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Background: Microcirculation abnormality in septic shock is closely associated with organ dysfunction and mortality rate. It was hypothesized that the arterial blood glucose and interstitial fluid (ISF) glucose difference (GA−I) as a marker for assessing the microcirculation status can effectively evaluate the severity of microcirculation disturbance in patients with septic shock. Methods: The present observational study enrolled patients with septic shock admitted to and treated in the intensive care unit (ICU) of a tertiary teaching hospital. The parameters reflecting organ and tissue perfusion, including lactic acid (Lac), skin mottling score, capillary refill time (CRT), venous-to-arterial carbon dioxide difference (Pv-aCO2), urine volume, central venous oxygen saturation (ScvO2) and GA−I of each enrolled patient were recorded at the time of enrollment (H0), H2, H4, H6, and H8. With ICU mortality as the primary outcome measure, the ICU mortality rate at any GA−I interval was analyzed. Results: A total of 43 septic shock patients were included, with median sequential organ failure assessment (SOFA) scores of 10.5 (6–16), and median Acute Physiology and Chronic Health Evaluation (APACHAE) II scores of 25.7 (9–40), of whom 18 died during ICU stay. The GA−I levels were negative correlation with CRT (r = 0.369, P < 0.001), Lac (r = -0.269, P < 0.001), skin mottling score (r=-0.223, P < 0.001), and were positively associated with urine volume (r = 0.135, P < 0.05). The ICU mortality rate of patients with septic shock presenting GA−I ≤ 0.30 mmol/L and ≥ 2.14 mmol/L was significantly higher than that of patients with GA−I at 0.30–2.14 mmol/L [65.2% vs. 15.0%, odds ratio (OR) = 10.625, 95% confidence interval (CI): 2.355–47.503]. Conclusion: GA−I was correlated with microcirculation parameters, and with differences in survival. Future studies are needed to further explore the potential impact of GA−I on microcirculation and clinical prognosis of septic shock, and the bedside monitoring of GA−I may be beneficial for clinicians to identify high-risk patients. [ABSTRACT FROM AUTHOR]

Highlights Doppler ultrasound may be used to assess leg blood flow (Q̇leg${{\dot{Q}}_{{\mathrm{leg}}}}$), but the reliability of this method remains unexplored in patients with chronic obstructive pulmonary disease (COPD), where between‐subject variability may be larger than healthy due to peripheral vascular changes. This study aimed to investigate the reliability of Doppler ultrasound in quantifying Q̇leg${{\dot{Q}}_{{\mathrm{leg}}}}$ during single‐leg knee‐extensor exercise (KEE) in COPD patients compared with those obtained from healthy matched controls. In this case–control study, 16 participants with COPD were matched based on sex and age with 16 healthy controls. All participants underwent measurement of Q̇leg${{\dot{Q}}_{{\mathrm{leg}}}}$ using Doppler ultrasound in a KEE set‐up at various intensities on two separate visits. Confounding factors on Q̇leg${{\dot{Q}}_{{\mathrm{leg}}}}$ were controlled for, and the ultrasound scans were consistently performed by the same sonographer. During exercise, smallest real difference (SRD) ranged from 367 mL to 583 mL in COPD and 438 mL to 667 mL in the control group. The coefficient of variation (CV) ranged from 7.9% to 14.3% in COPD and 9.4% to 10.4% in the control group. The intraclass correlation coefficient ranged from 0.75 to 0.92 in COPD and 0.67 to 0.84 in the control group. CV was lower in the control group during exercise at 0 W, but apart from that, reliability was not different between groups during exercise. Doppler ultrasound showed nearly equal reliability when evaluating Q̇leg${{\dot{Q}}_{{\mathrm{leg}}}}$ in COPD patients and healthy individuals with a CV below 15% during exercise for both groups. What is the central question of this study? What is the between‐day reliability of Doppler ultrasound when quantifying leg blood flow during single‐leg knee‐extensor exercise in COPD patients compared to healthy matched controls? What is the main finding and its importance? This study demonstrates a coefficient of variation ranging from 7.9 to 14.3% during single‐leg knee‐extensor exercise for between‐day reliability when applying Doppler ultrasound to assess leg blood flow in patients with COPD. Furthermore, it offers insights into the peripheral circulatory constraints in COPD, as evidenced by diminished leg blood flow. This study is the first of its kind to evaluate the reliability of Doppler ultrasound in the assessment of the peripheral circulation during exercise in COPD. What is the central question of this study?What is the between‐day reliability of Doppler ultrasound when quantifying leg blood flow during single‐leg knee‐extensor exercise in COPD patients compared to healthy matched controls?What is the main finding and its importance?This study demonstrates a coefficient of variation ranging from 7.9 to 14.3% during single‐leg knee‐extensor exercise for between‐day reliability when applying Doppler ultrasound to assess leg blood flow in patients with COPD. Furthermore, it offers insights into the peripheral circulatory constraints in COPD, as evidenced by diminished leg blood flow. This study is the first of its kind to evaluate the reliability of Doppler ultrasound in the assessment of the peripheral circulation during exercise in COPD. [ABSTRACT FROM AUTHOR]

Objective: Neutrophil extracellular traps (NETs) are important factors in initiating and perpetuating inflammation. However, the role of NETs in different subtypes of juvenile idiopathic arthritis (JIA) has been rarely studied. Therefore, we aimed to explore the ability of JIA-derived neutrophils to release NETs and the effect of TNF-α (tumor necrosis factor-alpha) inhibitors on NET formation both in vitro and in vivo, and evaluate the associations of NET-derived products with clinical and immune-related parameters. Methods: The ability of neutrophils to release NETs and the effect of adalimumab on NET formation was assessed via in vitro stimulation and inhibition studies. Plasma NET-derived products were detected to assess the incidence of NET formation in vivo. Furthermore, flow cytometry and western blotting were used to detect NET-associated signaling components in neutrophils. Results: Compared to those derived from HCs, neutrophils derived from patients with oligoarticular-JIA, polyarticular-JIA and enthesitis-related arthritis were more prone to generate NETs spontaneously and in response to TNF-α or PMA in vitro. Excessive NET formation existed in peripheral circulation of JIA patients, and elevated plasma levels of NET-derived products (cell-free DNA and MPO-DNA complexes) could accurately distinguish JIA patients from HCs and were positively correlated with disease activity. Multiple linear regression analysis showed that erythrocyte sedimentation rate and TNF-a levels were independent variables and were positively correlated with cell-free DNA concentration. Notably, TNF-a inhibitors could effectively prevent NET formation both in vitro and in vivo. Moreover, the phosphorylation levels of NET-associated kinases in JIA-derived neutrophils were markedly increased. Conclusion: Our data suggest that NETs might play pathogenic roles and may be involved in TNF-α-mediated inflammation in JIA. Circulating NET-derived products possess potential diagnostic and disease monitoring value. Furthermore, the preliminary results related to the molecular mechanisms of NET formation in JIA patients provide a theoretical basis for NETtargeted therapy. [ABSTRACT FROM AUTHOR]

Maternal obesity during pregnancy is associated with adverse pregnancy outcomes. This might be due to undesired obesity-induced changes in the maternal gut microbiota and related changes in the maternal immune adaptations during pregnancy. The current study examines how obesity affects gut microbiota and immunity in pregnant obese and lean mice during mid-pregnancy (gestational day 12 (GD12)). C57BL/6 mice were fed a high-fat diet or low-fat diet from 8 weeks before mating and during pregnancy. At GD12, we analyzed the gut microbiota composition in the feces and immune responses in the intestine (Peyer's patches, mesenteric lymph nodes) and the peripheral circulation (spleen and peripheral blood). Maternal obesity reduced beneficial bacteria (e.g., Bifidobacterium and Akkermansia) and changed intestinal and peripheral immune responses (e.g., dendritic cells, Th1/Th2/Th17/Treg axis, monocytes). Numerous correlations were found between obesity-associated bacterial genera and intestinal/peripheral immune anomalies. This study shows that maternal obesity impacts the abundance of specific bacterial gut genera as compared to lean mice and deranges maternal intestinal immune responses that subsequently change peripheral maternal immune responses in mid-pregnancy. Our findings underscore the opportunities for early intervention strategies targeting maternal obesity, ideally starting in the periconceptional period, to mitigate these obesity-related pregnancy effects. [ABSTRACT FROM AUTHOR]

