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Актуальность. В современной медицинской практике отсутствует четкий перечень гематологических, биохимических и иммунологических тестов как для первичной оценки состояния пациентов, так и для контроля динамики метаболического статуса после эндопротезирования суставов. Цель исследования: определить и установить диагностическую чувствительность биохимических и иммунологических маркеров крови в динамике послеоперационного периода у пациентов после эндопротезирования тазобедренного и коленного суставов для ранней диагностики перипротезной инфекции. Материалы и методы. Исследование выполнялось на 53 пациентах, которым было проведено 61 оперативное вмешательство на коленном и тазобедренном суставах. Осуществлены эндопротезирование коленного (n = 41) и тазобедренного (n = 14) суставов, дебридмент (n = 6), из них первичных эндопротезирований — 42, ревизионных эндопротезирований — 13 (мужчин — 16, женщин — 37, возраст больных — от 35 до 79 лет). Все больные были разделены на три группы: I группа — пациенты, которым была диагностирована перипротезная инфекция в срок до 4 недель после операции (n = 7), II — пациенты, у которых инфекция была диагностирована при обращении в клинику, но послеоперационный период после выполнения ревизионного вмешательства протекал без осложнений (n = 8), III — пациенты, у которых было нормальное течение послеоперационного периода (n = 46). В сыворотке крови определяли содержание общего белка, гликопротеинов, хондроитинсульфатов, глюкозы и С-реактивного белка, интерлейкинов (ИЛ-1β и ИЛ-6). Диагностическую чувствительность (ДЧ) лабораторных показателей рассчитывали по формуле: ДЧ = (ТП/Д) × 100 %, где ТП — истинно положительные результаты исследования, Д — количество больных в группе. Результаты. Во всех группах пациентов было установлено наличие воспалительно-деструктивных нарушений в организме по содержанию гликопротеинов, хондроитинсульфатов, ИЛ-1β и ИЛ-6, которые имели высокие показатели ДЧ. Выводы. У больных всех исследуемых групп независимо от обнаружения перипротезной инфекции наблюдались острые воспалительно-деструктивные процессы в организме, которые отражались в повышении содержания гликопротеинов, хондроитинсульфатов, С-реактивного белка, ИЛ-1β и ИЛ-6 в крови после эндопротезирования тазобедренного и коленного суставов, исследованные биохимические и иммунологические маркеры крови не являются специфичными для диагностики перипротезной инфекции; ДЧ во всех группах больных в послеоперационный период была самой высокой у гликопротеинов, хондроитинсульфатов, С-реактивного белка, ИЛ-1β и ИЛ-6, что позволяет использовать данные лабораторные маркеры для оценки степени воспалительного процесса в организме ортопедических пациентов после эндопротезирования тазобедренного и коленного суставов., Актуальність. У сучасній медичній практиці відсутній чіткий перелік гематологічних, біохімічних та імунологічних тестів як для первинної оцінки стану пацієнтів, так і для контролю динаміки метаболічного статусу після ендопротезування суглобів. Мета дослідження: визначити та встановити діагностичну чутливість біохімічних та імунологічних маркерів крові в динаміці післяопераційного періоду в пацієнтів після ендопротезування кульшового і колінного суглобів для ранньої діагностики перипротезної інфекції. Матеріали та методи. Дослідження виконувалось на 53 пацієнтах, яким було проведено 61 оперативне втручання на колінному і кульшовому суглобах. Здійснені ендопротезування колінного (n = 41) і кульшового (n = 14) суглобів, дебридмент (n = 6), із них первинних ендопротезувань — 42, ревізійних ендопротезувань — 13 (чоловіків — 16, жінок — 37, вік хворих — від 35 до 79 років). Усіх хворих було розподілено на три групи: І група — пацієнти, яким було діагностовано перипротезну інфекцію в термін до 4 тижнів після операції (n = 7), ІІ — пацієнти, в яких інфекцію було діагностовано при зверненні в клініку, але післяопераційний період після виконання ревізійного втручання перебігав без ускладнень (n = 8), ІІІ — пацієнти, у яких був нормальний перебіг післяопераційного періоду (n = 46). У сироватці крові визначали вміст загального білка, глікопротеїнів, хондроїтинсульфатів, глюкози, С-реактивного білка, інтерлейкінів (ІЛ-1β та ІЛ-6). Діагностичну чутливість (ДЧ) лабораторних показників розраховували за формулою: ДЧ = (ТП/Д) × × 100 %, де ТП — істино позитивні результати дослідження, Д — кількість хворих у групі. Результати. У всіх групах пацієнтів була встановлена наявність запально-деструктивних порушень в організмі за вмістом глікопротеїнів, хондроїтинсульфатів, ІЛ-1β та ІЛ-6, які мали найвищі показники ДЧ. Висновки. У хворих всіх дослідних груп незалежно від виявлення перипротезної інфекції спостерігались гострі запально-деструктивні процеси в організмі, які виявлялись у підвищенні вмісту глікопротеїнів, хондроїтинсульфатів, С-реактивного білка, ІЛ-1β та ІЛ-6 у крові після ендопротезування кульшового і колінного суглобів, досліджені біохімічні та імунологічні маркери крові не є специфічними для діагностики перипротезної інфекції; ДЧ у всіх групах хворих у післяопераційний період була найвищою у глікопротеїнів, хондроїтинсульфатів, С-реактивного білка, ІЛ-1β та ІЛ-6, що дозволяє використовувати дані лабораторні маркери для оцінки ступеня запального процесу в організмі ортопедичних пацієнтів після ендопротезування кульшового і колінного суглобів., Background. In modern medical practice, there is no clear list of hematological, biochemical and immunological tests for both primary assessment of patients’ condition and monitoring the dynamics of metabolic status after joint arthroplasty. The purpose of the study was to determine the diagnostic sensitivity of biochemical and immunological blood markers in the dynamics of the postoperative period in patients after hip and knee replacement for early diagnosis of periprosthetic infection. Materials and methods. The study was performed in 53 patients (16 men and 37 women aged 35 to 79 years) who underwent 61 operations on the knee and hip joints. Knee (n = 41) and hip (n = 14) arthroplasty was preformed, as well as debridement (n = 6), including 42 primary and 13 revision surgeries. All patients were divided into three groups. Group I consisted of patients who were diagnosed with periprosthetic infection within 4 weeks after surgery (n = 7); group II — persons whose infection was diagnosed when they went to the clinic, but the postoperative period after revision intervention was without complications (n = 8); group III — patients who had a normal course of the postoperative period (n = 46). In the blood serum, the content of total protein, glycoproteins, chondroitin sulfates, glucose, C-reactive protein, interleukins (IL-1β and IL-6) was determined. Diagnostic sensitivity (DS) of laboratory parameters was calculated according to the formula: DS = (TP / D) × 100 %, where TP — truly positive results of the study, D — number of patients in the group. Results. In all groups of patients, the presence of inflammatory-destructive disorders in the body was revealed in terms of glycoprotein, chondroitin sulfate, IL-1β and IL-6 content, which had highest rates of DS. Conclusions. In patients of all study groups, regardless of the detection of periprosthetic infection, acute inflammatory-destructive processes were observed in the form of an increase in the blood levels of glycoproteins, chondroitin sulfates, C-reactive protein, IL-1β and IL-6 after hip and knee replacement. Biochemical and immunological markers of the blood have no specificity for the diagnosis of periprosthetic infection. DS in all groups of patients in the postoperative period was highest in glycoproteins, chondroitin sulfates, C-reactive protein, IL-1β and IL-6, which allows the use of these laboratory markers to assess the degree of inflammation in the body of orthopedic patients after hip and knee replacement.

BACKGROUND Bacteraemia is a common cause of children presenting to the paediatric emergency with acute febrile illness. Blood cultures remain the gold standard for detection of bacteraemia but the positivity is low and also takes time to show positive results. A rapid and reliable biomarker like procalcitonin (PCT), C-reactive protein (CRP), total leucocyte count (TLC), and neutrophil-lymphocyte count ratio (NLCR) can be used to identify febrile children with greater risk for bacteraemia or serious bacterial infections. This would be very helpful to start early treatment of bacteraemia with antibiotics. METHODS The study was an observational cohort study conducted in the Department of Paediatrics of a tertiary care hospital in North India in children between age group 6 months to 12 years presenting with fever of > 100.4° F for 2 - 7 days. Blood samples were sent for PCT, CRP, TLC, NLCR and blood cultures. RESULTS The most sensitive biomarker was total leukocyte count (47.36 %) followed by the neutrophil percentage (26.32 %), C-reactive protein (21.05 %), and procalcitonin (15.79 %). The most specific biomarker was procalcitonin (75.14 %) followed by C-reactive protein (58.56 %), neutrophil percentage (22.65 %) and total leukocyte count (11.05 %). The only biomarker that was statistically significant between the bacteraemia and non-bacteraemia group in the present study was total leukocyte count (P – value < 0.05). CONCLUSIONS The sensitivity and specificity of each single biomarker is low and hence these cannot be used singly to predict bacteraemia. There should be a combination of biomarkers with adequate sensitivity and specificity that can be used to create an algorithm to aid in diagnosis and prognostication. KEYWORDS Procalcitonin, C-Reactive Protein, Blood Culture, Acute Febrile Patient

