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In this study, we aimed to identify an essential blood molecular signature for chacterizing the progression of sepsis-induced acute lung injury using integrated bioinformatic and machine learning analysis. The results showed that a total of 88 functionally related ALI-associated hub genes in sepsis were identified by MCODE analysis and they were enriched in infection and inflammtory responses, lung and cardiovascular disease pathways. These hub genes stratified ALI-sepsis and sepsis and further stratified two subtypes of sepsis-ALI with differential ALI scores, hub gene expression patterns, and levels of immune cells. A seven-gene signature including TNFRSF1A, NFKB1, FCGR2A, NFE2L2, ICAM1 and SOCS3 and PDCD1 was derived from the hub genes. These genes were significantly implicated in immune and metabolism pathways. They were expressed in six circulatory immune cells based on analysis of a single cell RNA sequencing dataset. Furthermore, the seven-gene signature was corrobarated using by integrating 12 machine learning algorithms. A premium three-gene signature NFE2L2, FCGR2A and PDCD1 for differentiating ALI-sepsis from sepsis were also derived from the seven-gene signature based on analysis of the seven core hub genes by the machine learning algorithms. Furthermore, the expressions of hub genes were verified in sepsis mice models. Therefore, our study provided an avenue to develop a molecular tool for identify and characterize progression of acute lung injury associated with sepsis. [ABSTRACT FROM AUTHOR]

• Routine serum inflammatory markers CRP, ESR, and WBC have limited diagnostic value in preoperative diagnosis of FRI. • Histology is characterized by high specificity, with the best sensitivity observed for the quantitative method. • Culture exhibits higher sensitivity than histology, whether qualitative or quantitative. • Microbiology can be improved by increasing sample number, implementing long-term culture, and adjunctive implant sonication. Although fracture-related infection (FRI) is a serious complication following bone fractures, a comprehensive definition and diagnostic criteria have only emerged in recent years. According to this consensus definition, the diagnosis of FRI is based on preoperative and intraoperative suggestive or confirmatory criteria. Serum markers, histology, and microbiological cultures are considered to play a crucial role in the FRI diagnostic pathway. However, at the time of publication of the FRI consensus definition in 2018 and its update in 2020, limited data was available on the accuracy of these diagnostic methods. This review aims to provide an overview of recent publications and discuss whether new evidence has been obtained regarding the value of these current diagnostic techniques. Meanwhile, several studies have confirmed the limited prognostic value of C-reactive protein, erythrocyte sedimentation ratio, and white blood cell count. Other serologic markers for preoperative diagnosis of FRI with promising diagnostic performance are d-dimer, plasma fibrinogen, platelet count to mean platelet volume ratio, and a risk prediction model that includes soft tissue injury type and fracture complexity in addition to blood markers. However, their true diagnostic value in daily clinical practice needs to be investigated in further studies. Data on histology in FRI diagnosis is still limited, but its potential as a confirmatory criterion seems to lie in its high specificity. Recent studies indicate that tissue culture exhibits moderate sensitivity and high specificity, with sensitivity improvements achieved by sampling of five specimens and long-term culture. Implant sonication also appears to enhance the sensitivity of culture and the detection rate of polymicrobial infections. In conclusion, the true value of diagnostic techniques is difficult to assess, in part because it is measured against a gold standard that is itself imperfect and still evolving, but also because of methodological differences in sample processing or the use of different thresholds. Nevertheless, this review has identified that the value of current diagnostic techniques is high when used in combination. To draw more accurate conclusions about the value of serum markers, histology, and culture including sonication, future studies should be prospective and utilize a greater standardization in sampling and methodological protocols. [ABSTRACT FROM AUTHOR]

