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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists throughout the world with over 65 million registered cases of survivors with post-COVID-19 sequelae, also known as LongCOVID-19 (LongC). LongC survivors exhibit various symptoms that span multiple organ systems, including the nervous system. To search for neurological markers of LongC, we investigated the soluble biomolecules present in the plasma and the proteins associated with plasma neuronal-enriched extracellular vesicles (nEVs) in 33 LongC patients with neurological impairment (nLongC), 12 COVID-19 survivors without any LongC symptoms (Cov), and 28 pre-COVID-19 healthy controls (HC). COVID-19 positive participants were infected between 2020 and 2022, not hospitalized, and were vaccinated or unvaccinated before infection. IL-1β was significantly increased in both nLongC and Cov and IL-8 was elevated in only nLongC. Both brain-derived neurotrophic factor and cortisol were significantly elevated in nLongC and Cov compared to HC. nEVs from people with nLongC had significantly elevated protein markers of neuronal dysfunction, including amyloid beta 42, pTau181 and TDP-43. This study shows chronic peripheral inflammation with increased stress after COVID-19 infection. Additionally, differentially expressed nEV neurodegenerative proteins were identified in people recovering from COVID-19 regardless of persistent symptoms.

Haptoglobin is a plasma protein of mammals that plays a crucial role in vascular homeostasis by binding free haemoglobin released from ruptured red blood cells. Trypanosoma brucei can exploit this by internalising haptoglobinhaemoglobin complex to acquire host haem. Here, we investigated the impact of haptoglobin deficiency (Hp-/-) on T. brucei brucei infection and the parasite´s capacity to internalise haemoglobin in a Hp-/- mouse model. The infected Hp-/- mice exhibited normal disease progression, with minimal weight loss and no apparent organ pathology, similarly to control mice. While the proteomic profile of mouse sera significantly changed in response to T. b. brucei, no differences in the infection response markers of blood plasma between Hp-/- and control Black mice were observed. Similarly, very few quantitative differences were observed between the proteomes of parasites harvested from Hp-/- and Black mice, including both endogenous proteins and internalised host proteins. While haptoglobin was indeed absent from parasites isolated from Hp-/-mice, haemoglobin peptides were unexpectedly detected in parasites from both Hp-/- and Black mice. Combined, the data support the dispensability of haptoglobin for haemoglobin internalisation by T. b. brucei during infection in mice. Since the trypanosomes knock-outs for their haptoglobin-haemoglobin receptor (HpHbR) internalised significantly less haemoglobin from Hp-/- mice compared to those isolated from Black mice, it suggests that T. b. brucei employs also an HpHbR-independent haptoglobin-mediated mode for haemoglobin internalisation. Our study reveals a so-far hidden flexibility of haemoglobin acquisition by T. b. brucei and offers novel insights into alternative haemoglobin uptake pathways. [ABSTRACT FROM AUTHOR]

A significant increase in circulating cell‐free DNA (cfDNA) occurs with physical exercise, which depends on the type of exertion and the duration. The aims of this study were as follows: (1) to investigate the time course of cfDNA and conventional markers of muscle damage from immediately after to 96 h after muscle‐damaging exercise; and (2) to investigate the relationship between cfDNA and indicators of primary (low‐frequency fatigue and maximal voluntary isometric contraction) and secondary (creatine kinase and delayed‐onset muscle soreness) muscle damage in young healthy males. Fourteen participants (age, 22 ± 2 years; weight, 84.4 ± 11.2 kg; height, 184.0 ± 7.4 cm) performed 50 intermittent drop jumps at 20 s intervals. We measured cfDNA and creatine kinase concentrations, maximal voluntary isometric contraction torque, low‐frequency fatigue and delayed‐onset muscle soreness before and at several time points up to 96 h after exercise. Plasma cfDNA levels increased from immediately postexercise until 72 h postexercise (P < 0.01). Elevation of postexercise cfDNA was correlated with both more pronounced low‐frequency fatigue (r = −0.52, P = 3.4 × 10−11) and delayed‐onset muscle soreness (r = 0.32, P = 0.00019). Levels of cfDNA change in response to severe primary and secondary muscle damage after exercise. Levels of cfDNA exhibit a stronger correlation with variables related to primary muscle damage than to secondary muscle damage, suggesting that cfDNA is a more sensitive marker of acute loss of muscle function than of secondary inflammation or damaged muscle fibres. What is the central question of this study?How do plasma cell‐free DNA (cfDNA) levels change in response to primary and secondary muscle damage when muscle‐damaging exercise is performed without metabolic stress?What is the main finding and its importance?In this study, we found that cfDNA concentration increases following severe primary and secondary muscle damage after 50 drop jumps. However, acute postexercise increases in cfDNA were higher than following secondary muscle damage and were more correlated with variables related to primary muscle damage (low‐frequency fatigue). This suggests that muscle‐damaging exercise causing no accumulation of metabolites can lead to acute and delayed increases in cfDNA levels. However, they are more sensitive to primary muscle damage. [ABSTRACT FROM AUTHOR]

Introduction: This randomized, placebo-controlled, double-blind, parallel study aimed to evaluate the effect of 3-month supplementation of bovine colostrum (BOV-COL; 8x400 mg per day) on the outcomes of depression treatment in hospitalized patients with substance use disorder (SUD). The hypothesis is that BOV-COL supplementation as an add-on treatment results in favorable alternations in selected blood inflammatory markers or neurotransmitters, leading to better depression treatment outcomes compared with placebo (PLA). Methods: Patients with a Minnesota Multiphasic Personality Inventory-2 score =60 points were enrolled. Twenty-nine participants (n=18 in the BOV-COL group and n=11 in the PLA group) completed the protocol. Results: The mean Beck Depression Inventory-II score was significantly reduced after supplementation in both groups. However, the mean 17-point Hamilton Depression Rating Scale score was decreased in the BOV-COL group, but not in the PLA group. In the BOV-COL group, there was a reduction in interleukin (IL)-1, IL-6, IL-10, the IL-6:IL-10 ratio, IL-17, and tumor necrosis factor alpha (TNF-a), while in the PLA group only IL-6 decreased. Favorable alternations in the total count and differentials of white blood cell subsets were more pronounced in the BOV-COL. There were no changes in neurotransmitter concentrations. Conclusions: BOV-COL supplementation is a promising add-on therapy in patients with depression and SUD. [ABSTRACT FROM AUTHOR]

Abstract A significant increase in circulating cell‐free DNA (cfDNA) occurs with physical exercise, which depends on the type of exertion and the duration. The aims of this study were as follows: (1) to investigate the time course of cfDNA and conventional markers of muscle damage from immediately after to 96 h after muscle‐damaging exercise; and (2) to investigate the relationship between cfDNA and indicators of primary (low‐frequency fatigue and maximal voluntary isometric contraction) and secondary (creatine kinase and delayed‐onset muscle soreness) muscle damage in young healthy males. Fourteen participants (age, 22 ± 2 years; weight, 84.4 ± 11.2 kg; height, 184.0 ± 7.4 cm) performed 50 intermittent drop jumps at 20 s intervals. We measured cfDNA and creatine kinase concentrations, maximal voluntary isometric contraction torque, low‐frequency fatigue and delayed‐onset muscle soreness before and at several time points up to 96 h after exercise. Plasma cfDNA levels increased from immediately postexercise until 72 h postexercise (P