Aims While preoperative bloodwork is routinely ordered, its value in determining which patients are at risk of postoperative readmission following total knee arthroplasty (TKA) and total hip arthroplasty (THA) is unclear. The objective of this study was to determine which routinely ordered preoperative blood markers have the strongest association with acute hospital readmission for patients undergoing elective TKA and THA. Methods Two population-based retrospective cohorts were assembled for all adult primary elective TKA (n = 137,969) and THA (n = 78,532) patients between 2011 to 2018 across 678 North American hospitals using the American College of Surgeons National Quality Improvement Programme (ACS-NSQIP) registry. Six routinely ordered preoperative blood markers - albumin, haematocrit, platelet count, white blood cell count (WBC), estimated glomerular filtration rate (eGFR), and sodium level - were queried. The association between preoperative blood marker values and all-cause readmission within 30 days of surgery was compared using univariable analysis and multivariable logistic regression adjusted for relevant patient and treatment factors. Results The mean TKA age was 66.6 years (SD 9.6) with 62% being females (n = 85,163/137,969), while in the THA cohort the mean age was 64.7 years (SD 11.4) with 54% being female (n = 42,637/78,532). In both cohorts, preoperative hypoalbuminemia (< 35 g/l) was associated with a 1.5- and 1.8-times increased odds of 30-day readmission following TKA and THA, respectively. In TKA patients, decreased eGFR demonstrated the strongest association with acute readmission with a standardized odds ratio of 0.75 per two standard deviations increase (p < 0.0001). Conclusion In this population level cohort analysis of arthroplasty patients, low albumin demonstrated the strongest association with acute readmission in comparison to five other commonly ordered preoperative blood markers. Identification and optimization of preoperative hypoalbuminemia could help healthcare providers recognize and address at-risk patients undergoing TKA and THA. This is the most comprehensive and rigorous examination of the association between preoperative blood markers and readmission for TKA and THA patients to date. Cite this article: Bone Jt Open 2021;2(6):388–396.

Aging is anecdotally associated with a prolonged recovery from resistance training, though current literature remains equivocal. This brief review considers the effects of resistance training on indirect markers of muscle damage and recovery (i.e., muscle soreness, blood markers, and muscle strength) in older males. With no date restrictions, four databases were searched for articles relating to aging, muscle damage, and recovery. Data from 11 studies were extracted for review. Of these, four reported worse symptoms in older compared with younger populations, while two have observed the opposite, and the remaining studies (n = 6) proposed no differences between age groups. It appears that resistance training can be practiced in older populations without concern for impaired recovery. To improve current knowledge, researchers are urged to utilize more ecologically valid muscle-damaging bouts and investigate the mechanisms which underpin the recovery of muscle soreness and strength after exercise in older populations.

Since the discovery of the severe acute respiratory syndrome coronarvirus 2 (SARS‐CoV‐2) numerous research was undertaken to delineate the various effects of the virus which manifests in many ways all over the body. The association between the SARS‐CoV‐2 invasion mechanism and the RAAS receptors, created many debates about the possible consequences of using RAAS modulating drugs including the ACE inhibitors (ACEi) and the Angiotensin II Receptor Blockers (ARBs) during the pandemic. Many clinical studies were conducted to assess the outcomes of COVID‐19 in patients who use ACEi/ARBs following the arguments claiming to discontinue these drugs as a precautionary measure. While several studies mainly analyzed the outcomes of the disease, this review aimed at comparing specific blood markers in both groups of COVID‐19 patients in order to gain a better insight into the interaction of ACEi/ARBs with the different body functions during the infection. Several databases were searched using a combination of keywords followed by screening and data extraction. Only 28 studies met our inclusion criteria, the majority of which showed no significant difference between the inflammation markers of COVID‐19 patients who used or did not use ACEi/ARBs. Interestingly, six studies reported lower inflammatory markers in COVID‐19 patients who used ACEi/ARBs and ten studies reported better outcomes among the same group. We therefore conclude that the use of ACEi/ARBs may not lead to worse prognosis of COVID‐19 and may even play a protective role against the hyperinflammatory response associated with COVID‐19. This article is protected by copyright. All rights reserved

BACKGROUND/AIM To investigate the blood markers for predicting pembrolizumab efficacy in advanced urothelial carcinoma (UC). PATIENTS AND METHODS This study included 91 advanced UC patients. The relationship between prognosis and markers from peripheral blood cell counts, including the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and systemic inflammation response index (SIRI=monocytes × neutrophils/lymphocytes), was evaluated. RESULTS Multivariate analysis indicated that pretreatment NLR and the 1-month-change NLR were both significantly associated with overall survival (OS) after pembrolizumab initiation. When the patients were divided into four groups according to calculated cutoffs using Cox proportional hazard model, the pretreatment NLR

Objective: Early diagnosis will significantly improve the survival rate of colorectal cancer (CRC); however, the existing methods for CRC screening were either invasive or inefficient. There is an emergency need for novel markers in CRC’s early diagnosis. Serum proteomics has gained great potential in discovering novel markers, providing markers that reflect the early stage of cancer and prognosis prediction of CRC. In this paper, the results of proteomics of CRC studies were summarized through a meta-analysis in order to obtain the diagnostic efficiency of novel markers. Methods: A systematic search on bibliographic databases was performed to collect the studies that explore blood-based markers for CRC applying proteomics. The detection and validation methods, as well as the specificity and sensitivity of the biomarkers in these studies, were evaluated. Newcastle- Ottawa Scale (NOS) case-control studies version was used for quality assessment of included studies. Results: Thirty-four studies were selected from 751 studies, in which markers detected by proteomics were summarized. In total, fifty-nine proteins were classified according to their biological function. The sensitivity, specificity, or AUC varied among these markers. Among them, Mammalian STE20-like protein kinase 1/ Serine threonine kinase 4 (MST1/STK4), S100 calcium-binding protein A9 (S100A9), and Tissue inhibitor of metalloproteinases 1 (TIMP1) were suitable for effect sizes merging, and their diagnostic efficiencies were recalculated after merging. MST1/STK4 obtained a sensitivity of 68% and a specificity of 78%. S100A9 achieved a sensitivity of 72%, a specificity of 83%, and an AUC of 0.88. TIMP1 obtained a sensitivity of 42%, a specificity of 88%, and an AUC of 0.71. Conclusion: MST1/STK4, S100A9, and TIMP1 showed excellent performance for CRC detection. Several other markers also presented optimized diagnostic efficacy for CRC early detection, but further verification is still needed before they are suitable for clinical use. The discovering of more efficient markers will benefit CRC treatment.

Objective: Sinonasal inverted papillomas are benign neoplasms of the nasal cavity and paranasal sinuses. They have characteristic features such as a high risk of recurrence and possible malignant transformation. This study was conducted to investigate the relationship between sinonasal inverted papilloma and inflammatory blood markers. Patients and Methods: Sixty-five patients who were diagnosed histologically as having sinonasal inverted papilloma and 65 age- and sex-matched healthy controls were included in the study. Inflammatory blood markers such as neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), red cell distribution width (RDW), mean platelet volume (MPV), and platelet distribution width (PDW) of the patient and control groups were compared. Results: There were no statistically significant differences between the patients and controls for white blood cell, platelet, hemoglobin, neutrophil, and lymphocyte counts ( P > .05). No statistically significant difference was found between the patients and controls for NLR, PLR, RDW, MPV, and PDW ( P > .05). In the logistic regression analysis model, which was created to investigate the effects of inflammatory blood markers in determining the patient group, the increase in the NLR and decrease in the PLR were found to be statistically significant factors ( P = .008, P = .039). Conclusion: This is the first study in the literature to investigate the relationship between sinonasal inverted papilloma and inflammatory blood markers, and the results suggest that NLR and PLR may be used to distinguish patients with sinonasal inverted papilloma from controls.

Romero-Parra, N, Rael, B, Alfaro-Magallanes, VM, Janse de Jonge, X, Cupeiro, R, and Peinado, AB; On Behalf of the IronFEMME Study Group. The effect of the oral contraceptive cycle phase on exercise-induced muscle damage after eccentric exercise in resistance-trained women. J Strength Cond Res 35(2): 353-359, 2021-To evaluate the influence of the active pill phase versus withdrawal phase of a monophasic oral contraceptive (OC) cycle on exercise-induced muscle damage and inflammation after eccentric resistance exercise. Eighteen resistance-trained female OC users (age: 25.6 ± 4.2 years, height: 162.4 ± 5.0 cm, and body mass: 58.1 ± 5.7 kg) performed an eccentric squat-based exercise during the active pill phase and withdrawal phase of their OC cycle. Muscle soreness, counter movement jump (CMJ), and blood markers of muscle damage and inflammation were evaluated before and postexercise (0, 2, 24, and 48 hours). Creatine kinase (CK) values were higher in the withdrawal (181.8 ± 89.8 U·L-1) than in the active pill phase (144.0 ± 39.7 U·L-1) (p < 0.001). The highest CK concentrations and muscle soreness values were observed 24 hours postexercise (217.9 ± 117.5 U·L-1 and 44.7 ± 19.7, respectively) compared with baseline (115.3 ± 37.4 U·L-1 and 4.4 ± 9.2, respectively; p < 0.001). In addition, a decrease in CMJ immediately postexercise (20.23 ± 4.6 cm) was observed in comparison with baseline (24.2 ± 6.1 cm), which was not yet recovered 24 hours postexercise (21.9 ± 5.9 cm; p < 0.001). No other phase or time effects were observed. An eccentric squat-based exercise session elicits muscle damage but no inflammation response in resistance-trained women. Furthermore, the highest CK concentrations observed in the withdrawal phase suggest that this phase might be more vulnerable to muscle damage and, therefore, less adequate to administer high training loads. However, the lack of differences in other muscle damage variables between OC phases does not warrant any guidance on the active pill versus withdrawal phase.

