND: Coronary artery disease is a global cause of morbidity and mortality, often managed by coronary artery bypass grafting (CABG). This study addresses a critical decision-making dilemma in CABG procedures for patients with severe asymptomatic carotid stenosis, comparing off-pump and on-pump techniques. METHODS: We conducted a retrospective single-center analysis, employing propensity scored matched-pair methodology to compare perioperative outcomes in patients with asymptomatic severe carotid stenosis undergoing off-pump or on-pump CABG. The primary endpoint was the occurrence of perioperative stroke. Secondary endpoints included postoperative delirium, intrahospital mortality, intensive care unit stay, length of hospitalization and long-term survival. RESULTS: The study involved 243 patients with asymptomatic severe carotid stenosis operated between July 2009 and October 2018, subsequently propensity score matched into two groups of 78 patients each (off-pump and on-pump). The incidence of perioperative stroke was significantly higher in the On-Pump group compared to the off-pump group (10.3% vs. 1.3%, P=0.03). However, secondary endpoints, such as intrahospital mortality and length of hospitalization, showed no significant differences between the two groups. Long-term survival rates were also comparable. CONCLUSIONS: Our findings indicate that off-pump CABG significantly reduces the risk of perioperative stroke in patients with severe asymptomatic carotid stenosis compared to on-pump CABG, without compromising long-term outcomes. These results support the preference for off-pump CABG in this high-risk patient population, highlighting the need for tailored surgical approaches based on individual patient risk profiles.

Survey-based qualitative exploration of user perspectives on the philips visual patient avatar in clinical situation management.

Philips Visual Patient Avatar is an innovative approach to patient monitoring. Computer-based simulation studies have shown that it can improve diagnostic accuracy and confidence while reducing perceived workload. Following its integration into clinical practice, we conducted a single-centre qualitative study at the University Hospital Zurich to explore the views of anaesthesia, post-anaesthesia and intensive care providers on their experience with the technology. We used an online survey to assess its contributions in different clinical situations. We analysed the data thematically to identify key themes. Of the 510 healthcare providers contacted, 131 (25.7%) completed the survey and 154 comments were collected. Key themes included the detection of specific vital sign changes, focusing on temperature and oxygen saturation (41.9%, 34/81 comments in the operating room; 38.6%, 17/44 comments in the intensive care unit; 10.3%, 3/29 comments in the post-anaesthesia care unit). Additionally, the technology was perceived to support daily routines and situational awareness (28.4%, 23/81 comments in the OR; 9.1%, 4/44 comments in the ICU; 10.3%, 3/29 comments in the PACU). The study provides early, but strong evidence that the Philips Visual Patient Avatar assists healthcare providers in specific clinical situations in the perioperative and critical care settings.

Pathogenesis and Surgical Treatment of Congenitally Corrected Transposition of the Great Arteries (ccTGA): Part III.

Congenitally corrected transposition of the great arteries (ccTGA) is an infrequent and complex congenital malformation, which accounts for approximately 0.5% of all congenital heart defects. This defect is characterized by both atrioventricular and ventriculoarterial discordance, with the right atrium connected to the morphological left ventricle (LV), ejecting blood into the pulmonary artery, while the left atrium is connected to the morphological right ventricle (RV), ejecting blood into the aorta. Due to this double discordance, the blood flow is physiologically normal. Most patients have coexisting cardiac abnormalities that require further treatment. Untreated natural course is often associated with progressive failure of the systemic right ventricle (RV), tricuspid valve (TV) regurgitation, arrhythmia, and sudden cardiac death, which occurs in approximately 50% of patients below the age of 40. Some patients do not require surgical intervention, but most undergo physiological repair leaving the right ventricle in the systemic position, anatomical surgery which restores the left ventricle as the systemic ventricle, or univentricular palliation. Various types of anatomic repair have been proposed for the correction of double discordance. They combine an atrial switch (Senning or Mustard procedure) with either an arterial switch operation (ASO) as a double-switch operation or, in the cases of relevant left ventricular outflow tract obstruction (LVOTO) and ventricular septal defect (VSD), intra-ventricular rerouting by a Rastelli procedure. More recently implemented procedures, variations of aortic root translocations such as the Nikaidoh or the half-turned truncal switch/en bloc rotation, improve left ventricular outflow tract (LVOT) geometry and supposedly prevent the recurrence of LVOTO. Anatomic repair for congenitally corrected ccTGA has been shown to enable patients to survive into adulthood.