Background Sepsis is a systemic inflammatory response caused by an imbalance of the host immune response to infectious factors, potentially leading to life-threatening organ dysfunction. The application of immature platelet fraction (IPF) to assessing the severity and prognosis of sepsis has been previously analyzed. However, the application of IPF combined with other biomarkers to predict sepsis has been rarely reported. Objective To explore the predictive value of IPF combined with other biomarkers in the severity and prognosis of sepsis. Methods A total of 60 sepsis patients admitted to the Department of Critical Care Medicine, Zhongshan Hospital, Fudan University (Xiamen Branch) from November 2020 to November 2022 were retrospectively recruited for analyzing their clinical data. Patients were classified into the severe sepsis group (n=24) and septic shock group (n=36) based on the severity of sepsis. Divided by the Sequential Organ Failure Assessment (SOFA) score, 60 sepsis patients were assigned into the low SOFA group (SOFA score

Abstract Background The influence of maternal oral and dental health on the occurrence of Preterm Premature Rupture of Membranes (P-PROM) and its underlying mechanisms remain uncertain. This research seeks to investigate the impact of maternal oral and dental health on the incidence of P-PROM and its association with inflammatory markers in the blood. Methods This study adopts a prospective case-control design methodology. The study involved 70 women diagnosed with P-PROM and delivered by an obstetrician and 79 women who had healthy deliveries with no prenatal complications. The values for DMFT (Number of decayed, missing and filled teeth) index, Gingival Index (GI), Plaque index (PI), Pocket depth (PD), Clinical attachment loss (CAL) and medical history were recorded. Mann-Whitney U test and hierarchical binomial logistic regression analysis were applied. It was considered statistically significant at p 0.05). In the regression analysis for possible risk factors that may be effective in P-PROM, oral and dental health parameters were the most effective. Conclusions Oral and dental health of women with P-PROM was found to be worse than that of the control group. Oral and dental health may be a potential risk factor that may contribute to adverse pregnancy outcomes associated with P-PROM.

Severe acute pancreatitis (SAP) is the most serious type of acute pancreatitis (AP) and a common critical disease in clinic. With the continuous improvement of medical level, the mortality rate in the early stage of SAP has decreased significantly, and the peak of death is mainly concentrated in the later stage of the disease and the main cause of death in the later stage is secondary sepsis after infection of pancreatic or peripancreatic necrosis. If the risk of secondary sepsis in SAP can be predicted early it can guide the medical staff to carry out appropriate early monitoring and intervention to improve the clinical outcome of patients, The article reviewed the application progress of blood markers to predict secondary sepsis in SAP. [ABSTRACT FROM AUTHOR]

Background: The influence of maternal oral and dental health on the occurrence of Preterm Premature Rupture of Membranes (P-PROM) and its underlying mechanisms remain uncertain. This research seeks to investigate the impact of maternal oral and dental health on the incidence of P-PROM and its association with inflammatory markers in the blood. Methods: This study adopts a prospective case-control design methodology. The study involved 70 women diagnosed with P-PROM and delivered by an obstetrician and 79 women who had healthy deliveries with no prenatal complications. The values for DMFT (Number of decayed, missing and filled teeth) index, Gingival Index (GI), Plaque index (PI), Pocket depth (PD), Clinical attachment loss (CAL) and medical history were recorded. Mann-Whitney U test and hierarchical binomial logistic regression analysis were applied. It was considered statistically significant at p < 0.05. Results: The case group's DMFT, PI, GI, PD values were statistically significantly higher than the control group (p < 0.001). There was no relationship between DMFT, GI, PD, CAL and inflammatory blood markers (p > 0.05). In the regression analysis for possible risk factors that may be effective in P-PROM, oral and dental health parameters were the most effective. Conclusions: Oral and dental health of women with P-PROM was found to be worse than that of the control group. Oral and dental health may be a potential risk factor that may contribute to adverse pregnancy outcomes associated with P-PROM. [ABSTRACT FROM AUTHOR]

Haptoglobin is a plasma protein of mammals that plays a crucial role in vascular homeostasis by binding free haemoglobin released from ruptured red blood cells. Trypanosoma brucei can exploit this by internalising haptoglobin-haemoglobin complex to acquire host haem. Here, we investigated the impact of haptoglobin deficiency (Hp-/-) on T. brucei brucei infection and the parasite´s capacity to internalise haemoglobin in a Hp-/- mouse model. The infected Hp-/- mice exhibited normal disease progression, with minimal weight loss and no apparent organ pathology, similarly to control mice. While the proteomic profile of mouse sera significantly changed in response to T. b. brucei, no differences in the infection response markers of blood plasma between Hp-/- and control Black mice were observed. Similarly, very few quantitative differences were observed between the proteomes of parasites harvested from Hp-/- and Black mice, including both endogenous proteins and internalised host proteins. While haptoglobin was indeed absent from parasites isolated from Hp-/-mice, haemoglobin peptides were unexpectedly detected in parasites from both Hp-/- and Black mice. Combined, the data support the dispensability of haptoglobin for haemoglobin internalisation by T. b. brucei during infection in mice. Since the trypanosomes knock-outs for their haptoglobin-haemoglobin receptor (HpHbR) internalised significantly less haemoglobin from Hp-/- mice compared to those isolated from Black mice, it suggests that T. b. brucei employs also an HpHbR-independent haptoglobin-mediated mode for haemoglobin internalisation. Our study reveals a so-far hidden flexibility of haemoglobin acquisition by T. b. brucei and offers novel insights into alternative haemoglobin uptake pathways.

Background and aim: A potentially fatal side effect of decompensated liver cirrhosis is ascites. One potentially dangerous consequence in cirrhotic individuals with ascites is spontaneous bacterial peritonitis (SBP). Diagnostic paracentesis is a method used to diagnose SBP, although it is an invasive procedure. Numerous noninvasive markers were investigated in SBP diagnosis. Thus, this study aimed to assess the clinical utility of the noninvasive markers for the diagnosis and treatment response in patients with SBP, namely the lymphocyte monocyte ratio (LMR), mean platelet volume (MPV), and absolute neutrophil count (ANC). Patients and methods: This study included 162 cirrhotic patients was conducted. They were divided into 2 groups, group I included 101 cirrhotic patients with SBP and group II included 61 cirrhotic patients without SBP. ascitic fluid sampling and complete blood count (CBC) including ANC, LMR and MPV were done. Results: There was a significant difference between the 2 groups as regard ANC and LMR (p

Exercise and passive heating induce some similar vascular hemodynamic, circulating blood marker, and perceptual responses. However, it remains unknown whether post exercise hot water immersion can synergise exercise derived responses and if they differ from hot water immersion alone. This study investigated the acute responses to post moderate‐intensity exercise hot water immersion (EX+HWI) when compared to exercise (EX+REST) and hot water immersion (HWI+HWI) alone. Sixteen physically inactive middle‐aged adults (nine males and seven females) completed a randomized cross‐over counterbalanced design. Each condition consisted of two 30‐min bouts separated by 10 min of rest. Cycling was set at a power output equivalent to 50% V̇o2 peak. Water temperature was controlled at 40°C up to the mid sternum with arms not submerged. Venous blood samples and artery ultrasound scans were assessed at 0 (baseline), 30 (immediately post stressor one), 70 (immediately post stressor two), and 100 min (recovery). Additional physiological and perceptual measures were assessed at 10‐min intervals. Brachial and superficial femoral artery shear rates were higher after EX+HWI and HWI+HWI when compared with EX+REST (p < 0.001). Plasma nitrite was higher immediately following EX+HWI and HWI+HWI than EX+REST (p < 0.01). Serum interleukin‐6 was higher immediately after EX+HWI compared to EX+REST (p = 0.046). Serum cortisol was lower at 30 min in the HWI+HWI condition in contrast to EX+REST (p = 0.026). EX+HWI and HWI+HWI were more enjoyable than EX+REST (p < 0.05). Irrespective of whether hot water immersion proceeded exercise or heating, hot water immersion enhanced vascular and blood marker responses, while also being more enjoyable than exercise alone. [ABSTRACT FROM AUTHOR]

Background and aim: A potentially fatal side effect of decompensated liver cirrhosis is ascites. One potentially dangerous consequence in cirrhotic individuals with ascites is spontaneous bacterial peritonitis (SBP). Diagnostic paracentesis is a method used to diagnose SBP, although it is an invasive procedure. Numerous noninvasive markers were investigated in SBP diagnosis. Thus, this study aimed to assess the clinical utility of the noninvasive markers for the diagnosis and treatment response in patients with SBP, namely the lymphocyte monocyte ratio (LMR), mean platelet volume (MPV), and absolute neutrophil count (ANC). Patients and methods: This study included 162 cirrhotic patients was conducted. They were divided into 2 groups, group I included 101 cirrhotic patients with SBP and group II included 61 cirrhotic patients without SBP. ascitic fluid sampling and complete blood count (CBC) including ANC, LMR and MPV were done. Results: There was a significant difference between the 2 groups as regard ANC and LMR (p<0.05). In SBP group there was a significant difference in ANC, LMR, MPV before and after the standard\antibiotic treatment. Absolute neutrophil count had sensitivity 79.21%, specificity 63.93% However, the LMR had sensitivity 91.09 %, specificity 68.85 % and MPV had sensitivity 83.17%, specificity 62.30%. When ANC, LMR and MPV were combined, the sensitivity was 91.10% and specificity was 91.80%. Conclusion: This study suggests that the ANC, MPV, and LMR may be utilized as noninvasive markers for the diagnosis of SBP and prediction of treatment response, enabling prompt detection of SBP to minimize its consequences. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic immune-mediated disease, linked to local and systemic inflammation and predisposing patients to a higher risk of associated comorbidities. Cytokine levels are not widely available for disease progression monitoring due to high costs. Validated low-cost and reliable markers are needed for assessing disease progression and outcome. This study aims to assess the reliability of blood-count-derived inflammatory markers as disease predictors and to identify prognostic factors for disease severity. Patients fulfilling the inclusion criteria were enrolled in this study. Patients were divided into three study groups according to disease severity measured by the Body Surface Area (BSA) score: mild, moderate, and severe psoriasis. White blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), derived neutrophil-to-lymphocyte ratio (d-NLR), systemic immune index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) positively were correlated with disease severity (p < 0.005). d-NLR, NLR, and SII are independent prognostic factors for mild and moderate psoriasis (p < 0.05). d-NLR is the only independent prognostic factor for all three study groups. Moderate psoriasis is defined by d-NLR values between 1.49 and 2.19. NLR, PLR, d-NLR, MLR, SII, SIRI, and AISI are useful indicators of systemic inflammation and disease severity in psoriasis. [ABSTRACT FROM AUTHOR]

IntroductionThis randomized, placebo-controlled, double-blind, parallel study aimed to evaluate the effect of 3-month supplementation of bovine colostrum (BOV-COL; 8x400 mg per day) on the outcomes of depression treatment in hospitalized patients with substance use disorder (SUD). The hypothesis is that BOV-COL supplementation as an add-on treatment results in favorable alternations in selected blood inflammatory markers or neurotransmitters, leading to better depression treatment outcomes compared with placebo (PLA).MethodsPatients with a Minnesota Multiphasic Personality Inventory-2 score ≥60 points were enrolled. Twenty-nine participants (n=18 in the BOV-COL group and n=11 in the PLA group) completed the protocol.ResultsThe mean Beck Depression Inventory-II score was significantly reduced after supplementation in both groups. However, the mean 17-point Hamilton Depression Rating Scale score was decreased in the BOV-COL group, but not in the PLA group. In the BOV-COL group, there was a reduction in interleukin (IL)-1, IL-6, IL-10, the IL-6:IL-10 ratio, IL-17, and tumor necrosis factor alpha (TNF-α), while in the PLA group only IL-6 decreased. Favorable alternations in the total count and differentials of white blood cell subsets were more pronounced in the BOV-COL. There were no changes in neurotransmitter concentrations.ConclusionsBOV-COL supplementation is a promising add-on therapy in patients with depression and SUD.

Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic condition with a broad phenotypic presentation. This study aims to establish the first Australian cohort of individuals affected by CADASIL (AusCADASIL) and examine its clinical features and longitudinal course, and to investigate neuroimaging and blood biomarkers to assist in early diagnosis and identify disease progression. Methods: Participants will be recruited from six study centres across Australia for an observational study of CADASIL. We aim to recruit 150 participants with diagnosed CADASIL, family history of CADASIL or suspected CADASIL symptoms, and 150 cognitively normal NOTCH3 negative individuals as controls. Participants will complete: 1) online questionnaires on medical and family history, mental health, and wellbeing; 2) neuropsychological evaluation; 3) neurological examination and brain MRI; 4) ocular examination and 5) blood sample donation. Participants will have annual follow-up for 4 years to assess their progression and will be asked to invite a study partner to corroborate their self-reported cognitive and functional abilities.Primary outcomes include cognitive function and neuroimaging abnormalities. Secondary outcomes include investigation of genetics and blood and ocular biomarkers. Data from the cohort will contribute to an international consortium, and cohort participants will be invited to access future treatment/health intervention trials. Discussion: AusCADASIL will be the first study of an Australian cohort of individuals with CADASIL. The study will identify common pathogenic variants in this cohort, and characterise the pattern of clinical presentation and longitudinal progression, including imaging features, blood and ocular biomarkers and cognitive profile.

Background & Objective: Blood markers and CT-scan results can be useful to the prognosis outcome of traumatic brain injury (TBI). This study aims to evaluate and compare markers and CT-scans during hospitalization regarding death and recovery as the outcomes. Materials & Methods: This longitudinal-observational retrospective study was performed on 133 patients with comatose caused by head trauma from admission to death/discharge in Shohada-E- Tajrish Hospital in Tehran during 2018-2020. The follow-up period lasted 15 days. The patients’ demographic and CT-scans were measured on admission. Blood markers were measured daily. Vital signs and GCS were collected every six hours. These variables were compared in survivor and nonsurvivor groups. Results: Death occurred for 78 patients (58.64%). Tachycardia (OR=60.1, P=0.003), SDH (OR=39.3, P<0.001), ICH (OR=9.91, P<0.001), SAH (OR=13.6, P<0.001) had a significant relationship to death on multivariate logistic regression. The mean TT, PT, INR, GCS, PR, and systolic and diastolic blood pressure at the beginning of hospitalization were significantly different in the surviving and non-surviving groups. GCS, Cr, BUN, PTT, PT, INR, FBS, and PH had separate lines with spacing without overlap in the two groups in the graphs during hospitalization. Conclusion: Based on the results, the factors such as age, tachycardia, and some CT-scan findings (SAH, ICH, and SDH), as well as high coagulation profile (INR, PTT) and low GCS on admission, were important variables to the prognosis of TBI patients. During hospitalization, high values of BUN, PR, Cr, FBS, PT, and INR and low values of GCS, RR, and PH were associated with a worthwhile outcome. In addition, high changes in BUN, GCS, RR, PR, and BP during hospitalization should be considered a worthwhile prognosis. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists throughout the world with over 65 million registered cases of survivors with post-COVID-19 sequelae, also known as LongCOVID-19 (LongC). LongC survivors exhibit various symptoms that span multiple organ systems, including the nervous system. To search for neurological markers of LongC, we investigated the soluble biomolecules present in the plasma and the proteins associated with plasma neuronal-enriched extracellular vesicles (nEVs) in 33 LongC patients with neurological impairment (nLongC), 12 COVID-19 survivors without any LongC symptoms (Cov), and 28 pre-COVID-19 healthy controls (HC). COVID-19 positive participants were infected between 2020 and 2022, not hospitalized, and were vaccinated or unvaccinated before infection. IL-1β was significantly increased in both nLongC and Cov and IL-8 was elevated in only nLongC. Both brain-derived neurotrophic factor and cortisol were significantly elevated in nLongC and Cov compared to HC. nEVs from people with nLongC had significantly elevated protein markers of neuronal dysfunction, including amyloid beta 42, pTau181 and TDP-43. This study shows chronic peripheral inflammation with increased stress after COVID-19 infection. Additionally, differentially expressed nEV neurodegenerative proteins were identified in people recovering from COVID-19 regardless of persistent symptoms.

Psoriasis is a chronic immune-mediated disease, linked to local and systemic inflammation and predisposing patients to a higher risk of associated comorbidities. Cytokine levels are not widely available for disease progression monitoring due to high costs. Validated low-cost and reliable markers are needed for assessing disease progression and outcome. This study aims to assess the reliability of blood-count-derived inflammatory markers as disease predictors and to identify prognostic factors for disease severity. Patients fulfilling the inclusion criteria were enrolled in this study. Patients were divided into three study groups according to disease severity measured by the Body Surface Area (BSA) score: mild, moderate, and severe psoriasis. White blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), derived neutrophil-to-lymphocyte ratio (d-NLR), systemic immune index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) positively were correlated with disease severity (p < 0.005). d-NLR, NLR, and SII are independent prognostic factors for mild and moderate psoriasis (p < 0.05). d-NLR is the only independent prognostic factor for all three study groups. Moderate psoriasis is defined by d-NLR values between 1.49 and 2.19. NLR, PLR, d-NLR, MLR, SII, SIRI, and AISI are useful indicators of systemic inflammation and disease severity in psoriasis.

Backgrounds This study explored the contribution of peripheral blood markers in diagnosis and prognosis estimation of different stages of laryngeal dysplasia and early glottic cancer. Methods Retrospective analysis of clinical, histopathological and laboratory data of 220 patients including hemoglobin, neutrophil, lymphocyte, monocyte and platelet counts, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR). Results The mean hemoglobin level and platelets count showed differences between histopathological stages of lesions (p = 0.041 and 0.046, respectively). In patients with recurrent lesions mean level of lymphocyte count, NLR and PLR were significant in assessing progression and cancerization (p = 0.005, 0.028 and 0.023, respectively). The univariate analysis recognized level of PLR ≥ 141.74 as significant risk factor of the recurrence of vocal fold hypertrophic lesions (OR = 1.963). Conclusions The levels of blood cells and their ratios seem to be effective in predicting the recurrence of lesion and even more their potential role in indicating malignant progression.

The effectiveness of Branched Chain Amino Acids (BCAAs) supplementation on enhancing exercise performance in both young and older adults remains a topic of debate. Recent research suggests that BCAAs combined with regular exercise might have an impact on human erythropoiesis, blood dynamics, and iron homeostasis. Given the increasing longevity of the global population, it is crucial to investigate the potential benefits of BCAA supplementation and regular exercise as non-pharmacological interventions for improving the overall health of frail older adults. To assess the influence of a 40-week multicomponent exercise intervention (MEP) combined BCCA supplementation on the haematological indicators of frail older adults (83–93 years old) residing in nursing homes. A prospective, naturalistic, controlled clinical trial employing an intervention-washout-intervention was conducted for this purpose. The study included four experimental groups: MEP plus BCAA supplementation (MEP + BCAA, n = 8), MEP only (n = 7), BCAA supplementation only (n = 7), and control group non exercising (CG, n = 13). Fried's physical frailty (PF) protocol was employed to stratify the participants. Additionally, the assessment included the evaluation of nutritional status, comorbidities, and anthropometric measurements. Among the several haematological markers examined, only mean cellular Haemoglobin Concentration (MCH) [F = 4.09; p

IntroductionCranial and upper-airway anatomy of short-nosed, flat-faced brachycephalic dogs predisposes them to brachycephalic obstructive airway syndrome (BOAS). Periodic apnoea increased inspiratory resistance, and an inability to thermoregulate effectively are characteristic of BOAS, but internationally accepted objective markers of BOAS severity are missing. The objective of this study was to compare the selected blood parameters between non-brachycephalic (NC) and brachycephalic (BC) dogs, exploring the possibility of developing a blood test for BOAS severity grading in the future.MethodsWe evaluated blood biochemistry, complete blood cell counts, red blood cell (RBC) indices, reticulocyte counts, a blood-born marker of intermittent hypoxia (glutathione, NO production), RBC hydration, deformability, and blood markers of metabolic changes and stress between BC (n = 18) and NC (meso- and dolichocephalic, n = 22) dogs.ResultsReticulocyte counts and the abundance of middle-fluorescence immature reticulocytes were significantly (p < 0.05) higher in BC dogs compared to NC dogs. BC dogs had significantly more NO-derived NO2-/NO3- in plasma than NC dogs. RBCs of BC dogs were shedding significantly more membrane, as follows from the intensity of eosin maleimide staining, and had a significantly higher mean corpuscular hemoglobin concentration than NC dogs. Intracellular reduced glutathione content in RBCs of BC dogs was significantly lower, while plasma lactate was significantly higher in BC dogs compared to NC dogs. Plasma cholesterol and triglycerides were significantly lower, and cortisol was significantly higher in BC dogs compared to NC dogs. Eosinophil counts were significantly lower and the neutrophil-to-lymphocyte ratio was higher in BC dogs compared to NC dogs.DiscussionTaken together, our findings suggest that the brachycephalic phenotype in dogs is associated with alterations at the level of blood cells and, systemically, with oxidation and metabolic changes. The parameters identified within this study should be further investigated for their potential as objective indicators for BOAS.

