Investigating urinary characteristics and optimal urine white blood cell threshold in paediatric urinary tract infection: A prospective observational study.

Introduction: While the definitive diagnosis of urinary tract infection (UTI) requires a positive urine culture, the likelihood of UTI can be determined by urinalysis that includes white blood cell (WBC) count. We aimed to determine the optimal urine WBC threshold in urinalysis to predict UTIs in children presenting at the emergency department (ED). Method: We performed a prospective observational study in the ED at KK Women's and Children's Hospital for children below 18 years old who underwent both urine microscopy and urine cultures, between 10 January and 7 November 2022. We assessed the various urine WBC thresholds associated with culture-proven UTIs using sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and area under receiver operating characteristic curve. Results: We found a culture-proven UTI rate of 460/1188 (38.7%) among all patients analysed, and 278/998 (27.9%) among those with nitrite-negative urine samples. Among all patients, a urinalysis WBC threshold of 100/µL had a sensitivity of 82.2% (95% confidence interval [CI] 78.4-85.5) and negative predictive value of 86.2% (95% CI 83.6-88.4). Among those who were nitrite-negative, a WBC threshold of ≥100/µL resulted in a potential missed rate of 48/278 (17.3%). By lowering the WBC threshold to ