Standard Clinical Procedures Research Articles

Evaluation of the Human Placental Microbiota in Early- and Late-Onset Pre-Eclampsia.

Despite many decades of research, the exact etiology of pre-eclampsia (PE) remains unknown. Several etiopathologies have been suggested, including the role of the placental microbiota. However, the existence of placental microbiota and its possible contribution to pregnancy complications, particularly PE has remained controversial. The present study was designed to identify different microbes that co-exist the placenta of women with early- and late-onset PE. Thirty age-matched normotensive and early-onset as well as age-matched normotensive and late-onset pre-eclamptic women respectively, were recruited. After obtaining an informed consent, the placental tissues were obtained through caesarian section with sterile and standardized clinical procedures. DNA was extracted from each tissue and microbiome analysis was conducted using a targeted 16S analysis and the reads were analyzed with bioinformatics. There was a significance difference between the blood pressure of early-/late-onset PE compared with age-matched normotensive controls, respectively. In addition, the reads from placencental samples were classified as belonging to the phyla, Actinobacteria, Firmicutes, Bacteroidetes, Proteobacteria, with Proteobacteria dominated by the classes Pseudomonadales and Gammaproteobacteria with smaller amounts of Actinobacteria and Bacteroidetes. There was no significant difference between the placental bacterial species of early-/late-onset PE compared with age-matched normotensive controls, respectively. Further analysis found no correlation between bacterial species and early- or late-onset PE. The present results demonstrate a low biomass of bacterial species, which might further indicate that the placental samples had very low levels of bacteria species and there is no correlation between the bacterial composition and early- or late-onset PE.

A review of label-free photonics-based techniques for cancer detection in the digestive and urinary systems

Abstract For a long time, it has been known that optics can provide a broad range of tools for addressing clinical needs, particularly diagnostics. Optical techniques can help in identifying diseases and detecting pathological tissues with non/minimally invasive and label-free methods. Given the current limitations of standard clinical procedures, such an approach could provide a powerful tool in detecting gastrointestinal and bladder cancers. However, each technique has serious limitations regarding one or more of the following features: biomarker sensitivity, penetration depth, acquisition times, or adaptation to the clinical environment. Hence there is an increasing need for approaches and instruments based on the concept of multimodality; in this regard, we review the application of different imaging/spectroscopy tools and methods operating in the first two optical windows (SHG, SPEF, TPEF, THG, 3PEF, CARS, Raman and reflectance) for tumour detection in the digestive and urinary systems. This article also explores the possibility of exploiting the third bio-tissue transmission window (1600-1900 nm) by reviewing state of the art in ultrafast laser sources development. Finally, we summarise the most recent results in developing multiphoton endoscopes – a key element for clinical in vivo translation of photonics-based diagnostics.

Just Keep Spinning? The Impact of Auditory and Somatosensory Cues on Rotary Chair Testing.

The purpose of this study was to determine whether providing realistic auditory or somatosensory cues to spatial location would affect measures of vestibulo-ocular reflex gain in a rotary chair testing (RCT) context. This was a fully within-subject design. Thirty young adults age 18-30 years (16 men, 14 women by self-identification) completed sinusoidal harmonic acceleration testing in a rotary chair under five different conditions, each at three rotational frequencies (0.01, 0.08, and 0.32 Hz). We recorded gain as the ratio of the amplitude of eye movement to chair movement using standard clinical procedures. The five conditions consisted of two without spatial information (silence, tasking via headphones) and three with either auditory (refrigerator sound, tasking via speaker) or somatosensory (fan) information. Two of the conditions also included mental tasking (tasking via headphones, tasking via speaker) and differed only in terms of the spatial localizability of the verbal instructions. We used linear mixed-effects modeling to compare pairs of conditions, specifically examining the effects of the availability of spatial cues in the environment. This study was preregistered on Open Science Framework (https://osf.io/2gqcf/). Results showed significant effects of frequency in all conditions (p < .05), but the only pairs of conditions that were significantly different were those including tasking in one condition but not the other (e.g., tasking via headphones vs. silence). Post hoc equivalence testing showed that the lack of significance in the other comparisons could be confirmed as not meaningfully different. These findings suggest that the presence of externally localizable sensory information, whether auditory or somatosensory, does not affect measures of gain in RCT to any relevant degree. However, these findings also contribute to the increasing body of evidence suggesting that mental engagement ("tasking") does increase gain whether or not it is provided via localizable instructions.