Objective To explore the value of peripheral blood circulating DNA in predicting the efficacy and prognosis of immunotherapy for advanced non-small cell lung cancer. Method A retrospective study was conducted on 78 NSCLC patients who were admitted to the Respiratory and Critical Care Medicine Department of the First Affiliated Hospital of Hebei North University and were treated with tirelizumab for advanced driver gene negativity from January 2021 to December 2021. After 2 cycles of immunotherapy, the efficacy was evaluated according to the Solid Tumor Efficacy Evaluation Criteria (RECIST 1.1), including complete remission, partial remission, disease stability, and disease progression. CR and PR patients were defined as the experimental group (n = 48) Other patients were defined as the control group (n = 30), and the ctDNA levels in peripheral blood were measured before and after treatment in both groups. ROC curves were used to analyze the predictive value of periph eral blood ctDNA levels for achieving objective remission after immunotherapy.All patients were followed up and their progression free survival were calcutated.Using univariate and multivariate regression analysis identified the factors affecting the prognosis of patients after immunotherapy. Using Spearman correlation coefficient analyzed the correlation between ctDNA levels and PFS. Kalplan Meier survival curve were used for survival analysis. Result The peripheral blood ctDNA levels before and after treatment in the experimental group were (4.47 ± 1.21)ng/μL and (2.65 ± 1.14) ng/μL, respectively (t = 7.559,P < 0.001), while those in the control group were (4.54 ± 1.15)ng/mL and (4.29 ± 1.57) ng/μL, respectively (t = 0.699,P = 0.487). There was no statistically significant difference in peripheral blood ctDNA levels between the two groups before treatment (t = -0.25,P = 0.801). The peripheral blood ctDNA levels in the experimental group decreased compared to the control group after treatment (t = -5.35,P < 0.001). The ROC curve analysis showed that the area under the curve for predicting objective remission after immunotherapy based on peripheral blood ctDNA levels was 0.819, with a sensitivity of 81.3% and specificity of 80%. Peripheral blood ctDNA levels were negatively correlated with progression free survival (r = -0.784,P = 0.000). Single factor COX regression was used to analyze the clinical and pathological characteristics and ctDNA levels of enrolled patients, and the results showed that the maximum tumor diameter was greater than 5 cm (HR = 0.501, 95% CI: 6.731 ~ 35.567) Tumor stage IV (HR = 0.392,95% CI: 0.227 ~ 0.677), treatment approach (HR = 15.473,95% CI: 6.731 ~ 35.567), and ctDNA levels (HR = 4.657,95% CI: 3.182 ~ 6.555) are all influencing factors for PFS in advanced NSCLC patients after immunotherapy. Multiple factor analysis was conducted on the appeal indicators with statistical differences, and the results showed that treatment approach (HR = 2.981,95% CI:1.019 ~ 8.722) and peripheral blood ctDNA levels (HR = 3.918,95% CI: 2.619 ~ 5.861) It is an independent influencing factor of PFS in advanced NSCLC patients. The Kalplan Meier survival curve was used for analysis, and the results showed that the median PFS of the treatment effective group was 8.4 months, while the median PFS of the control group was 5.4 months. (χ² = 49.277, P = 0.000). Conclusion Immunotherapy combined with chemotherapy can enhance the ability to kill tumor cells, and peripheral blood ctDNA levels can evaluate the efficacy and prognosis of immunotherapy, which can be used to guide immunotherapy in advanced NSCLC patients. [ABSTRACT FROM AUTHOR]

The treatment of patients diagnosed with hematologic malignancies typically includes hematopoietic stem cell transplantation (HSCT) as part of a therapeutic standard of care. The primary graft source of hematopoietic stem and progenitor cells (HSPCs) for HSCT is mobilized from the bone marrow into the peripheral blood of allogeneic donors or patients. More recently, these mobilized HSPCs have also been the source for gene editing strategies to treat diseases such as sickle-cell anemia. For a HSCT to be successful, it requires the infusion of a sufficient number of HSPCs that are capable of adequate homing to the bone marrow niche and the subsequent regeneration of stable trilineage hematopoiesis in a timely manner. Granulocyte-colony-stimulating factor (G-CSF) is currently the most frequently used agent for HSPC mobilization. However, it requires five or more daily infusions to produce an adequate number of HSPCs and the use of G-CSF alone often results in suboptimal stem cell yields in a significant number of patients. Furthermore, there are several undesirable side effects associated with G-CSF, and it is contraindicated for use in sickle-cell anemia patients, where it has been linked to serious vaso-occlusive and thrombotic events. The chemokine receptor CXCR4 and the cell surface integrin α4β1 (very late antigen 4 (VLA4)) are both involved in the homing and retention of HSPCs within the bone marrow microenvironment. Preclinical and/or clinical studies have shown that targeted disruption of the interaction of the CXCR4 or VLA4 receptors with their endogenous ligands within the bone marrow niche results in the rapid and reversible mobilization of HSPCs into the peripheral circulation and is synergistic when combined with G-CSF. In this review, we discuss the roles CXCR4 and VLA4 play in bone marrow homing and retention and will summarize more recent development of small-molecule CXCR4 and VLA4 inhibitors that, when combined, can synergistically improve the magnitude, quality and convenience of HSPC mobilization for stem cell transplantation and ex vivo gene therapy after the administration of just a single dose. This optimized regimen has the potential to afford a superior alternative to G-CSF for HSPC mobilization. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) have regenerative and immunomodulatory potential and may be used to treat injured tissues. Pregnancy has been associated with increased MSCs in the peripheral circulation in multiple species, but to date, there are no reports on this matter in horses. This study aimed to evaluate the effect of pregnancy on isolation efficiency and proliferation capacity of equine MSCs derived from the peripheral blood (PB) of mares. Venous blood samples were collected at the 11th month of gestation and 1 month after delivery from clinically healthy Arabian mares that presented normal pregnancies. Blood samples were processed for in vitro cellular culture and hormonal and metabolic profiles. MSCs were isolated and characterized by trilineage differentiation potential, immunophenotyping, analyzed by gene sequencing and proliferation assays. The isolation of peripheral blood mononuclear cells (PBMCs) of pregnant mares were associated with higher isolation efficiency and proliferative capacity of MSCs derived from peripheral blood (PB-MSCs) recovered pre-partum than those isolated post-partum. Although fetal gender, parity, 5α-reduced pregnanes, insulin, and cortisol were shown to affect cellular proliferation, individual factors and the small population studied must be considered. This study suggests that PB-MSCs from pregnant mares could be a valuable alternative source of MSCs for therapeutic purposes. • Lack of reports onthe isolation of mesenchymal stromal cells (MSCs) from peripheral blood (PB-MSCs) in pregnant mares. • Pregnancy in Arabian mares was associated with higher isolation efficiency and proliferative capacity of PB-MSCs. • Fetal gender, parity, and levels of 5α-reduced pregnanes, insulin and cortisol were shown to affect cellular proliferation. • Pregnant mares could be a valuable, readily available source of MSCs for therapeutic purposes. [ABSTRACT FROM AUTHOR]

Skin tissue-resident memory T (Trm) cells are produced by antigenic stimulation and remain in the skin for a long time without entering the peripheral circulation. In the healthy state Trm cells can play a patrolling and surveillance role, but in the disease state Trm cells differentiate into various phenotypes associated with different diseases, exhibit different localizations, and consequently have local protective or pathogenic roles, such as disease recurrence in vitiligo and maintenance of immune homeostasis in melanoma. The most common surface marker of Trm cells is CD69/CD103. However, the plasticity of tissueresident memory T cells after colonization remains somewhat uncertain. This ambiguity is largely due to the variation in the functionality and ultimate destination of Trm cells produced from memory cells differentiated from diverse precursors. Notably, the presence of Trm cells is not stationary across numerous non-lymphoid tissues, most notably in the skin. These cells may reenter the blood and distant tissue sites during the recall response, revealing the recycling and migration potential of the Trm cell progeny. This review focuses on the origin and function of skin Trm cells, and provides new insights into the role of skin Trm cells in the treatment of autoimmune skin diseases, infectious skin diseases, and tumors. [ABSTRACT FROM AUTHOR]

The blood-brain barrier (BBB) is an extensive capillary network that protects the brain from environmental and metabolic toxins while limiting drug delivery to the central nervous system (CNS). The ATP-binding cassette transporter breast cancer resistance protein (Bcrp) reduces drug delivery across the BBB by actively transporting its clinical substrates back into peripheral circulation before their entry into the CNS compartment. 17β-Estradiol (E2)-elicited changes in Bcrp transport activity and expression have been documented previously. We report a novel signaling mechanism by which E2 decreases Bcrp transport activity in mouse brain capillaries via rapid nongenomic signaling through estrogen receptor α. We extended this finding to investigate the effects of different endocrine-disrupting compounds (EDCs) and selective estrogen receptor modulators (SERMs) on Bcrp transport function. We also demonstrate sex-dependent expression of Bcrp and E2-sensitive Bcrp transport activity at the BBB ex vivo. This work establishes an explanted tissue-based model by which to interrogate EDCs and SERMs as modulators of nongenomic estrogenic signaling with implications for sex and hormonal regulation of therapeutic delivery into the CNS. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to evaluate the ability of the peripheral perfusion index (PPI) to predict reintubation of critically ill surgical patients. Methods: This prospective observational study included mechanically ventilated adults who were extubated after a successful spontaneous breathing trial (SBT). The patients were followed up for the next 48 h for the need for reintubation. The heart rate, systolic blood pressure, respiratory rate, peripheral arterial oxygen saturation (SpO2), and PPI were measured before-, at the end of SBT, 1 and 2 h postextubation. The primary outcome was the ability of PPI 1 h postextubation to predict reintubation using area under the receiver operating characteristic curve (AUC) analysis. Univariate and multivariate analyses were performed to identify predictors for reintubation. Results: Data from 62 patients were analysed. Reintubation occurred in 12/62 (19%) of the patients. Reintubated patients had higher heart rate and respiratory rate; and lower SpO2 and PPI than successfully weaned patients. The AUC (95%confidence interval) for the ability of PPI at 1 h postextubation to predict reintubation was 0.82 (0.71–0.91) with a negative predictive value of 97%, at a cutoff value of ≤ 2.5. Low PPI and high respiratory rate were the independent predictors for reintubation. Conclusion: PPI early after extubation is a useful tool for prediction of reintubation. Low PPI is an independent risk factor for reintubation. A PPI > 2.5, one hour after extubation can confirm successful extubation. [ABSTRACT FROM AUTHOR]

In eukaryotic RNA, N6‐methyladenosine (m6A) is a prevalent form of methylation modification. The m6A modification process is reversible and dynamic, written by m6A methyltransferase complex, erased by m6A demethylase, and recognized by m6A binding proteins. Through mediating RNA stability, decay, alternative splicing, and translation processes, m6A modification regulates gene expression at the post‐transcriptional level. Erythropoiesis is the process of hematopoietic stem cells undergoing proliferation, a series of differentiation and maturation to form red blood cells (RBCs). Thalassemia is a common monogenic disease characterized by excessive production of ineffective RBCs in the peripheral circulation, resulting in hemolytic anemia. Increasing evidence suggests that m6A modification plays a crucial role in erythropoiesis. In this review, we comprehensively summarize the function of m6A modification in erythropoiesis and further generalize the mechanism of m6A modification regulating ineffective erythropoiesis and fetal hemoglobin expression. The purpose is to improve the understanding of the pathogenesis of erythroid dysplasia and offer new perspectives for the diagnosis and treatment of thalassemia. [ABSTRACT FROM AUTHOR]