Remote ischaemic per-conditioning (RIC) is neuroprotective in experimental ischaemic stroke. Several neurohumoral, vascular and inflammatory mediators are implicated. The effect of RIC on plasma biomarkers was assessed using clinical data from the REmote ischaemic Conditioning After Stroke Trial (RECAST-1).RECAST-1 was a pilot sham-controlled blinded trial in 26 patients with ischaemic stroke, randomized to receive four 5-min cycles of RIC within 24 h of ictus. Plasma taken pre-intervention, immediately post-intervention and on day 4 was analysed for nitric oxide (nitrate/nitrite) using chemiluminescence and all other biomarkers by multiplex analysis. Biomarkers were correlated with clinical outcome (day 90 National Institutes of Health Stroke Scale, modified Rankin Scale, Barthel index).Remote ischaemic per-conditioning reduced serum amyloid protein (SAP) and tissue necrosis factor α (TNF-α) levels from pre- to post-intervention (n = 13, two-way ANOVA, p 0.05). Overall (n = 26), increases in SAP pre- to post-intervention and pre-intervention to day 4 were moderately correlated with worse day 90 clinical outcomes. No consistent significant changes over time, or by treatment, or correlations with outcome were seen for other biomarkers.Remote ischaemic per-conditioning reduced SAP and TNF-α levels from pre- to post-intervention. Increases in plasma levels of SAP were associated with worse clinical outcomes after ischaemic stroke. Larger studies assessing biomarkers and the safety and efficacy of RIC in acute ischaemic stroke are warranted to further understand these relationships.

ETLI, MUSTAFA/0000-0001-9320-3971; Aslan, Ahmet/0000-0001-5797-1287; Gulcu, Anil/0000-0002-9012-8053 WOS: 000575112600001 PubMed: 33021061 Diabetic foot is challenging progressive disease which requires multisystemic control. Neuropathy, arteriopathy, and cellular responses should treated collaboratively. Despite all medical advances, diabetic foot can highly resulted with amputation and also re-amputation can be required because of failed wound healing. In this study, we aimed to investigate the relation between blood parameters and amputation events. Diabetic 323 patients include to the study who referred to orthopaedic clinic for amputation. Amputation levels (amputation levels phalanx, metatarsal, lisfranc, syme, below knee, knee-disarticulation, above-knee amputation) and re-amputations recorded and compared with routine blood parameters. Re-amputation was observed at 69 patients. The significant difference detected between lower albumin, higher HbA1c, higher CRP levels (P < 0.05) in regards to gross amputation levels, and increased wound depth. Furthermore, lower albumin levels and higher levels of WBC, HbA1c, CRP, and Creatinine were detected in re-amputation levels. Especially, HbA1c, CRP, and Creatinine levels were found as upper bound of reference line for re-amputation. The statistically optimal HbA1c cutoff point for diabetes was >= 7.05%, with a sensitivity of 86% and a specificity of 59%. In according to our results, simple blood parameters can be useful for observing the progress of amputation in diabetic foot. Particularly, lower albumin, and higher HbA1c, CRP, and Creatinine levels detected as related with poor prognosis. Besides, screening of HbA1c level seems to be highly sensitive for detecting of re-amputation possibility.

The present study investigated whether athletes can be classified as responders or non-responders based on their individual change in total hemoglobin mass (tHb-mass) following altitude training while also identifying the potential factors that may affect responsiveness to altitude exposure. Measurements were completed with 59 elite endurance athletes who participated in national team altitude training camps. Fifteen athletes participated in the altitude training camp at least twice. Total Hb-mass using a CO rebreathing method and other blood markers were measured before and after a total of 82 altitude training camps (1350-2500 m) in 59 athletes. In 46 (56%) altitude training camps, tHb-mass increased. The amount of positive responses increased to 65% when only camps above 2000 m were considered. From the fifteen athletes who participated in altitude training camps at least twice, 27% always had positive tHb-mass responses, 13% only negative responses, and 60% both positive and negative responses. Logistic regression analysis showed that altitude was the most significant factor explaining positive tHb-mass response. Furthermore, male athletes had greater tHb-mass response than female athletes. In endurance athletes, tHb-mass is likely to increase after altitude training given that hypoxic stimulus is appropriate. However, great inter- and intra-individual variability in tHb-mass response does not support classification of an athlete permanently as a responder or non-responder. This variability warrants efforts to control numerous factors affecting an athlete's response to each altitude training camp.

Individualisation can improve resistance training prescription. This is accomplished via monitoring or autoregulating training. Autoregulation adjusts variables at an individualised pace per performance, readiness, or recovery. Many autoregulation and monitoring methods exist; therefore, this review’s objective was to examine approaches intended to optimise adaptation. Up to July 2019, PubMed, Medline, SPORTDiscus, Scopus and CINAHL were searched. Only studies on methods of athlete monitoring useful for resistance-training regulation, or autoregulated training methods were included. Eleven monitoring and regulation themes emerged across 90 studies. Some physiological, performance, and perceptual measures correlated strongly (r ≥ 0.68) with resistance training performance. Testosterone, cortisol, catecholamines, cell-free DNA, jump height, throwing distance, barbell velocity, isometric and dynamic peak force, maximal voluntary isometric contractions, and sessional, repetitions in reserve-(RIR) based, and post-set Borg-scale ratings of perceived exertion (RPE) were strongly associated with training performance, respectively. Despite strong correlations, many physiological and performance methods are logistically restrictive or limited to lab-settings, such as blood markers, electromyography or kinetic measurements. Some practical performance tests such as jump height or throw distance may be useful, low-risk stand-ins for maximal strength tests. Performance-based individualisation of load progression, flexible training configurations, and intensity and volume modifications based on velocity and RIR-based RPE scores are practical, reliable and show preliminary utility for enhancing performance.

Background: Pure osteosarcoma arising from the uterus is extremely rare. It is difficult to diagnose and predict disease progression with blood markers, because of the rarity. In this study, we des...

Background Gastroesophageal adenocarcinoma (GOA) has poor clinical outcomes and lacks reliable blood markers. Here we present circulating tumour DNA (ctDNA) as an emerging biomarker. Methods Forty patients (17 palliative and 23 curative) were followed by serial plasma monitoring. Primary tumour DNA was analysed by targeted next-generation sequencing to identify somatic single-nucleotide variants (SNVs), and Nanostring nCounter® to detect copy number alterations (CNAs). Patient-specific SNVs and CNA amplifications (CNAamp) were analysed in plasma using digital droplet PCR and quantitative PCR, respectively. Results Thirty-five patients (13 palliative, 22 curative) had ≥1 SNVs and/or CNAamp detected in primary tumour DNA suitable for tracking in plasma. Eighteen of 35 patients (nine palliative, nine curative) had ≥1 ctDNA-positive plasma sample. Detection of postoperative ctDNA predicted short RFS (190 vs 934 days, HR = 3.7, p = 0.028) and subsequent relapse (PPV for relapse 0.83). High ctDNA levels (>60.5 copies/ml) at diagnosis of metastatic disease predicted poor OS (90 vs 372 days, HR = 11.7 p Conclusion Sensitive ctDNA detection allows disease monitoring and prediction of short OS in metastatic patients. Presence of ctDNA postoperatively predicts relapse and defines a ‘molecular relapse’ before overt clinical disease. This lead time defines a potential therapeutic window for additional anticancer therapy.

Prevention is essential to reduce Colorectal Cancer (CRC) mortality. We previously reported a panel of four genes: CEACAM6, LGALS4, TSPAN8, COL1A2 (CELTiC) able to discriminate patients with CRC. Here, we assessed the CELTiC panel by quantitative polymerase chain reaction, in the blood of 174 healthy subjects, who resulted negative to the faecal immunochemical test (FITN). Using non-parametric statistic and multinomial logistic models, the FITN were compared to previously analysed subjects: 36 false positive FIT (NFIT), who were negative at colonoscopy, 36 patients with low risk lesions (LR) and 92 patients with high risk lesions or CRC (HR/CRC). FITN showed a significantly lower expression of the four genes when compared to HR/CRC. Moreover, FITN showed a significantly lower expression of TSPAN8 and COL1A2 compared to NFIT and LR patients. The multinomial logistic model confirmed that TSPAN8 alone specifically discriminated FITN from NFIT, LR and HR/CRC, while LGALS4 was able to differentiate FITN from false positive FIT. Finally, ROC curves analysis of the comparisons between FITN and HR/CRC, LR or NFIT reported AUC greater than 0.87, with a sensitivity and specificity of 83% and 76%, respectively. The CELTiC panel was confirmed a useful tool to identify CRC patients and to discriminate false FIT positive subjects.

Background Wintering is associated with distress to humans who work in the isolated and confined environment of Antarctica and yoga has been proved helpful for coping with stress. Therefore, a study was conducted on 14 winter expedition members of Indian Scientific Antarctic Expedition (2016) to find out the effects of yoga on stress-related markers. Methods Participants were divided into yoga, and control (non-yoga) groups. The yoga group practiced yoga for 10 months (from January to October 2016) daily in the morning for an hour. The Resilience test questionnaire was administrated at baseline and endpoint of the study. Blood samples were collected during the study at different intervals for the estimation of 8-hydroxydeoxyguanosine (8-OHdG), brain-derived neurotrophic factor (BDNF), serotonin and cortisol using ELISA. Results A trend of improvement was observed in the resilience test score in the yoga group. From January to October, 8-OHdG serum values in the yoga group declined by 55.9% from 1010.0 ± 67.8 pg/mL to 445.6 ± 60.5 pg/mL (Mean ± SD); in the control group, the decline was 49.9% from 1060.4 ± 54.6 pg/mL to 531.1 ± 81.8 pg/mL. In serotonin serum levels in the yoga group, there was a 3.1% increase from 6.4 ± 1.6 ng/mL to 6.6 ± 0.4 ng/mL while no increase was noticed in the control group. Cortisol values in the yoga group decreased by 19.9% from 321.0 ± 189.6 ng/mL to 257.1 ± 133.8 ng/mL; in the control group it increased by 2.8% from 241.2 ± 51.8 ng/mL to 247.8 ± 90.9 ng/mL. Conclusions It could be concluded from the present study that following 10 months yoga practice may be useful for better resilience and management of stress-related blood markers for the polar sojourners.

Oxidative stress has been implicated in the initiation of several cancers, including colorectal cancer (CRC). Whether it also plays a role in CRC prognosis is unclear. We assessed the associations of two oxidative stress biomarkers (Diacron's reactive oxygen metabolites [d-ROMs] and total thiol level [TTL]) with CRC prognosis. CRC patients who were diagnosed in 2003 to 2012 and recruited into a population-based study in Germany (n = 3361) were followed for up to 6 years. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations of d-ROMs and TTL (measured from blood samples collected shortly after CRC diagnosis) with overall survival (OS) and disease-specific survival (DSS) were estimated using multivariable Cox regression. Particularly pronounced associations of higher d-ROMs with lower survival were observed in stage IV patients, with patients in the highest (vs lowest) tertile having much lower OS (HR = 1.52, 95% CI = 1.14-2.04) and DSS (HR = 1.61, 95% CI = 1.20-2.17). For TTL, strong inverse associations of TTL with mortality were observed within all stages. In patients of all stages, those in the highest (vs lowest) quintile had substantially higher OS (HR = 0.48, 95% CI = 0.38-0.62) and DSS (HR = 0.52, 95% CI = 0.39-0.69). The addition of these biomarkers to models that included age, sex, tumor stage and subsite significantly improved the prediction of CRC prognosis. The observed strong associations of higher d-ROMs and lower TTL levels with poorer prognosis even in stage IV patients suggest that oxidative stress contributes significantly to premature mortality in CRC patients and demonstrate a large potential of these biomarkers in enhancing the prediction of CRC prognosis beyond tumor stage.

Background: There is limited information regarding the effects of air pollutants, such as nitrogen oxides (NOx) nitric oxide (NO2), nitrous oxide (NO) and particulate matter with a diameter smaller than 10 mu m (PM10), on acute limb ischaemia (ALI), a peripheral arterial disease (PAD) often with a poor clinical outcome. Patients and methods: We conducted an 18-year retrospective cohort study using routinely collected healthcare records from Ninevvells Hospital, Dundee, and Perth Royal Infirmary, in Tayside, Scotland, UK from 2000 to 2017. ALI hospitalisation events and deaths were linked to daily NOx, NO2, NO and PM10 levels extracted from publicly available data over this same time period. Distributed tag models were used to estimate risk ratios for ALI hospitalisation and for ALI mortality, adjusting for temperature, humidity, day of the week, month and public holiday. Results: 5,608 hospital admissions in 2,697 patients were identified over the study period (mean age 71.2 years, +/- 11.1). NOx and NO were associated with an increase of ALI hospital admissions on days of exposure to pollutant (p=.018), white PM10 was associated with a cumulative (tag 0-9 days) increase (p=.027) of ALI hospital admissions in our study. There was no increase of ALI mortality associated with pollution levels. Conclusions: ALI hospital admissions were positively associated with ambient NOx and NO on day of high measured pollution levels and a cumulative effect was seen with PM10. This study was funded by the Miller Bequest and the Institute for Cardiovascular Research charity. We should also like to acknowledge the safe haven, The Health Informatics Centre, University of Dundee, who provided the linkage data.

Background The coexistence of cirrhosis complicates the early detection of hepatocellular carcinoma (HCC). Thus, novel biomarkers for HCC early detection are needed urgently. Traditionally, HCC detection is carried out by evaluating alpha-fetoprotein (AFP) levels combined with imaging techniques. This work aimed to assess interleukin (IL-6) and insulin-like growth factor 2 (IGF 2) as possible HCC markers in comparison to AFP in patients with and without HCC. Results ROC analysis showed that IGF2 had the highest area under the curve (AUC) for discriminating HCC from liver cirrhosis (0.86), followed by IL6 (0.82), AFP (0.72), and platelet count (0.6). A four-marker model was developed and discriminated HCC from liver cirrhosis with an AUC of 0.97. The best cut-off was 1.28, at which sensitivity and specificity were 90% and 85%, respectively. For small tumor (< 2 cm), the model had an AUC of 0.95 compared to AFP (0.72). Also, the model achieved perfect performance with AUC of 0.93, 0.94, and 0.95 for BCLC (0-A), CLIP (0-1), and Okuda (stage I), respectively, compared to AFP (AUC of 0.71, 0.69, and 0.67, respectively). Conclusions The four markers may serve as a diagnostic model for HCC early stages and help overcome AFP poor sensitivity.

Acute exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) and community acquired pneumonia (CAP) are two common acute attacks in COPD patients and it is not always easy to determine whether a COPD patient at admission has parenchymal infection or bronchial infection. Comprehensive comparison between AECOPD patients and CAP patients with COPD (COPD + CAP) can help us understand them better. We retrospectively collected the medical records of AECOPD and COPD + CAP patients. Systemic inflammation, eosinophilic inflammation, damage to other organs, common chronic comorbidities, structural changes, phenotype and endotype distributions and coagulation functions between two groups were compared and correlations of these characteristics in total subjects, AECOPD patients and COPD + CAP patients were analyzed. Logistic regression analysis was performed to select helpful biomarkers for distinguishing between them. Receiver operator characteristic (ROC) curve was plotted to assess the diagnostic value of selected biomarkers and their combination. A nomogram was established for the differential diagnosis of AECOPD and COPD + CAP. A total of 206 patients were included into our analysis. In these subjects, 104 patients were classified as AECOPD group and 102 patients were considered to have COPD + CAP mainly based on their chest CT scan results. The counts of eosinophils (EOS), basophils (BAS) and lymphocytes (LYM) and percentage of total white blood cell count, hemoglobin and hematocrit were increased in AECOPD patients compared with COPD + CAP patients. The counts of neutrophils (NEU) and percentage of total white blood cell count, C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR), fibrinogen, D-dimer and N-Terminal pro-brain natriuretic peptide (NT-proBNP) levels were increased in COPD + CAP patients. After logistic regression analysis, EOS0.5 × 10

BackgroundCereblon (CRBN) is a direct target of immunomodulatory drugs (IMiDs) and is known to be sensitive and responsive to IMiD therapy. We evaluated CRBN expression in bone marrow plasma cells and analyzed whether CRBN expression was associated with multiple myeloma prognosis. Lastly, we developed a nomogram model for predicting high CRBN expression based on clinically significant blood markers.MethodsWe evaluated 143 multiple myeloma patients (internal dataset) who underwent bone marrow examinations. For evaluating the prognostic ability of the nomogram model, two external cohorts (235 patients in external dataset 1 and 156 patients in external dataset 2) were analyzed. The expression of CRBN in bone marrow aspirate samples was evaluated using immunohistochemistry. High CRBN expression was defined as the study-defined H-score ≥6.ResultsIn the high CRBN group, the median progression-free survival (PFS) and overall survival (OS) of patients receiving the IMiD-based therapy and non-IMiD therapy were 29 and 10 months for PFS, and NR (not reached) and 54 months for OS, respectively. IMiD-based therapy was significantly associated with better PFS and OS outcomes. High CRBN expression was independently predicted by female sex, high serum free-light chain (FLC) ratio, higher serum M-protein level, and higher β2-microglobulin level. Based on these results, we constructed a new nomogram model to predict high CRBN expression and the effectiveness of IMiD therapy in multiple myeloma.ConclusionThis nomogram could improve the prognostic evaluation of myeloma patients exhibiting high CRBN expression treated with IMiD therapy and might help provide personalized treatment strategies to clinicians.