Analysis of Selected Physical Fitness, Physiological, and Psychological Variables among Government, Government-Aided, and Private School Boys in Chennai District

Purpose: This study aims to analyze and compare selected physical fitness, physiological, and psychological variables among boys from government, government- aided, and private schools in the Chennai district. The purpose is to understand how different school environments impact these variables and to provide insights that can inform policy and practice in physical education and health promotion.  Methodology: A sample of 300 boys aged 12-15 years was selected through stratified random sampling, with 100 boys from each school type (government, government-aided, and private schools). Physical fitness was measured using the Fitness Gram test battery, physiological variables such as BMI, resting heart rate, and blood pressure were assessed using standard clinical procedures, and psychological variables were evaluated using the Rosenberg Self- Esteem Scale and the Perceived Stress Scale. Data were analyzed using ANOVA to compare the means across the three school types, with post-hoc tests conducted to identify specific group differences.  Conclusion: The study found significant differences in physical fitness, physiological health, and psychological well-being among boys from different types of schools. Boys from private schools exhibited better physical fitness and lower stress levels compared to their peers in government and government-aided schools. These findings highlight the influence of socio-economic factors and access to resources on students' health and suggest the need for targeted interventions in government and government- aided schools to improve physical and psychological well- being among students.

Comparative studies between humans and golden Syrian hamsters via thromboelastography.

Thromboelastography (TEG) is a widely utilized clinical testing method for real-time monitoring of platelet function and the thrombosis process. Lipid metabolism disorders are crucial risk factors for thrombosis. The lipid metabolism characteristics of hamsters resemble those of humans more closely than mice and rats, and their relatively large blood volume makes them suitable for studying the mechanisms of thrombosis related to plasma lipid mechanisms. Whole blood samples from golden Syrian hamsters and healthy humans were obtained following standard clinical procedures. TEG was employed to evaluate coagulation factor function, fibrinogen (Fib) function, platelet function, and the fibrinolytic system. The whole blood from hamster or healthy human was isolated following the clinical procedure, and TEG was employed to evaluate the coagulation factor function, Fib function, platelet function, and fibrinolytic system. Coagulation analysis used ACLTOP750 automatic coagulation analysis pipeline. Blood routine testing used XN-2000 automatic blood analyzer. TEG parameters revealed that hamsters exhibited stronger coagulation factor function than humans (reaction time [R], p = 0.0117), with stronger Fib function (alpha angle, p < 0.0001; K-time [K], p < 0.0001). Platelet function did not differ significantly (maximum amplitude [MA], p = 0.077). Hamsters displayed higher coagulation status than humans (coagulation index [CI], p = 0.0023), and the rate of blood clot dissolution in hamsters differed from that in humans (percentage lysis 30 min after MA, p = 0.02). Coagulation analysis parameters indicated that prothrombin time (PT) and activated partial thromboplastin time (APTT) were faster in hamsters than in humans (PT, p = 0.0014; APTT, p = 0.03), whereas the Fib content was significantly lower in hamsters than in humans (p < 0.0001). No significant difference was observed in thrombin time (p = 0.1949). In summary, TEG could be used to evaluate thrombosis and bleeding parameters in whole blood samples from hamsters. The platelet function of hamsters closely resembled that of humans, whereas their coagulation function was significantly stronger.

The psychosocial outcomes of advanced hybrid closed-loop system in children and adolescents with type 1 diabetes