Background: Neurofilament light chain (NfL) is released into the peripheral circulation by damaged axons. Objective s : To evaluate the diagnostic value of serum NfL concentration in dogs with intracranial diseases. Animals: Study included 37 healthy dogs, 31 dogs with idiopathic epilepsy (IE), 45 dogs with meningoencephalitis of unknown etiology (MUE), 20 dogs with hydrocephalus, and 19 dogs with brain tumors. Methods: Cohort study. Serum NfL concentrations were measured in all dogs using single‐molecule array technology. Results: Serum NfL concentration in dogs with each structural disease was significantly higher than in healthy dogs and dogs with IE (P =.01). The area under the receiver operating characteristic curve of NfL for differentiating between dogs with structural diseases and IE was 0.868. An optimal cutoff value of the NfL 27.10 pg/mL had a sensitivity of 86.67% and a specificity of 74.19% to differentiate the dogs with IE from those with structural brain diseases. There were significant correlations between NfL concentrations and lesion size: (1) MUE, P =.01, r = 0.429; (2) hydrocephalus, P =.01, r = 0.563. Conclusions and Clinical Importance: Serum NfL could be a useful biomarker for distinguishing IE from structural diseases in dogs and predicting the lesion sizes of MUE and hydrocephalus. [ABSTRACT FROM AUTHOR]

Gut microbiome dysbiosis is a major contributing factor to several pathological conditions. However, the mechanistic understanding of the communication between gut microbiota and extra‐intestinal organs remains largely elusive. Extracellular vesicles (EVs), secreted by almost every form of life, including bacteria, could play a critical role in this inter‐kingdom crosstalk and are the focus of present study. Here, we present a novel approach for isolating lipopolysaccharide (LPS)+ bacterial extracellular vesicles (bEVLPS) from complex biological samples, including faeces, plasma and the liver from lean and diet‐induced obese (DIO) mice. bEVLPS were extensively characterised using nanoparticle tracking analyses, immunogold labelling coupled with transmission electron microscopy, flow cytometry, super‐resolution microscopy and 16S sequencing. In liver tissues, the protein expressions of TLR4 and a few macrophage‐specific biomarkers were assessed by immunohistochemistry, and the gene expressions of inflammation‐related cytokines and their receptors (n = 89 genes) were measured using a PCR array. Faecal samples from DIO mice revealed a remarkably lower concentration of total EVs but a significantly higher percentage of LPS+ EVs. Interestingly, DIO faecal bEVLPS showed a higher abundance of Proteobacteria by 16S sequencing. Importantly, in DIO mice, a higher number of total EVs and bEVLPS consistently entered the hepatic portal vein and subsequently reached the liver, associated with increased expression of TLR4, macrophage markers (F4/80, CD86 and CD206), cytokines and receptors (Il1rn, Ccr1, Cxcl10, Il2rg and Ccr2). Furthermore, a portion of bEVLPS escaped liver and entered the peripheral circulation. In conclusion, bEV could be the key mediator orchestrating various well‐established biological effects induced by gut bacteria on distant organs. [ABSTRACT FROM AUTHOR]

Pro-inflammatory cytokines mediate the course of rosacea, anxiety, and depression through various means such as immunity and inflammation. This study aims to further explore the relationship between rosacea, anxiety, and depression through changes in the levels of pro-inflammatory cytokines. Methods: 280 rosacea patients were included in the rosacea group, divided into: rosacea without mental disorders, rosacea with anxiety, rosacea with depression, and rosacea with combined anxiety and depression. The mental control group included 210 anxiety and depression patients, divided into: anxiety, depression, and combined anxiety and depression. The healthy control group consisted of 70 healthy individuals. Serum specimens were collected and ELISA was used to detect major pro-inflammatory cytokines. CEA, IGA, GFSS, RosaQoL, HAMA, and HAMD-24 were used for the diagnosis and severity assessment of rosacea and anxiety and depression. Results: This study primarily used the Chi-Square test, Kruskal–Wallis H-test, generalized linear model, and binary logistic regression to evaluate the data. IL-1β, IL-17, and IL-8 levels in rosacea patients and anxiety/depression patients were higher than those in the healthy population (P< 0.001), and TNF-α levels in rosacea patients were higher than those in the healthy population (P< 0.001). There was an interaction between rosacea, anxiety, and depression in terms of IL-1β, IL-17, and IL-8 levels (P< 0.001). Elevated levels of IL-1β, IL-17, and IL-8 are positively correlated with anxiety and depression in rosacea (all P<=0.05). Conclusion: It was confirmed that the elevated levels of IL-1β, IL-17, and IL-8 are positively correlated with the onset of anxiety and depression in rosacea. The interaction of the above inflammatory factors suggests a possible common inflammatory mechanism in the coexistence of rosacea and mental disorders. TNF-α only increased in patients with rosacea, combined with the skin-to-mental irreversible phenomenon, indicating that this cytokine may be a key and potential therapeutic target for the onset of rosacea. [ABSTRACT FROM AUTHOR]

Abstract Background Microcirculation abnormality in septic shock is closely associated with organ dysfunction and mortality rate. It was hypothesized that the arterial blood glucose and interstitial fluid (ISF) glucose difference (GA−I) as a marker for assessing the microcirculation status can effectively evaluate the severity of microcirculation disturbance in patients with septic shock. Methods The present observational study enrolled patients with septic shock admitted to and treated in the intensive care unit (ICU) of a tertiary teaching hospital. The parameters reflecting organ and tissue perfusion, including lactic acid (Lac), skin mottling score, capillary refill time (CRT), venous-to-arterial carbon dioxide difference (Pv-aCO2), urine volume, central venous oxygen saturation (ScvO2) and GA−I of each enrolled patient were recorded at the time of enrollment (H0), H2, H4, H6, and H8. With ICU mortality as the primary outcome measure, the ICU mortality rate at any GA−I interval was analyzed. Results A total of 43 septic shock patients were included, with median sequential organ failure assessment (SOFA) scores of 10.5 (6–16), and median Acute Physiology and Chronic Health Evaluation (APACHAE) II scores of 25.7 (9–40), of whom 18 died during ICU stay. The GA−I levels were negative correlation with CRT (r = 0.369, P

Dirofilaria immitis is a mosquito-borne parasitic nematode that causes fatal heartworm disease in canids. The microfilariae are essential for research, including drug screening and mosquito-parasite interactions. However, no reliable methods for maintaining microfilaria long-term are currently available. Therefore, we used severe combined immunodeficiency (SCID) mice to develop a reliable method for maintaining D. immitis microfilaria. SCID mice were injected intravenously with microfilariae isolated from a D. immitis-infected dog. Microfilariae were detected in blood collected from the tail vein 218 days post-inoculation (dpi) and via cardiac puncture 296 dpi. Microfilariae maintained in and extracted from SCID mice showed infectivity and matured into third-stage larvae (L3s) in the vector mosquito Aedes aegypti. L3s can develop into the fourth stage larvae in vitro. Microfilariae from SCID mice respond normally to ivermectin in vitro. The microfilariae in SCID mice displayed periodicity in the peripheral circulation. The SCID mouse model aided in the separation of microfilariae from cryopreserved specimens. The use of SCID mice enabled the isolation and sustained cultivation of microfilariae from clinical samples. These findings highlight the usefulness of the SCID mouse model for studying D. immitis microfilaremia in canine heartworm research. [ABSTRACT FROM AUTHOR]

Introduction: This study assesses the accuracy of neutrophil activation markers, including neutrophil extracellular traps (NETs) and calprotectin, as biomarkers of disease activity in patients with established rheumatoid arthritis (RA). We also analyse the relationship between NETs and various types of therapies as well as their association with autoimmunity. Methods: Observational cross-sectional study of patients with RA receiving treatment with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (JAK-inhibitors) for at least 3 months. Plasma calprotectin levels were measured using an enzyme-linked immunosorbent assay test kit and NETs by measuring their remnants in plasma (neutrophil elastase-DNA and histone-DNA complexes). We also assessed clinical disease activity, joint ultrasound findings and autoantibody status [reumatoid factor (RF), anti-citrullinated peptide/protein antibodies (ACPAs) and anti-carbamylated protein (anti-CarP)]. Associations between neutrophilic biomarkers and clinical or ultrasound scores were sought using correlation analysis. The discriminatory capacity of both neutrophilic biomarkers to detect ultrasound synovitis was analysed through receiver-operating characteristic (ROC) curves. Results: One hundred fourteen patients were included. Two control groups were included to compare NET levels. The active control group consisted of 15 patients. The second control group consisted of 30 healthy subjects. Plasma NET levels did not correlate with clinical disease status, regardless of the clinic index analysed or the biological therapy administered. No significant correlation was observed between NET remnants and ultrasound synovitis. There was no correlation between plasma NET and autoantibodies. In contrast, plasma calprotectin positively correlated with clinical parameters (swollen joint count [SJC] rho = 0.49; P < 0.001, Clinical Disease Activity Index [CDAI] rho = 0.30; P < 0.001) and ultrasound parameters (rho > 0.50; P < 0.001). Notably, this correlation was stronger than that observed with acute phase reactants. Conclusion: While NET formation induced by neutrophils may play a role in RA pathogenesis, our study raises questions about the utility of NET remnants in peripheral circulation as a biomarker for inflammatory activity. In contrast, this study strongly supports the usefulness of calprotectin as a biomarker of inflammatory activity in patients with RA. [ABSTRACT FROM AUTHOR]

