Short-term Markers Research Articles

Prognostic value of baseline and follow-up ECG in patients with biopsy-proven fulminant myocarditis

Abstract Background Fulminant myocarditis represents a life-threatening condition with poor outcomes characterized by increased short- and long-term mortality and need for heart transplant. Treatment largely relies on mechanical support and immunosuppressive therapy guided by histologic and virology findings but reliable short-term prognostic markers guiding therapy and management are still lacking. We hypothesised that baseline and short-term ECG evolution may provide relevant easily accessible prognostic information in these patients. Purpose We sought to assess the prognostic value of baseline and short-term follow-up ECG in patients affected by fulminant myocarditis. Methods We retrospectively enrolled patients with biopsy-proven fulminant myocarditis according to current diagnostic criteria. We evaluated baseline and follow-up ECG (performed 3 to 7 days after admission) together with clinical, laboratory and histologic data. The primary endpoint was a composite of in-hospital mortality or need for urgent heart transplantation. Results We enrolled 39 patients (22/39 M, 56.4%) and a mean age of 38 years. Histology demonstrated lymphocytic myocarditis in 35/39 cases, 2 eosinophilic and 1 giant cell myocarditis, 1 sarcoidosis. All patients received vasopressor and/or inotrope therapy with 19/39 requiring mechanical circulatory support. Follow-up ECGs were performed after 4.8±1.3 days from admission. The primary endpoint was reached in 7/39 patients (17.9%) with 5 deaths and 2 urgent cardiac transplants. These patients more commonly required mechanical (85.7% vs 40.6%, p=0.044) or extracorporeal membrane oxygenator (85.7% vs 12.5%, p<0.001) support and showed higher lactate levels on admission (11.0±7.3 vs 4.2±3.1 mmol/L, p=0.001). They also more frequently had cardiac arrest as first clinical presentation (50. 0% vs 9.7%, p=0.022) and sustained ventricular tachycardia (71.4% vs 15.6%, p=0.007) in the acute phase. Patients with a worse outcome showed persistence of low voltages (< 5 mm in all peripheral leads) at follow-up ECG (100.0% vs 37.5%, p=0.003) with lower R wave amplitude in lead II (1.1±0.9 vs 4.0±2.6 mm, p=0.004), III (0.7±0.5 vs 2.5±2.2 mm, p=0.043), aVF (0.9±0.7 vs 3.0±2.0 mm, p=0.01) and V6 (3.0±2.8 vs 7.5±4.2 mm, p=0.011) and reduced S wave amplitude in V1 (2.6±3.9 vs 6.4±4.4 mm, p=0.047), V2 (3.9±3.9 vs 10.2±6.7 mm, p=0.035), V3 (3.3±3.2 vs 10.7±6.7 mm, p=0.007) leads. Low QRS voltages at baseline ECG were not associated with worse prognosis (71.4% vs 46.9%, p=0.407). No significant difference in terms of steroid (85.7% vs 78.1%, p=0.929) or other immunosuppressive (14.3% vs 31.2%, p=0.366) therapy was observed between the groups. Conclusions In patients with fulminant myocarditis, persistence of low QRS voltages at 5-day follow-up ECG is associated with adverse in-hospital outcomes. Short-term ECG evolution can identify high-risk patients requiring earlier and more intensive mechanical and pharmacological treatment.

The protective effect of Astaxanthin on scopolamine - induced Alzheimer's model in mice.

To investigate the fundamental mechanisms of the neuroprotective impact of Astaxanthin (AST) in a mouse model of Alzheimer's disease (AD) induced by scopolamine. This research constituted an in vivo animal study encompassing 36 adult male mice, divided into 6 groups: Control, 100mg/kg AST, 2mg/kg scopolamine (AD group), 100mg/kg AST+2mg/kg scopolamine, 3mg/kg galantamine+2mg/kg scopolamine, and 100mg/kg AST+3mg/kg galantamine+2mg/kg scopolamine. After 14 days, the mice's short-term memory, hippocampus tissue, oxidative and inflammatory markers were evaluated. The AST demonstrated a beneficial influence on short-term memory and a reduction in acetylcholinesterase activity in the brain. It exhibited neuroprotective and anti-amyloidogenic properties, significantly decreased pro-inflammatory markers and oxidative stress, and reversed the decline of the Akt-1 and phosphorylated Akt pathway, a crucial regulator of abnormal tau. Furthermore, AST enhanced the effect of galantamine in reducing inflammation and oxidative stress. The findings indicate that AST may offer therapeutic benefits against cognitive dysfunction in AD. This is attributed to its ability to reduce oxidative stress, control neuroinflammation, and enhance Akt-1 and pAkt levels, thereby underscoring its potential in AD treatment strategies.