The study was carried out to determine the psychosocial outcomes of advanced hybrid closed-loop (AHCL) systems in children and adolescents with type 1 diabetes (T1D). Single-center and cohort study with a duration 6 months consisted of 60 children and adolescents with T1D. Standard clinical procedures, including both glycemic indicators, e.g., sensor-measured time within the 70–180 mg/dL range and glycated hemoglobin (HbA1c) levels, and psychosocial metrics were used for data collection. The psychosocial metrics included the Pediatric Quality of Life Inventory (PedsQL) 3.0 Diabetes Module for both children (8–12 years) and parents; the Quality of Life for Youth scale for adolescents (13–18 years); the Strengths and Difficulties Questionnaire (SDQ); the Hypoglycemia Fear Survey for Children (HFS-C); the Revised Child Anxiety and Depression Scale (R-CADS); and AHCLS-specific DTSEQ satisfaction and expectation survey. These metrics were evaluated at the baseline and after 6 months of AHCL use. Of the 60 children and adolescents with T1D for whom the AHCL system was utilized, 41 of them, 23 female and 18 male, completed the surveys. The mean age of the 41 children and adolescents was 12.5 ± 3.2 (min. 6.7, max. 18) years. The time spent within the target glycemic range, i.e., time-in-range (TIR), improved from 76.9 ± 9% at the baseline to 80.4 ± 5% after 6 months of AHCL system use (p = 0.03). Additionally, HbA1c levels reduced from 7.1% ± 0.7% at the baseline to 6.8% ± 0.8% after 6 months of AHCL system use (p = 0.03). The most notable decline in HbA1c was observed in participants with higher baseline HbA1c levels. All patients’ HFS-C and AHCL system-specific DTSEQ satisfaction and expectation survey scores were within the normal range at the baseline and remained unchanged during the follow-up period. No significant difference was found in the R-CADS scores of children and adolescents between baseline and after 6 months of AHCL system use. However, there was a significant decrease in the R-CADS scores of the parents. Patients’ PedsQL scores were high both at the baseline and after 6 months. The SDQ scores were high at baseline, and there was no significant improvement at the end of 6 months. Conclusion: This is the first study to investigate in detail the psychosocial outcomes of AHCL system use in T1D patients and their parents. Although state-of-the-art technologies such as AHCL provide patients with more flexibility in their daily lives and information about glucose fluctuations, the AHCL resulted in a TIR above the recommended target range without a change in QOL, HFS-C, SDQ, and R-CADS scores. The scores obtained from the R-CADS conducted by the parents of the children indicated that the use of pumps caused a psychological improvement in the long term, with a significant decrease in the R-CADS scores of the children and adolescents with T1D.What is Known:• Previous studies focused on clinical outcomes of AHCL systems in pediatric T1D patients, showing glycemic control improvements.• Limited attention given to psychosocial outcomes of AHCL systems in children and adolescents with T1D.• Crucial psychosocial factors like quality of life, emotional well-being, and fear of hypoglycemia underexplored in AHCL system context.What is New:• First study to comprehensively examine psychosocial outcomes of AHCL systems in pediatric T1D patients.• Study's robust methodology sets new standard for diabetes technology research and its impact on qualiy of life.

Estimation of local arterial stiffness using non-invasive flow measurements: a study on a stenosed carotid artery

Arterial stiffness is a well-established independent prognostic bio-marker in the human cardiovascular system (CVS). Despite its value as a predictive bio-marker, the inclusion of vascular stiffness into standard clinical procedures or guidelines is limited. This has come about as a result of the abundance of tools created to estimate and evaluate local arterial stiffness in people. This study employs a non-invasive technique to measure local arterial stiffness in the human carotid arteries using proximal flow measurements. Within this work, a viscoelastic lumped-parameter (0D) model of the carotid arteries is developed in complement with the non-invasive flow measurements obtained from the Doppler ultrasound. Further, concepts of sensitivity analysis and parameter estimation are applied to estimate arterial stiffness using the flow measurement taken at the common carotid artery (CCA). After the successful estimation of arterial stiffness in CCA, results show good agreement between model simulations and actual measurement.

The association between dietary total antioxidant capacity and hearing loss: results from the Tehran employees Cohort Study

BackgroundDespite numerous studies that have explored the association between individual antioxidants or specific combinations and the risk of hearing loss, there is lack of information regarding the relationship between dietary total antioxidant capacity (dTAC) and hearing loss. The conflicting results on this association further highlight the need for more research in this area. This study aims to investigate the association between overall dietary antioxidant intake and the risk of hearing loss among Iranian adults.MethodsThis cross-sectional study recruited 3443 adult participants aged between 19 and 67 years (with an average age of 41.4 years ± 8.8) who were employed at Tehran University of Medical Sciences in Iran. Participants underwent dietary assessment using a validated Food Frequency Questionnaire (FFQ). The hearing status of each participant was evaluated by a licensed audiologist in a soundproof room, using diagnostic audiometry that adhered to American National Standards specifications and followed standard audiometric clinical procedures. The dietary total antioxidant capacity (dTAC) was calculated using the Ferric Reducing-Antioxidant Power (FRAP) values.Results43.6% of male participants had hearing loss, while 26.8% among female participants. After accounting for various confounding factors, no significant association was observed between higher levels of dTAC and reduced odds of hearing loss in the overall population. However, among men under the age of 40, higher levels of dTAC were associated with decreased odds of hearing loss, even after adjusting for several covariates (OR: 0.56, 95% CI: 0.31–1.02, Ptrend = 0.02). This relationship was not evident in men over 40 years of age or among women.ConclusionThe study found an inverse relationship between higher antioxidant intake in the diet and lower odds of hearing loss, specifically among men who were 40 years old or younger. However, this relationship was not observed in the overall population or among women. Additional prospective studies are necessary to validate these results.