Cows experience a significant negative protein balance during the first 30 d of lactation. Given the functional effects of AA on health, especially in challenging periods such as calving, higher levels of protein and specific AA in the diet may act to improve health and feed intake. The response of dairy cows to 3 protein supplementation strategies during the transition period and through the first 45 d in milk was evaluated. The final data set had 39 Holstein cows blocked based on parity (primiparous vs. multiparous) and expected calving and randomly assigned within each block to one of 3 dietary treatments: low protein (LP), high protein (HP), or high protein plus rumen-protected methionine (HPM). Treatments were offered from d −18 ± 5 to 45 d relative to parturition. Pre- and postpartum diets were formulated for high metabolizable protein (MP) supply from soybean meal, and HP and HPM provided higher MP balance than LP. Preplanned contrasts were LP versus HP+HPM and HP versus HPM. Significance was declared at P ≤ 0.05 and trends at 0.05 < P ≤ 0.10. Cows fed HP and HPM had greater fry matter intake (DMI) prepartum than LP (+2 kg/d), and there was a trend for greater DMI with HPM than with HP (+1.6 kg/d). Body weight and condition score before and after calving did not differ among treatments. High protein (HP and HPM) tended to increase milk yield during the first 45 d of lactation (+1.75 kg/d), increased milk lactose content and urea-N in milk and plasma, tended to increase blood BHB 14 d postpartum, and tended to reduce milk/DMI compared with LP. Blood concentrations of calcium at calving and of glucose, and nonesterified fatty acids pre- and postpartum did not differ. High protein induced lower concentration of plasma IL-1 at calving and lowered blood lymphocytes 21 d postpartum, suggestive of a reduced inflammatory status compared with LP. The concentrations of IL-10, tumor necrosis factor alpha, and other hemogram variables did not differ among treatments. Addition of rumen-protected methionine to the HP diet did not alter milk yield but increased fat and total solids concentrations. The rumen-protected methionine had no effect on blood metabolites and immunity markers, with the exception of increased pre-partum insulin concentrations. The data indicate that dairy cows around calving respond positively to an increase in the supply of MP and to rumen-protected methionine supplementation of the HP diet by increasing intake and improving immune status. [ABSTRACT FROM AUTHOR]

Highlights • PgACC glutamatergic and peripheral Acet-Tub/TRF changes are neg. correlated 24h after ketamine infusion in healthy subjects. • Gender has influence on basal levels and relative change of Acet-Tub/TRF post- ketamine infusion. • Glutamate change 24h post- ketamine infusion is gender unspecific. Abstract Ketamine acts as a rapid–acting antidepressant by restoring glutamatergic deficits and activating synaptic plasticity processes, with peak activity 24 h after infusion. Microtubule dynamics are known to play a key role in modulation of cytoskeleton and synaptic plasticity, as well as in signalling events in peripheral blood cells. Here, we correlated ketamine-induced change in glutamate/creatinine (Glu/Cr) levels in the pregenual anterior cingulate cortex (pgACC) with peripheral markers of microtubule dynamics, namely acetylated α-tubulin (Acet-Tub), with particular attention to gender specificity. Eighty healthy controls (age = 25.89 ± 5.29, 33 women) were administered intravenous infusion of either ketamine (0.5 mg/kg) or placebo (saline). Blood samples were obtained at baseline and 24 h after infusion and plasma levels of Acet-Tub and transferrin (TRF; loading control) were measured via infrared western blotting. Glu/Cr levels were measured via high-field (7 T) proton magnetic resonance spectroscopy [1H-MRS] in the pgACC at the same time points. Gender differences were observed in baseline Acet–Tub/TRF levels (p < 0.001), and an interaction of time by treatment by gender (F = 5.13, p = 0.027) was found, with a significant increase in Acet–Tub/TRF for ketamine group in females only (p = 0.038). Ketamine-induced gender-independent Glu/Cr changes at 24 h (F(1, 69) = 4.08, p = 0.047), and changes in the pgACC were negatively correlated with the Acet-Tub/TRF expression (r= -0.464, p = 0.010) in the ketamine group, in which, separated by sex, only women showed significant correlation. Our findings indicate a temporal association between changes in central ketamine-induced glutamatergic effects and peripheral markers of cytoskeleton reorganization, particularly in females. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine effect of the diet containing 1200 betaine diet on blood biomarkers, electrolytes, gas and cecum short-chain fatty acid profile in meat ducks exposed to very hot environment (high relative humidity) conditions from d 21–42 (11:00 to 17:00 h; 33–43 °C; 70% relative humidity). On the day of hatching, a total of 320 meat ducks(average, 48.6 g body weight) were randomly assigned to 4 treatments with 4 pens per treatment and 20 ducks per pen for 42 d. Dietary treatments consisted of: 1) the control diet fed ad libitum, 2) the betaine diet fed ad libitum, 3) the betaine diet fed from 05:00 to 10:00 and 17:00 to 20:00 h, and 4) the betaine diet fed from 17:00 to 20:00 h. Ducks fed the betaine diets had greater body weight at d 42 than those fed the control diet ( P <0.05). The total red blood cell counts, hematocrit, hemoglobin, mean corpuscular volume, red cell distribution width, platelet count, plateletcrit and mean platelet volume concentration in ducks fed the control diet were lower than those fed the betaine diets ( P <0.05). Blood electrolyte concentrations in ducks fed the betaine diet at different feeding times had greater values than those fed the control diet ( P <0.05). Partial pressure of carbon dioxide, partial pressure of oxygen, base excess of extracellular fluid, bicarbonate and total carbon dioxide concentrations in ducks fed the control diets were lower than those on the betaine treatments ( P <0.05). Respective to ducks fed the betaine diets had greater concentrations of total SCFA, acetic acid, propionic acid in the cecum than those fed the control diet ( P <0.05). However, ducks fed the betaine diets had lower levels of butyric acid, isobutyric acid, valeric acid, isovaleric acid than those fed the control diet ( P <0.05). The body weight, feed intake, sodium, hematocrit, hemoglobin, base excess of extracelluar fluid, mean corpuscular volume in ducks fed the betaine diet from fed 05:00 to 10:00 and 17:00 to 20:00 h were greater ( P <0.05) than those fed the betaine diet ad libitum and from 17:00 to 20:00 h. The results of this study indicated that restricted feeding of the diet with 1200 ppm betaine in morning and afternoon can have beneficial effects on meat ducks exposed to the very hot environment (high relative humidity) condition. [ABSTRACT FROM AUTHOR]