Environmental exposure to polycyclic aromatic hydrocarbons: An underestimated risk factor for systemic lupus erythematosus onset and progression

ObjectiveTo investigate the link between systemic lupus erythematosus (SLE) incidence and exposure to environmental polycyclic aromatic hydrocarbons (PAH). MethodsA case-control study (ChiCTR2000038187) involving 316 SLE patients and 851 healthy controls (HCs) was executed. Environmental exposure was assessed via a questionnaire, stratified by gender and age (females <35 and ≥35 years, males). Blood samples collected from 89 HCs, 85 inactive, and 95 active SLE patients were used to measure serum benzo[a]pyrene diol epoxide -albumin (BPDE-Alb) adducts and PAH concentrations, indicating long-term and short-term exposure respectively. Intergroup comparisons and statistical analyses were conducted using R version 4.3.1. ResultsDiverse patterns were found in how environmental factors affect SLE onset across different demographics. Lifestyle exposure factors were found to be a stronger determinant of SLE onset than occupational exposure factors in women under 35. Indoor air pollution had a significant impact on SLE incidence, potentially comparable to outdoor air pollution. Lifestyle-related PAH exposure had a greater impact on SLE than occupational PAH exposure. PAH exposure levels progressively increase from HCs to inactive and active SLE patients. Active SLE patients show markedly higher BPDE-Alb levels than HCs. ConclusionsEnvironmental PAH, particularly lifestyle-related, are significant, yet under-recognized, risk factors for SLE. Statement of environmental implicationWe examined the relationship between exposure to environmental polycyclic aromatic hydrocarbons (PAH) and the incidence of systemic lupus erythematosus (SLE). PAH, prevalent in sources such as cigarette smoke, air pollution, and charred food, pose significant health hazards. This study is the first to investigate specific PAH exposure levels in SLE patients. We determined actual PAH exposure levels in both SLE patients and healthy individuals and indicated that long-term PAH exposure biomarker is more reliable for evaluating exposure in non-occupationally exposed groups like SLE, compared to short-term markers. These findings provide valuable insights for future research on similar non-occupationally exposed populations.

Abstract P297: Associations Between Short-Term Outdoor Heat Measures and Markers of Immune Response and Inflammation

Introduction: Extreme-heat events increase mortality, and excessive deaths due to heat waves are overwhelmingly cardiovascular in origin. However, many previous studies only consider ambient temperature, which fails to capture the actual heat stress experienced by populations. Hot weather can interfere with a variety of biological processes including the promotion of systemic inflammatory responses, which play a critical role in the progression of cardiovascular disease (e.g., atherosclerosis). Our objective was to assess how short-term heat exposures are related to markers of inflammation and the immune response using physiologically-relevant heat metrics that capture additional meteorological conditions. Methods: Adult participants, aged 20-70 years, were recruited from a neighborhood in Louisville, KY during the summer months of 2018 and 2019. Circulating cytokines and immune cells were measured in 624 participants at baseline. Heat metrics, including temperature, net effective temperature, and Universal Thermal Climate Index (UTCI) were calculated as the 24hr mean on the day of participants’ clinical visit. Linear regression models were used to estimate associations between heat metrics and each biomarker, adjusting for socio-demographic and behavioral factors. Results: Participants were predominantly female (59%) and White (77%), with an average age of 49.5 years. The median daily temperature during study visits was 24.5 degrees C (IQR=3.8 degrees). The mean daily UTCI was positively associated with total circulating monocytes (4.2% per IQR; 95% CI: 0.3, 8.3), and classical monocytes (CD14 hi CD16 lo ), while nonclassical monocytes (CD14 lo CD16 hi ) displayed a negative association. We also observed positive associations with eosinophils 9.5% per IQR (95% CI: 0.6, 19.1) and Natural Killer T-Cells 9.9% per IQR (95% CI:2.8, 17.5), and a negative association with B-cells -6.8% per IQR (95% CI: -12.1, -1.1). In our cytokine analysis, UTCI was positively associated with TNF-alpha 7.0% per IQR (95% CI:2.8, 11.4) as well as IL-5 and MIP-1α. Similar, but attenuated associations were observed using daily temperature and other heat metrics. Conclusion: Short-term heat exposure may trigger an inflammatory response characterized by innate immune activation as evidenced by our results of higher total monocytes, classical monocytes, and TNF-alpha. Moreover, short-term heat exposure may impair adaptive immune response. These results suggest that exposure to high temperatures may increase susceptibility to infectious agents, environmental exposures, and accelerate the progression of cardiovascular disease.