Parents caring and sham-feeding their child born with Esophageal atresia at home while waiting for reconstructive surgery.

PURPOSE: For children with Esophageal atresia who have to wait for reconstructive surgery, long hospital stay, delayed introduction of oral feeds and hampered oro-motor function has traditionally been draw-backs for this treatment as the patients have minimal training of oro-motor function while waiting for surgery. In this paper, we present the concept of sham-feed at home awaiting reconstructive surgery with the aim to obliviate these problems. The aim was to describe the characteristics of patients with Esophageal atresia waiting for reconstructive surgery sham-feeding at home by their parents and further describe adverse events that arose. METHODS: The study is a retrospective descriptive single center study on all children with a delayed reconstruction of Esophageal atresia who was sham-fed by their parents at home before reconstructive surgery between January 2010 and January 2023 at the Karolinska University Hospital, Stockholm. RESULTS: Nine patients where home waiting for reconstructive surgery for a median of 72 days. No adverse events were reported related to the sham-feed procedure at home. The children had reconstructive surgery at a median 120 days of age. Five of the children ate full meals orally day 8-27 after surgery. Two children ate fully before 1 year after surgery. Two children had surgery less than 1 year ago and were not eating fully orally at the time of data collection. CONCLUSION: Sham-feeding at home by the parents was safe and feasible with the benefits of a prolonged time out of hospital awaiting reconstructive surgery.

Reconstitution of BNIP3/NIX-mediated autophagy reveals two pathways and hierarchical flexibility of the initiation machinery.

Selective autophagy is a lysosomal degradation pathway that is critical for maintaining cellular homeostasis by disposing of harmful cellular material. While the mechanisms by which soluble cargo receptors recruit the autophagy machinery are becoming increasingly clear, the principles governing how organelle-localized transmembrane cargo receptors initiate selective autophagy remain poorly understood. Here, we demonstrate that transmembrane cargo receptors can initiate autophagosome biogenesis not only by recruiting the upstream FIP200/ULK1 complex but also via a WIPI-ATG13 complex. This latter pathway is employed by the BNIP3/NIX receptors to trigger mitophagy. Additionally, other transmembrane mitophagy receptors, including FUNDC1 and BCL2L13, exclusively use the FIP200/ULK1 complex, while FKBP8 and the ER-phagy receptor TEX264 are capable of utilizing both pathways to initiate autophagy. Our study defines the molecular rules for initiation by transmembrane cargo receptors, revealing remarkable flexibility in the assembly and activation of the autophagy machinery, with significant implications for therapeutic interventions.

Fluorescence guidance in skull base surgery: Applications and limitations - A systematic review.

Introduction: Intraoperative fluorescence guidance is a well-established surgical adjunct in high-grade glioma surgery. In contrast, the clinical use of such dyes and technology has been scarcely reported in skull base surgery. Research question: We aimed to systematically review the clinical applications of different fluorophores in both open and endonasal skull base surgery. Material and methods: We performed a systematic review and discussed the current literature on fluorescence guidance in skull base surgery. Results: After a comprehensive literature search, 77 articles on skull base fluorescence guidance were evaluated. A qualitative analysis of the articles is presented, discussing clinical indications and current controversies. The use of intrathecal fluorescein was the most frequently reported in the literature. Beyond that, 5-ALA and ICG were two other fluorescent dyes most extensively discussed, with some experimental fluorophore applications in skull base surgery. Discussion and conclusion: Intraoperative fluorescence imaging can serve as an adjunct technology in skull base surgery. The scope of initial indications of these fluorophores has expanded beyond malignant glioma resection alone. We discuss current use and controversies and present an extensive overview of additional indications for fluorescence imaging in skull base pathologies. Further quantitative studies will be needed in the future, focusing on tissue selectivity and time-dependency of the different fluorophores currently commercially available, as well as the development of new compounds to expand applications and facilitate skull base surgeries.

