Changes in sex hormones and their interactions are related to pain perception between different menstrual subphases.

Whether sex hormones are related to pain perception across the menstrual cycle is unclear. We examined changes in experimental pain perception in healthy young females between the early to midfollicular subphase (emF) and the midluteal subphase (mL) and explored the role of sex hormones. Sixty-six participants were involved in the study. We tested pressure pain, cold pain, ischemic pain, and needle pain, while at the same time we measured sex hormones levels in two menstrual subphases. Only the right ulna pressure test showed a significant reduction in pain threshold (PPTh3) during the mL. The absolute change of PPTh3 (PPTh3mL - PPTh3emF) was related to the absolute change of prolactin. The relative change of the range of pain tolerance for pressure pain of the right ulna (RPT3rc) was related to the relative change of progesterone (Prc) and estradiol (E2rc) levels, and the interaction effects showed that at Prc ≤ 30, E2rc was positively correlated with RPT3rc. The same, the relative change of pressure pain tolerance of the pulp of the middle finger on the right hand (PPTo4rc) was related to E2rc and Prc, and the results of the interaction between E2rc and Prc suggest that when E2rc is ≤0.8, Prc is positively correlated with PPTo4rc. Two different formulas were applied in this study and showed inconsistent results. Most pain tests showed no difference between the two subphases of the menstrual cycle. Only the relative changes of the PPTo4 and RPT3 are related to the E2rc and Prc, respectively, between menstrual subphases in an interactive way in healthy young women.

A spatiotemporal analysis of NO 2 concentrations during the Italian 2020 COVID-19 lockdown.

When a new environmental policy or a specific intervention is taken in order to improve air quality, it is paramount to assess and quantify-in space and time-the effectiveness of the adopted strategy. The lockdown measures taken worldwide in 2020 to reduce the spread of the SARS-CoV-2 virus can be envisioned as a policy intervention with an indirect effect on air quality. In this paper we propose a statistical spatiotemporal model as a tool for intervention analysis, able to take into account the effect of weather and other confounding factor, as well as the spatial and temporal correlation existing in the data. In particular, we focus here on the 2019/2020 relative change in nitrogen dioxide (NO 2 ) concentrations in the north of Italy, for the period of March and April during which the lockdown measure was in force. We found that during March and April 2020 most of the studied area is characterized by negative relative changes (median values around - 25%), with the exception of the first week of March and the fourth week of April (median values around 5%). As these changes cannot be attributed to a weather effect, it is likely that they are a byproduct of the lockdown measures. There are two aspects of our research that are equally interesting. First, we provide a unique statistical perspective for calculating the relative change in the NO 2 by jointly modeling pollutant concentrations time series. Second, as an output we provide a collection of weekly continuous maps, describing the spatial pattern of the NO 2 2019/2020 relative changes.

The absolute and relative changes in high-sensitivity cardiac troponin I are associated with the in-hospital mortality of patients with fulminant myocarditis.