A sixty-three day study that involved twenty (20) West African Dwarf (WAD) sheep aged 8 - 9 months with average live-weight of 7.44 ± 0.18 kgW0.75 was carried out to evaluate nutrients intake, nitrogen metabolism, weight gain and blood profile of sheep fed Pennisetum purpureum was substituted with white mulberry leaves. The sheep were divided into 5 groups of four sheep per group and allotted to individual pens in a Completely Randomized Design. Five diets fed to the sheep were formulated thus: diets A (100 % P. purpureum), B (75 % P. purpureum + 25 % mulberry leaves), C (50 % P. purpureum + 50 % mulberry leaves), D (25 % P. purpureum + 75 % mulberry) and E (100 % mulberry leaves). Dry matter ranged 89.03 - 90.16 % and the highest (21.05 %) crude protein was obtained in diet E. Nutrients intake, daily weight gain and feed to gain ratio were significantly (p<0.05) influenced by the treatments. The highest DM (250.38 gW0.75/day) and CP (52.70 gW0.75/day) intake were observed in sheep fed diet E. The diets were adequately digested, highest nitrogen balance (5.75 gW0.75) was obtained in sheep fed diet E. Consequently, the best daily weight gain (16.10 gW0.75g/day) and least feed conversion ratio (15.55). Haematological and serum biochemical indices were within normal range for WAD sheep. Thus, sole feeding of white mulberry leave could offer a reliable source of protein for improved nutrients digestibility and nitrogen utilization by WAD sheep without detrimental effects on their wellbeing. [ABSTRACT FROM AUTHOR]

During training camps, training load is purposefully intensified. Intensified training loads (TL) are associated with psychological variations, increased fatigue, insufficient recovery, decreased muscular performance, and biological changes in adult athletes, but whether these changes occur during training camps in youth athletes has not been established. The aim of this study was to assess changes in psychometric status, vertical jump performance (i.e., height), and hematological markers before and after an intensive training camp in youth soccer players. In this case, 15male youth soccer players (mean ± SD: age: 14.8 ± 0.4 years; height: 172.0 ± 6.9 cm, body mass: 60.8 ± 7.9 kg; training experience: 5.2 ± 0.7 years) completed a 2-week training program consisting of 1 week of moderate TL (MT) and 1 week of intensive training camp (TC). Rate of perceived exertion (RPE), TL, monotony, strain, and psychometric status (total quality of recovery (TQR) and well-being indices (sleep, stress, fatigue, and muscle soreness) were monitored before each first daily training session across two weeks. The profile of mood states (POMS), countermovement jump (CMJ) height, and blood markers (complete blood count, urea, and creatinine) were assessed before and after TC. TL (d = 5.39, large), monotony (d = 3.03, large), strain (d = 4.38, large), and well-being index (d = 7.5, large) scores increased and TQR (d = 4.6, large) decreased during TC. The TC increased tension, fatigue, and total mood disturbance and decreased vigor (all p <0.01). CMJ performance p < 0.01, d = 0.52, moderate), creatinine (p < 0.01, d = 1.29, large), and leukocyte concentration (p < 0.01, d = 1.4, large) and granulocyte concentration (p < 0.01, d = 1.93, large) increased after TC. Percentage of lymphocytes (p < 0.05, d = 1.17, large) and monocytes (p < 0.01, d = 1.05, large) decreased while the percentage of granulocytes (p < 0.05, d = 0.86, large) increased significantly. Well-being, quality of recovery, mood, granulocyte concentration, and creatinine were all altered during the week-long intensified training camp. These results may provide coaches with valuable information about psychometric status and physiological fatigue and recovery of youth soccer players to better prescribe and adjust training loads during intensive training periods. [ABSTRACT FROM AUTHOR]

Flavonoids are naturally occurring compounds widely distributed in the Citrus genus. These natural compounds have many health benefits, mainly for metabolic and cardiovascular diseases. In fact, some these compounds are components of drug products with approved indications for peripheral vascular insufficiency and hemorrhoids. However, information on pharmacological effects of these compounds remains disperse and there is scarce comprehensive analysis of whole data and evidence. These kinds of evidence analyses could be necessary in drug design and the development of novel and innovate drug products in diabetes and hypertension. We aimed to systematically search for evidence on the efficacy of citroflavonoids in diabetes and hypertension in in vivo models. We searched four literature databases based on a PICO strategy. After database curation, twenty-nine articles were retrieved to analyze experimental data. There was high heterogeneity in both outcomes and methodology. Naringenin and hesperetin derivates were the most studied citroflavonoids in both experimental models. More investigation is still needed to determine its potential for drug design and development. [ABSTRACT FROM AUTHOR]

COVID-19 is a recent respiratory illness with high morbidity and mortality; therefore, the study and characterization of blood markers associated with the improvement or deterioration of COVID-19 patients are crucial. This study compared levels of interleukin 6 (IL-6), procalcitonin (PCT), D-dimer, cortisol, dehydroepiandrosterone sulfate (DHEA-S), c-reactive protein (CRP), 25-OH vitamin D, anti-SARS-CoV-2 IgG antibodies, and viremia in mild–moderate and severe–critical COVID-19 patients. In addition, the time course of blood markers was studied in severe–critical cases. The results show that levels of IL-6, PCT, D-dimer, and CRP, the cortisol/DHEA-S ratio, as well as positive viremia and anti-Spike IgGs were higher in severe–critical patients requiring hospitalization. During follow-up, most severe–critical cases displayed similar time patterns of IL-6 and viral load, whereas anti-SARS-CoV-2 antibody curves showed an inverse pattern. A decrease in IL-6 levels was associated with the improvement of COVID-19 patients, mostly through a reduced oxygen requirement. This preliminary study suggests that an increase in serum IL-6, PCT, D-dimer and CRP levels and the cortisol/DHEA-S ratio could support the selection of patients with poorer prognosis and the need for an intensive or alternative treatment. Additionally, changes in IL-6 during hospitalization were associated with changes in patient's status mainly with a decrease in oxygen requirements, which indicates that serial measurements of IL-6 could predict the outcome of severe–critical patients with COVID-19 pneumonia. [ABSTRACT FROM AUTHOR]