Background: Autonomic dysfunction precedes endothelial dysfunction in Parkinson's disease (PD) and causes blood pressure and circulation abnormalities that are highly disruptive to one's quality of life. While exercise interventions have proven helpful for motor symptoms of PD, improving associated non-motor symptoms is limited. Low-intensity resistance training with blood flow restriction (LIRT-BFR) improves autonomic dysfunction in non-PD patients and high-intensity resistance training (HIRT) is recommended for motor symptom improvements for people with PD (PwPD). Objective: To determine the effects of LIRT-BFR and HIRT on homocysteine and autonomic and endothelial function in PwPD and to determine the hemodynamic loads during LIRT-BFR and HIRT in PwPD using a novel exercise protocol. Methods: Thirty-eight PwPD were assigned LIRT-BFR, HIRT or to a control (CNTRL) group. The LIRT-BFR and HIRT groups exercised three days per week for four weeks. The LIRT-BFR protocol used 60% limb occlusion pressure (LOP) and performed three sets of 20 repetitions at 20% of the one-repetition maximum (1RM). The HIRT group performed three sets of eight repetitions at 80% 1RM. The CNTRL group was asked to continue their normal daily routines. Results: LIRT-BFR significantly improved orthostatic hypotension (p = 0.026), homocysteine levels (p < 0.001), peripheral circulation (p = 0.003), supine blood pressure (p = 0.028) and heart rate variability (p = 0.041); LIRT-BFR improved homocysteine levels (p < 0.018), peripheral circulation (p = 0.005), supine blood pressure (p = 0.007) and heart rate variability (p = 0.047) more than HIRT; and hemodynamic loads for LIRT-BFR and HIRT were similar. Conclusions: LIRT-BFR may be more effective than HIRT for autonomic and endothelial function improvements in PwPD and hemodynamic loads may be lessened in LIRT-BFR protocols using single-joint exercises with intermittent blood flow restriction. Further research is needed to determine if non-motor symptoms improve over time and if results are sustainable. [ABSTRACT FROM AUTHOR]

This study examined the impact of continuous blood flow restriction (BFR) during repeated‐sprint exercise (RSE) on acute performance, peripheral, systemic physiological, and perceptual responses. In a randomized crossover design, 26 adult male semi‐professional and amateur team‐sport players completed two RSE sessions (3 sets of 5 × 5‐s sprints with 25 s of passive recovery and 3 min of rest) with continuous BFR (45% arterial occlusion; excluding during between‐set rest periods) or without (non‐BFR). Mean and peak power output were significantly lower (p < 0.001) during BFR compared to non‐BFR (dz = 0.85 and 0.77, respectively). Minimum tissue saturation index during the sprints and rest periods was significantly reduced (p < 0.001) for BFR (dz = 1.26 and 1.21, respectively). Electromyography root mean square was significantly decreased (p < 0.01) for biceps femoris and lateral gastrocnemius muscles during BFR (dz = 0.35 and 0.79, respectively), but remained unchanged for the vastus lateralis muscle in both conditions. Oxygen consumption and minute ventilation were significantly reduced (both p < 0.01) for BFR (dz = 1.46 and 0.43, respectively). Perceived limb discomfort was significantly higher (p < 0.001) for BFR (dz = 0.78). No differences (p > 0.05) in blood lactate concentration or rating of perceived exertion were observed between conditions. Blood flow‐restricted RSE reduced performance and likely increased the physiological and perceptual stimulus for the periphery with greater reliance on anaerobic glycolysis, despite comparable or decreased systemic demands. Highlights: Continuous cuff inflation reduces external loads during repeated sprints which is suitable for athletes undertaking demanding training blocks or rehabilitating an injury.Blood flow‐restricted repeated sprints likely increase anaerobic energy contribution from further muscle deoxygenation.Inflatable cuffs likely reduce antagonistic muscle activation during cycling repeated sprints to maintain efficient inter‐muscle coordination given the deteriorated contractility of prime mover muscles with metabolic stress. [ABSTRACT FROM AUTHOR]

Background: The hypothalamus plays a crucial role in the health and productivity of dairy cows, yet studies on its functionality and its impact on peripheral circulation in these animals are relatively scarce, particularly regarding dietary interventions. Therefore, our study undertook a comprehensive analysis, incorporating both metabolomics and transcriptomics, to explore the effects of a grain-based diet on the functionality of the hypothalamus, as well as on blood and milk in dairy cows. Results: The hypothalamic metabolome analysis revealed a significant reduction in prostaglandin E2 (PGE2) level as a prominent response to the grain-based diet introduction. Furthermore, the hypothalamic transcriptome profiling showed a notable upregulation in amino acid metabolism due to the grain-based diet. Conversely, the grain-based diet led to the downregulation of genes involved in the metabolic pathway from lecithin to PGE2, including phospholipase A2 (PLA2G4E, PLA2G2A, and PLA2G12B), cyclooxygenase-2 (COX2), and prostaglandin E synthase (PTGES). Additionally, the plasma metabolome analysis indicated a substantial decrease in the level of PGE2, along with a decline in adrenal steroid hormones (tetrahydrocortisol and pregnenolone) following the grain-based diet introduction. Analysis of the milk metabolome showed that the grain-based diet significantly increased uric acid level while notably decreasing PGE2 level. Importantly, PGE2 was identified as a critical metabolic marker in the hypothalamus, blood, and milk in response to grain intervention. Correlation analysis demonstrated a significant correlation among metabolic alterations in the hypothalamus, blood, and milk following the grain-based diet. Conclusions: Our findings suggest a potential link between hypothalamic changes and alterations in peripheral circulation resulting from the introduction of a grain-based diet. [ABSTRACT FROM AUTHOR]

Oxidative stress plays a key role in brain damage because of the sensitivity of brain tissue to oxidative damage. Biomarkers with easy measurement can be a candidate for reflecting the oxidative stress issue in humans. For this reason, we need to focus on specific metabolic products of the brain. End products of free radical reactions such as malondialdehydes form fluorescent products known as lipophilic fluorescent products (LFPs). The distinctive feature of LFPs is their autofluorescent properties. LFPs are detectable in the brain and cerebrospinal fluid. Furthermore, because of the diffusion into the bloodstream, these lipophilic molecules can be detected in the blood. Accumulations of these compounds produce more reactive oxygen species and increase the sensitivity of cells to oxidative damage. Hence, LFPs can be considered a danger signal for neurons and can be introduced as a strong index of oxidative damage both in the central and in the peripheral. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) are tissue-resident immune cells distributed in all tissues and strategically located close to blood and lymphatic vessels and nerves. Thanks to the expression of a wide array of receptors, MCs act as tissue sentinels, able to detect the presence of bacteria and parasites and to respond to different environmental stimuli. MCs originate from bone marrow (BM) progenitors that enter the circulation and mature in peripheral organs under the influence of microenvironment factors, thus differentiating into heterogeneous tissue-specific subsets. Even though MC activation has been traditionally linked to IgE-mediated allergic reactions, a role for these cells in other pathological conditions including tumor progression has recently emerged. However, several aspects of MC biology remain to be clarified. The advent of single-cell RNA sequencing platforms has provided the opportunity to understand MCs' origin and differentiation as well as their phenotype and functions within different tissues, including the gut. This review recapitulates how single-cell transcriptomic studies provided insight into MC development as well as into the functional role of intestinal MC subsets in health and disease. [ABSTRACT FROM AUTHOR]

Context.--In 2018 the College of American Pathologists Diagnostic Immunology and Flow Cytometry Committee designed and implemented a new plasma cell neoplasia flow cytometry proficiency testing program--PCNEO--to allow clinical flow cytometry laboratories to monitor and assess their performance compared with a peer group. Objective.--To report the results from the first 4 years of the PCNEO program. Design.--Program participants were sent 2 sets of challenges per year, each including 1 wet challenge and 2 dry challenges, with associated clinical and laboratory findings. The wet challenges were composed of myeloma cell line specimens (with or without dilution in preserved whole blood) for flow cytometric analysis. The dry (paper) challenges were composed of clinical case summaries and images of flow cytometric test results from various flow cytometry laboratories of committee members. Results.--A total of 116 to 145 laboratories from 17 countries enrolled in the proficiency testing program. For the wet challenges, almost all participants (97%--100%; cumulative, 98.2%) correctly identified the presence of neoplastic plasma cell populations based on flow cytometric analysis of undiluted myeloma cell lines. Slightly fewer participants (89.0%--97.4%; cumulative, 95.2%) correctly identified the presence of neoplastic plasma cell populations based on flow cytometric analysis of diluted myeloma cell lines (10% or 50% dilutions into peripheral blood) intended to better represent a typical clinical sample. There was generally agreement among 80% or more of participants for positive or negative staining for CD38, CD138, CD19, CD20, and surface and cytoplasmic K and λ light chains. Similarly, 84% to 100% of participants were able to correctly identify the presence of neoplastic plasma cell populations in paper challenges, including the presence of small, neoplastic plasma cell populations (0.01%--5.0% clonal plasma cells) and the presence of nonneoplastic plasma cell populations (correctly identified by 91%--96% of participants). Conclusions.--Participant performance in the new proficiency testing program was excellent overall, with the vast majority of participants able to perform flow cytometric analysis and identify neoplastic plasma cell populations and to identify small plasma cell clones or expanded populations of reactive plasma cells in dry challenge flow cytometry results. This program will allow laboratories to verify the accuracy of their testing program and test interpretations for the assessment of patients suspected of having a plasma cell neoplasm. [ABSTRACT FROM AUTHOR]