O117: Comparing the effect of using Virtual reality versus Simulation, to manage an acute surgical scenario, on academic buoyancy

Abstract Background Simulation is regularly used in surgical training to allow trainees to practice skills safely. Virtual reality (VR) is a recent simulation modality which offers immersive computer-generated medical and surgical training scenarios. Much of trainee performance can be hindered by stress, self-consciousness, performance anxiety, fear of criticism and self-perceived poor task execution. Academic buoyancy is a learner’s ability to successfully deal with short-term, minor academic setbacks, such as poor grades and exam pressures, and having academic buoyancy can translate into long-term academic resilience. We aimed to compare academic buoyancy between junior doctors after managing an acute surgical scenario using VR and mannequin-based simulation. Method Eighteen junior doctor volunteers (Foundation and Core Trainee Year 1) were recruited, with ten participants randomly allocated to VR and eight to mannequin-based Simulation. Participants assessed and managed a 15-minute pneumothorax scenario. The academic buoyancy scale (ABS), which consists of four questions on a self-rated 7-point Likert scale, was used to measure pre-session and post-session academic buoyancy. Results ABS scores increased for both study groups, although this was only statistically significant for VR participants (p≤0.01), suggesting that VR may provide a more comfortable environment for trainees to hone their clinical skills. VR participants also had higher overall simulation scores than mannequin-based simulation participants, however no correlation was found between ABS scores and overall simulation scores. Conclusion VR as a simulation modality benefits by improving short-term markers of confidence. Future research should establish whether spaced VR teaching sessions translate into improved long-term markers of resilience.

Asymmetric and symmetric dimethylarginine as markers of endothelial dysfunction in cerebrovascular disease: A prospective study

Background and aimAsymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) have been proposed as mediators of endothelial dysfunction. In this study, we aimed to investigate the diagnostic and prognostic role of ADMA and SDMA in acute cerebrovascular disease. Methods and resultsA prospective case-control study was performed, enrolling 48 patients affected by ischemic stroke with no cardioembolic origin, 20 patients affected by TIA, 40 subjects at high cardiovascular risk and 68 healthy subjects.ADMA levels were significantly lower in high-risk subjects (18.85 [11.78–22.83] μmol/L) than in patients with brain ischemic event, both transient (25.70 [13.15–40.20] μmol/L; p = 0.032) and permanent (24.50 [18.0–41.33] μmol/L; p = 0.001). SDMA levels were different not only between high-risk subjects and ischemic patients, but also between TIA and stroke patients, reaching higher levels in TIA group and lower levels in stroke group (1.15 [0.90–2.0] vs 0.68 [0.30–1.07] μmol/L; p < 0.001). SDMA was also correlated with short-term prognosis, with lower levels in case of adverse clinical course, evaluated by type of discharge (p = 0.009) and need of prolonged rehabilitation (p = 0.042). ConclusionsThe present study highlights the relationship between l-arginine, ADMA, SDMA and acute cerebrovascular events. Therefore, our results suggested a potential role of SDMA as a specific marker of transient ischemic damage and as a short-term positive prognostic marker.