Protoporphyrin IX in serum of high-grade glioma patients: A novel target for disease monitoring via liquid biopsy.

High-grade gliomas (HGG) carry a dismal prognosis. Diagnosis comprises MRI followed by histopathological evaluation of tissue; no blood biomarker is available. Patients are subjected to serial MRIs and, if unclear,surgery for monitoring of tumor recurrence, which is laborious. MRI provides only limited diagnostic information regarding the differentiation of true tumor progression from therapy-associated side effects. 5-aminolevulinic acid (5-ALA)is routinely used for induction of protoporphyrin IX (PpIX) accumulation in malignant glioma tissue, enablingimproved tumor visualizationduring fluorescence-guided resection (FGR). We investigated whether PpIX can also serve as a serum HGG marker to monitor relapse. Patients (HGG: n = 23 primary, pHGG; n = 5 recurrent, rHGG) undergoing FGR received 5-ALA following standard clinical procedure. The control group of eight healthy volunteers (HCTR) also received 5-ALA. Serum was collected before and repeatedly up to 72h after drug administration. Significant PpIX accumulation in HGG was observed after 5-ALA administration (ANOVA: p = 0.005, post-hoc: HCTR vs. pHGG p = 0.029, HCTR vs. rHGG p = 0.006). Separation of HCTR from pHGG was possible when maximum serum PpIX levels were reached (CI95% of tMax). ROC analysis of serum PpIX within CI95% of tMax showed successful classification of HCTR and pHGG (AUCROC 0.943, CI95% 0.884-1.000, p < 0.001); the optimal cut-off for diagnosis was 1275pmolPpIX/ml serum, reaching 87.0% accuracy, 90.5% positive predictive and 84.0% negative predictive value. Baseline PpIX level was similar in patient and control groups. Thus, 5-ALA is required for PpIX induction, which is safe at the standard clinical dosage. PpIX is a new target for liquid biopsy in glioma. More extensive clinical studies are required to characterize its full potential.

The higher dietary inflammation is associated with a higher burden of multimorbidity of cardio-metabolic and mental health disorders in an urbanizing community of southern India: A cross-sectional analysis for the APCAPS cohort

Background & aimsHabitual dietary pattern has been shown to be a major modulator of systemic inflammation and is considered a modifiable risk factor for cardio-metabolic diseases (CMDs) and mental health disorders. We examined whether dietary-inflammation is associated with the multimorbidity of CMDs and mental health disorders in urbanizing-villages in southern India. We hypothesized that the participants with higher dietary-inflammation would have a higher burden of multimorbidity. Materials & methodsWe conducted a cross-sectional analysis of 5984 adults (53% male) participating in the Andhra Pradesh Children and Parents' Study. We assessed dietary-inflammation using dietary inflammatory index (DII®) based on intake of 27 micro- and macro-nutrients which were measured using a validated food-frequency-questionnaires. The CMDs and mental health disorders were assessed using standardized clinical procedures and validated questionnaires. ‘Multimorbidity’ was defined as a co-existence of one or more CMDs (hypertension, diabetes, myocardial infarction, heart failure, angina and stroke) and one or more mental health disorders (depression and anxiety). The association of multimorbidity with dietary-inflammation was examined using robust Poisson regression. ResultsThe prevalence of multimorbidity was 3.5% and ∼75% of participants were consuming a pro-inflammatory diet (DII >0.0). As compared to the 1st DII-quartile (least dietary-inflammatory group), the adjusted prevalence ratio (95% confidence interval) for the presence of multimorbidity was 1.46(0.87, 2.46) for 2nd, 1.75(1.05, 2.89) for 3rd, and 1.77(1.06, 2.96) for 4th DII-quartile (p-trend = 0.021). There was no evidence of an interaction between DII and sex on multimorbidity. ConclusionsDietary-inflammation had a positive linear association with the multimorbidity, which suggest that even modest reduction in dietary-inflammation may reduce the multimorbidity burden.