Association between caseload volume and outcomes in left ventricular assist device implantations - a EUROMACS analysis.

AIMS: This EUROMACS study was conducted with the primary aim of investigating the association between a centre's annual caseload and postoperative outcomes among patients undergoing left ventricular assist device (LVAD) implantation. METHODS AND RESULTS: A total of 4802 patients identified between 2011 and 2020 from 35 participating centres were dichotomized based on the annual caseload of the treating centre at the time of device implant (≤30 vs. >30 LVAD implantations/year). The primary endpoint was 1-year survival. Secondary outcomes included overall survival analysis, device-related adverse events and readmissions. Cumulative follow-up was 10 003 patient-years, with a median follow-up of 1.54 years (interquartile range 0.52-3.15). Patients from higher volume centres more frequently presented in INTERMACS levels 1 and 2, suffered from right heart dysfunction and needed inotropic support. No difference was observed in adjusted 1-year survival. Adjusted overall survival probability was lower in higher volume centres (p = 0.002). In the subgroup analysis of HeartMate 3 devices only, higher volume centres were associated with decreased odds of 1-year survival (adjusted odds ratio 0.43, 95% confidence interval 0.20-0.97, p = 0.041). Similar findings were observed in the cumulative (i.e. learning curve) caseload analyses. CONCLUSION: In patients undergoing LVAD implantation, centre volume was not associated with 1-year survival, but was related to device-related adverse events. Patient profiles differed with respect to centre size. These findings underscore the necessity for ongoing quality improvement initiatives in all centres, regardless of their annual caseload. Efforts are needed to standardize patient selection and preconditioning to further improve patient outcome.

Pathogenesis and Surgical Treatment of Dextro-Transposition of the Great Arteries (D-TGA): Part II.

Dextro-transposition of the great arteries (D-TGA) is the second most common cyanotic heart disease, accounting for 5-7% of all congenital heart defects (CHDs). It is characterized by ventriculoarterial (VA) connection discordance, atrioventricular (AV) concordance, and a parallel relationship with D-TGA. As a result, the pulmonary and systemic circulations are separated [the morphological right ventricle (RV) is connected to the aorta and the morphological left ventricle (LV) is connected to the pulmonary artery]. This anomaly is included in the group of developmental disorders of embryonic heart conotruncal irregularities, and their pathogenesis is multifactorial. The anomaly's development is influenced by genetic, epigenetic, and environmental factors. It can occur either as an isolated anomaly, or in association with other cardiac defects. The typical concomitant cardiac anomalies that may occur in patients with D-TGA include ventriculoseptal defects, patent ductus arteriosus, left ventricular outflow tract obstruction (LVOTO), mitral and tricuspid valve abnormalities, and coronary artery variations. Correction of the defect during infancy is the preferred treatment for D-TGA. Balloon atrial septostomy (BAS) is necessary prior to the operation. The recommended surgical correction methods include arterial switch operation (ASO) and atrial switch operation (AtrSR), as well as the Rastelli and Nikaidoh procedures. The most common postoperative complications include coronary artery stenosis, neoaortic root dilation, neoaortic insufficiency and neopulmonic stenosis, right ventricular (RV) outflow tract obstruction (RVOTO), left ventricular (LV) dysfunction, arrhythmias, and heart failure. Early diagnosis and treatment of D-TGA is paramount to the prognosis of the patient. Improved surgical techniques have made it possible for patients with D-TGA to survive into adulthood.