BACKGROUND: We sought to describe the tendency and extent of high-sensitivity cardiac troponin I (hs-cTnI) changes in patients with fulminant myocarditis (FM) after admission and to explore the relationship between the in-hospital mortality of FM and the absolute and relative changes in hs-cTnI within 24 h and 48 h after admission. METHODS: In the retrospective study, the object are patients diagnosed with FM in our single centre. The value of cardiac troponin was recorded after patients admitted to hospital in succession. The absolute and relative changes in hs-cTnI within 24 h and 48 h were described as range distributions. Receiver operating characteristic (ROC) curve and Cox analyses were performed to determine the relationship between in-hospital mortality of FM and hs-cTnI changes. RESULTS: A total of 83 FM patients admitted to our centre from January 1, 2010 to December 31, 2019 were included; 69 patients survived and 14 patients died. In the survival group, 78% of patients experienced a decline in hs-cTnI within 24 h, while 36% of the mortality group exhibited a declining tendency in hs-cTnI (P = 0.003). Nearly 60% of survival group had a 0-2000 ng/l reduction in troponin from baseline within 24 h of admission. However, troponin levels of 50% of patients in the mortality group were 0-10,000 ng/ L higher than baseline 24 h after admission. Multivariable logistic analysis revealed that the declining tendency of hs-cTnI within 24 h, in addition to time from onset to admittance to hospital, intravenous immunoglobulin treatment and the abnormal level of creatinine, were associated with the in-hospital mortality of FM (for the declining tendency of hs-cTnI within 24 h, OR = 0.10, 95% CI 0.02-0.68, P = 0.018). The ROC curve revealed optimal cut-off values of - 618 ng/l for absolute change within 24 h (AUC = 0.800, P < 0.01), - 4389 ng/l for absolute change within 48 h (area under the curve = 0.711, P < 0.01), - 28.46% for relative change within 24 h (AUC = 0.810, P < 0.01), and - 52.23% for relative change within 48 h (AUC = 0.795, P < 0.01). Absolute changes and relative changes in hs-cTnI within 24 h and 48 h were strong predictors of in-hospital mortality by Cox regression analysis after adjustment for sex, time from onset to admission, and occurrence of ventricular tachycardia or ventricular fibrillation. CONCLUSION: Most FM patients who survived experienced a decline in hs-cTnI within 24 h. The absolute and relative changes in hs-cTnI within 24 h and 48 h were strong predictors of in-hospital mortality.

Impacts of COVID-19 on urban rail transit ridership using the Synthetic Control Method.

The outbreak of COVID-19 in 2020 has had drastic impacts on urban economies and activities, with transit systems around the world witnessing an unprecedented decline in ridership. This paper attempts to estimate the effect of COVID-19 on the daily ridership of urban rail transit (URT) using the Synthetic Control Method (SCM). Six variables are selected as the predictors, among which four variables unaffected by the pandemic are employed. A total of 22 cities from Asia, Europe, and the US with varying timelines of the pandemic outbreak are selected in this study. The effect of COVID-19 on the URT ridership in 11 cities in Asia is investigated using the difference between their observed ridership reduction and the potential ridership generated by the other 11 cities. Additionally, the effect of the system closure in Wuhan on ridership recovery is analyzed. A series of placebo tests are rolled out to confirm the significance of these analyses. Two traditional methods (causal impact analysis and straightforward analysis) are employed to illustrate the usefulness of the SCM. Most Chinese cities experienced about a 90% reduction in ridership with some variation among different cities. Seoul and Singapore experienced a minor decrease compared to Chinese cities. The results suggest that URT ridership reductions are associated with the severity and duration of restrictions and lockdowns. Full system closure can have severe impacts on the speed of ridership recovery following resumption of service, as demonstrated in the case of Wuhan with about 22% slower recovery. The results of this study can provide support for policymakers to monitor the URT ridership during the recovery period and understand the likely effects of system closure if considered in future emergency events.

Relative changes in handgrip strength and skeletal muscle volume in patients with chronic liver disease over a 2-year observation period.