Introduction: Nowadays, some aspects of neuroendocrine and immune systems intercalation are already known. Accordingly, it has been shown that certain immune cells, such as monocytes, can produce and store dopamine in their secretory vesicles. This study was conducted to investigate the effects of dopamine on some immunological functions of the rat peripheral blood monocytes. Material & Methods: In this experimental study, peripheral blood mononuclear cells of rats were isolated by a ficoll-hypaque gradient. Afterward, the plastic adherent fractions were used as monocytes. Monocytes in the treatment group cocultured for 24 h with 5×10-7 M dopamine, and then their phagocytosis performance, respiratory burst, killing ability, nitric oxide production, neutral red harvest, vital ability, and NFκB gene expression were investigated. Results: The results of this study showed that both control or treatment monocytes showed no significant difference in phagocytosis after the challenge with opsonized yeast. Nevertheless, the neutral red uptake, respiratory burst, and nitric oxide production after the challenge with opsonized yeast, and also the expression of NFκB, were decreased in dopamine-treated monocytes compared to monocytes in the control group (P<0.05). The monocyte vitality of the treatment group did not show any significant effects compared to the monocytes of the control group. Discussion & Conclusion: It seems that dopamine dynamically creates an antiinflammatory phenotype in the monocyte. Therefore, alongside a decrease in the lysosomal compartment activity, the monocytes produce lower levels of free oxygen and nitrogen radicals. [ABSTRACT FROM AUTHOR]

Aging population has led to an increased prevalence of chronic and degenerative pathologies. A manifestation of unhealthy aging is frailty, a geriatric syndrome that implies a non-specific state of greater vulnerability. Currently, methods for frailty diagnosis are based exclusively on clinical observation. The aim of this study is to determine whether the bioenergetic capacity defined as mitochondrial oxygen consumption rate (OCR) of peripheral circulation mononuclear cells (PBMC) associates with the frailty phenotype in older adults and with their nutritional status. This is a cross-sectional analytic study of 58 participants 70 years and older, 18 frail and 40 non-frail adults, from the ALEXANDROS cohort study, previously described. Participants were characterized through sociodemographic and anthropometric assessments. Frail individuals displayed a higher frequency of osteoporosis and depression. Themean age of the participants was 80.2 ± 5.2 years, similar in both groups of men andwomen. Regarding the nutritional status defined as the bodymass index, most non-frail individuals were normal or overweight,while frail participants were mostly overweight or obese. We observed that OCR was significantly decreased in frail men (p < 0.01). Age was also associated with significant differences in oxygen consumption in frail patients, with lower oxygen consumption being observed in those over 80 years of age. Therefore, the use of PBMC can result in an accessible fingerprint thatmay identify initial stages of frailty in a minimally invasive way. [ABSTRACT FROM AUTHOR]

Passive whole‐body hyperthermia increases limb blood flow and cardiac output (Q̇$\dot Q$), but the interplay between peripheral and central thermo‐haemodynamic mechanisms remains unclear. Here we tested the hypothesis that local hyperthermia‐induced alterations in peripheral blood flow and blood kinetic energy modulate flow to the heart and Q̇$\dot Q$. Body temperatures, regional (leg, arm, head) and systemic haemodynamics, and left ventricular (LV) volumes and functions were assessed in eight healthy males during: (1) 3 h control (normothermic condition); (2) 3 h of single‐leg heating; (3) 3 h of two‐leg heating; and (4) 2.5 h of whole‐body heating. Leg, forearm, and extracranial blood flow increased in close association with local rises in temperature while brain perfusion remained unchanged. Increases in blood velocity with small to no changes in the conduit artery diameter underpinned the augmented limb and extracranial perfusion. In all heating conditions, Q̇$\dot Q$ increased in association with proportional elevations in systemic vascular conductance, related to enhanced blood flow, blood velocity, vascular conductance and kinetic energy in the limbs and head (all R2 ≥ 0.803; P < 0.001), but not in the brain. LV systolic (end‐systolic elastance and twist) and diastolic functional profiles (untwisting rate), pulmonary ventilation and systemic aerobic metabolism were only altered in whole‐body heating. These findings substantiate the idea that local hyperthermia‐induced selective alterations in peripheral blood flow modulate the magnitude of flow to the heart and Q̇$\dot Q$ through changes in blood velocity and kinetic energy. Localised heat‐activated events in the peripheral circulation therefore affect the human heart's output. Key points: Local and whole‐body hyperthermia increases limb and systemic perfusion, but the underlying peripheral and central heat‐sensitive mechanisms are not fully established.Here we investigated the regional (leg, arm and head) and systemic haemodynamics (cardiac output: Q̇$\dot Q$) during passive single‐leg, two‐leg and whole‐body hyperthermia to determine the contribution of peripheral and central thermosensitive factors in the control of human circulation.Single‐leg, two‐leg, and whole‐body hyperthermia induced graded increases in leg blood flow and Q̇$\dot Q$. Brain blood flow, however, remained unchanged in all conditions. Ventilation, extracranial blood flow and cardiac systolic and diastolic functions only increased during whole‐body hyperthermia.The augmented Q̇$\dot Q$ with hyperthermia was tightly related to increased limb and head blood velocity, flow and kinetic energy.The findings indicate that local thermosensitive mechanisms modulate regional blood velocity, flow and kinetic energy, thereby controlling the magnitude of flow to the heart and thus the coupling of peripheral and central circulation during hyperthermia. [ABSTRACT FROM AUTHOR]

Introduction. Cardiovascular disease (CVD) is highly prevalent in patients with type 1 diabetes (T1DM) and is responsible for a significant reduction in life expectancy. Objective. To compare the arterial stiffness indices, arterial compliance and vascular resistance assessed centrally and peripherally between healthy adolescents and young adults (CTRL group) and those with T1DM. Methods. This is an observational cross-sectional study involving 90 adolescents and young adults, with half of them being considered healthy (n = 45) and the other half with T1DM (n = 45), matched by age and sex. Cardiovascular parameters were evaluated using the oscillometric method of brachial artery pressure assessment for a noninvasive estimation of central arterial pressures. Results. Weight and body mass index were significantly higher in the T1DM group. AIx@75 was significantly higher in the T1DM group (24.96% ± 8.88%) compared to the CTRL (20.16% ± 9.95%). Peripheral and central arterial compliance were significantly lower in the T1DM group (0.79 ± 0.21; 1.16 ± 0.27 ml/m2/mmHg) compared to the CTRL (0.98 ± 0.32; 1.47 ± 0.61 ml/m2/mmHg). Peripheral and central vascular resistance were significantly higher in the T1DM group (1.32 ± 0.32; 0.91 ± 0.21 mmHg/ml/m2) compared to the CTRL (1.11 ± 0.30; 0.75 ± 0.22 mmHg/ml/m2). Conclusion. Our data confirm premature aging of the vascular system in adolescents and young adults with T1DM and extend our knowledge by showing important changes in central and peripheral hemodynamics indices. [ABSTRACT FROM AUTHOR]

Background: Certain demyelinating disorders, such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) exhibit serum autoantibodies against aquaporin-4 (αAQP4) and myelin oligodendrocyte glycoprotein (αMOG). The variability of the autoantibody presentation warrants further research into subtyping each case. Methods: To elucidate the relationship between astroglial and neuronal protein concentrations in the peripheral circulation with occurrence of these autoantibodies, 86 serum samples were analyzed using immunoassays. The protein concentration of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL) and tau protein was measured in 3 groups of subcategories of suspected NMOSD: αAQP4 positive (n = 20), αMOG positive (n = 32) and αMOG/αAQP4 seronegative (n = 34). Kruskal-Wallis analysis, univariate predictor analysis, and multivariate logistic regression with ROC curves were performed. Results: GFAP and NFL concentrations were significantly elevated in the αAQP4 positive group (p = 0.003; p = 0.042, respectively), and tau was elevated in the αMOG/αAQP4 seronegative group (p < 0.001). A logistic regression model to classify serostatus was able to separate αAQP4 seropositivity using GFAP + tau, and αMOG seropositivity using tau. The areas under the ROC curves (AUCs) were 0.77 and 0.72, respectively. Finally, a combined seropositivity versus negative status logistic regression model was generated, with AUC = 0.80. Conclusion: The 3 markers can univariately and multivariately classify with moderate accuracy the samples with seropositivity and seronegativity for αAQP4 and αMOG. [ABSTRACT FROM AUTHOR]

Background: Molecular-based approaches to understanding concussion pathophysiology provide complex biological information that can advance concussion research and identify potential diagnostic and/or prognostic biomarkers of injury. Objective: The aim of this study was to identify gene expression changes in peripheral blood that are initiated following concussion and are relevant to concussion response and recovery. Methods: We analyzed whole blood transcriptomes in a large cohort of concussed and control collegiate athletes who were participating in the multicenter prospective cohort Concussion Assessment, Research, and Education (CARE) Consortium study. Blood samples were collected from collegiate athletes at preseason (baseline), within 6 h of concussion injury, and at four additional prescribed time points spanning 24 h to 6 months post-injury. RNA sequencing was performed on samples from 230 concussed, 130 contact control, and 102 non-contact control athletes. Differential gene expression and deconvolution analysis were performed at each time point relative to baseline. Results: Cytokine and immune response signaling pathways were activated immediately after concussion, but at later time points these pathways appeared to be suppressed relative to the contact control group. We also found that the proportion of neutrophils increased and natural killer cells decreased in the blood following concussion. Conclusions: Transcriptome signatures in the blood reflect the known pathophysiology of concussion and may be useful for defining the immediate biological response and the time course for recovery. In addition, the identified immune response pathways and changes in immune cell type proportions following a concussion may inform future treatment strategies. [ABSTRACT FROM AUTHOR]