Abstract Background Inflammatory blood markers have been associated with oncological outcomes in several cancers, but evidence for head and neck squamous cell carcinoma (HNSCC) is scanty. Therefore, this study aims at investigating the association between five different inflammatory blood markers and several oncological outcomes. Methods This multi-centre retrospective analysis included 925 consecutive patients with primary HPV-negative HNSCC (median age: 68 years) diagnosed between April 2004 and June 2018, whose pre-treatment blood parameters were available. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated; their associations with local, regional, and distant failure, disease-free survival (DFS), and overall survival (OS) was calculated. Results The median follow-up was 53 months. All five indexes were significantly associated with OS; the highest accuracy in predicting patients’ survival was found for SIM (10-year OS = 53.2% for SIM

Background Several millions of humans all over the world were affected by the novel coronavirus that emerged in Wuhan, Hubei, China, at the end of December 2019, known as severe acute respiratory syndrome coronavirus 2. The epidemic has gradually spread to 208 countries, leading to the death of more than two million and a half people, and this number is rapidly increasing. The rationale of the current study was to assess the role of some simple blood markers in suspecting the outcome of patients with severe infection. Patients and methods A cohort retrospective study was carried out that included critically ill coronavirus disease 2019-infected patients with positive PCR test result who were admitted to the critical care unit within 2 months. Information concerning clinical presentation, laboratory, and radiological findings was collected; moreover, the outcome and the length of critical care stay were documented. Statistical analysis was done, where collected data were compared between survivors and nonsurvivors. Receiver operating characteristic curve was used for the assessment of sensitivity and specificity of blood markers in predicting mortality. Results The number of patients included in the present study was 103. Most patients presented with fever and cough, and the main radiological finding was bilateral ground-glass lesions. On comparing both groups, the group that survived had elevated baseline values of PaO2/FiO2 ratio and lymphocyte count. However, the number of neutrophils, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, D-dimer, and serum level of ferritin were lower in this group; nonsurvivors had longer ICU stay. The following parameters were predictors for mortality: older age; increased neutrophil count, NLR, and D-dimer levels; and lower values of PaO2/FiO2 ratio. D-dimer and NLR had the highest sensitivity (81.3 and 87.5%, respectively) with area under the curve of 0.82 and 0.76, respectively. Conclusion Simple blood markers are sensitive parameters for suspecting outcome of severe coronavirus disease 2019 infection.

Abstract 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.

Background Several millions of humans all over the world were affected by the novel coronavirus that emerged in Wuhan, Hubei, China, at the end of December 2019, known as severe acute respiratory syndrome coronavirus 2. The epidemic has gradually spread to 208 countries, leading to the death of more than two million and a half people, and this number is rapidly increasing. The rationale of the current study was to assess the role of some simple blood markers in suspecting the outcome of patients with severe infection. Patients and methods A cohort retrospective study was carried out that included critically ill coronavirus disease 2019-infected patients with positive PCR test result who were admitted to the critical care unit within 2 months. Information concerning clinical presentation, laboratory, and radiological findings was collected; moreover, the outcome and the length of critical care stay were documented. Statistical analysis was done, where collected data were compared between survivors and nonsurvivors. Receiver operating characteristic curve was used for the assessment of sensitivity and specificity of blood markers in predicting mortality. Results The number of patients included in the present study was 103. Most patients presented with fever and cough, and the main radiological finding was bilateral ground-glass lesions. On comparing both groups, the group that survived had elevated baseline values of PaO2/FiO2 ratio and lymphocyte count. However, the number of neutrophils, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, D-dimer, and serum level of ferritin were lower in this group; nonsurvivors had longer ICU stay. The following parameters were predictors for mortality: older age; increased neutrophil count, NLR, and D-dimer levels; and lower values of PaO2/FiO2 ratio. D-dimer and NLR had the highest sensitivity (81.3 and 87.5%, respectively) with area under the curve of 0.82 and 0.76, respectively. Conclusion Simple blood markers are sensitive parameters for suspecting outcome of severe coronavirus disease 2019 infection. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Neuroinflammation is an important pathogenic mechanism in many neurodegenerative diseases, including those caused by frontotemporal lobar degeneration (FTLD). Postmortem and in vivo imaging studies have shown brain inflammation early in these conditions, proportionate to symptom severity and rate of progression. However, evidence for corresponding blood markers of inflammation and their relationship with central inflammation and clinical outcome are limited. There is a pressing need for such scalable, accessible and mechanistically relevant blood markers as these will reduce the time, risk, and costs of experimental medicine trials. We therefore assessed inflammatory patterns of serum cytokines from 214 patients with clinical syndromes associated with FTLD as compared to healthy controls, including their correlation with brain regional microglial activation and disease progression. Serum assays used the MesoScale Discovery V-Plex-Human Cytokine 36 plex panel plus five additional cytokine assays. A sub-group of patients underwent 11C-PK11195 TSPO PET imaging, as an index of microglial activation. A Principal Component Analysis (PCA) was used to reduce the dimensionality of cytokine data, excluding cytokines that were undetectable in >50% of participants. Frequentist and Bayesian analyses were performed on the principal components, to compare each patient cohort to controls, and test for associations with central inflammation, neurodegeneration-related plasma markers and survival. The first component identified by the PCA (explaining 21.5% variance) was strongly loaded by pro-inflammatory cytokines, including TNF-α, TNF-R1, M-CSF, IL-17A, IL-12, IP-10 and IL-6. Individual scores of the component showed significant differences between each patient cohort and controls. The degree to which a patient expressed this peripheral inflammatory profile at baseline correlated negatively with survival (higher inflammation, shorter survival), even when correcting for baseline clinical severity. Higher pro-inflammatory profile scores were associated with higher microglial activation in frontal and brainstem regions, as quantified with 11C-PK11195 TSPO PET. A permutation-based Canonical Correlation Analysis confirmed the association between the same cytokine-derived pattern and central inflammation across brain regions in a fully data-based manner. This data-driven approach identified a pro-inflammatory profile across the FTLD clinical spectrum, which is associated with central neuroinflammation and worse clinical outcome. Blood-based markers of inflammation could increase the scalability and access to neuroinflammatory assessment of people with dementia, to facilitate clinical trials and experimental medicine studies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction: To date, no validated predictors of response before neoadjuvant therapy (NAD) are currently available in locally advanced non-small-cell lung cancer (NSCLC). In this study, different peripheral blood markers were investigated before NAD (pre-NAD) and after NAD/before surgery (post-NAD) to evaluate their influence on the treatment outcomes. Methods: Patients affected by locally advanced NSCLC (cT1-T4/N0-2/M0) who underwent NAD followed by surgery from January 1996 to December 2019 were considered for this retrospective analysis. The impact of peripheral blood markers on downstaging post-NAD and on overall survival (OS) was evaluated using multivariate logistic and Cox regression models. Time to event analysis was performed by means of Kaplan–Meier survival curves and Log Rank tests at 5 years from surgery. Results: Two hundred and seventy-two consecutive patients were included. Most of the patients had Stage III NSCLC (83.5%). N2 disease was reported in 188 (69.1%) patients. Surgical resection was performed in patients with stable disease or downstaging post-NAD. Nodal downstaging was observed in 80% of clinical N2 (cN2) patients. The median follow-up of the total series was 74 months (range 6–302). Five-year OS in the overall population and in N2 population was 74.6% and 73.5%, respectively. The pre-surgery platelets level (PLT) (p = 0.019) and the variation (pre-NAD/post-NAD) of the neutrophil/lymphocyte ratio (p = 0.024) were identified as independent prognostic factors of OS. The preoperative PLT value (p value = 0.031) was confirmed as the only predictor of NAD response. Conclusions: The clinical role of peripheral blood markers in locally advanced NSCLC needs to be further investigated. Based on these preliminary results, these factors may be used as auxiliary markers for the prediction of response to neoadjuvant treatment and as prognostic factors for stratification in multimodal approaches. [ABSTRACT FROM AUTHOR]