AIM: There are few reports regarding relative changes in muscle function of patients with chronic liver disease (CLD). We examined CLD patients to evaluate relative changes in handgrip strength and muscle volume. METHODS: We enrolled 413 CLD outpatients who underwent handgrip strength measurements in both 2015 and 2017 (age 67.9 ± 10.0 years; male / female = 242/171; hepatitis C virus [HCV] / hepatitis B virus [HBV] / HBV and HCV / alcohol / others = 239/92/4/22/56; Child-Pugh score [CPS] in 2015 [5/6/7/8/9/≥10 = 335/51/12/11/3/1]). Relative change in muscle volume (ΔPI) from 2015 to 2017 was evaluated using computed tomography findings in 230 of the patients, using a previously reported method. Clinical characteristics, as well as relative changes of handgrip strength (ΔHGS) and ΔPI were analyzed. RESULTS: For the patient cohort as a whole, CPS became significantly worse in 2017 (5/6/7/8/9/≥10 = 319/56/13/11/5/9; P = 0.002). In individual patients with CPS decline, serum albumin level was significantly decreased (3.78 ± 0.50 to 3.33 ± 0.61 g/dL; P < 0.001), whereas no decrease was seen in those without such a decline (4.16 ± 0.48 to 4.20 ± 0.44 g/dL; P = 0.028). Furthermore, ΔHGS (-1.4 ± 4.8 [n = 59] vs. 0.7 ± 4.8 kg [n = 354]; P = 0.002) and ΔPI (-0.44 ± 0.88 [n = 38] vs. 0.03 ± 0.64 cm2 /m2 [n = 192]; P = 0.003) were worse in patients with, compared to those without, a decline in CPS. Age was not significantly different between patients with and without handgrip strength decline (66.5 ± 10.3 vs. 65.3 ± 9.9 years; P = 0.256). There was a significant relationship between ΔHGS, ΔPI and relative change in serum albumin (r = 0.161, P = 0.001 and r = 0.225, P < 0.001, respectively). CONCLUSION: Decline in CPS, especially decreasing serum albumin level, showed a significant relationship with muscle function reduction and muscle volume loss.

Stability of cytokines, chemokines and soluble activation markers in unprocessed blood stored under different conditions.

BACKGROUND: Biomarkers such as cytokines, chemokines, and soluble activation markers can be unstable when processing of blood is delayed. The stability of various biomarkers in serum and plasma was investigated when unprocessed blood samples were stored for up to 24h at room and refrigerator temperature. METHODS: Blood was collected from 16 healthy volunteers. Unprocessed serum, EDTA and heparinized blood was stored at room (20-25°C) and refrigerator temperature (4-8°C) for 0.5, 2, 4, 6, 8, and 24h after collection before centrifugation and separation of serum and plasma. Samples were batch tested for various biomarkers using commercially available immunoassays. Statistically significant changes were determined using the generalized estimating equation. RESULTS: IFN-γ, sIL-2Rα, sTNF-RII and ß2-microglobulin were stable in unprocessed serum, EDTA and heparinized blood samples stored at either room or refrigerator temperature for up to 24h. IL-6, TNF-α, MIP-1ß and RANTES were unstable in heparinized blood at room temperature; TNF-α, and MIP-1ß were unstable in unprocessed serum at room temperature; IL-12 was unstable in unprocessed serum at refrigerator temperature; and neopterin was unstable in unprocessed EDTA blood at room temperature. IL-1ra was stable only in unprocessed serum at room temperature. CONCLUSION: All the biomarkers studied, with the exception of IL-1ra, were stable in unprocessed EDTA blood stored at refrigerator temperature for 24h. This indicates that blood for these biomarkers should be collected in EDTA and if delays in processing are anticipated the unseparated blood should be stored at refrigerator temperature until processing.

Baseline neutrophil-to- ratio combined with the change during treatment provides risk stratification for metastatic malignant melanoma patients treated with PD-1 inhibitors in a Chinese population.