Purpose:The effect of playing surface on physical performance during a repeated-sprint ability (RSA) test and the mechanisms for any potential playing-surface-dependent effects on RSA performance are equivocal. The purpose of this study was to investigate the effect of natural grass (NG) and artificial turf (AT) on physical performance, ratings of perceived exertion, feeling scale, and blood biomarkers related to anaerobic contribution (blood lactate [Lac]), muscle damage (creatine kinase and lactate dehydrogenase), inflammation (C-reactive protein), and immune function (neutrophils [NEU], lymphocytes [LYM], and monocytes) in response to an RSA test.Methods:A total of 9 male professional football players from the same regional team completed 2 sessions of RSA testing (6 × 30 s interspersed with a 35-s recovery) on NG and AT in a randomized order. During the RSA test, total (sum of distances) and peak (highest distance covered in a single repetition) distance covered were determined using a measuring tape, and the decrement in sprinting performance from the first to the last repetition was calculated. Before and after the RSA test, ratings of perceived exertion, feeling scale, and Lac, creatine kinase, lactate dehydrogenase, C-reactive protein, NEU, LYM, and monocytes were recorded in both NG and AT conditions.Results:Although physical performance declined during the RSA blocks on both surfaces (P = .001), the distance covered declined more on NG (15%) than on AT (11%;P = .04; effect size [ES] = −0.34; 95% confidence interval [CI], −1.21 to 0.56) with a higher total distance covered (+6% [2%]) on AT (P = .018; ES = 1.15; 95% CI, 0.16 to 2.04). In addition, lower ratings of perceived exertion (P = .04; ES = −0.49; 95% CI, −1.36 to 0.42), Lac, NEU, and LYM (P = .03; ES = −0.80; 95% CI, −1.67 to 0.14; ES = −0.16; 95% CI, −1.03 to 0.72; and ES = −0.94; 95% CI, −1.82 to 0.02, respectively) and more positive feelings (P = .02; ES = 0.81; 95% CI, −0.13 to 1.69) were observed after the RSA test performed on AT than on NG. No differences were observed in the remaining physical and blood markers.Conclusion:These findings suggest that RSA performance is enhanced on AT compared with NG. This effect was accompanied by lower fatigue perception and Lac, NEU, and LYM and a more pleasurable feeling. These observations might have implications for physical performance in intermittent team-sport athletes who train and compete on different playing surfaces.

Steamed ginger ethanolic extract (SGE) is a product with a high 6-shogaol contents and is thought to be more potent than other ginger products. We conducted a 12-week, randomized, double-blind, placebo-controlled clinical trial to determine the effects of SGE on weight and body fat loss. Eighty healthy obese participants were recruited and randomly divided into the SGE and placebo groups. The outcome measures comprised indicators of efficacy (body weight, body mass index, body composition, and blood markers) and safety. Following the supplementation period, mean body weight, body mass index, and body fat level were significantly lower in the SGE group than in the placebo group. No clinically significant changes were observed for any safety parameter. These results suggest that SGE is a potent anti-obesity agent that does not cause significant side effects. Therefore, SGE supplementation combined with lifestyle modification could be effective in the management of body weight and fat mass. Electronic supplementary material The online version of this article (10.1007/s10068-019-00649-x) contains supplementary material, which is available to authorized users.

Background Malnutrition has become a prevalent condition, with European and international studies reporting rates of approximately 25–40% in hospitals. We set out to perform a multi-center cross-sectional study to assess malnutrition rates in Slovenian hospitals and to convert the findings into a mobile application suitable for use by nurses and staff at the bedside. In addition, we examined the association of the results of this mobile application with parameters for body composition measured by bioimpedance method, muscle strength, anthropometrics, and specific blood markers. Methods We selected the Nutritional Risk Screening 2002 (NRS-2002) method, the second version of the modified short-form of Mini-Nutritional Assessment (MNA-SF), and the diagnostic criteria for cachexia proposed by Evans (CDE) as evidence-based methods for estimating the risk of and prevalence of malnutrition or/and cachexia. The methods were converted into the Android mobile application named MalNut that was used in three Slovenian hospitals by nurses and dietitians. Results We applied NRS-2002 and MNA-SF to screen for malnutrition risk and to assess malnutrition in 207 individuals aged 18 years and older, regardless of gender or reason for hospitalization during 1-week periods. Totally, 98% of these patients consider nutrition an important part of medical treatment care. NRS-2002 estimated the malnutrition risk to be 66.3%, which includes both patients to be at risk for malnutrition and patients that are truly malnourished. The malnutrition risk in the elderly (65+) estimated by MNA-SF was 39.6% and malnutrition 42.5%. When applying the CDE score in these two categories, 66.7% were identified as cachectic and 21.4% as pre-cachectic. In the patients assessed with the CDE score, malnutrition risk increased with higher extracellular water and decreased body mass index, hemoglobin, phase angle, and muscle strength. In all, 75% of patients assessed as high risk for malnutrition by NRS-2002, were identified as cachectic and 15.7% as pre-cachectic. In NRS-2002 assessed patients, this risk increased with higher C-reactive protein and lower phase angle. Conclusions The study showed that both malnutrition and cachexia are largely overlapping notions and are common in hospitalized adults in Slovenia. The MNA-SF and NRS-2002 tools showed that malnutrition risk was not significantly correlated with age, gender, serum albumin, but was correlated with lower phase angle, CRP, and muscle strength in elderly patients. The results have been used to develop further nutritional interventions in Slovenia.

The aim of the present study was to establish whether markers of oxidative stress and the enzymatic defense system of the blood are related to moderate physical activity in younger old and the oldest old men. They were divided into four groups according to the age and level of physical activity (groups YN and YA—inactive and active younger old men aged 65-74 years, groups ON and OA—inactive and active oldest old men aged 90-99 years). Venous blood was collected from the subjects in the morning before breakfast. MDA concentration and antioxidant enzyme activities (SOD, CAT, GPx, and GR) in erythrocyte hemolysates were assayed. The concentration of isoprostanes (8-iso-PGF2α) and carbonyl groups in protein (CP) was measured in plasma and serum. All assayed antioxidant enzyme activities and the SOD/GPx ratios were significantly higher in the active younger old males than in all the inactive ones. In the group of oldest old active participants, only the GPx activity was significantly higher compared to the inactive oldest old males. The activity of CAT and GPx in the younger old inactive men was significantly lower than that in the oldest old inactive subjects. However, SOD, CAT, and GR activities and SOD/GPx ratio were significantly higher in the younger old active men compared to the oldest old active participants. The concentrations of isoprostanes, protein carbonyls, and MDA were significantly lower in both active and inactive younger old males than in the respective groups of the oldest old men and in both groups of active men, independently of age, compared to the respective inactive subjects. The present study confirmed that oxidative stress is related to age. Physical activity caused a decrease of oxidative stress markers independently of age and resulted in an increase of GPx activity in both younger old and the oldest old active groups.

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Major depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BD) have both shared and discrete genetic risk factors, and are associated with peripheral abnormalities. The relationships between such genetic architectures and blood-based markers are, however, unclear. We investigated relationships between polygenic risk scores (PRS) for these disorders and peripheral markers in the UK Biobank cohort. We calculated polygenic risk scores for n = 367,329 (MDD PRS), n = 366,465 (SCZ PRS), and n = 366,383 (BD PRS) UK Biobank cohort subjects. We then examined associations between disorder PRS and 58 inflammatory/immune, hematological, bone, cardiovascular, hormone, liver, renal and diabetes-associated blood markers using two generalized linear regression models: ‘minimally adjusted’ controlling for variables such as age and sex, and ‘fully adjusted’ including additional lifestyle covariates: BMI, alcohol and smoking status, and medication intake. There were 38/58 MDD PRS, 32/58 SCZ PRS, and 20/58 BD PRS-blood marker associations detected for our minimally adjusted model. Of these, 13/38 (MDD PRS), 14/32 (SCZ PRS), and 10/20 (BD PRS) associations remained significant after controlling for lifestyle factors. Many were disorder-specific, with 8/13 unique MDD PRS associations identified. Several disorder-specific associations for MDD and SCZ were immune-related, with mostly positive and negative associations identified for MDD and SCZ PRS respectively. This study suggests that MDD, SCZ and BD have both shared and distinct peripheral markers associated with disorder-specific genetic risk. The results also implicate inflammatory dysfunction in MDD and SCZ, albeit with differences in patterns between the two conditions, and enrich our understanding of potential underlying pathophysiological mechanisms in major psychiatric disorders.