Thyroid Eye Disease (TED) is an autoimmune disease that affects the extraocular muscles and periorbital fat. It most commonly occurs with Graves' Disease (GD) as an extrathyroidal manifestation, hence, it is also sometimes used interchangeably with Graves' Ophthalmopathy (GO). Well-known autoimmune markers for GD include thyroid stimulating hormone (TSH) receptor antibodies (TSH-R-Ab) which contribute to hyperthyroidism and ocular signs. Currently, apart from radiological investigations, detection of TED is based on clinical signs and symptoms which is largely subjective, with no established biomarkers which could differentiate TED from merely GD. We evaluated a total of 28 studies on potential biomarkers for diagnosis of TED. Articles included were published in English, which investigated clinical markers in tear fluid, orbital adipose-connective tissues, orbital fibroblasts and extraocular muscles, serum, thyroid tissue, as well as imaging biomarkers. Results demonstrated that biomarkers with reported diagnostic power have high sensitivity and specificity for TED, including those using a combination of biomarkers to differentiate between TED and GD, as well as the use of magnetic resonance imaging (MRI). Other biomarkers which were upregulated include cytokines, proinflammatory markers, and acute phase reactants in subjects with TED, which are however, deemed less specific to TED. Further clinical investigations for these biomarkers, scrutinising their specificity and sensitivity on a larger sample of patients, may point towards selection of suitable biomarkers for aiding detection and prognosis of TED in the future. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In recent years, many researchers have taken serum ubiquitin c-terminal hydrolase (Uch-L1) as an indicator of post-traumatic brain injury and associated it with cognitive impairment. Alzheimer’s disease is characterized by cognitive impairment and energy metabolism disorders. The purpose of this study was to detect whether serum Uch-L1 is related to cognition and brain energy metabolism in healthy people, and to explore whether it can be used as an early blood marker of Alzheimer’s disease. PATIENTS AND METHODS: In this prospective cohort study, adult outpatients from a Grade 3A hospital were recruited. They completed the 18F-FDG-PET/CT examination in the nuclear medicine department and were screened by the Mini Mental State scale (MMSE) and the Montreal Cognitive Assessment scale (MoCA). Blood samples were collected from all outpatients to detect the concentration of serum Uch-L1, and the mean standard uptake value (SUVmean) of energy metabolism in the hippocampus during PET/CT examination was collected. RESULTS: A total of 37 participants, 14 participants with cognitive impairment (MMSE score < 27) and 23 controls (MMSE score 27-30) were included. There was a significant difference in the SUVmean of the hippocampus between the cognitive impairment group and the normal control group (p < 0.05). There was a significant correlation between the SUVmean of the hippocampus and the total score of MMSE in all participants [r = 0.439, 95% CI: (0.139-0.668), p = 0.007]. There were also significant correlations between serum Uch-L1 and MMSE. Based on the significant differences of demographic variables between groups, we conducted a multivariate linear regression analysis of MMSE cognitive scores based on age (X1), length of education (X2) and SUVmean of hippocampus (X3). The regression equation is as follows: Y = 25.709-0.072 X1 + 0.422 X2 + 0.232 X3. CONCLUSIONS: Brain cognitive ability is closely related to energy metabolism and serum Uch-L1 concentration, so serum Uch-L1 may become a blood marker for extensive screening of dementia in the future. We look forward to the introduction of a more accurate and low-cost method for detecting serum Uch-L1 concentration. [ABSTRACT FROM AUTHOR]

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Background: Blood biomarkers are first-line tools for identifying periprosthetic joint infection (PJI). C-reactive protein (CRP) is currently recognized as the standard biomarker for PJI diagnosis. Other recently reported novel biomarkers, including plasma fibrinogen, platelet count, monocyte/lymphocyte ratio (MLR), neutrophil/lymphocyte ratio (NLR), and platelet count/lymphocyte ratio (PLR), have also shown promise in diagnosing PJI. This study aimed to evaluate whether these biomarkers were superior to CRP for identifying PJI. Methods: Patients who underwent revision hip or knee arthroplasty at our hospital from January 2008 to September 2020 were included consecutively and divided into infected and non-infected groups according to the 2013 International Consensus Meeting Criteria. Blood samples were collected preoperatively, and erythrocyte sedimentation rate (ESR), CRP, interleukin-6, fibrinogen, platelet count, MLR, NLR, and PLR were analyzed. The diagnostic values of the tested biomarkers and their combinations were compared with CRP based on the area under the receiver operating characteristic curve (AUC) using the z-test. Classification trees were constructed to explore more accurate combinations of the tested markers for identifying PJI. Results: A total of 543 patients were included, of whom 245 had PJI. Among the tested biomarkers, CRP with a cutoff of 7.39 mg/L showed the highest AUC, which gave a sensitivity of 79.1% and specificity of 86.0%. The AUCs of pairwise combinations of tested markers including CRP also were inferior to CRP itself, as were combinations derived from classification trees. Conclusions: Preoperative serum CRP with a low cutoff may be the best reliable blood biomarker for identifying PJI, and those traditional or novel available blood biomarkers could not further improve the diagnostic ability on the basis of CRP. [ABSTRACT FROM AUTHOR]

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.