Background: Previous studies have suggested that an elevated baseline neutrophil-to-lymphocyte ratio (BLNLR) and elevated relative change of NLR (ΔNLR%) is associated with worse outcomes in patients with a variety of cancers. This study aims to investigate the value of BLNLR and ΔNLR% before the third cycle of treatment on the prognosis of patients with metastatic malignant melanoma treated with PD-1 inhibitors. Methods: A total of 63 patients with metastatic malignant melanoma treated with PD-1 inhibitors in the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2021 were retrospectively analyzed. BLNLR and ΔNLR% before the third cycle of treatment were collected. The Kaplan-Meier method was used to draw survival curves and Log-Rank test was used for survival analysis. Univariate and multivariate Cox regression analysis were used to analyze the relationship between BLNLR, ΔNLR% and clinical characteristics with progression-free survival (PFS) and overall survival (OS). Results: Univariate analysis showed that PFS and OS were associated with BLNLR, ΔNLR%, BMI and number of metastatic organs (P < 0.05). Multivariate analysis showed that BLNLR, ΔNLR%, BMI and number of metastatic organs were independent predictors of OS and BLNLR and ΔNLR% were independent predictors of PFS. Patients were divided into four groups according to BLNLR (<3, ≥3) and ΔNLR% (< 30%, ≥30%): low-BLNLR + low-ΔNLR% group, low-BLNLR + high-ΔNLR% group, high-BLNLR + low-ΔNLR% group, high-BLNLR + high-ΔNLR% group. The median OS was 20 months, 8 months, 9 months, 5 months and the median PFS was 8 months, 3 months, 2 months, 2 months, respectively. Conclusion: BLNLR combined with ΔNLR% can be used to predict the prognosis of PD-1 inhibitors in patients with metastatic malignant melanoma.

Baroreflex activity through the analysis of the cardio-respiratory variability influence over blood pressure in cardiomyopathy patients.

A large portion of the elderly population are affected by cardiovascular diseases. Early prognosis of cardiomyopathies remains a challenge. The aim of this study was to classify cardiomyopathy patients by their etiology based on significant indexes extracted from the characterization of the baroreflex mechanism in function of the influence of the cardio-respiratory activity over the blood pressure. Forty-one cardiomyopathy patients (CMP) classified as ischemic (ICM-24 patients) and dilated (DCM-17 patients) were considered. In addition, thirty-nine control (CON) subjects were used as reference. The beat-to-beat (BBI) time series, from the electrocardiographic (ECG) signal, the systolic (SBP), and diastolic (DBP) time series, from the blood pressure signal (BP), and the respiratory time (TT), from the respiratory flow (RF) signal, were extracted. The three-dimensional representation of the cardiorespiratory and vascular activities was characterized geometrically, by fitting a polygon that contains 95% of data, and by statistical descriptive indices. DCM patients presented specific patterns in the respiratory response to decreasing blood pressure activity. ICM patients presented more stable cardiorespiratory activity in comparison with DCM patients. In general, CMP shown limited ability to regulate changes in blood pressure. In addition, patients also shown a limited ability of their cardiac and respiratory systems response to regulate incremental changes of the vascular variability and a lower heart rate variability. The best classifiers were used to build support vector machine models. The optimal model to classify ICM versus DCM patients achieved 92.7% accuracy, 94.1% sensitivity, and 91.7% specificity. When comparing CMP patients and CON subjects, the best model achieved 86.2% accuracy, 82.9% sensitivity, and 89.7% specificity. When comparing ICM patients and CON subjects, the best model achieved 88.9% accuracy, 87.5% sensitivity, and 89.7% specificity. When comparing DCM patients and CON subjects, the best model achieved 87.5% accuracy, 76.5% sensitivity, and 92.3% specificity. In conclusion, this study introduced a new method for the classification of patients by their etiology based on new indices from the analysis of the baroreflex mechanism.

Statistical Evaluation of Responder Analysis in Stem Cell Clinical Trials.

BACKGROUND: In evaluating treatment efficacy, there is an ongoing discussion about which endpoint is more efficient to represent the treatment effect. Absolute change (AC) is the difference between before and after treatment, while relative change (RC) is the AC relative to the baseline value. Principal investigators sometimes support the credibility of relative change, but the FDA is more likely to support absolute change. Therefore, whether these two endpoints can be translated or combined is worth investigating in order to satisfy both parties. METHODS: In this article, a motivating example is presented to show that the choice of endpoint will result in different conclusions. The compared relationship of AC and RC is discussed in terms of required sample size, power, and precision. A new type of responder endpoint that combines the concepts of AC and RC is proposed. The comparative relationship regarding sample size, power, and precision of the proposed responder endpoint and the original two endpoints are also investigated. RESULTS: As a result, the performance of AC and RC is highly dependent on the choice of threshold that is often informed based on minimum clinically important difference or other clinical experience. Therefore, an absolute translation between them is hard to achieve. Inspired by the concept of responder analysis, three types of responder endpoints are proposed and discussed. The pattern of the third type of responder endpoint is having higher power, higher precision, and less required sample size in estimating the treatment effect compared to AC and RC within a range of thresholds. This advantage becomes more obvious when applying higher AC and RC thresholds and lower [Formula: see text] threshold. CONCLUSION: The proposed endpoint incorporates the information from the AC and RC endpoints and could be another wise choice when designing clinical trials especially when there is no absolute preference between AC and RC.