A PILOT FAMILY COACHING INTERVENTION FOR PEOPLE WITH TYPE 2 DIABETES AND A FAMILY MEMBER

Abstract Type 2 diabetes is a common chronic condition in later life that requires substantial lifestyle changes. Most diabetes management occurs at home with the help – and sometimes hindrance – of family members. Although coaching has become a common strategy in healthcare to supplement diabetes education, few interventions have prepared family members to be coaches, despite the documented benefit of including family members in chronic disease management interventions. The overall goal of our pilot intervention was to develop and test a family coaching approach to enhance patients’ diabetes self-management while preserving relationship quality and both individuals’ well-being. Participants were recruited from local diabetes education classes and through provider referrals, and included 20 dyads in the intervention group (patient Mage=59.12) and 20 dyads in the control group (patient Mage=57.06). The intervention, involving 5 interactive group sessions (in-person or virtual) led by a facilitator, covered evidence-based material developed by the investigators on diabetes education and coaching strategies. Behavioral, clinical, emotional, and relational metrics were assessed via a survey at baseline, post-intervention, and 3 months later; intervention participants also completed a program evaluation survey and participated in a focus group. Survey findings revealed some positive effects for diabetes self-management behaviors, no effects for short-term clinical markers, negative effects for emotional well-being, and both positive and negative effects for relational well-being. Participants reported being satisfied with the program overall; they indicated learning a lot and having a positive experience. A translation and cultural adaptation of this program for Spanish-speaking populations is currently underway.

Plasma neurofilament light and brain volumetric outcomes among middle‐aged urban adults

AbstractBackgroundElevated plasma neurofilament light chain (NfL) is associated with dementia, but the specific underlying mechanisms are largely unknown. We examined cross‐sectional and longitudinal relationships of plasma NfL with selected brain structural magnetic resonance imaging (sMRI) prognostic markers of dementia, namely global and cortical brain, hippocampal and white matter lesion volumes (WMLV).MethodData were extracted from three prospective visits within the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, selecting participants with complete v1 (2004‐2009) and v2 (2009‐2013) plasma NfL exposure and ancillary sMRI data at vscan (2011‐2015, n = 179, mean v1 to vscan time: 5.4y). Multivariable‐adjusted linear regression models were conducted, overall, by sex, and by race, correcting for multiple testing with q‐values.ResultNfL(v1) (Loge transformed) had a moderately strong association with larger WMLV at follow‐up vscan visit, after a period of 5‐6 years of follow‐up, overall (β = +2.131±0.660, b = +0.29, p = 0.001, q = 0.0029). Moreover, a 1 unit increase in NfLv2 was linked to a left hippocampal volume that was lower by 125 mm3 (p = 0.004, q = 0.015), using minimally adjusted models and mainly among males. Associations were largely unaltered by further adjustment for downstream health‐related factors.ConclusionIn summary, plasma NfL may be an independent medium‐term (within 5 years) marker for increase in WMLV, and a short term (within 1 year) marker for smaller hippocampal volumes normalized to the intracranial volume, independently of other confounding factors. Therefore, plasma NfL holds promise as a blood‐based marker to predict future subclinical brain pathologies in middle‐aged adults.

Holocene vertical velocity fields in the Calabrian Arc (southern Italy): New insights from uplifted sea-level markers in the Crotone Peninsula

The study of fossil coastlines is one of the most widely used methods to unravel the vertical movements of the Earth's solid surface. All along the coast of the Calabrian Subduction Arc, well preserved Pleistocene marine terrace sequences document a protracted uplift history. Although Pleistocene vertical movements have been extensively explored, the Holocene history is not well understood. Numerous uplifted coastlines of the Holocene period have been studied along the Tyrrhenian side of Calabria, but the Ionian coastal sector is considerably under-studied. Our new data from the coast of the Crotone Peninsula fill this crucial data-gap. AMS 14C dating of seventeen sea level markers, elevated above the current mean sea level, show ages between 2300 and 7000 Cal. Yr BP. The elevation of the markers was corrected for the paleo sea level using the most updated GIA models ICE-6G (VM5a) and ICE-7G (VM7). We found that a coastline dated to 7 ka shows uplift rates of 0.8 mm/yr, consistent with late Pleistocene uplift rates (≈0.8 mm/yr). In contrast, a 2.3 ka coastline was uplifted by only 1 m, resulting in lower uplift rates of ≈0.5 mm/yr. However, there are clues that the abandonment of this younger coastline may have occurred with a rapid uplift pulse. Reconstructing the past vertical movements of the Crotone Peninsula reveals an unsteady uplift history. At some times fast uplift rates are required, while for other periods, lasting as long as 3–4 kyr, the uplift rate is slower or zero. An uplift history consisting of periods of accelerated uplift, or even coseismic pulses, would also explain the difference in uplift rates between short term (<5 ka) and long term (>5 ka) markers through a metric we have defined as uplift rate sensitivity. Understanding the details of this uplift history has social relevance. The co-seismic uplift hypothesis requires further investigation but if confirmed would likely affect the seismic and tsunami hazard of the Crotone Peninsula. Similarly, the unsteady uplift rate would cause a risk given the current rapid rate of global sea level rise. Periods of sustained vertical stability would increase the risk of flooding even in areas characterized by long-term uplift and thus considered safe.