Unlabelled: Previous studies have identified altered molecular profiles in blood samples from individuals with schizophrenia and with bipolar disorder using multianalyte immunoassay platforms but there has been little comparison of the two groups in the same investigation. A total of 337 participants including 146 with schizophrenia, 79 with bipolar disorder, and 112 non-psychiatric controls had a blood sample drawn from which 166 analytes were measured. The initial dataset was split; classification models were developed in a training dataset and their performance evaluated in a test dataset. Principal component analysis was used to generate factor scores that were then compared between the groups. In a training set, a total of 7 independent factors were generated using 29 markers that were both normally distributed and significantly associated with diagnosis. Many of these analytes are components of the immune system and involved in the inflammatory response to infectious agents and foreign antigens. Two of the seven principal component scores discriminated between individuals with schizophrenia and with bipolar disorder; additional factors distinguished individuals with either schizophrenia or bipolar disorder from control individuals, while two factors were not significantly different between any of the diagnostic groups. In a test dataset, the schizophrenia vs. control Receiver Operating Curve (ROC) analysis shows an overall accuracy of 77% for schizophrenia vs. bipolar disorder, 84% for schizophrenia vs. controls, and 72% for bipolar disorder vs.Controls: An increased understanding of the role of altered pathways in serious psychiatric disorders may lead to novel methods for disease diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Objectives Resistance exercise is used as a non-pharmacological tool to elicit both gains in and maintenance of physical function in the elderly. Thus, the present study examined the acute response of creatine kinase and interleukin-6 following an eccentric resistance exercise session in elderly obese women classified as high responders or normal responders. Design Cross-sectional field study. Methods Ninety elderly obese women (69.4 ± 6.01 years) were tested for a 10 repetition maximum on the leg extension exercise and then completed an acute eccentric resistance exercise session consisting of seven sets of 10 repetitions at 110% of 10 repetition maximum with a rest of 3 min between sets. Subjects were divided into normal response or high response on the basis of the peak serum interleukin-6 (NR = 59 and HR = 7) and creatine kinase (NR = 81 and HR = 9) concentration being greater than (HR) or less than (NR) the 90th percentile. Results Creatine kinase was higher at 0 h, 3 h, 24 h and 48 h following the ERE for the HR group. The peak creatine kinase was significantly higher in HR group versus the normal response group. The average increase in the serum interleukin-6Δ for the HR group (∼850%) was significantly higher versus the normal response group (∼55%). Serum interleukin-6 was significantly higher at 0 h and 24 h following eccentric resistance exercise only for the high response group, while peak levels were significantly higher in high response group versus the normal response group ( p ≤ 0.005). Only one subject met the criteria to be classified as high response for both creatine kinase and interleukin-6 responsiveness. Conclusions Elderly individuals classified as high response experienced greater creatine kinase and interleukin-6 responses to ERE. Thus, a prudent approach for eccentric resistance exercise prescription might be programming additional recovery days and/or lower intensity training, especially in the beginning stages of a program. [ABSTRACT FROM AUTHOR]