Mass spectrometry in clinical laboratory: applications and future prospects

Innovations in laboratory medicine face additional challenges due to the unmet need for extremely precise methods of disease diagnosis. Developments in mass spectrometry-based disease biomarker identification are constantly expanding the field of clinical diagnosis. More mass spectrometry-based in vitro diagnostics are anticipated to move from the bench to the bedside shortly, although several are currently incorporated into standard clinical procedures. The molecular detection by mass spectrometry technique is very effective in diagnosis of the disease and therapeutic monitoring because of its extremely high sensitivity, specificity, and short turnaround time. Mass spectrometry is a potent analytical instrument that may be used to analyse a variety of materials and matrices; its use in clinical laboratory medicine applications is rising. For clinical prognostics and diagnostic purposes, mass spectrometry imaging has been widely utilized to distinguish between healthy and diseased tissues. Modern single-cell studies will benefit from its cutting-edge applications, which will offer comprehensive cellular biochemical data for mechanistic comprehension and, eventually, the development of therapeutic interventions. Within the field of laboratory medicine, the application of mass spectrometry is crucial, especially in terms of diagnostics and therapeutic drug monitoring. This review on the clinical application of mass spectrometry and its future prospects promises an insightful exploration of the evolving landscape of mass spectrometry in clinical settings, delving into its current applications and shedding light on its potential future advancements, for which a comprehensive search in the PubMed, ScienceDirect, and Web of Science databases was conducted.

Advanced Diffusion MRI of White Matter in Aging and AD

AbstractChanges in brain white matter occur in normal aging and prior to the onset of cognitive impairment. We have shown that advanced diffusion MRI and biophysical modeling yield sensitive and specific metrics that distinguish age‐related (e.g. myelin remodeling) from amyloid‐related pathological processes (e.g. myelin repair) in the preclinical stage. In this presentation we provide an update on our ongoing observational longitudinal study to determine the extent to which these metrics can serve as predictive biomarkers of incident cognitive impairment. Cognitively unimpaired older adults completed brain MRI (including Diffusional Kurtosis Imaging) and standard clinical procedures (NACC UDS v3) at baseline and ∼2 years later, with 91.2% retention and 13.1% incident MCI (CDR = 0.5) at follow‐up. We found that in participants with preclinical AD, late‐myelinating white matter tracts demonstrate signs of myelin repair/gliosis as evidenced by greater diffusion restriction. We also observed that greater diffusion restriction predicts incident MCI over and above age, a finding we did not observe with other AD neuroimaging biomarkers of amyloid pathology, neurodegeneration, and white matter lesions. In the next 5 years of funding, we will expand our cohort in size and representativeness, incorporate complementary MRI biomarkers of myelin/gliosis (i.e. myelin water imaging [ViSTa] and 1H‐MRS of myo‐inositol and NAA) to test our inferences, and further develop diffusion MRI‐based biophysical modeling techniques (i.e. Fiber Ball Imaging‐based white matter modeling). Expected outcomes from this work include clinically feasible MRI biomarkers with which to empirically test a proposed conceptual model of white matter‐related changes in aging and AD, thereby providing translational support for trials of myelin/glia‐focused therapies which are grossly underexplored for asymptomatic AD. Our goal is to have an impact on the evolving conceptualization of how aging leads to AD and, critically, to illuminate novel mechanisms by which AD can be prevented or treated.

Trajectories of healthy aging and their association with prodromal parkinson disease: The HELIAD study

Background: The aim of the present study was to investigate the association of prodromal PD (pPD) with trajectories of healthy aging, according to its latest definition by the WHO. Methods: In a sample of 1,226 older adults (704 women), PD diagnosis was reached through standard clinical research procedures. Probability of pPD was calculated according to the International Parkinson and Movement Disorder Society’s research criteria for PD-free participants. A healthy aging metric was introduced using an item response theory approach (IRT) based on information from validated questionnaires assessing functionality. Four trajectories of healthy aging were created based on whether the healthy aging status of participants was above or below the median at baseline and follow up: High-High, High-Low, Low-High and Low-Low. Results: 34.3% belonged to the High-High group, 15.7% to the High-Low, 18.6% to the Low-High and 31.4% to the Low-Low group. Participants with possible/probable pPD were 78% less likely to belong in High-High trajectory of healthy aging as compared to those without pPD (OR = 0.22, 95%CI 0.06-0.79, p-value = 0,02). Conclusion: Our findings suggest an inverse association of pPD probability with healthy aging among older adults; Further research is needed to investigate the clinical implications of this association.