New insights into early biochemical prediction of internal browning disorder in 'Conference' pears

This study aimed to identify markers in pear capable of predicting the development of internal browning disorder (IBD) at harvest or during early storage. ´Conference´ pears were harvested from different orchards at commercial maturity and stored under high CO2 atmosphere conditions to induce disorders. The predictive markers studied were associated with 1-aminocyclopropane-1-carboxylic acid (ACC) metabolism, antioxidants and the tricarboxylic acid cycle (TCA cycle). The partial least square (PLS) model built for prediction at harvest identified ACC, malonyl ACC (MACC), and dehydroascorbic acid (DHA): the oxidized form of ascorbate, as the best markers for defining initial fruit sensitivity to IBD. A clear relationship was also found between increases in succinate levels during the first two weeks of storage and the incidence and severity of IBD after storage. Collectively, the results presented in this work reinforce the idea that IBD is determined by initial fruit maturity. They also question the current dogma concerning ascorbate, suggesting that rather than ascorbate, the most reliable marker for sensibility at harvest is DHA. Our results also highlighted that increased succinate levels should be considered one of the earliest responses to damaging storage conditions and offer an interesting short-term marker for IBD. The paper discusses how succinate is regulated during storage in relation to IBD development and an explanatory model is presented.

Testing or Trusting? Urine Cotinine Levels in Plastic Surgery.

Preoperative laboratory examinations are a common practice throughout all surgical disciplines. Smoking prior to and shortly after elective aesthetic surgery is generally discouraged, but abstinence is rarely examined. Nicotine's major metabolite is cotinine, which is distributed in various body fluids, including blood, saliva, and urine. Urine cotinine levels are a useful short-term marker of nicotine exposure, whether active or passive, and correlate with daily tobacco use. Urinary levels are precise, rapid, easy to examine, and accessible. The aim of this literature review was to describe the current body of knowledge relevant to cotinine levels in the fields of general and plastic surgery. It was hypothesized that the current available data are enough to support the judicial use of such tests in high-risk surgical candidates, especially in aesthetic surgeries. A literature review via PubMed was conducted to identify publications that used the terms "cotinine" and "surgery," according to the PRISMA standard flowchart. After subtracting duplications, the search results yielded 312 papers. After a reduction process as per exclusion criteria, 61 articles were identified and fully reviewed by both authors. Fifteen full-text articles were eligible for qualitative synthesis. Enough data have accumulated to strongly support the judicial use of cotinine tests prior to elective surgery and specifically in aesthetic surgery.

The Consciousness Domain Index: External Validation and Prognostic Relevance of a Data-Driven Assessment.

The prognosis of neurological outcomes in patients with prolonged Disorders of Consciousness (pDoC) has improved in the last decades. Currently, the level of consciousness at admission to post-acute rehabilitation is diagnosed by the Coma Recovery Scale-Revised (CRS-R) and this assessment is also part of the used prognostic markers. The consciousness disorder diagnosis is based on scores of single CRS-R sub-scales, each of which can independently assign or not a specific level of consciousness to a patient in a univariate fashion. In this work, a multidomain indicator of consciousness based on CRS-R sub-scales, the Consciousness-Domain-Index (CDI), was derived by unsupervised learning techniques. The CDI was computed and internally validated on one dataset (N=190) and then externally validated on another dataset (N=86). Then, the CDI effectiveness as a short-term prognostic marker was assessed by supervised Elastic-Net logistic regression. The prediction accuracy of the neurological prognosis was compared with models trained on the level of consciousness at admission based on clinical state assessments. CDI-based prediction of emergence from a pDoC improved the clinical assessment-based one by 5.3% and 3.7%, respectively for the two datasets. This result confirms that the data-driven assessment of consciousness levels based on multidimensional scoring of the CRS-R sub-scales improve short-term neurological prognosis with respect to the classical univariately-derived level of consciousness at admission.