Absolute Versus Relative Changes in Cardiac Troponins in the Diagnosis of Myocardial Infarction: A Systematic Review and Meta-Analysis.

Ischemic heart disease (IHD) is one of the leading causes of death globally. Rapid diagnosis of myocardial infarction (MI) will enable earlier initiation of the treatment and improve patient outcomes. Practice guidelines for non-ST-elevation acute coronary syndromes by the American College of Cardiology (ACC)/American Heart Association (AHA) had listed the diagnostic performance of absolute versus relative changes in evidence gaps. We aimed to address this evidence gap by examining the diagnostic accuracy of absolute versus relative changes in cardiac troponins at various time intervals in diagnosing MI. Grey literature, conference abstracts, animal studies, and reports published before 2009 and in languages other than English were excluded. We included reports that investigated absolute or relative changes in highly sensitive cardiac troponin T (hs-cTnT) or sensitive/highly sensitive cardiac troponin I (s/hs-cTnI) assays after specific time intervals (1, 2, or 3 h) in patients presenting with symptoms suggestive of the acute coronary syndrome. After screening, we arranged the reports in 12 separate groups based on the variables for which the data was reported. Quality assessment of the diagnostic accuracy studies-2 (QUADAS-2) was used to assess the risk of bias in the included studies. The weighted summary area under the curve (AUC) was calculated for each pool. We then performed two-sided (or two-tailed) tests to compare independent receiver operating characteristic (ROC) curves. MedCalc version 20.106 (MedCalc Software Ltd., Ostend, Belgium) was used for all statistical analysis. We included eight reports with 23,450 patients in the meta-analysis. Weighted summary estimates and their respective 95% confidence intervals (CI) under random-effects model for ROC-AUC are as follows: absolute hs-cTnI at 1 h - 0.94 (95% CI: 0.922 to 0.959, p < 0.001); absolute hs-cTnT at 1 h - 0.921 (95% CI: 0.902 to 0.941, p < 0.001); absolute s/hs-cTnI at 2 h - 0.953 (95% CI: 0.926 to 0.980, p < 0.001); absolute hs-cTnT at 2 h 0.951 (95% CI: 0.940 to 0.962, p < 0.001); relative hs-cTnT at 2 h - 0.818 (95% CI: 0.733 to 0.903, p < 0.001); relative s/hs-cTnI at 2 h - 0.762 (95% CI: 0.726 to 0.798, p < 0.001); absolute hs-cTnI at 3 h - 0.967 (95% CI: 0.95 to 0.984, p < 0.001); absolute hs-cTnT at 3 h - 0.959 (95% CI: 0.950 to 0.968, p < 0.001); and relative hs-cTnT at 3 h - 0.926 (95% CI: 0.907 to 0.945, p < 0.001). P-values of comparison of absolute and relative changes are as follows: hs-cTnT at 1 h: <0.0001; hs-cTnI at 1 h: <0.0001; hs-cTnT at 2 h: 0.0024; s/hs-cTnI at 2 h: <0.0001; hs-cTnT at 3 h: 0.0022; and hs-cTnI at 3 h: 0.0005. Our analysis found absolute changes to be superior to relative changes in both hs-cTnT and s/hs-cTnI at 1, 2, and 3 h in the diagnosis of MI. There was no statistically significant difference in comparing s/hs-cTnI vs. hs-cTnT using absolute or relative changes at any time interval. Our findings suggest that future research investigating a potential 0 h/30 min algorithm should use absolute Δ over relative Δ. A suboptimal number of reports in the groups limited our ability to establish the robustness of the results. We did not receive any funding for this review.