Insight into the Interaction of Humulus lupulus L. Specialized Metabolites and Gastrointestinal Bitter Taste Receptors: In Vitro Study in STC-1 Cells and Molecular Docking.

Bitter taste receptors, also known as taste 2 receptors (T2R), are expressed throughout the body and are involved in regulating different physiological processes. T2R expression in the intestinal tract regulates orexigenic and anorexigenic peptide secretion, thus becoming potential a potential target for controlling food intake and the prevalence of obesity and overweight. The present study aims to investigate the implication of hop bitter compounds such as α-acids, ß-acids, and xanthohumol in the secretion of anorexigenic hormones and T2R expression in intestinal STC-1 cells. The tested bitter compounds induced the secretion of the anorexigenic hormones glucagon-like peptide 1 and cholecystokinin concurrently with a selective increase of murine Tas2r expression. Xanthohumol and α-acids selectively increase Tas2r138 and Tas2r130-Tas2r138 expression, respectively, in STC-1 cells, while ß-acids increased the expression of all bitter receptors studied, including Tas2r119, Tas2r105, Tas2r138, Tas2r120, and Tas2r130. Increased intracellular calcium levels confirmed this activity. As all investigated bitter molecules increased Tas2r138 expression, computational studies were performed on Tas2r138 and its human orthologue T2R38 for the first time. Molecular docking experiments showed that all molecules might be able to bind both bitter receptors, providing an excellent basis for applying hop bitter molecules as lead compounds to further design gastrointestinal-permeable T2R agonists.

The core microbiome of cultured Pacific oyster spat is affected by age but not mortality.

The Pacific oyster is the most widely cultured shellfish worldwide, but production has been affected by mortality events, including in hatcheries that supply the seed for growers. Several pathogens cause disease in oysters, but in many cases, mortality events cannot be attributed to a single agent and appear to be multifactorial, involving environmental variables and microbial interactions. As an organism's microbiome can provide resilience against pathogens and environmental stressors, we investigated the microbiomes in cohorts of freshly settled oyster spat, some of which experienced notable mortality. Deep sequencing of 16S rRNA gene fragments did not show a significant difference among the microbiomes of cohorts experiencing different mortality levels, but revealed a characteristic core microbiome comprising 74 taxa. Irrespective of mortality, the relative abundance of taxa in the core microbiomes changed significantly as the spat aged, yet remained distinct from the microbial community in the surrounding water. The core microbiome was dominated by bacteria in the families Rhodobacteraceae, Nitrosomonadaceae, Flavobacteriaceae, Pirellulaeceae, and Saprospiraceae. Within these families, 14 taxa designated as the "Hard-Core Microbiome" were indicative of changes in the core microbiome as the spat aged. The variability in diversity and richness of the core taxa decreased with age, implying niche occupation. As well, there was exchange of microbes with surrounding water during development of the core microbiome. The shift in the core microbiome demonstrates the dynamic nature of the microbiome as oyster spat age.IMPORTANCEThe Pacific oyster (Magallana gigas, also known as Crassostrea gigas) is the most widely cultivated shellfish and is important to the economy of many coastal communities. However, high mortality of spat during the first few days following metamorphosis can affect the seed supply to oyster growers. Here, we show that the microbiome composition of recently settled oyster spat experiencing low or high mortality was not significantly different. Instead, development of the core microbiome was associated with spat aging and was partially driven by dispersal through the water. These findings imply the importance of early-stage rearing conditions for spat microbiome development in aquaculture facilities. Furthermore, shellfish growers could gain information about the developmental state of the oyster spat microbiome by assessing key taxa. Additionally, the study provides a baseline microbiome for future hypothesis testing and potential probiotic applications on developing spat.

Gut microbiota metabolically mediate intestinal helminth infection in Zebrafish.