BIOM-21. LIQUID BIOPSY IN SERA OF HIGH-GRADE GLIOMA PATIENTS: PROTOPORPHYRIN IX AS A BIOMARKER

Abstract High-grade gliomas (HGG) carry a dismal prognosis. Diagnosis comprises magnetic resonance imaging (MRI) followed by histopathological evaluation of tumor tissue after biopsy collection; no blood biomarker is currently available. Patients are subjected to repeated surgery and MRI for relapse monitoring. Protoporphyrin IX (PpIX) is already in routine use for selectively visualizing HGG tissue during fluorescence-guided resection (FGR). We investigated if it can also serve as serum HGG marker. Patients (HGG: n = 23 primary, pHGG; n = 5 recurrent, rHGG) undergoing FGR received 5-aminolevulinic acid (5-ALA) following standard clinical procedure. The control group of eight healthy volunteers (HCTR) also received 5-ALA. Serum was collected before and repeatedly up to 72 h after drug administration. PpIX was analyzed following liquid-liquid and solid-phase extraction using liquid chromatography coupled to ion trap mass spectrometry. The serum PpIX level before 5-ALA administration was similar in patient and control groups. Significant PpIX accumulation in HGG was observed after 5-ALA administration (ANOVA: p = 0.005, post-hoc: HCTR vs. pHGG p = 0.029, HCTR vs. rHGG p = 0.006). Separation of HCTR from pHGG was possible within CI95% of tMax (AUC: 0.943, CI95% 0.884 - 1.000, p &amp;lt; 0.001); the optimal cut-off for diagnosis was 1275 pmol PpIX/ml serum, reaching 87.0 % accuracy, 90.5 % positive predictive value and 84.0 % negative predictive value. Distinguishing pHGG patients from healthy controls based on serum PpIX is possible. The prodrug 5-ALA is required for PpIX induction, which is safe for the standard clinical dosage. Thus, PpIX is a new target for liquid biopsy in glioma, but larger clinical studies are required to characterize its full potential.

An optimization framework for targeted spinal cord stimulation

Objective. Spinal cord stimulation (SCS) is a common neurostimulation therapy to manage chronic pain. Technological advances have produced new neurostimulation systems with expanded capabilities in an attempt to improve the clinical outcomes associated with SCS. However, these expanded capabilities have dramatically increased the number of possible stimulation parameters and made it intractable to efficiently explore this large parameter space within the context of standard clinical programming procedures. Therefore, in this study, we developed an optimization approach to define the optimal current amplitudes or fractions across individual contacts in an SCS electrode array(s). Approach. We developed an analytic method using the Lagrange multiplier method along with smoothing approximations. To test our optimization framework, we used a hybrid computational modeling approach that consisted of a finite element method model and multi-compartment models of axons and cells within the spinal cord. Moreover, we extended our approach to multi-objective optimization to explore the trade-off between activating regions of interest (ROIs) and regions of avoidance (ROAs). Main results. For simple ROIs, our framework suggested optimized configurations that resembled simple bipolar configurations. However, when we considered multi-objective optimization, our framework suggested nontrivial stimulation configurations that could be selected from Pareto fronts to target multiple ROIs or avoid ROAs. Significance. We developed an optimization framework for targeted SCS. Our method is analytic, which allows for the fast calculation of optimal solutions. For the first time, we provided a multi-objective approach for selective SCS. Through this approach, we were able to show that novel configurations can provide neural recruitment profiles that are not possible with conventional stimulation configurations (e.g. bipolar stimulation). Most importantly, once integrated with computational models that account for sources of interpatient variability (e.g. anatomy, electrode placement), our optimization framework can be utilized to provide stimulation settings tailored to the needs of individual patients.

Identification of potential biomarkers in malnutrition children with severity by 1H-NMR-based metabolomics: a preliminary study in the Chinese population.

Child malnutrition is a global public health problem, but the underlying pathophysiologic mechanisms with severity remain poorly understood, and the potential biomarkers served to the clinical diagnosis are still not available. This study aimed to identify the serum metabolic characteristics of malnourished children with severity. Fasted overnight serum samples were collected following clinical standard procedures among275 malnourished and 199 healthy children from the Women and Children's Hospital, Xiamen University Child Health Department from July 2020 to May 2022. Nuclear magnetic resonance (NMR)-based metabolomics strategy was applied to identify the potential serum biomarkers of malnutrition from 275 malnourished children aged 4 to 84 months with mild (Mil, 199 cases), moderate (Mod, 101 cases), and severe (Sev, 7 cases) malnutrition. Ten, fifteen, and fifteen differential metabolites were identified from the Mil, Mod, and Sev malnutrition groups, respectively. Eight common metabolites, including increased acetoacetate, acetone, ethanol, succinate, 3-hydroxybutyrate, and decreased alanine, methionine, and N-acetyl-glycoprotein, could be the potential biomarkers for malnourished children. The altered metabolic pathways were mainly related to energy metabolism and amino acid metabolism via the network-based pathway enrichment. Eight potential biomarkers, including acetoacetate, acetone, ethanol, succinate, 3-hydroxybutyrate, alanine, methionine, and N-acetyl-glycoprotein, could characterize the child malnutrition. Child malnutrition-induced abnormal energy metabolism, impaired nutrition utilization and the reduced nutrient availability, and more metabolic disturbance will appear with the severity. Our results are valuable for further studies on the etiology and pathogenesis of malnutrition for clinical intervention and improvement.