Background: Inflammatory blood markers have been associated with oncological outcomes in several cancers, but evidence for head and neck squamous cell carcinoma (HNSCC) is scanty. Therefore, this study aims at investigating the association between five different inflammatory blood markers and several oncological outcomes.Methods: This multi-centre retrospective analysis included 925 consecutive patients with primary HPV-negative HNSCC (median age: 68 years) diagnosed between April 2004 and June 2018, whose pre-treatment blood parameters were available. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated; their associations with local, regional, and distant failure, disease-free survival (DFS), and overall survival (OS) was calculated.Results: The median follow-up was 53 months. All five indexes were significantly associated with OS; the highest accuracy in predicting patients' survival was found for SIM (10-year OS = 53.2% for SIM < 1.40 and 40.9% for SIM ≥ 2.46; c-index = 0.569) and LMR (10-year OS = 60.4% for LMR ≥ 3.76 and 40.5% for LMR < 2.92; c-index = 0.568). While LMR showed the strongest association with local failure (HR = 2.16; 95% CI:1.22-3.84), PLR showed the strongest association with regional (HR = 1.98; 95% CI:1.24-3.15) and distant failure (HR = 1.67; 95% CI:1.08-2.58).Conclusion: Different inflammatory blood markers may be useful to identify patients at risk of local, regional, or distant recurrences who may benefit from treatment intensification or intensive surveillance programs. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the usability of blood markers for predicting controlled ovarian stimulation (COS) outcomes in patients with breast cancer undergoing fertility preservation (FP). In total, 91 patients with breast cancer who had undergone COS using a letrozole-combined gonadotropin-releasing hormone (GnRH) antagonist protocol before chemotherapy were enrolled retrospectively in a single tertiary hospital. FP outcomes were compared in terms of the mean platelet volume (MPV), MPV/platelet count (PC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). The cutoff values for obtaining 10 or more mature oocytes as favorable prognoses were obtained for each parameter, and the COS outcomes were compared based on the cutoff values. The optimal cutoff levels for MPV and MPV/PC were 10.15 [sensitivity: 90.0%; specificity: 45.1%; AUC: 0.687; 95% CI (0.563, 0.810)] and 0.41 [sensitivity: 65.0%; specificity: 67.6%; AUC: 0.682; 95% CI (0.568, 0.796)], respectively. The oocyte numbers did not significantly differ with respect to the cutoff values of NLR, PLR, and LMR (p > 0.05). However, the total number of acquired and mature oocytes were significantly lower in the group with MPV<10.15 than in that with MPV≥10.15 (8.0 ± 5.1 vs. 12.6 ± 9.1, p=0.003; 4.0 ± 3.7 vs. 7.3 ± 6.3, p=0.002, respectively). Similarly, considering the cutoff of MPV/PC as 0.41, the low-MPV/PC group showed a significantly lower total oocyte yield than the high-MPV/PC group (9.5 ± 7.1 vs. 13.1 ± 9.1, p=0.048), whereas the number of mature oocytes showed similar patterns with no statistical significance (5.3 ± 5.4 vs. 7.3 ± 6.1, p=0.092). From logistic regression analysis, age, anti-Müllerian hormone (AMH) level, MPV, and MPV/PC≥0.41 were found to be significant factors for the acquisition of 10 or more MII oocytes (p=0.049, OR: 0.850; p<0.001, OR: 1.622; p=0.018, OR: 3.184; p=0.013, OR: 9.251, respectively). MPV or MPV/PC can be a reliable marker for predicting FP outcome in patients with breast cancer. Protocols to acquire more mature oocytes, such as the dual-trigger approach, could be recommended for patients with breast cancer with MPV<10.15. Furthermore, a higher dose of gonadotropins was considered to obtain more oocytes in patients with MPV/PC<0.41. [ABSTRACT FROM AUTHOR]

Deep Neural Networks (DNN) have been recently developed for the estimation of Biological Age (BA), the hypothetical underlying age of an organism, which can differ from its chronological age (CA). Although promising, these population-specific algorithms warrant further characterization and validation, since their biological, clinical and environmental correlates remain largely unexplored. Here, an accurate DNN was trained to compute BA based on 36 circulating biomarkers in an Italian population (N = 23,858; age ≥ 35 years; 51.7% women). This estimate was heavily influenced by markers of metabolic, heart, kidney and liver function. The resulting Δage (BA–CA) significantly predicted mortality and hospitalization risk for all and specific causes. Slowed biological aging (Δage < 0) was associated with higher physical and mental wellbeing, healthy lifestyles (e.g. adherence to Mediterranean diet) and higher socioeconomic status (educational attainment, household income and occupational status), while accelerated aging (Δage > 0) was associated with smoking and obesity. Together, lifestyles and socioeconomic variables explained ~48% of the total variance in Δage, potentially suggesting the existence of a genetic basis. These findings validate blood-based biological aging as a marker of public health in adult Italians and provide a robust body of knowledge on its biological architecture, clinical implications and potential environmental influences. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the usability of blood markers for predicting controlled ovarian stimulation (COS) outcomes in patients with breast cancer undergoing fertility preservation (FP). In total, 91 patients with breast cancer who had undergone COS using a letrozole-combined gonadotropin-releasing hormone (GnRH) antagonist protocol before chemotherapy were enrolled retrospectively in a single tertiary hospital. FP outcomes were compared in terms of the mean platelet volume (MPV), MPV/platelet count (PC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). The cutoff values for obtaining 10 or more mature oocytes as favorable prognoses were obtained for each parameter, and the COS outcomes were compared based on the cutoff values. The optimal cutoff levels for MPV and MPV/PC were 10.15 [sensitivity: 90.0%; specificity: 45.1%; AUC: 0.687; 95% CI (0.563, 0.810)] and 0.41 [sensitivity: 65.0%; specificity: 67.6%; AUC: 0.682; 95% CI (0.568, 0.796)], respectively. The oocyte numbers did not significantly differ with respect to the cutoff values of NLR, PLR, and LMR (p > 0.05). However, the total number of acquired and mature oocytes were significantly lower in the group with MPV

Background: Patients with severe acute pancreatitis (SAP) have a high mortality, thus early diagnosis and interventions are critical for improving survival. However, conventional tests are limited in acute pancreatitis (AP) stratification. We aimed to assess AP severity by integrating the informative clinical measurements with cell free DNA (cfDNA) methylation markers. Methods: One hundred and seventy-five blood samples were collected from 61 AP patients at multiple time points, plus 24 samples from healthy individuals. Genome-wide cfDNA methylation profiles of all samples were characterized with reduced representative bisulfite sequencing. Clinical blood tests covering 93 biomarkers were performed on AP patients within 24 h. SAP predication models were built based on cfDNA methylation and conventional blood biomarkers separately and in combination. Results: We identified 565 and 59 cfDNA methylation markers informative for acute pancreatitis and its severity. These markers were used to develop prediction models for AP and SAP with area under the receiver operating characteristic of 0.92 and 0.81, respectively. Twelve blood biomarkers were systematically screened for a predictor of SAP with a sensitivity of 87.5% for SAP, and a specificity of 100% in mild acute pancreatitis, significantly higher than existing blood tests. An expanded model integrating 12 conventional blood biomarkers with 59 cfDNA methylation markers further improved the SAP prediction sensitivity to 92.2%. Conclusions: These findings have demonstrated that accurate prediction of SAP by the integration of conventional and novel blood molecular markers, paving the way for early and effective SAP intervention through a non-invasive rapid diagnostic test. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

[Display omitted] • First study of blood marker associations with MDD/SCZ/BD polygenic risk scores. • Depression and Schizophrenia risk scores are associated with inflammatory markers. • All disorder risk scores are associated with several peripheral markers. • Many peripheral marker associations are disorder-specific. • Evidence for pathophysiological differences between major psychiatric disorders. 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. [ABSTRACT FROM AUTHOR]