Differential Item Functioning Analysis Without A Priori Information on Anchor Items: QQ Plots and Graphical Test.

Differential item functioning (DIF) analysis is an important step in establishing the validity of measurements. Most traditional methods for DIF analysis use an item-by-item strategy via anchor items that are assumed DIF-free. If anchor items are flawed, these methods will yield misleading results due to biased scales. In this article, based on the fact that the item's relative change of difficulty difference (RCD) does not depend on the mean ability of individual groups, a new DIF detection method (RCD-DIF) is proposed by comparing the observed differences against those with simulated data that are known DIF-free. The RCD-DIF method consists of a D-QQ (quantile quantile) plot that permits the identification of internal references points (similar to anchor items), a RCD-QQ plot that facilitates visual examination of DIF, and a RCD graphical test that synchronizes DIF analysis at the test level with that at the item level via confidence intervals on individual items. The RCD procedure visually reveals the overall pattern of DIF in the test and the size of DIF for each item and is expected to work properly even when the majority of the items possess DIF and the DIF pattern is unbalanced. Results of two simulation studies indicate that the RCD graphical test has Type I error rate comparable to those of existing methods but with greater power.

Changes in serum KL-6 levels during short-term strict antigen avoidance are associated with the prognosis of patients with fibrotic hypersensitivity pneumonitis caused by avian antigens.

BACKGROUND: Bird-related hypersensitivity pneumonitis (BRHP) is the most common type of fibrotic hypersensitivity pneumonitis (HP). Antigen avoidance (AA) is a key step in the diagnosis and management of HP, but not all fibrotic HP patients improve through AA. Because of the poor prognosis of fibrotic HP, predictive biomarkers to identify patients showing rapid progression during AA are urgently needed. METHODS: From a retrospective review of the medical records of 1941 patients with interstitial lung disease, 75 cases of fibrotic BRHP confirmed by a provocation test or surgical lung biopsy were identified. To identify potential prognostic markers obtained at or around diagnosis, physiological and serological variables at diagnosis and the relative changes in those variables during strict AA were evaluated. Cox proportional hazards models with log-rank testing were used to compare the associations between these variables and survival. RESULTS: Univariate analyses showed that gender, smoking status, and the relative change in the serum levels of Krebs von den Lungen-6 (KL-6) were associated with prognosis (P = 0.02, 0.04, and 0.02, respectively), but the presence of honeycombing and the forced vital capacity were not associated with survival. The relative change in KL-6 levels (greater than vs. less than a 10% decrease) was significantly associated with survival in a stratified analysis (73.9 vs. 34.9 months; P = 0.04). CONCLUSIONS: The relative change in KL-6 levels is associated with the prognosis of patients with fibrotic BRHP independent of previously identified prognostic biomarkers. This finding could help pulmonologists identify fibrotic BRHP patients that are likely to show rapid progression.

Structural and Exchange Components in Processes of Neighbourhood Change: A Social Mobility Approach.