Relationship between Nutritional Risk, Clinical and Demographic Characteristics, and Pressure Ulcers in Patients with Severe Acquired Brain Injuries Attending a Rehabilitative Program.

Preliminary evidence in the literature suggests a high prevalence of malnutrition (undernutrition) in patients with severe acquired brain injuries (sABI), with an expected negative impact on clinical outcomes and pressure ulcers (PUs) in particular. In a retrospective cohort study on patients discharged from intensive care units (ICU) and admitted to an intensive rehabilitation unit (IRU), the risk of malnutrition was systematically assessed, in addition to standard clinical procedures (including PUs evaluation), using two different tools: the Malnutrition Universal Screening Tool (MUST) and the Controlling Nutritional Status (CONUT) tool. Eighty-eight patients were included in the analysis. A high proportion (79.5%) of patients with sABI suffered from PUs, being older and more frequently men, with a longer ICU stay between the event and admission to IRU, and a greater MUST score. At discharge, when compared to patients whose PUs had healed, those with persisting PUs were more often men and had the worst cognitive performance at admission. As for nutritional risk, the baseline CONUT score was identified as an independent negative predictor of PUs at discharge by the logistic regression model. In conclusion, the assessment of nutritional risk using simple standard tools may be useful in the clinical evaluation of sABI patients with PUs.

P-687 Serum Anti-Müllerian hormone to antral follicle count ratio does not predict euploidy rate in young patients who had at least 1 zygote after fertilization

Abstract Study question Does serum Anti-Müllerian hormone to antral follicle count ratio predict euploidy rate in young patients who had at least 1 zygote after fertilization? Summary answer Serum Anti-Müllerian hormone to antral follicle count ratio (AMH/AFC) does not predict euploidy rate in young patients who had at least 1 zygote after fertilization. What is known already AMH is produced by the granulosa cells of the growing follicles. It has been demonstrated that the antral follicles are the main contributors to its serum values. AMH´s role as a quantitative predictor of the ovarian response to stimulation is undeniable. However, studies looking at its correlation with oocyte quality, assessed as embryo ploidy, have yielded conflicting results. All of them include only patients who had at least one blastocyst for biopsy obviating those who had all embryos arrested, which might be genetically abnormal. Besides, no study before has considered the per-follicle production of AMH when evaluating serum AMH levels. Study design, size, duration Retrospective analysis of women undergoing Preimplantation Genetic Testing for Aneuploidy at the blastocyst stage according to standard clinical procedures in a tertiary referral IVF center from April 2017 to August 2022. As linear regression excluded an effect of age on euploidy rate until 35 years, 570 patients below this age were included. AMH/AFC ratio was calculated as a marker of per-follicle AMH production. Patients were classified into quartiles. Euploidy rates/zygote were compared among them. Participants/materials, setting, methods Patients who had at least 1 zygote were included. AMH was measured by Elecsys within 6 months before start of stimulation. Scans were performed by 3 experienced sonographers. Women with an AMH &amp;gt; 5,98 ng/ml, endometriosis, autoimmune disease, non-functional ovarian cyst, hormonal treatment prior to AMH measurement or history of ovarian surgery, men with less than 1 million of sperm/milliliter of ejaculate, and couples with an abnormal karyotype or history or gonadotoxic treatment were excluded. Main results and the role of chance Included patients had a median (+ interquartile range) AMH of 2.73 ng/ml (1.68-3.77), median BMI of 25.7 kg/m2 (22.8-28.9) and median antral follicle count of 14 (11-19). Median number of oocytes collected was 14 (10-20) and median number of metaphase II oocytes was 11 (7-15). Thresholds for p25th and p75th AMH/AFC ratios were 0.13 and 0.24 respectively. The number of patients included in the &amp;lt;p25th, p25th-p75th and &amp;gt;p75th groups were 134, 297 and 139, respectively. Whereas median age and BMI wereńt statistically different among groups, significant differences were found in median AMH (&amp;lt;p25th: 1.38 ng/ml (0.8-2.1); p25th-p75th: 2.75 ng/ml (2-3.7); &amp;gt;p75th: 3.9 ng/ml (3.1-4.8), p &amp;lt; 0.001) and AFC (&amp;lt;p25th: 14 (9.2-20) p25th-p75th: 16 (12-20); &amp;gt;p75th: 13 (10-16), p &amp;lt; 0.001). No significant differences were found in the fertilization rate (&amp;lt;p25th: 0.75 (0.6-0.8); p25th-p75th: 0.75 (0.6-0.9); &amp;gt;p75th: 0.78 (0.7-0.9)) nor in the biopsy rate/zygote (&amp;lt;p25th: 0.64 (0.5-0.8), p25th-p75th: 0.6 (0.4-0.8), &amp;gt;p75th: 0.6 (0.5-0.7)). Euploidy rate/zygote wasńt statistically different among groups: &amp;lt;p25th: 0.36 (0.2-0.5); p25th-p75th: 0.33 (0.2-0.5); &amp;gt;p75th: 0.33 (0.2-0.5). When compared with p25th-p75th, patients with an AMH/AFC &amp;lt;p25th showed a tendency towards a higher risk of not having an euploid embryo, due to culture arrest or aneuploidy (19.4% vs 10.8%, p 0.065). Limitations, reasons for caution The retrospective design of the study might restrict an adequate control of confounding factors. The small size of the lower quartile group might compromise the accuracy of the findings. Wider implications of the findings The association between AMH levels and live birth rate after In Vitro Fertilization remains debated. Whereas this study didńt find a correlation between AMH/AFC ratio and euploidy rate/zygote, further research will have to evaluate other markers of oocyte quality that might by affected by a low per-follicle production of AMH. Trial registration number Not applicable