Abstract: Background: This study aimed to develop and evaluate a predictive score named Fibrosis Routine Test (FRT) for liver fibrosis staging and to compare FRT with APRI, Lok, GUCI, FI, FibroQ, FCI, FIB-4 and 4RLB scores in large numbers of untreated HCV-monoinfected patients. Methods: Large numbers of estimation (N=2045) and validation patients (N=3212) were included in this study. Stepwise linear discriminant analysis and area under receiver-operating characteristic curves (AUCs) were used to create a predictive score comprising age, AFP, APRI and albumin. Results: In the estimation study, FRT produced AUCs 0.84, 0.85 and 0.86 for significant (F2–F4), advanced fibrosis (F3–F4) and cirrhosis (F4), respectively. FRT >4 was 83% specific and 73% sensitive for F2–F4, FRT >5 was 83% specific and 71% sensitive for F3–F4 and FRT >5.5 was 81% specific and 73% sensitive for F4. In the validation study, FRT produced AUCs 0.81, 0.89 and 0.95 for F2–F4, F3–F4 and F4, respectively. The above eight scores demonstrated lower AUCs than FRT. Conclusion: While liver biopsy is invasive, costly and associated with complications, Fibrosis Routine Test (FRT) is a non-invasive, inexpensive, simple and may reduce the need of liver biopsy. [Copyright &y& Elsevier]

Abstract: Background: This study was undertaken to investigate whether serum cytokeratin-1 (CK1) could complement alpha-fetoprotein (AFP) to improve the diagnosis of hepatocellular carcinoma (HCC). Methods: CK1 was identified using western blot and ELISA in serum samples from 250 Egyptian patients including 150 with HCC, 100 with liver cirrhosis (LC) and 50 healthy controls. Multivariate discriminant analysis (MDA) and ROC curve analyses were used to create a predictive model including CK1 in addition to a panel of routine blood markers. Results: CK1 was identified at 67kDa and quantified in sera of HCC patients using western blot and ELISA. MDA selected a score for the prediction of HCC from LC patients based on levels of CK1, albumin and AFP. An area under the ROC curves (AUC) of the score was 0.87. The score showed a sensitivity of 87% vs 39% sensitivity of AFP at cutoff value of 200IU/ml for prediction HCC. Absolute specificity (100%) was obtained to discriminate HCC from healthy individuals. Conclusions: This study suggests that the use of a combination of score including CK1, AFP and albumin in clinical practice provides a non invasive and simple test that could increase significantly the sensitivity of HCC diagnosis. [Copyright &y& Elsevier]