Intestinal helminth parasite (IHP) infection induces alterations in the composition of microbial communities across vertebrates, although how gut microbiota may facilitate or hinder parasite infection remains poorly defined. In this work we utilized a zebrafish model to investigate the relationship between gut microbiota, gut metabolites, and IHP infection. We found that extreme disparity in zebrafish parasite infection burden is linked to the composition of the gut microbiome, and that changes in the gut microbiome are associated with variation in a class of endogenously-produced signaling compounds, N-acylethanolamines, that are known to be involved in parasite infection. Using a statistical mediation analysis, we uncovered a set of gut microbes whose relative abundance explains the association between gut metabolites and infection outcomes. Experimental investigation of one of the compounds in this analysis reveals salicylaldehyde, which is putatively produced by the gut microbe Pelomonas, as a potent anthelmintic with activity against Pseudocapillaria tomentosa egg hatching, both in vitro and in vivo. Collectively, our findings underscore the importance of the gut microbiome as a mediating agent in parasitic infection and highlights specific gut metabolites as tools for the advancement of novel therapeutic interventions against IHP infection.

Comparison of 5-year cup and stem migration between ceramic-on-ceramic and ceramic-on-polyethylene bearing in press-fit total hip arthroplasty: a randomised controlled trial using radiostereometric analysis.

INTRODUCTION: The inelasticity of ceramic bearings might affect primary stability and migration of implants in press-fit total hip arthroplasty (THA). This randomised controlled trial compares migration patterns of the uncemented Delta-TT cup and H-MAX S stem between ceramic and polyethylene liners, up to 5 years follow-up. METHODS: Patients receiving primary press-fit THA were randomly allocated to a ceramic (n = 28) or polyethylene (n = 25) liner. Migration was measured using model-based radiostereometric analysis (RSA) at baseline and 1.5, 3, 6, 12, 24 and 60 months postoperatively and compared between groups using mixed models statistical analysis. The focus of this study is on the 2- to 5-year migration of the Delta-TT cup and migration during complete follow-up of the H-MAX S stem up to 5-years. RESULTS: At 5-year follow-up, mean (95% CI) proximal cup translation was 0.56 (0.37-0.74) mm in ceramic and 0.58 (0.25-0.90) mm in polyethylene (p = 0.729). The mean change in adduction was 1.05° (0.27-1.82°) in ceramic and 0.78° (-0.16-1.71°) in polyethylene. Mixed modelling showed that all between-group effects were ⩽0.20 mm for translation and ⩽0.22° for rotation at 5 years postoperatively (p ⩾ 0.23). Mean cup migration between 2 and 5 years was limited (all parameters <0.17 mm and <0.30°). At 5-year follow-up, mean stem subsidence was 2.09 mm (0.89-3.29 mm) in ceramic and 2.55 (0.97-4.12) mm in polyethylene. The mean change in internal rotation was 3.69° (1.98-5.40°) in ceramic and 4.01° (2.20-5.81°) in polyethylene. Most stem migration occurred up to 1.5 months, stabilising afterwards. All between-group effects were ⩽0.75 mm for translations and ⩽1.41° for rotations (p ⩾ 0.26). CONCLUSIONS: 5-year migration patterns of press-fit cups and stems were similar between ceramic and polyethylene liners. The Delta-TT cup and H-MAX S stem showed secondary stabilisation and remained stable up to 5 years in both groups, which is promising for long-term survival with both liner types. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03093038).

Cortical microstructure and hemispheric specialization-A diffusion-imaging analysis in younger and older adults.