Neighbourhood socioeconomic change is a complex phenomenon which is driven by multiple processes. Most research has focused on the role of urban-level processes, which lead to an exchange of relative positions among neighbourhoods of a single metropolitan area. Consequently, the effects of structural processes on neighbourhood socioeconomic change, such as overall income growth or decline, and increasing inequality, have been neglected. This is reflected in the standard methodological practices; the common measures of neighbourhood change exclude the effect of overall growth or decline and confound the effects of urban processes with the effect of increase in inequality. This paper proposes a method that was originally developed for understanding income mobility of individuals, to decompose total neighbourhood socioeconomic change measured in absolute terms into its contributing components. The approach enables to take account of all processes that generate neighbourhood socioeconomic change, while distinguishing between them. The method is demonstrated in an empirical analysis of neighbourhood socioeconomic change across 22 metropolitan areas in the US. The findings indicate that structural processes can be most substantial in generating change. Neighbourhood socioeconomic change in 'superstar cities' is mostly generated by the growth in overall incomes, with a relatively low contribution of increasing inequality. Conversely, in declining cities it is mostly driven by overall decline and increasing inequality. An additional finding relates to the interaction between urban processes and increasing inequality. These processes work in opposite directions such that any increase in positions of low-income neighbourhoods can be totally offset by an income decrease due to increasing inequality.

Estimating short- and long-term reference change values and index of individuality for tests of platelet function.

BACKGROUND: In order to manage risks of bleeding and thrombosis after some surgical procedures, platelet function is often measured repeatedly over days or weeks using laboratory tests of platelet function. To interpret test results in the perioperative period, it is necessary to understand analytical, biological and between-person variation. METHODS: We collected three separate blood specimens from 16 healthy volunteers on the first study day, and one additional specimen from each volunteer 1, 2, and 3 months later. Arachidonic acid-induced and adenosine diphosphate (ADP)-induced platelet function were measured in duplicate by whole blood impedance aggregometry using Multiplate (ASPI/ADP tests) and VerifyNow (Aspirin Reaction Units [ARU] and P2Y12 Reaction Units [PRU]). The analytical variation (CVA), within-subject variation (CVI), between-subject variation (CVG), index of individuality (II), and reference change values (RCV) were calculated. RESULTS: VerifyNow ARU demonstrated the smallest short-term and long-term variability (CVA, CVI, and CVG ~1%), resulting in short- and long-term RCV values <5%. II was also higher (1.92) for VerifyNow ARU than other platelet function tests. Multiplate ASPI and ADP tests had the highest RCV both short-(19.0% and 25.2%, respectively) and long-term (32.1% and 39.6%, respectively) due to increased CVA (>5%) and CVI (3.9-13.1%). VerifyNow PRU had a lower RCV than Multiplate ADP; but was the only test with II <0.6. CONCLUSIONS: VerifyNow ARU results can be interpreted relative to a fixed cut-off or population-based reference interval; or relative to small changes in an individual's previous values. VerifyNow PRU and Multiplate ASPI and ADP tests should only be interpreted based upon relative change; and can only distinguish relatively large (>23%) changes over several weeks.

Protocol for management after thyroidectomy: a retrospective study based on one-center experience.

BACKGROUND AND AIM: The optimal approach to detect and treat symptomatic hypocalcemia (SxH) after thyroidectomy is still uncertain. In our retrospective study, we sought to set a standardized postoperative management protocol on the basis of relative change of parathyroid hormone (PTH) and absolute value of postoperative day 1 (POD1) PTH. METHODS: Patients who underwent thyroidectomy were identified retrospectively in our prospective database. Blood was collected 1 day before surgery and on POD1. Extra calcium and calcitriol supplement was prescribed when necessary. Meanwhile, postoperative signs of SxH were treated and recorded in detail. Patients were followed up for 1 month after surgery and then 3 months thereafter. RESULTS: A total of 744 patients were included in the final analysis. Transient SxH occurred in 86 (11.6%) patients, and persistent SxH occurred in 4 (0.54%) patients in more than half year after surgery. Relative decrease of PTH reached its maximal discriminative effect at 70% (area under the curve [AUC] =0.754), with a sensitivity of 72.1% and a specificity of 75%. In Group 1 (≤70%), 24 (4.67%) patients were interpreted as having SxH, whereas in Group 2, 62 (27.0%) patients had SxH (>70%), P<0.001. Days of symptom relief in Group 1-1 (1, 2) were significantly shorter than those in Group 2-2 (1, 10), P=0.023. In Group 2, 112 (80%) patients with POD1 PTH <1 pmol/L were treated with calcitriol, whereas only 8 (8.89%) patients with POD1 PTH ≥1 pmol/L were treated with calcitriol (P<0.001). According to relief of SxH and recovery of parathyroid function, treating with and without calcitriol showed no difference in patients with POD1 PTH <1 and ≥1 pmol/L. CONCLUSION: Relative decrease of PTH >70% is a significant risk factor for SxH in post-thyroidectomy. The decreasing percent of PTH ≤70% ensures discharge on POD1, but longer hospitalization was advocated for patients with decreasing percent of PTH >70%, who needed extra calcitriol supplement when POD1 PTH <1 pmol/L.