Abstract: Background and study aims: Non-invasive methods for the assessment of liver fibrosis are clinically important where hepatitis C virus (HCV) is common in Egypt. Our aim was to evaluate the diagnostic performance of a panel of simple blood markers of liver fibrosis in chronic hepatitis C (CHC) patients. Patients and methods: A total of 199 patients with CHC evaluated for eligibility for antiviral therapy were included. Liver biochemical profile including transaminases, bilirubin, alkaline phosphatase, serum albumin, complete blood count prothrombin time and AFP were estimated. Liver biopsy was done. Statistical analyses were performed by logistic regression and receiver operating characteristic (ROC) curves to assess and compare diagnostic accuracy of blood markers. A stepwise combination algorithm was developed and validated prospectively in 135 additional patients. Results: α-Foetoprotein (AFP) was the most efficient marker among other markers tested. The areas under the curves (AUCs) of AFP were 0.77 for significant liver fibrosis (F2–F4), 0.75 for advanced liver fibrosis (F3–F4) and 0.76 for liver cirrhosis (F4). The stepwise multivariate discriminant analysis (MDA) selected a novel non-invasive index for discriminating patients with significant liver fibrosis, named Fibro-α score. Fibro-α score=(1.35 (numeric constant) +AFP (IUml−1)×0.009584+aspartate aminotransferase (AST)/alanine aminotransferase (ALT)×0.243−platelet count (×109 l−1)×0.001624). The Fibro-α score was used for patients with advanced liver fibrosis and liver cirrhosis. The AUCs of Fibro-α score were 0.82 for patients with advanced liver fibrosis and 0.80 for those with cirrhosis. These results were reproduced in a validation study with no significant difference. Conclusion: While liver biopsy is invasive, expensive and, in some settings, impossible to do, Fibro-α score is simple, cheap, non-invasive and may be useful for predicting significant liver fibrosis. [Copyright &y& Elsevier]

Abstract: Objectives: To evaluate the diagnostic accuracy of liver fibrosis tests and its influencing factors in a meta-analysis with individual data. Design and methods: Four independent centers provided four blood tests and Metavir staging from 825 patients with chronic hepatitis C. Results: FibroMeter AUROC (0.840) for significant fibrosis was superior to those of Fibrotest (0.803, p =0.049), APRI (0.789, p =0.001) and Hepascore (0.781, p <0.001). The misclassification rate was lower for FibroMeter (23%) than for Fibrotest and Hepascore (both 28%, p <0.001). The variation in the diagnostic cut-offs of tests among centers, reflecting the overall reproducibility, was: FibroMeter: 4.2%, APRI: 24.0%, Fibrotest: 24.2%, Hepascore: 35.0%. Accordingly, the proportion of patients diagnosed with significant fibrosis changed: FibroMeter: 0.8%, Hepascore: 2.4% (p =0.02 vs FibroMeter), Fibrotest: 5.8% (p <10−3), APRI: 18.2% (p <10−3). Conclusions: This study on clinical applicability shows significant differences in diagnostic accuracy, inter-center reproducibility, and robustness of biomarkers to changes in population characteristics between blood tests. [Copyright &y& Elsevier]

Background Cognitive decline and Alzheimer disease are more prevalent in our aging population. Modifiable risk factors, such as diet and sedentary lifestyle, have been proposed as key to potentially ameliorating cognitive decline. Both exercise and Mediterranean diet (MedDiet) have been linked to reduced levels of cardiovascular disease and other comorbidities. Higher levels of exercise and MedDiet adherence may prove to be cognitively protective, both individually and synergistically. Objectives The aim was to investigate the effect of a 6-mo program of MedDiet, exercise, and a combination of both, on cognition, mood, and general health in older persons living independently in aged-care communities. Methods The Lifestyle Intervention in Independent Living Aged Care (LIILAC) Study (ACTRN12614001133628) involved 102 participants, aged 60–90 y, who were randomly assigned to 1 of 4 intervention groups. Change in overall memory performance was assessed as the primary outcome. Additionally, changes in cognitive task performance, as well as mood, wellness, cardiovascular function, and blood biomarkers, were investigated. Results While there was no significant change in overall memory performance, there was a significant improvement in spatial working memory performance in the combined exercise and diet group, relative to controls. This combined intervention group also showed an overall improvement in their emotional state, as assessed by the Depression Anxiety Stress Scale, as did the exercise-only group. Conclusions This research indicates that diet and exercise programs have the potential to improve aspects of cognition and mood in an aging population. However, given the lower than optimal sample size and lack of resources to reinforce the interventions during the trial, further larger randomized controlled trials are required to substantiate whether the introduction of diet and exercise programs into independent-living facilities is a viable method to preserve cognitive health in older people. This trial was registered at www.ANZCTR.org.au ACTRN 12614001133628 (LIILAC Study) [ABSTRACT FROM AUTHOR]