In this study, the multi-year data of meteorology and O3 from remote sensing and ground observations are applied to characterize the 3-D changes of O3 in the troposphere over central and eastern China (CEC) induced by the tropical cyclones (TCs) in the tropical and subtropical ocean regions over Northwest Pacific. The CEC-regional average of near-surface O3 levels is significantly elevated with 6.0 ppb in the large coverage by the TCs in the subtropical ocean, while the TCs in the tropical ocean alter near-surface O3 weakly, indicating the latitudinal-located TCs in the subtropical offshore ocean could largely influence the O3 variations over CEC. The sub-seasonal change with the positive and negative anomalies of near-surface O3 is induced by the tropical TCs from June to July and from August to October. The peripheral circulation of TCs in the subtropical offshore ocean persistently enhances the O3 concentrations over CEC during the season of East Asian summer monsoons. The positive O3 anomalies maintain from the entire troposphere to the lower stratosphere over CEC in the peripheries of subtropical TCs, while the tropical TCs cause the positive O3 anomalies merely in the lower troposphere. The O3 transport and accumulation, photochemical production and stratospheric intrusion are climatologically confirmed as the major meteorological mechanisms of TCs affecting the O3 variations. This study reveals that the downward transport of stratospheric O3 of TCs in the subtropical ocean exerts a large impact on the atmospheric environment over CEC, while the regional O3 transport and photochemical productions dominate the lower troposphere over CEC with less impact of stratospheric intrusion from the TCs in the tropical ocean region. These results present the climatology of tropospheric O3 anomalies in China induced by the TCs over the Northwest Pacific with enhancing our comprehension of the meteorological impact on O3 variations over the East Asian monsoon region. [ABSTRACT FROM AUTHOR]

Introduction: Chronic Myelomonocytic Leukemia (CMML) and Myelodysplastic Syndromes (MDS) are increasingly represented in the general population. We propose a screening strategy based on algorithms calculated from quantitative and analytical data from the XN analyser. Materials and Methods: We tested the performance of previously published MDS and CMML scores on an evaluation cohort of 749 individual eligible patients over 50 years of age. These patients were classified into 3 groups as follows: 713 patients without MDS or CMML, 18 patients with MDS, and finally 18 patients with CMML. In a second step, a routine cohort of 37 828 samples was studied to evaluate the impact of this approach. Results: The concordance rate between cytology and the two scores is 92.1%. The sensitivity and specificity of the CMML score are 100% and 96.2%, respectively. For the MDS score, they are 83.3% and 89.6% respectively. The ratio of platelets measured by fluorescence on board (PLT‐F) as reflex tests generated is 1.5% after 6 months. The additional smear ratio for suspected MDS is calculated at 0.6%. Conclusion: We propose a flowchart using embedded artificial intelligence to help the cytologist in an optimized smear review and thus improve guidance to the clinician and the patients in the diagnosis process. This strategy permits a more comprehensive approach to MDS and CMML detection fitting with the new definition of CMML according to the recommendations of the World Health Organization (WHO) published in 2022. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is the most common cancer in men. The pursuit of novel biomarkers for early detection of prostate cancer poses a contemporary challenge given the age-associated escalation in prostate cancer risk and severity. Our focus was directed towards evaluating leukocyte telomere length (LTL) and myeloid-derived suppressor cells (MDSC) in prostate cancer patients, considering their potential as adjunctive diagnostic markers. In a study of 102 patients who underwent prostate biopsy, those diagnosed with prostate cancer demonstrated significantly shorter LTL and an increased proportion of M-MDSC prior to diagnosis, along with elevated PSA levels and age, in comparison to controls. Furthermore, a significant negative correlation was observed between LTL and MDSC levels. This initial report of those findings could potentially contribute to a deeper understanding of the molecular, biological, and immunological factors involved in cancer development. Background: Leukocyte telomere length (LTL) and myeloid-derived suppressor cells (MDSC) are associated with aging and the development and progression of cancer. However, the exact nature of this relationship remains unclear. Our study aimed to investigate the potential of LTL and MDSC as diagnostic biomarkers for prostate cancer while also seeking to deepen our understanding of the relationship of these potential biomarkers to each other. Methods: Our study involved patients undergoing a prostate biopsy. We analyzed the relative LTL in genomic DNA obtained from peripheral blood leukocytes as well as the percentage of MDSC and their subtypes in peripheral blood mononuclear cells (PBMC). Our evaluation focused on examining the relationship between LTL and MDSC and pathological diagnoses as well as investigating the correlation between LTL and MDSC levels. Results: In our study of 102 participants, 56 were pathologically diagnosed with localized prostate cancer (cancer group), while 46 tested negative (control group). The cancer group exhibited significantly shorter LTL in comparison to the control group (p = 0.024). Additionally, the cancer group showed a tendency towards a higher percentage of monocytic MDSC (M-MDSC), although this difference did not reach statistical significance (p = 0.056). Our multivariate logistic regression analysis revealed that patients with shorter LTL and higher percentages of M-MDSC had a 2.98-fold (95% CI = 1.001–8.869, p = 0.049) and 3.03-fold (95% CI = 1.152–7.977, p = 0.025) increased risk of prostate cancer diagnosis, respectively. There was also a significant negative correlation between LTL and M-MDSC. (r = −0.347, p < 0.001). Conclusions: Our research has established a correlation between LTL and MDSC in patients undergoing biopsy for prostate cancer. Notably, we observed that individuals with localized prostate cancer tend to have shorter LTL and a higher percentage of M-MDSC prior to their diagnosis. These findings suggest that LTL and M-MDSC could potentially serve as adjunctive biomarkers for the early diagnosis of prostate cancer. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) accounts for over 50% of all heart failure cases nationwide and continues to rise in its prevalence. The complex, multi‐organ involvement of the HFpEF clinical syndrome requires clinicians and investigators to adopt an integrative approach that considers the contribution of both cardiac and non‐cardiac function to HFpEF pathophysiology. Thus, this symposium review outlines the key points from presentations covering the contributions of disease‐related changes in cardiac function, arterial stiffness, peripheral vascular function, and oxygen delivery and utilization to exercise tolerance in patients with HFpEF. While many aspects of HFpEF pathophysiology remain poorly understood, there is accumulating evidence for a decline in vascular health in this patient group that may be remediable through pharmacological and lifestyle interventions and could improve outcomes and clinical status in this ever‐growing patient population. What is the topic of this review?This symposium review provides an integrative view of how disease‐related changes in cardiac, vascular and skeletal muscle function contribute to exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF).What advances does it highlight?Emerging evidence continues to highlight the importance of considering both cardiac and non‐cardiac abnormalities in patients with HFpEF, with accumulating evidence for 'plasticity' in vascular function that emphasizes the need for a greater focus on strategies targeting the peripheral circulation as a means to improve exercise intolerance. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to examine the proportion of CD161 on CD56+ natural killer (NK) cells in peripheral blood of primary Sjögren's syndrome (pSS) and investigate its clinical relevance of pSS. Methods: The proportion of CD56+ NK cells and CD161 on CD56+ NK cells was detected by flow cytometry in 31 pSS patients and 29 healthy controls (HCs). The correlations between the proportion of CD161+CD56+ NK cells and clinical features and disease activity of pSS were further analyzed. Meanwhile, we drew the receiver operating characteristic curve to evaluate the diagnostic value of CD161+CD56+ NK cells in pSS. In addition, we evaluated the differences in the effects of CD161+ cells and CD161− cells in peripheral blood on the function of CD56+ NK cells in 5 pSS patients. Results: The proportion of CD56+ NK cells and CD161+CD56+ NK cells decreased markedly in pSS patients compared to HCs. The correlation analysis showed that the proportion of CD161+CD56+ NK cells negatively correlated with white blood cells, Immunoglobulin A (IgA), IgM, IgG, European League Against Rheumatism Sjogren's Syndrome Patient Reported Index and European League Against Rheumatism Sjogren's Syndrome Disease Activity Index, and positively correlated with complement C4. The proportion of CD161+CD56+ NK cells in pSS patients with decayed tooth, fatigue, arthralgia, skin involvement, primary biliary cirrhosis, interstitial lung disease, anti‐SSA/Ro60 positive, anti‐SSB positive and high IgG was lower than that in negative patients. Furthermore, compared with inactive patients, the proportion of CD161+CD56+ NK cells decreased obviously in active patients. The area under the curve was 0.7375 (p =.0016), the results indicated that CD161+CD56+ NK cells had certain diagnostic values for pSS. In addition, the proportion of CD86, HLA‐DR, Ki67, FasL, TNF‐α, and IFN‐γ on CD161+CD56+ NK cells was lower than that on CD161−CD56+ NK cells in the peripheral blood of pSS patients. Conclusion: This study suggested that the proportion of CD56+ NK cells and CD161+CD56+ NK cells decreased significantly in pSS patients, and the proportion of CD161+CD56+ NK cells negatively associated with the clinical features and disease activity of pSS patients. CD161 expression inhibited the function of CD56+ NK cells in peripheral blood of pSS patients. The CD161+CD56+ NK cells may present as a potential target for therapy and a biomarker of disease activity in pSS. [ABSTRACT FROM AUTHOR]

The blood-brain barrier (BBB) is located at the interface between the vascular system and the brain parenchyma, and is responsible for communication with systemic circulation and peripheral tissues. During life, the BBB can be subjected to a wide range of perturbations or stresses that may be endogenous or exogenous, pathological or therapeutic, or intended or unintended. The risk factors for many diseases of the brain are multifactorial and involve perturbations that may occur simultaneously (e.g., two-hit model for Alzheimer's disease) and result in different outcomes. Therefore, it is important to understand the influence of individual perturbations on BBB function in isolation. Here we review the effects of eight perturbations: mechanical forces, temperature, electromagnetic radiation, hypoxia, endogenous factors, exogenous factors, chemical factors, and pathogens. While some perturbations may result in acute or chronic BBB disruption, many are also exploited for diagnostic or therapeutic purposes. The resultant outcome on BBB function depends on the dose (or magnitude) and duration of the perturbation. Homeostasis may be restored by self-repair, for example, via processes such as proliferation of affected cells or angiogenesis to create new vasculature. Transient or sustained BBB dysfunction may result in acute or pathological symptoms, for example, microhemorrhages or hypoperfusion. In more extreme cases, perturbations may lead to cytotoxicity and cell death, for example, through exposure to cytotoxic plaques. [ABSTRACT FROM AUTHOR]