Tackling proteome changes in the longissimus thoracis bovine muscle in response to pre-slaughter stress.

Pre-slaughter stress has adverse effects on meat quality that can lead to the occurrence of Dark Firm Dry (DFD) meat in cattle. This study explores the previously uncharacterized proteome changes linked to pre-slaughter stress in the longissimus thoracis (LT) bovine muscle. Differential proteome profiles of DFD and normal (non-DFD) LT meat samples from male calves of the Rubia Gallega breed were assessed by 2-DE coupled to MS analysis (LC-MS/MS and MALDI TOF/TOF MS). A total of seven structural-contractile proteins (three different myosin light chain isoforms, two fast skeletal myosin light chain 2 isoforms, troponin C type 2 and cofilin-2) and three metabolism enzymes (triosephosphate isomerase, ATP synthase and beta-galactoside alpha-2,6-sialyltransferase) were found to have statistically significant differential abundance in sample groups. In addition, 2-DE in combination with the phosphoprotein-specific fluorescent dye Pro-Q DPS revealed that highly phosphorylated fast skeletal myosin regulatory light chain 2 isoforms underwent the most intense relative change in muscle conversion to DFD meat. Therefore, they appear to be the most sensitive biomarkers of stress just prior to slaughter in Rubia Gallega. Overall, these findings will facilitate a more integrative understanding of the biochemical processes associated with stress in cattle muscle and their effects in meat quality. BIOLOGICAL SIGNIFICANCE: Pre-slaughter stress is a crucial factor in meat production. Animals destined for slaughter are stressed by a variety of endogenous and exogenous factors that negatively affect the complex post-mortem biochemical events underlying the conversion of muscle into meat. The study of the muscle proteome has a great relevance for understanding the molecular mechanisms associated with stress. However, there is no information available on the molecular changes linked to pre-slaughter stress in cattle on the proteome scale. Our study led to the identification of a number of candidate proteins associated with the response to pre-slaughter stress in the LT bovine muscle of the Rubia Gallega breed. The functions of those significantly changed proteins have a clear biological relationship with stress response. These findings contribute to a deeper insight into the molecular pathways that respond to stress in cattle.

Gene regulatory network inference and validation using relative change ratio analysis and time-delayed dynamic Bayesian network.

The Dialogue for Reverse Engineering Assessments and Methods (DREAM) project was initiated in 2006 as a community-wide effort for the development of network inference challenges for rigorous assessment of reverse engineering methods for biological networks. We participated in the in silico network inference challenge of DREAM3 in 2008. Here we report the details of our approach and its performance on the synthetic challenge datasets. In our methodology, we first developed a model called relative change ratio (RCR), which took advantage of the heterozygous knockdown data and null-mutant knockout data provided by the challenge, in order to identify the potential regulators for the genes. With this information, a time-delayed dynamic Bayesian network (TDBN) approach was then used to infer gene regulatory networks from time series trajectory datasets. Our approach considerably reduced the searching space of TDBN; hence, it gained a much higher efficiency and accuracy. The networks predicted using our approach were evaluated comparatively along with 29 other submissions by two metrics (area under the ROC curve and area under the precision-recall curve). The overall performance of our approach ranked the second among all participating teams.