Validating the ORACollect for the detection of cytomegalovirus

Targeted screening for Cytomegalovirus (CMV) in Deaf and Hard of Hearing (DHH) children is now internationally recommended. With newborn genomic screening for DHH children a future possibility, the commercially-available human genomic DNA collection kit (ORACollect, Oragene OCR-100) could enable one single sample to screen for CMV and genetic causes of deafness at scale with minimal additional costs. Our pilot study validated ORACollect against Copan FLOQswabs® (gold standard clinical procedure) for detecting CMV using 15 sets of saliva samples from 14 infants/children, comparing CMV PCR results using different testing protocols. ORACollect stored at room temperature had high sensitivity (up to 89%), specificity (up to 80%) and percent agreement (up to 86%) in detecting CMV DNA compared to FLOQswabs®. This suggests that ORACollect is an appropriate alternative to FLOQswabs® for collecting viral CMV DNA for PCR testing, independent of the DNA extraction approach. This could be revolutionary in facilitating dual genomic and viral screening in newborns and would enable CMV screening in non-tertiary hospital settings where laboratory facilities are not available.

MEG language mapping using a novel automatic ECD algorithm in comparison with MNE, dSPM, and DICS beamformer.

The single equivalent current dipole (sECD) is the standard clinical procedure for presurgical language mapping in epilepsy using magnetoencephalography (MEG). However, the sECD approach has not been widely used in clinical assessments, mainly because it requires subjective judgements in selecting several critical parameters. To address this limitation, we developed an automatic sECD algorithm (AsECDa) for language mapping. The localization accuracy of the AsECDa was evaluated using synthetic MEG data. Subsequently, the reliability and efficiency of AsECDa were compared to three other common source localization methods using MEG data recorded during two sessions of a receptive language task in 21 epilepsy patients. These methods include minimum norm estimation (MNE), dynamic statistical parametric mapping (dSPM), and dynamic imaging of coherent sources (DICS) beamformer. For the synthetic single dipole MEG data with a typical signal-to-noise ratio, the average localization error of AsECDa was less than 2 mm for simulated superficial and deep dipoles. For the patient data, AsECDa showed better test-retest reliability (TRR) of the language laterality index (LI) than MNE, dSPM, and DICS beamformer. Specifically, the LI calculated with AsECDa revealed excellent TRR between the two MEG sessions across all patients (Cor = 0.80), while the LI for MNE, dSPM, DICS-event-related desynchronization (ERD) in the alpha band, and DICS-ERD in the low beta band ranged lower (Cor = 0.71, 0.64, 0.54, and 0.48, respectively). Furthermore, AsECDa identified 38% of patients with atypical language lateralization (i.e., right lateralization or bilateral), compared to 73%, 68%, 55%, and 50% identified by DICS-ERD in the low beta band, DICS-ERD in the alpha band, MNE, and dSPM, respectively. Compared to other methods, AsECDa's results were more consistent with previous studies that reported atypical language lateralization in 20-30% of epilepsy patients. Our study suggests that AsECDa is a promising approach for presurgical language mapping, and its fully automated nature makes it easy to implement and reliable for clinical evaluations.