This paper presents a predictive model to potentially identify high-risk COVID-19 infected patients based on easily analyzed circulatory blood markers. These findings can enable effective and efficient care programs for high-risk patients and periodic monitoring for the low-risk ones, thereby easing the hospital flow of patients and can further be utilized for hospital bed utilization assessment. The present machine learning-based SV-LAR model results in a high 87% f1 score, harmonic mean of 91% precision, and 83% recall to classify COVID-19, infected patients, as high-risk patients needing hospitalization.

We sought to find clinical subtypes of posttraumatic stress disorder (PTSD) in veterans 6–10 years post-trauma exposure based on current symptom assessments and to examine whether blood biomarkers could differentiate them. Samples were males deployed to Iraq and Afghanistan studied by the PTSD Systems Biology Consortium: a discovery sample of 74 PTSD cases and 71 healthy controls (HC), and a validation sample of 26 PTSD cases and 36 HC. A machine learning method, random forests (RF), in conjunction with a clustering method, partitioning around medoids, were used to identify subtypes derived from 16 self-report and clinician assessment scales, including the clinician-administered PTSD scale for DSM-IV (CAPS). Two subtypes were identified, designated S1 and S2, differing on mean current CAPS total scores: S2 = 75.6 (sd 14.6) and S1 = 54.3 (sd 6.6). S2 had greater symptom severity scores than both S1 and HC on all scale items. The mean first principal component score derived from clinical summary scales was three times higher in S2 than in S1. Distinct RFs were grown to classify S1 and S2 vs. HCs and vs. each other on multi-omic blood markers feature classes of current medical comorbidities, neurocognitive functioning, demographics, pre-military trauma, and psychiatric history. Among these classes, in each RF intergroup comparison of S1, S2, and HC, multi-omic biomarkers yielded the highest AUC-ROCs (0.819–0.922); other classes added little to further discrimination of the subtypes. Among the top five biomarkers in each of these RFs were methylation, micro RNA, and lactate markers, suggesting their biological role in symptom severity.

Введение. Новорожденные, родившиеся у матерей с патологией во время беременности, составляют группу высокого риска тромботических и геморрагических осложнений, которые повышаются при наличии у новорожденных перинатальной патологии. Цель исследования: оценить показатели, характеризующие состояние системы фибринолиза и сосудистой стенки в крови новорожденных, родившихся у матерей с преэклампсией (ПЭ), для прогнозирования риска тромботических и геморрагических осложнений у таких детей. Материалы и методы. Обследовано 60 новорожденных, родившихся у матерей с ПЭ. Контрольную группу составили 30 новорожденных от матерей без ПЭ. Исследовали венозную кровь, взятую у новорожденных на 3–5-е сутки жизни. В крови определяли уровень тканевого активатора плазминогена (t-РА), ингибитора тканевого активатора плазминогена (PAI-1) и тромбомодулина. Результаты. Выявлено, что у новорожденных от матерей с ПЭ на 3–5-е сутки жизни отмечаются признаки повреждения эндотелия и повышение фибринолитической активности крови, на что указывает повышение содержания t-РА, PAI-1 и тромбомодулина в крови. Заключение. Полученные данные свидетельствуют о риске развития геморрагических осложнений у таких детей. Background. Neonates born to mothers with pathology during pregnancy are at high risk of thrombotic and hemorrhagic complications that are increased if neonates have perinatal pathology. Objectives: to assess blood parameters characterizing fibrinolysis and vascular wall of neonates born to mothers with preeclampsia (РЕ), to predict the risk of hemorrhagic complications in these children. Patients/Methods. 60 neonates born to mothers with РЕ were examined. The control group consisted of 30 neonates born to mothers without РЕ. We studied levels of tissue plasminogen activator (t-PA), inhibitor of tissue plasminogen activator (PAI-1) and thrombomodulin (TM) in venous blood taken from neonates on the 3–5th days of life. Results. In neonates born to mothers with PE we revealed on the 3–5th days of life increased blood levels of t-PA, PAI-1 and TM that characterized endothelial damage and increased blood fibrinolytic activity. Conclusions. The data obtained indicate the risk of hemorrhagic complications development in these children.

Although plant-based diets provide well-established physical and environmental health benefits, omitting meat or meat products has also been associated with a risk of being deficient in specific nutrients, such as iron. As data on the iron status among Norwegian vegans, vegetarians and pescatarians are lacking, the present study aimed to assess iron status in these groups of healthy adults. Blood markers for iron status were measured in 191 participants (18–60 years old) comprising 106 vegans, 54 vegetarians and 31 pescatarians: serum-ferritin (S-Fe), serum-iron (S-Iron) and serum-total iron binding capacity (S-TIBC). Serum-transferrin-saturation (S-TSAT) was estimated (S-Iron/S-TIBC × 100). The median concentration of blood markers for iron status were within the normal range with no difference between the different dietary practices. In total, 9% reported iron supplement use the last 24 h. S-Fe concentrations below reference (&lt, 15 μg/L) were found in 8% of the participating women, of which one participant reported iron supplement use. In multiple regression analysis, duration of adherence to dietary practices and the female gender were found to be the strongest predictors for decreased S-Fe concentration. In conclusion, although the participants were eating a plant-based diet, the majority had sufficient iron status. Female vegans and vegetarians of reproductive age are at risk of low iron status and should have their iron status monitored.

Highlights • rtfMRI-nf LA emotional training reduces depressive symptoms. • rtfMRI-nf LA training increases KynA/3-HK, a neuroprotective index. • Baseline KynA/QA is associated with the ability to upregulate the LA. • In partial responder group LA upregulation positively correlates with KynA/QA. • In partial responder group LA upregulation inversely correlates with MADRS. • Modulation of the KP may drive rtfMRI-nf-induced changes in neuroplasticity. • Non-specific effects cannot be ruled out due to the lack of a sham control., Real-time fMRI neurofeedback (rtfMRI-nf) left amygdala (LA) training is a promising intervention for major depressive disorder (MDD). We have previously proposed that rtfMRI-nf LA training may reverse depression-associated regional impairments in neuroplasticity and restore information flow within emotion-regulating neural circuits. Inflammatory cytokines as well as the neuroactive metabolites of an immunoregulatory pathway, i.e. the kynurenine pathway (KP), have previously been implicated in neuroplasticity. Therefore, in this proof-of-principle study, we investigated the association between rtfMRI-nf LA training and circulating inflammatory mediators and KP metabolites. Based on our previous work, the primary variable of interest was the ratio of the NMDA-receptor antagonist, kynurenic acid to the NMDA receptor agonist, quinolinic acid (KynA/QA), a putative neuroprotective index. We tested two main hypotheses. i. Whether rtfMRI-nf acutely modulates KynA/QA, and ii. whether baseline KynA/QA predicts response to rtfMRI-nf. Twenty-nine unmedicated participants who met DSM-5 criteria for MDD based on the Mini-International Neuropsychiatric Interview and had current depressive symptoms (Montgomery-Åsberg Depression Rating Scale (MADRS) score > 6) completed two rtfMRI-nf sessions to upregulate LA activity (Visit1 and 2), as well as a follow-up (Visit3) without rtfMRI-nf. All visits occurred at two-week intervals. At all three visits, the MADRS was administered to participants and serum samples for the quantification of inflammatory cytokines and KP metabolites were obtained. First, the longitudinal changes in the MADRS score and immune markers were tested by linear mixed effect model analysis. Further, utilizing a linear regression model, we investigated the relationship between rtfMRI-nf performance and immune markers. After two sessions of rtfMRI-nf, MADRS scores were significantly reduced (t[58] = −4.07, p = 0.009, d = 0.56). Thirteen participants showed a ≥ 25% reduction in the MADRS score (the partial responder group). There was a significant effect of visit (F[2,58] = 3.17, p = 0.05) for the neuroprotective index, KynA to 3-hydroxykynurenine (3-HK), that was driven by a significant increase in KynA/3-HK between Visit1 and Visit3 (t[58] = 2.50, p = 0.03, d = 0.38). A higher baseline level of KynA/QA (β = 5.23, p = 0.06; rho = 0.49, p = 0.02) was associated with greater ability to upregulate the LA. Finally, for exploratory purposes correlation analyses were performed between the partial responder and the non-responder groups as well as in the whole sample including all KP metabolites and cytokines. In the partial responder group, greater ability to upregulate the LA was correlated with an increase in KynA/QA after rtfMRI-nf (rho = 0.75, p = 0.03). The results are consistent with the possibility that rtfMRI-nf decreases metabolism down the so-called neurotoxic branch of the KP. Nevertheless, non-specific effects cannot be ruled out due to the lack of a sham control. Future, controlled studies are needed to determine whether the increase in KynA/3HK and KynA/QA is specific to rtfMRI-nf or whether it is a non-specific correlate of the resolution of depressive symptoms. Similarly, replication studies are needed to determine whether KynA/QA has clinical utility as a treatment response biomarker.