The association between real-life markers of phone use and cognitive performance, health-related quality of life and sleep

IntroductionThe real-life short-term implications of electromagnetic fields (RF-EMF) on cognitive performance and health-related quality of life have not been well studied. The SPUTNIC study (Study Panel on Upcoming Technologies to study Non-Ionizing radiation and Cognition) aimed to investigate possible correlations between mobile phone radiation and human health, including cognition, health-related quality of life and sleep. MethodsAdult participants tracked various daily markers of RF-EMF exposures (cordless calls, mobile calls, and mobile screen time 4 h prior to each assessment) as well as three health outcomes over ten study days: 1) cognitive performance, 2) health-related quality of life (HRQoL), and 3) sleep duration and quality. Cognitive performance was measured through six “game-like” tests, assessing verbal and visuo-spatial performance repeatedly. HRQoL was assessed as fatigue, mood and stress on a Likert-scale (1–10). Sleep duration and efficiency was measured using activity trackers. We fitted mixed models with random intercepts per participant on cognitive, HRQoL and sleep scores. Possible time-varying confounders were assessed at daily intervals by questionnaire and used for model adjustment. ResultsA total of 121 participants ultimately took part in the SPUTNIC study, including 63 from Besancon and 58 from Basel. Self-reported wireless phone use and screen time were sporadically associated with visuo-spatial and verbal cognitive performance, compatible with chance findings. We found a small but robust significant increase in stress 0.03 (0.00–0.06; on a 1–10 Likert-scale) in relation to a 10-min increase in mobile phone screen time. Sleep duration and quality were not associated with either cordless or mobile phone calls, or with screen time. DiscussionThe study did not find associations between short-term RF-EMF markers and cognitive performance, HRQoL, or sleep duration and quality. The most consistent finding was increased stress in relation to more screen time, but no association with cordless or mobile phone call time.

Relationship between efficacy and common metabolic parameters in first-treatment drug-naïve patients with early non-response schizophrenia: a retrospective study

BackgroundComorbid metabolic disorders in patients with schizophrenia are very common. Patients with schizophrenia who respond to therapy early are often strongly predictive of better treatment outcomes. However, the differences in short-term metabolic markers between early responders and early non-responders in schizophrenia are unclear.Methods143 first-treatment drug-naïve schizophrenia patients were included in this study and were given a single antipsychotic medication for 6 weeks after admission. After 2 weeks, the sample was divided into an early response group and an early non-response group based on psychopathological changes. For the study endpoints, we depicted the change curves of psychopathology in both subgroups and compared the differences between the two groups in terms of remission rates and multiple metabolic parameters.ResultsThe early non-response had 73 cases (51.05%) in the 2nd week. In the 6th week, the remission rate was significantly higher in the early response group than in the early non-response group (30,42.86% vs. 8,10.96%); the body weight, body mass index, blood creatinine, blood uric acid, total cholesterol, triglyceride, low-density lipoprotein, fasting blood glucose, and prolactin of the enrolled samples were significantly increased, and high-density lipoprotein was significantly decreased. ANOVAs revealed a significant effect of treatment time on abdominal circumference, blood uric acid, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, fasting blood glucose and prolactin, and a significant negative effect of early non-response to treatment on abdominal circumference, blood creatinine, triglyceride, fasting blood glucose.ConclusionsSchizophrenia patients with early non-response had lower rates of short-term remission and more extensive and severe abnormal metabolic indicators. In clinical practice, patients with early non-response should be given a targeted management strategy, antipsychotic drugs should be switched on time, and active and effective interventions for their metabolic disorders should be given.

Salivary 1,5-Anhydroglucitol and its Correlation with Postprandial Hyperglycemia: Development and Validation of a Novel Assay.

Saliva has the potential to be used as a noninvasive sample for testing hyperglycemia in diabetes mellitus. Serum 1,5-anhydroglucitol (1,5-AG) decreases with an increase in blood sugar >180 mg/dl. We hypothesized that salivary 1,5-AG can be used to identify blood sugar higher than 180 mg/dl using a novel biochemical method. This study aimed to develop a novel biochemical method for serum and salivary assessment of 1,5-AG and assess its correlation with postprandial blood sugar (PPBS) >180 mg/dl. The study comprised 45 controls (healthy individuals) and 45 cases (type 2 diabetic patients with PPBS >180 mg/dl). Blood and salivary samples were collected according to the study protocol. A new method was developed for the quantification of 1,5-AG in serum and saliva using liquid chromatography-mass spectrometry. The value of serum (mean -22.19 μg/ml and median -22.12 μg/ml) and salivary (mean -0.124 μg/ml and median -0.088 μg/ml) 1,5-AG was higher in healthy individuals compared to corresponding serum (mean -3.89 μg/ml and median -2.52 μg/ml) and salivary (mean -0.025 μg/ml and median - 0.025 μg/ml) levels in diabetics with PPBS >180 mg/dl. In diabetics, a significant negative correlation was noticed with PPBS levels and 1,5-AG levels in serum and saliva. Salivary 1,5-AG level <0.054 μg/ml had an 86.4% sensitivity and 87.2% specificity in predicting a blood sugar value >180 mg/dl. The results of our study suggest that the short-term glycemic marker 1,5-AG can be detected in saliva and can be useful as an adjunct marker in monitoring of glycemic status in diabetic patients.