Characterizing cortical plasticity becomes increasingly important for identifying compensatory mechanisms and structural reserve in the ageing population. While cortical thickness (CT) largely contributed to systems neuroscience, it incompletely informs about the underlying neuroplastic pathophysiology. In turn, microstructural characteristics may correspond to atrophy mechanisms in a more sensitive way. Fractional anisotropy, a diffusion tensor imaging (DTI) measure, is inversely related to cortical histologic complexity. Axial diffusivity and radial diffusivity are assumed to be linked to the density of structures oriented perpendicular and parallel to the cortical surface, respectively. We hypothesized (1) that cortical DTI will reveal microstructural correlates for hemispheric specialization, particularly in the language and motor systems, and (2) that lateralization of cortical DTI parameters will show an age effect, paralleling age-related changes in activation, especially in the prefrontal cortex. We analysed data from healthy younger and older adult participants (N = 91). DTI and CT data were extracted from regions of the Destrieux atlas. Diffusion measures showed lateralization in specialized motor, language, visual, auditory and inferior parietal cortices. Age-dependent increased lateralization for DTI measures was observed in the prefrontal, angular, superior temporal and lateral occipital cortex. CT did not show any age-dependent alterations in lateralization. Our observations argue that cortical DTI can capture microstructural properties associated with functional specialization, resembling findings from histology. Age effects on diffusion measures in the integrative prefrontal and parietal areas may shed novel light on the atrophy-related plasticity in healthy ageing.

Acute Myocardial Injury in Spontaneous Intracerebral Hemorrhage: A Secondary Observational Analysis of the FAST Trial.

BACKGROUND: Acute myocardial injury is associated with poor outcomes in patients with acute ischemic stroke, but its prognostic significance in patients with spontaneous intracerebral hemorrhage remains unclear. We investigated whether acute myocardial injury and the direction of the cardiac troponin I (cTnI) change (rising versus falling) affect post-intracerebral hemorrhage outcomes. METHODS AND RESULTS: We re-analyzed the FAST (Factor-Seven-for-Acute-Hemorrhagic-Stroke) trial. Acute myocardial injury was defined as at least 1 cTnI value above the upper reference limit with a rise/fall of >20%. Logistic regression tested for associations (1) between acute myocardial injury (presence versus absence) and poor outcome (modified Rankin Scale 4-6) and mortality at 15 and 90 days; (2) among 3 groups (rising versus falling versus no acute myocardial injury) and outcomes. Among the 841 FAST participants, 785 patients were included. Acute myocardial injury was detected in 29% (n=227); 170 had rising cTnI. At 15 and 90 days, respectively, those with acute myocardial injury had higher odds of poor outcome (adjusted odds ratio) ([aOR] 2.3 [95% CI, 1.3-3.9]); and adjusted odds ratio 2.5 [95% CI, 1.6-3.9];, and higher odds of mortality (adjusted odds ratio 2.4 [95% CI, 1.4-4.3]; and adjusted odds ratio 2.2 [CI, 1.3-3.6]) than patients without. There was no interaction between FAST group assignment and myocardial injury, and associations between myocardial injury and outcomes were consistent across group assignments. Rising cTnI was associated with the highest risk of poor outcomes and mortality. CONCLUSIONS: In this secondary analysis of the FAST trial, acute myocardial injury was common and associated with poor outcomes. The direction of the cTnI change might provide additional risk stratification after intracerebral hemorrhage.

Liquid chromatography-mass spectrometry quantification of phytochemicals in Withania somnifera using data-dependent acquisition, multiple-reaction-monitoring, and parallel-reaction-monitoring with an inclusion list.

Characterization of botanical extracts by mass spectrometry-based metabolomics analysis helps in determining the phytochemical composition that underlies their bioactivity and potential health benefits, while also supporting reproducibility of effects in clinical trials. The quantification of seven withanolides in Withania somnifera using three mass-spectrometry methods was evaluated using Deming regression. Two high-resolution time-of-flight mass spectrometry methods were used, one operating in data-dependent acquisition mode and the other in parallel-reaction-monitoring mode with an inclusion list. The two high-resolution time-of-flight mass spectrometry methods were compared to a multiple-reaction-monitoring method. We evaluated in-source fragmentation of steroidal glycosides and optimized the methods accordingly. A novel software approach to integrating parallel-reaction-monitoring data acquired with an inclusion list was developed. Combining and comparing quantitative results allowed for quantitative specificity, good precision, and adjustment of instrument source conditions for optimal quantification by multiple-reaction-monitoring mass spectrometry, an analytical method that is widely accessible in analytical and phytochemical laboratories.