Sepsis is one of the leading causes of death worldwide with high mortality rates and a pathological complexity hindering early and accurate diagnosis. Today, laboratory culture tests are the epitome of pathogen recognition in sepsis. However, their consistency remains an issue of controversy with false negative results often observed. Clinically used blood markers, C reactive protein (CRP) and procalcitonin (PCT) are indicators of an acute-phase response and thus lack specificity, offering limited diagnostic efficacy. In addition to poor diagnosis, inefficient drug delivery and the increasing prevalence of antibiotic-resistant microorganisms constitute significant barriers in antibiotic stewardship and impede effective therapy. These challenges have prompted the exploration for alternative strategies that pursue accurate diagnosis and effective treatment. Nanomaterials are examined for both diagnostic and therapeutic purposes in sepsis. The nanoparticle (NP)-enabled capture of sepsis causative agents and/or sepsis biomarkers in biofluids can revolutionize sepsis diagnosis. From the therapeutic point of view, currently existing nanoscale drug delivery systems have proven to be excellent allies in targeted therapy, while many other nanotherapeutic applications are envisioned. Herein, the most relevant applications of nanomedicine for the diagnosis, prognosis, and treatment of sepsis is reviewed, providing a critical assessment of their potentiality for clinical translation., The authors gratefully acknowledge the financial support from the Manchester Molecular Pathology Innovation Centre (MMPathIC). P.D. acknowledges the financial support from the Manchester NIHR Biomedical Research Centre.

Objective: To explore the effectiveness and safety of integrated traditional Chinese and western medicine in the treatment of MCI patients. Methods: Search three English databases, four Chinese databases, and assess the risk of bias according to Cochrane tools. Statistics will be used for heterogeneity assessment, sensitivity analysis, data synthesis, funnel chart generation and subgroup analysis. If a sufficiently uniform study is found, a meta-analysis will be performed and any differences will be described in groups. Results: A total of 15 studies were included, 11 studies treated MMSE as an outcome indicator, 7 studies used MoCA as an outcome indicator, 6 studies reported overall effectiveness, 3 studies used ADL as an outcome indicator, and 2 studies reported blood The data of markers and the results of 15 studies are beneficial to the traditional Chinese medicine combined with western medicine group. Conclusion: The conclusion shows that the treatment of mild cognitive impairment with integrated traditional Chinese and western medicine is superior to the single use of traditional Chinese medicine or western medicine in improving MMSE, MoCA, ADL, total effective rate score and reducing blood markers Aβ and IT-6, and the incidence of adverse reactions Lower, higher safety, for clinical reference. However, there are flaws in the research methodology, which need to be confirmed by more high-quality literature.

Background: One of the most challenging environmental extremes is immersion in cold/icy water, and consequent common assumption is that even a brief exposure to cold can lead to cold-related illnesses. The increase in the concentrations of the stress hormones cortisol, epinephrine (Epi), and norepinephrine (NE) in response to acute cold stress are thought to suppress the release of proinflammatory cytokines. No previous study has explored the residual consequences of whole-body short-term cold-water immersion (CWI; 14 °C for 10 min) on the immune response in healthy non-acclimated young adult men (aged 20–30 years). Materials and methods: In the current study, we tested the hypothesis that short-term acute whole-body CWI would induce high blood levels of cortisol, NE, and Epi, which in turn would increase circulating leukocyte numbers and delay the production of proinflammatory cytokines (tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6). Results: Short-term whole-body CWI produced a stressful physiological reaction, as manifested by hyperventilation and increased muscle shivering, metabolic heat production, and heart rate. CWI also induced the marked release of the stress hormones Epi, NE, and cortisol. The change in IL-6 concentration after CWI was delayed and TNF-α production was decreased, but IL-1β was not affected within 48 h after CWI. A delayed increase in neutrophil percentage and decrease in lymphocyte percentage occurred after CWI. Conclusion: These findings suggest that, even though CWI caused changes in stress and immune markers, the participants showed no predisposition to symptoms of the common cold within 48 h after CWI.

Household air pollution (HAP) from biomass stoves is a leading risk factor for cardiopulmonary outcomes; however, its toxicity pathways and relationship with inflammation markers are poorly understood. Among 180 adult women in rural Peru, we examined the cross-sectional exposure-response relationship between biomass HAP and markers of inflammation in blood using baseline measurements from a randomized trial. We measured markers of inflammation (CRP, IL-6, IL-10, IL-1β, and TNF-α) with dried blood spots, 48-h kitchen area concentrations and personal exposures to fine particulate matter (PM(2.5) ), black carbon (BC), and carbon monoxide (CO), and 48-h kitchen concentrations of nitrogen dioxide (NO(2) ) in a subset of 97 participants. We conducted an exposure-response analysis between quintiles of HAP levels and markers of inflammation. Markers of inflammation were more strongly associated with kitchen area concentrations of BC than PM(2.5) . As expected, kitchen area BC concentrations were positively associated with TNF-α (pro-inflammatory) concentrations and negatively associated with IL-10, an anti-inflammatory marker, controlling for confounders in single- and multi-pollutant models. However, contrary to expectations, kitchen area BC and NO(2) concentrations were negatively associated with IL-1β, a pro-inflammatory marker. No associations were identified for IL-6 or CRP, or for any marker in relation to personal exposures.

Liquid biopsy via protein biomarkers holds out hopes for early detection of malignancies and monitoring disease course. However, despite extensive efforts current protein assays largely fail to provide the required diagnostic accuracy. In this Review we propose that realizing the hopes for valuable diagnostic assays will require a combination of intelligent selection of biomarker candidate proteins, and substantially improved assay techniques., Cancer diagnostics based on the detection of protein biomarkers in blood has promising potential for early detection and continuous monitoring of disease. However, the currently available protein biomarkers and assay formats largely fail to live up to expectations, mainly due to insufficient diagnostic specificity. Here, we discuss what kinds of plasma proteins might prove useful as biomarkers of malignant processes in specific organs. We consider the need to search for biomarkers deep down in the lowest reaches of the proteome, below current detection levels. In this regard, we comment on the poor molecular detection sensitivity of current protein assays compared to nucleic acid detection reactions, and we discuss requirements for achieving detection of vanishingly small amounts of proteins, to ensure detection of early stages of malignant growth through liquid biopsy.

Extensive research has been carried out to find associations between arterial stiffness markers and blood levels of low-density lipoprotein cholesterol (LDL-Chol), triglycerides (TG), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-Chol) relating to assessment of cardiovascular diseases’ (CVD) risk factors and early detection of atherosclerosis. However, data on levels of atherogenic lipoproteins as apolipoprotein B (apoB), low-density lipoprotein(a) (Lp(a)) and high-density apolipoprotein A (apoA) related to arterial biomechanical properties are scarce.

Management of severe malaria remains a critical global challenge. In this study, using a multiplexed quantitative proteomics pipeline we systematically investigated the plasma proteome alterations in non-severe and severe malaria patients. We identified a few parasite proteins in severe malaria patients, which could be promising from a diagnostic perspective. Further, from host proteome analysis we observed substantial modulations in many crucial physiological pathways, including lipid metabolism, cytokine signaling, complement, and coagulation cascades in severe malaria. We propose that severe manifestations of malaria are possibly underpinned by modulations of the host physiology and defense machinery, which is evidently reflected in the plasma proteome alterations. Importantly, we identified multiple blood markers that can effectively define different complications of severe falciparum malaria, including cerebral syndromes and severe anemia. The ability of our identified blood markers to distinguish different severe complications of malaria may aid in developing new clinical tests for monitoring malaria severity., Kumar et al. use proteomes of patients with falciparum and vivax malaria and dengue fever, and identify differentially abundant proteins and their associated functions in the different severities and diseases. This study offers mechanistic pathways to malaria severity, and adopts a machine learning approach for predictive proteins for the malarial types and severities.

Multivisceral transplant (MVTx) and isolated intestinal transplant (ITx) are complex surgical procedures. The subsequent proinflammatory state in the immediate postoperative period makes interpretation of blood markers difficult.We aimed to establish the course of various blood markers after MVTx/ITx, and to evaluate their use as diagnostic markers of complications. This was a single center prospective cohort. We analyzed blood markers collected preoperatively, on alternate days for the first postoperative week, and then weekly for 4 weeks. This study was in compliance with The Declaration of Helsinki.Over a 16-month period (July 2017-October 2018), 20 subjects aged 2 to 67 years with a median age of 24.5 years received MVTx/ITx. Twelve recipients (60%) had an infection. Neutrophil lymphocyte count ratio (NLCR) was higher than established upper limits of normal, regardless of infection status. NLCR and white blood cell count were useful to identify infected MVTx/ITx recipients, with P values .05 for 2 and 1 of 7 time points post transplant, respectively. Higher preoperative eosinophil% predicted future acute cellular rejection (P value .023).This is the first study to extensively track the course of blood markers post MVTx/ITx and identified NLCR and white blood cell count as potential diagnostic blood markers of infection.