Reactive focal drug administration associated with decreased malaria transmission in an elimination setting: Serological evidence from the cluster-randomized CoRE study

Efforts to eliminate malaria transmission need evidence-based strategies. However, accurately assessing end-game malaria elimination strategies is challenging due to the low level of transmission and the rarity of infections. We hypothesised that presumptively treating individuals during reactive case detection (RCD) would reduce transmission and that serology would more sensitively detect this change over standard approaches. We conducted a cluster randomised control trial (NCT02654912) of presumptive reactive focal drug administration (RFDA-intervention) compared to the standard of care, reactive focal test and treat (RFTAT-control) in Southern Province, Zambia-an area of low seasonal transmission (overall incidence of ~3 per 1,000). We measured routine malaria incidence from health facilities as well as PCR parasite prevalence / antimalarial seroprevalence in an endline cross-sectional population survey. No significant difference was identified from routine incidence data and endline prevalence by polymerase chain reaction (PCR) had insufficient numbers of malaria infections (i.e., 16 infections among 6,276 children) to assess the intervention. Comparing long-term serological markers, we found a 19% (95% CI = 4-32%) reduction in seropositivity for the RFDA intervention using a difference in differences approach incorporating serological positivity and age. We also found a 37% (95% CI = 2-59%) reduction in seropositivity to short-term serological markers in a post-only comparison. These serological analyses provide compelling evidence that RFDA both has an impact on malaria transmission and is an appropriate end-game malaria elimination strategy. Furthermore, serology provides a more sensitive approach to measure changes in transmission that other approaches miss, particularly in very low transmission settings. Trial Registration: Registered at www.clinicaltrials.gov (NCT02654912, 13/1/2016).

Left ventricular stroke volume index following transcatheter aortic valve replacement is an early predictor of 1-year survival.

Adverse cardiac events are common following transcatheter aortic valve replacement (TAVR). Our aim was to investigate the low left ventricular stroke volume index (LVSVI) 30 days after TAVR as an early echocardiographic marker of survival. Steady-state (30-day) LVSVI after TAVR is associated with 1-year mortality. A single-center retrospective analysis of all patients undergoing TAVR from 2017 to 2019. Baseline and 30-day post-TAVR echocardiographic LVSVI were calculated. Patients were stratified by pre-TAVR transaortic gradient, surgical risk, and change in transvalvular flow following TAVR. This analysis focuses on 238 patients treated with TAVR. The 1-year mortality rate was 9% and 124 (52%) patients had normal flow post-TAVR. Of those with pre-TAVR low flow, 67% of patients did not normalize LVSVI at 30 days. The 30-day normal flow was associated with lower 1-year mortality when compared to low flow (4% vs. 14%, p = .007). This association remained significant after adjusting for known predictors of risk (adjusted odds ratio [OR] of 3.45, 95% confidence interval: 1.02-11.63 [per 1 ml/m2 decrease], p = .046). Normalized transvalvular flow following TAVR was associated with reduced mortality (8%) when compared to those with persistent (15%) or new-onset low flow (12%) (p = .01). LVSVI at 30 days following TAVR is an early echocardiographic predictor of 1-year mortality and identifies patients with worse intermediate outcomes. More work is needed to understand if this short-term imaging marker might represent a novel therapeutic target.