Background: Diabetes Mellitus (DM) poses significant challenges, including peripheral neuropathy and impaired muscle function. Neuromuscular taping has emerged as a noninvasive therapeutic approach, potentially offering benefits in managing DM-related complications. Materials and Methods: A comprehensive literature search was conducted to identify relevant studies investigating the use of neuromuscular taping in individuals with DM. Key databases were explored using Boolean operators (AND, OR, etc.), and articles were selected based on predefined inclusion criteria. Results: The review identifies 22 relevant articles, with 8 specifically addressing NMT in DM. Out of these, 5 were randomized controlled trials, highlighting the research interest in assessing the effectiveness of NMT. The findings suggest that NMT may positively impact the Ankle Brachial Index, indicative of improved peripheral blood circulation and many other health-related parameters. Neuromuscular taping principles and application methods are outlined, providing a foundation for understanding its potential therapeutic effects. Discussion: The potential therapeutic mechanisms of neuromuscular taping are explored, emphasizing its influence on sensory feedback, muscle activation, and circulation. Safety considerations and the feasibility of integrating neuromuscular taping into comprehensive DM management are discussed. Conclusion: Neuromuscular taping holds promise as an adjunctive therapy for managing DM-related complications. This structured narrative review provides a comprehensive overview for health care limitations such as a lack of standardized protocols and heterogeneity in study designs are noted. [ABSTRACT FROM AUTHOR]

This document is a letter published in the journal Clinical Chemistry & Laboratory Medicine. It discusses the topic of pseudoeosinophilia, which is a condition where eosinophil levels appear elevated but are actually due to other factors. The letter presents two case studies and analyzes the causes of pseudoeosinophilia. It discusses the use of automated haematology analyzers and manual microscopic examinations to confirm the results. The letter also explores various factors that can lead to false elevations or reductions in eosinophil counts. [Extracted from the article]

The chronic inflammatory component of asthma is propagated by granulocytes, including neutrophils and eosinophils, in the peripheral circulation and airway. Previous studies have suggested that these cells have an altered expression of adhesion-related molecules and a propensity for the release of granule contents that may contribute to tissue damage and enhance inflammatory complications in patients with status asthmaticus. The goal of this prospective cohort study at a tertiary care pediatric hospital with a large population of asthma patients was to assess the role of granulocyte-based inflammation in the development of asthma exacerbation. Subjects were enrolled from two patient populations: those with mild-to-moderate asthma exacerbations seen in the emergency department and those with severe asthma admitted to the intensive care unit (PICU). Clinical data were collected, and blood was drawn. Granulocytes were immediately purified, and the phenotype was assessed, including the expression of cell surface markers, elastase release, and cytokine production. Severe asthmatics admitted to the PICU displayed a significantly higher total neutrophil count when compared with healthy donors. Moreover, little to no eosinophils were found in granulocyte preparations from severe asthmatics. Circulating neutrophils from severe asthmatics admitted to the PICU displayed significantly increased elastase release ex vivo when compared with the PMN from healthy donors. These data suggest that the neutrophil-based activation and release of inflammatory products displayed by severe asthmatics may contribute to the propagation of asthma exacerbations. [ABSTRACT FROM AUTHOR]

Background: Tracking preload dependency non-invasively to maintain adequate tissue perfusion in the perioperative period can be challenging.The effect of phenylephrine on stroke volume is dependent upon preload. Changes in stroke volume induced by phenylephrine administration can be used to predict preload dependency. The change in the peripheral perfusion index derived from photoplethysmography signals reportedly corresponds with changes in stroke volume in situations such as body position changes in the operating room. Thus, the peripheral perfusion index can be used as a non-invasive potential alternative to stroke volume to predict preload dependency. Herein, we aimed to determine whether changes in perfusion index induced by the administration of phenylephrine could be used to predict preload dependency. Methods: We conducted a prospective single-centre observational study. The haemodynamic parameters and perfusion index were recorded before and 1 and 2 min after administering 0.1 mg of phenylephrine during post-induction hypotension in patients scheduled to undergo surgery. Preload dependency was defined as a stroke volume variation of ≥ 12% before phenylephrine administration at a mean arterial pressure of < 65 mmHg. Patients were divided into four groups according to total peripheral resistance and preload dependency. Results: Forty-two patients were included in this study. The stroke volume in patients with preload dependency (n = 23) increased after phenylephrine administration. However, phenylephrine administration did not impact the stroke volume in patients without preload dependency (n = 19). The perfusion index decreased regardless of preload dependency. The changes in the perfusion index after phenylephrine administration exhibited low accuracy for predicting preload dependency. Based on subgroup analysis, patients with high total peripheral resistance tended to exhibit increased stroke volume following phenylephrine administration, which was particularly prominent in patients with high total peripheral resistance and preload dependency. Conclusion: The findings of the current study revealed that changes in the perfusion index induced by administering 0.1 mg of phenylephrine could not predict preload dependency. This may be attributed to the different phenylephrine-induced stroke volume patterns observed in patients according to the degree of total peripheral resistance and preload dependency. Trial registration: University Hospital Medical Information Network (UMIN000049994 on 9/01/2023). [ABSTRACT FROM AUTHOR]

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Thiacloprid is an insecticide of the neonicotinoid family that acts on the insect's nAChR receptor and causes its paralysis and subsequent death. The genotoxicity of the insecticide Calypso® 480 SC (with the active substance thiacloprid) to human peripheral lymphocytes was examined in vitro by comet analysis and phosphorylated H2AX, where we detected DNA breaks. To detect DNA damage in comet analysis, we used thiacloprid-based insecticide in three different concentrations (60, 240, and 480 μg.ml−1) during 2 h of exposure. We recorded a statistically significant percentage of damage at a concentration of 240 and 480 μg.ml−1. We monitored the toxicity of thiacloprid using yH2AX foci, and we did not observe a statistically significant number of foci compared to the negative control. [ABSTRACT FROM AUTHOR]

Backgroud: The tumor immune microenvironment influences the efficiency of concurrent chemoradiotherapy (CCRT) in high-grade glioma (HGG). This study investigated peripheral blood T lymphocyte subsets as clinical indicators of therapeutic response and prognosis in pediatric high-grade glioma (pHGG). Methods: This retrospective study included 77 patients with postoperative pHGG who were treated concurrently with temozolomide and external beam radiotherapy between January 1, 2012, and December 31, 2018. The median follow-up was 26 (range: 5-106) months. Peripheral venous blood samples were collected before and after CCRT. The proportions of peripheral blood T lymphocytes and their association with treatment outcome and survival were determined. Results: Sixty-four (83.1%) patients achieved complete remission, partial remission, and stable disease, and 13 (16.9%) patients had progressive disease. Higher CD3+ T cell, CD4+ T cell, and CD8+ CD28+ T cell ratios were predictive of better response, while a higher CD8+ CD28− T cell ratio was predictive of poorer response. Binary logistic regression analysis showed that the CD8+ CD28+ T cell ratio was a significant independent predictor of CCRT response (odds ratio [OR] = 53.521, 95% confidence interval [CI] = 4.294-667.119, P =.002). Univariate and multivariate analysis of prognostic factors associated with survival showed that the CD8+ CD28+ T lymphocyte ratio was a significant independent predictor of progression-free survival (hazard ratio [HR] = 1.80, 95% CI = 1.06-3.08, P =.03), but none of the subsets were significantly associated with overall survival. Conclusion: Peripheral blood T lymphocytes have potential as predictors of CCRT response and prognosis in pHGG. [ABSTRACT FROM AUTHOR]

Under pathological conditions, the immune-specialized brain microenvironment contains both resident microglia and bone marrow-derived myeloid cells recruited from peripheral circulation. Due to largely overlapping phenotypic similarities between these ontogenically distinct myeloid populations, studying their individual functions in central nervous system diseases has been challenging. Recently, transmembrane protein 119 (Tmem119) has been reported as a marker for resident microglia which is not expressed by bone marrow-derived myeloid cells. However, several studies have reported the loss or reduction of Tmem119 expression in pathologically activated microglia. Here, we examined whether Tmem119 could be used as a robust marker to identify brain metastasis-associated microglia. In addition, we also compared Tmem119 expression of primary microglia to the immortalized microglia-like BV2 cell line and characterized expression changes after LPS treatment. Lastly, we used a commercially available transgenic mouse line (Tmem119-eGFP) to compare Tmem119 expression patterns to the traditional antibody-based detection methods. Our results indicate that brain metastasis-associated microglia have reduced Tmem119 gene and protein expression. [ABSTRACT FROM AUTHOR]

Southern elephant seals (SES) experience a 'catastrophic molt', a costly event characterized by the renewal of both hair and epidermis that requires high peripheral vascular circulation. Molting animals are therefore constrained by high metabolic heat loss and are thought to fast and remain on land. To examine the ability of individuals to balance the energetic constraints of molting on land we investigate the stomach temperature and movement patterns of molting female SES. We find that 79% of females swam and 61% ingested water or prey items, despite the cost of cold-water exposure while molting. This behavior was related to periods of warm and low wind conditions, and females that dived and ingested more often, lost less body mass. We conclude that the paradigm of fasting during the molt in this species, and the fitness consequences of this behavior should be reconsidered, especially in the context of a changing climate. This study investigates the ability to balance the energetic constraints of molting on land in a diving mammal, the southern elephant seal, the only phocid to experiment a catastrophic molt in a cold and windy environment. [ABSTRACT FROM AUTHOR]