Background Urgent Suspected Cancer (2WW) referrals have been successful in improving early cancer detection but are increasingly a major burden on NHS services. This has been exacerbated by the COVID-19 pandemic. Method We developed and validated tests to assess the risk of any cancer for 2WW patients. The tests use routine blood measurements (FBC, U&E, LFTs, tumour markers), combining them using machine learning and statistical modelling. Algorithms were developed and validated for nine 2WW pathways using retrospective data from 371,799 referrals to Leeds Teaching Hospitals Trust (development set 2011-16, validation set 2017-19). A minimum set of blood measurements were required for inclusion, and missing data were modelled internally by the algorithms. Findings We present results for two clinical use-cases. In use-case 1, the algorithms correctly identify 20% of patients who do not have cancer and may not need an urgent 2WW referral. In use-case 2, they identify 90% of cancer cases with a high probability of cancer that could be prioritised for review. Interpretation Combining a panel of widely available blood markers produces effective blood tests for cancer for NHS 2WW patients. The tests are cost-effective, can be deployed rapidly to any NHS pathology laboratory with no additional hardware requirements, and are of particular value during the COVID-19 pandemic. Funding Aspects of this work were supported by Innovate UK, MRC, Leeds City Region Enterprise Partnership (LEP), NIHR Leeds In Vitro Diagnostic Co-operative, CRUK CanTest Collaborative, and PinPoint Data Science Ltd

Synbiotics intake can alter the composition of intestinal microbes beneficially. We aimed to detect the changes in the intestinal microbiomes of 37 healthy elderly Korean women after the intake of a synbiotic drink. This was a longitudinal study controlled with a temporal series, including a control period of 3 weeks before intake, synbiotic intake for 3 weeks, and a washout period of 3 weeks. Fecal microbiota composition was analyzed by sequencing the V3-V4 hypervariable regions of 16S rRNA. Physical fecal activity increased with improvement in fecal shape. Thirty intestinal bacterial taxa were observed to change only after the intake period. In particular, Ellagibacter appeared only after ingestion. In addition, the abundance of Terrisporobacter showed a positive correlation with C-reactive protein, triglyceride. Lachnospiraceae_uc, Eubacterium_g5, and Blautia had a positive correlation with creatinine, whereas PAC001100_g had a negative correlation with creatinine. Short-term (3 weeks) intake of symbiotic organisms changes the composition of the gut microbiota in healthy elderly Korean women.

Background Appendicitis is the most common indication for emergency surgery in the world. There is no one laboratory or radiological test that is used to diagnose it. Various routine and novel blood markers have been identified, however none have proved to be conclusive. The aim of this study was to combine routine blood markers to increase the sensitivity and specificity in diagnosing histologically confirmed appendicitis. Methods We retrospectively reviewed the theatre logs for the calendar year of 2015 to identify all of the appendectomies which were performed. We reviewed all of the admission bloods for the patients - including their white blood cell (WBC) count, their neutrophil count, and their C-Reactive protein (CRP) value. We also reviewed all of the histology to identify the inflamed appendices, and analysed all of this information together. Results The neutrophil count is the most sensitive of the three blood markers with a score of 82%. It has a specificity of 63%. The CRP value is the most specific of the three blood markers with a value of 67% and a sensitivity of 76%. WBC has a sensitivity of 75% and a specificity of 63%. Combining all of the blood values (i.e. elevated white blood cell count or elevated neutrophil count or elevated CRP) demonstrates a sensitivity of 96% and a specificity of 45%. Conclusion Combining routine admission blood markers (WBC, neutrophil count, and CRP) can assist in diagnosing appendicitis in unwell patients with abdominal pain.

Examination of the patterns of free-radical processes (FRP) and changes of the early screening markers to predict the course of hemorrhagic stroke (HS) and applied pathophysiologically based therapy can be of great practical importance. This study aimed to determine early changes in the parameters of oxidative stress and routine biochemistry blood tests in patients with HS and to assess their relationship with clinical outcome. The effects of early applied cytoflavin were also investigated. The prospective study included 151 patients with HS. Forty-eight percent of patients in the standard conservative therapy were given cytoflavin antioxidant energy therapy from the first day of hospitalization. The neurological status, neuroimaging, biochemical blood tests and FRP were assessed on days 1, 5, 10, and 20 of hospitalization. In patients with HS, an imbalance of all stages of FRP was detected proportionately to the severity of HS. The malondialdehyde concentration above 5.3 μmol/L, the number of leukocytes above 15 800, glucose above 11.9 mmol/L, lactate dehydrogenase above 574 IU/L, and lactate above 2.5 mmol/L, detected on the first day, predetermined a high risk of death. Additional cytoflavin treatment allowed stabilizing the clinical laboratory picture of HS, improved the treatment results, and reduced hospital mortality rate.

Rationale: Exergaming may be a viable alternative to more traditional exercise. As high-intensity exercise can provide substantial health benefits, the purpose of this study was to investigate the long-term effectiveness of providing inactive adults with access to a high-intensity exergaming platform. Methods: In this study, 52 inactive adults (

This study analyzed the effects of nutrition labeling and examined whether nutrition labeling usage influences the levels of blood markers, such as high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) in body-size self-conscious individuals. The dependent variables were HDL-C and TG, the independent variables were the respondents&rsquo, awareness of nutrition labeling use, sociodemographic factors, perceived health status, stress, lifestyle, frequency of eating out, family history of hyperlipidemia, survey year, body mass index, total energy intake, and cholesterol levels. Body-size perception was assessed by matching body mass index with subjective body-shape recognition using data from the Korean National Health and Nutrition Examination Survey (2013&ndash, 2018). Differences were observed in HDL-C and TG levels according to nutrition labeling usage and body-image perception. The group that recognized body image correctly showed high HDL-C and low TG levels when they actively used nutrition labeling, whereas the group that recognized body image incorrectly showed no significant changes in HDL-C and TG levels even when actively using nutrition labeling. The standard nutritional information, which does not consider individual body-size perceptions, has a restrictive effect. Policies should be developed towards tailored intervention strategies considering individual body-size perception.

Introduction the outbreak of coronavirus disease 2019 (COVID-19) started in China in December 2019 and spread causing more than 14 million cases all over the world on July 19th, 2020. Although, real-time reverse transcription polymerase chain reaction (rRT-PCR) test is the gold standard test, it needs a long time and requires specialized laboratories and highly trained personnel. All these difficulties forced many countries with reduced health resources to limit rRT-PCR tests to individuals with severe symptoms. Thus, routine blood marker that may help physicians to suspect COVID-19 and hence, prioritize patients for molecular diagnosis is badly needed. Methods fifty-six Sudanese COVID-19 patients admitted to Jabra hospital were included in this study. For all the patients we analyzed complete blood count (CBC), CBC, plasma levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), liver function tests (LFT) and renal function tests (RFT). Statistical analysis was done using SPSS program with a significance level of p≤0.05 and confidence limits (CLs) 95%. The difference between groups was tested using Mann-Whitney test was for quantitative variables while qualitative variables was tested using chi-square (Fisher exact) test. Results the result shows that, 35 out of the 56 patients (62.5%) were male and 21 (37.5%) were females with a median age of 60-year-old for both sexes. Lymphocytes % showed decrease to 9.2 (P-value=0.000) and significant increase in neutrophils to 83.05 (P-value=0.005), ESR to 65.54 (P-value=0.000) and CRP to 91.07 (P-value=0.000). The receiver operating characteristic curve (ROC)/area under the curve (AUC) ensured the expellant result of lymphocytes % as a predictor with 92% area under the curve, neutrophils were 90% and ESR 95.8%. The percent of detecting COVID-19 positive RT-PCR (98%) for suspected individuals using ROC showed best cutoff of ≤21.8 for lymphocytes %, ≥67.7 for neutrophils, ≥37.5 for ESR, ≥6.2 for CRP and ≥7.15 for WBCs. Conclusion the results also showed that, lymphocyte percentages, neutrophils, CRP and ESR may be used as markers for COVID-19 helping prioritizing individuals for rRT-PCR test.

Police officers are frequently engaged in a variety of high-stress scenarios, such as high-speed chases and other suspect conflicts, that cause significant increases in a variety of physiological and psychological stress markers. The purpose of this study was to investigate salivary and blood markers of stress in response to an active shooter training drill (ASD). Thirty-one participants (n = 31, males = 15, females = 16, Age: 21 &plusmn, 3.5 years) participated in an ASD involving professional actors playing the role of one active gunman, as well as four victims. The ASD lasted approximately 50 s. Blood samples were collected 15 min prior as well as after the ASD and analyzed for epinephrine (EPI) and norepinephrine (NE) levels. Saliva samples were collected 30 and 5 min prior to the ASD and 5 and 30 min after the ASD, were analyzed for cortisol, &alpha, amylase, and secretory immunoglobulin-A (SigA). The ASD resulted in significant (p &lt, 0.05) increases in EPI, &alpha, amylase, and SigA levels. The increase in NE from pre to post ASD approached significance (p = 0.06). These results demonstrate that a short duration (~50 s) ASD results in significant increases in both blood and salivary markers of stress. These data may provide meaningful implications for those engaged in high-stress tactical occupations, especially law enforcement and military personnel, as chronic exposure to such occupational stressors can contribute to cardiometabolic disease.