The Effect of the Topmost Layer and the Type of Bone Morphogenetic Protein-2 Immobilization on the Mesenchymal Stem Cell Response.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) plays a key role in the stem cell response, not only via its influence on osteogenesis, but also on cellular adhesion, migration, and proliferation. However, when applied clinically, its supra-physiological levels cause many adverse effects. Therefore, there is a need to concomitantly retain the biological activity of BMP-2 and reduce its doses. Currently, the most promising strategies involve site-specific and site-directed immobilization of rhBMP-2. This work investigated the covalent and electrostatic binding of rhBMP-2 to ultrathin-multilayers with chondroitin sulfate (CS) or diazoresin (DR) as the topmost layer. Angle-resolved X-ray photoelectron spectroscopy was used to study the exposed chemical groups. The rhBMP-2 binding efficiency and protein state were studied with time-of-flight secondary ion mass spectrometry. Quartz crystal microbalance, atomic force microscopy, and enzyme-linked immunosorbent assay were used to analyze protein–substrate interactions. The effect of the topmost layer was tested on initial cell adhesion and short-term osteogenesis marker expression. The results show the highest expression of selected osteomarkers in cells cultured on the DR-ended layer, while the cellular flattening was rather poor compared to the CS-ended system. rhBMP-2 adhesion was observed only on negatively charged layers. Cell flattening became more prominent in the presence of the protein, even though the osteogenic gene expression decreased.

Etramp5 as a useful serological marker in children to assess the immediate effects of mass drug campaigns for malaria

IntroductionSerological methods provide useful metrics to estimate age-specific period prevalence in settings of low malaria transmission; however, evidence on the use of seropositivity as an endpoint remains scarce in studies to evaluate combinations of malaria control measures, especially in children. This study aims to evaluate the immediate effects of a targeted mass drug administration campaign (tMDA) in Haiti by using serological markers.MethodsThe tMDA was implemented in September–October 2018 using sulfadoxine-pyrimethamine and single low-dose primaquine. A natural quasi-experimental study was designed, using a pretest and posttest in a cohort of 754 randomly selected school children, among which 23% reported having received tMDA. Five antigens were selected as outcomes (MSP1-19, AMA-1, Etramp5 antigen 1, HSP40, and GLURP-R0). Posttest was conducted 2–6 weeks after the intervention.ResultsAt baseline, there was no statistical difference in seroprevalence between the groups of children that were or were not exposed during the posttest. A lower seroprevalence was observed for markers informative of recent exposure (Etramp5 antigen 1, HSP40, and GLURP-R0). Exposure to tMDA was significantly associated with a 50% reduction in the odds of seropositivity for Etramp5 antigen 1 and a 21% reduction in the odds of seropositivity for MSP119.ConclusionSerological markers can be used to evaluate the effects of interventions against malaria on the risk of infection in settings of low transmission. Antibody responses against Etramp5 antigen 1 in Haitian children were reduced in the 2–6 weeks following a tMDA campaign, confirming its usefulness as a short-term marker in child populations.

Circulating 1,5-Anhydroglucitol as a Biomarker of ß-cell Mass Independent of a Diabetes Phenotype in Human Subjects.

During an asymptomatic prediabetic state, the functional ß-cell mass decreases to a critical threshold, triggering diabetes and related symptoms. To date, there are no reliable readouts able to capture in vivo a potential drop of the ß-cell mass. Beside its use as a short-term marker of glycemic control, the deoxyhexose 1,5-anhydroglucitol was identified in rodents as a circulating biomarker of the functional ß-cell mass already in the asymptomatic prediabetic stage. The present study investigated the putative corresponding relevance of circulating 1,5-anhydroglucitol in different human cohorts. We analyzed clinical and blood parameters in patients with established type 2 diabetes and subjects considered at high risk of developing diabetes, as well as patients with no history of diabetes scheduled for pancreaticoduodenectomy. Circulating 1,5-anhydroglucitol was reduced in type 2 diabetic patients, negatively correlating with fasting plasma glucose (P < 0.0001) and hemoglobin A1c (P < 0.0001). In healthy subjects, 1,5-AG levels positively correlated with body mass index (P = 0.004) and Homeostatic Model Assessment of Insulin Resistance %S (P < 0.03) and was particularly high in nondiabetic obese individuals, potentially accounting for compensatory ß-cell expansion. Patients with no history of diabetes undergoing pancreaticoduodenectomy exhibited a 50% reduction of circulating 1,5-anhydroglucitol levels following surgery leading to an acute loss of their ß-cell mass (P = 0.002), regardless their glucose tolerance status. In summary, plasma concentration of 1,5-anhydroglucitol follows the ß-cell mass and its noninvasive monitoring may alert about the loss of ß cells in subjects at risk for diabetes, an event that cannot be captured by other clinical parameters of glycemic control.