Background: Lateral ventricular volume (LVV) enlargement has been repeatedly linked to schizophrenia; yet, what biological factors shape LVV during early development remain unclear. DNA methylation (DNAm), an essential process for neurodevelopment that is altered in schizophrenia, is a key molecular system of interest. Methods: In this study, we conducted the first epigenome‐wide association study of neonatal DNAm in cord blood with LVV in childhood (measured using T1‐weighted brain scans at 10 years), based on data from a large population‐based birth cohort, the Generation R Study (N = 840). Employing both probe‐level and methylation profile score (MPS) approaches, we further examined whether epigenetic modifications identified at birth in cord blood are: (a) also observed cross‐sectionally in childhood using peripheral blood DNAm at age of 10 years (Generation R, N = 370) and (b) prospectively associated with LVV measured in young adulthood in an all‐male sample from the Avon Longitudinal Study of Parents and Children (ALSPAC, N = 114). Results: At birth, DNAm levels at four CpGs (annotated to potassium channel tetramerization domain containing 3, KCTD3; SHH signaling and ciliogenesis regulator, SDCCAG8; glutaredoxin, GLRX) prospectively associated with childhood LVV after genome‐wide correction; these genes have been implicated in brain development and psychiatric traits including schizophrenia. An MPS capturing a broader epigenetic profile of LVV – but not individual top hits – showed significant cross‐sectional associations with LVV in childhood in Generation R and prospectively associated with LVV in early adulthood within ALSPAC. Conclusions: This study finds suggestive evidence that DNAm at birth prospectively associates with LVV at different life stages, albeit with small effect sizes. The prediction of MPS on LVV in a childhood sample and an independent male adult sample further underscores the stability and reproducibility of DNAm as a potential marker for LVV. Future studies with larger samples and comparable time points across development are needed to further elucidate how DNAm associates with this clinically relevant brain structure and risk for neuropsychiatric disorders, and what factors explain the identified DNAm profile of LVV at birth. [ABSTRACT FROM AUTHOR]

Background: A previous meta-analysis reported that: (i) an acute bout of prolonged uninterrupted sitting induces a significant increase in peripheral blood pressure (BP) and (ii) the increase in BP can be offset by interrupting the sitting bout with light aerobic activities such as walking. However, the temporal association between prolonged uninterrupted sitting and BP was not determined. A better understanding of temporality, for example, how long it takes BP to increase, will assist in prescribing sitting interruption strategies. Objectives: We aimed to determine: (1) the temporal association between the duration of uninterrupted sitting and BP and (2) whether regular sitting interruptions moderate the association between uninterrupted sitting and BP. Data Sources: Electronic databases (PubMed, Web of Science, SPORTDiscus) were searched from inception to July 2022. Reference lists of eligible studies and relevant reviews were also screened. Study Selection: Inclusion criteria for objective (1) were: (i) participants aged ≥ 18 years; (ii) a prolonged sitting bout ≥ 1 h; and (iii) peripheral BP measurements (systolic BP, diastolic BP, and/or mean arterial pressure) at more than two timepoints during the sitting bout. Additional criteria for objective (2) were: (i) the sitting interruption strategy was implemented during the sitting bout (i.e., not prior to engaging in sitting) and (ii) the study included a control (uninterrupted sitting) condition or group. Appraisal and Synthesis Methods: There were 1555 articles identified, of which 33 met inclusion criteria for objective (1). Of those articles, 20 met inclusion criteria for objective (2). To investigate the effect of sitting duration on the BP response, unstandardized b coefficients (mmHg/h) and 95% confidence intervals (CIs) were calculated using a three-level mixed-effect meta-regression. Results: Increased sitting duration was positively associated with systolic BP (b = 0.42 mmHg/h, 95% CI 0.18–0.60), diastolic BP (b = 0.24 mmHg/h, 95% CI 0.06–0.42), and mean arterial pressure (b = 0.66 mmHg/h, 95% CI 0.36–0.90). In trials where sitting was interrupted, there was a significant decrease in systolic BP (b = − 0.24 mmHg/h, 95% CI − 0.42 to − 0.06) and diastolic BP (b = − 0.24 mmHg/h, 95% CI − 0.42 to − 0.12), and a non-significant change in mean arterial pressure (p = 0.69). Conclusions: Increased uninterrupted sitting duration results in greater increases in BP; however, regularly interrupting sitting may offset negative effects. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to investigate the expression of T-cell immunoglobulin and ITIM domain (TIGIT) in peripheral circulation of primary Sjögren's syndrome (pSS) and its role in the development of pSS. Methods: The expression of TIGIT on T cells, B cells, natural killer (NK) cells, and CD14 + monocytes was detected by flow cytometry in pSS and healthy control (HC). The correlations between expression of TIGIT and clinical features and laboratory parameters of pSS were analyzed. Meanwhile, we analyzed the change in expression of TIGIT before and after treatment, and its role in the prognosis of pSS treatment was evaluated. Results: The expression of TIGIT on CD3 + , CD4 + , and CD8 + T cells increased and decreased on CD14 + monocytes in pSS compared to HC; however, there was no significance of B lymphocytes and NK cells. The correlation analysis between the expression of TIGIT on T lymphocytes and CD14 + monocytes and clinical features of pSS showed that the decrease in TIGIT expression on CD14 + monocytes was more closely related to pSS. The expression of TIGIT + CD14 + monocytes negatively correlated with the disease activity of pSS. The expression of TIGIT + CD14 + monocytes of pSS with arthralgia, fatigue, decayed tooth, xerostomia, interstitial lung disease, anti-Ro52 positive, and high IgG decreased compared to that in negative patients. Furthermore, it was significantly lower in active patients than in nonactive patients. After treatment, the expression of TIGIT + CD14 + monocytes tended to increase. Conclusion: Our study suggested that decreased TIGIT expression on CD14 + monocytes was associated with the clinical manifestations, disease activity, and prognosis of pSS patients. TIGIT + CD14 + monocytes may present as a potential target and a biomarker of the prognosis for immunomodulatory therapy in pSS. Key Points • The expression of TIGIT+CD14+ monocytes significantly decreased in pSS patients compared to HC. • There was a negative correlation between TIGIT+CD14+ monocytes and the disease activity of pSS. • TIGIT+CD14+ monocyte expression was associated with the clinical manifestations, autoantibodies, IgG, and prognosis of pSS patients. [ABSTRACT FROM AUTHOR]

A technique called arch-clamping was used at our institute to ensure perfusion of the lower body and brain during total arch replacement with frozen elephant trunk (TAR and FET). The aortic arch clamp is inserted between the left common carotid artery and the left subclavian artery after inserting the stented elephant trunk into the true lumen of the descending aorta during the procedure, and then clamps the aorta and graft together as the distal anastomotic edge of the aorta. After the arch clamp was in place, lower body perfusion was resumed through the femoral artery was resumed and time to circulatory arrest was reduced to approximately 4 min. Cardiopulmonary bypass (CPB) flow was gradually restored to full rate. Thereafter, the left carotid artery anastomosis was completed and rewarming began. Finally, during the rewarming period, other branches of the aortic arch and ascending aorta were reconstructed. In this paper, we describe the perfusion management strategy, discuss intraoperative monitoring parameters, and examine the feasibility of the technique from a perfusion perspective. [ABSTRACT FROM AUTHOR]

Simple Summary: Infrared thermography can indirectly assess peripheral vascular diseases because skin surface temperature depends on blood flow and heat dissipation through skin microvasculature. The present review aims to summarize and analyze the application of infrared thermography in veterinary medicine as a method to indirectly assess peripheral vascular integrity and its relation to the amount of radiated heat and as a diagnostic technique for tissue viability, degree of damage, and wound care. Although additional research is needed to establish the utility of thermal imaging to monitor vascular integrity in veterinary medicine, studies performed in animals diagnosed with thromboembolisms or thermal impairment due to neuropathies or are in need of burn wound management suggest a promising application of infrared thermography to evaluate peripheral vascular alterations and tissue viability. Infrared thermography (IRT) is a technique that indirectly assesses peripheral blood circulation and its resulting amount of radiated heat. Due to these properties, thermal imaging is currently applied in human medicine to noninvasively evaluate peripheral vascular disorders such as thrombosis, thromboembolisms, and other ischemic processes. Moreover, tissular damage (e.g., burn injuries) also causes microvasculature compromise. Therefore, thermography can be applied to determine the degree of damage according to the viability of tissues and blood vessels, and it can also be used as a technique to monitor skin transplant procedures such as grafting and free flaps. The present review aims to summarize and analyze the application of IRT in veterinary medicine as a method to indirectly assess peripheral vascular integrity and its relation to the amount of radiated heat and as a diagnostic technique for tissue viability, degree of damage, and wound care. [ABSTRACT FROM AUTHOR]

Introduction Acute myeloid leukemia (AML) is a heterogeneous disease marked by clonal growth of myeloblasts in the bone marrow and peripheral circulation, leading to inefficient hematopoiesis and bone marrow failure. Single-nucleotide polymorphisms (SNPs) in genes involved in the metabolism of gold standard drugs used in AML treatment influence treatment-related toxicities, response, and survival. Aim To study SNP rs (532545) of the CDA gene and SNP rs(2291075) of the SLCO1B1 gene in newly diagnosed adults with AML. Patients and methods The study included 75 newly diagnosed adult patients with AML admitted to Alexandria Main University Hospital in the period between November 2020 and December 2021. Clinical data and bone marrow samples were obtained. Molecular genetic analysis involving CDA and SLCO1B1 single-nucleotide gene polymorphisms was done using PCR-restriction fragment length polymorphism-coupled analys real time PCR. Results The mean age was 40.3±13.12 years. After induction chemotherapy with a 3+7 protocol, 29 (38.7%) patients achieved complete remission. Patients with homozygous variant T/T of SLCO1B1 gene had a lower risk of treatment-related anemia in comparison with C/T and C/C genotypes (P<0.001). The heterozygous C/T variant of the CDA gene rs (532545) had better relapse-free survival and overall survival when compared with the C/C and T/T genotypes, respectively. No statistically significant correlation between CDA and SLCO1B1 single-nucleotide gene polymorphisms and postinduction treatment response was found. Conclusion Polymorphisms in SLCO1B1 and CDA genes involved in chemotherapy metabolism pathways can be useful in assessment of treatment-related toxicities and overall survival. [ABSTRACT FROM AUTHOR]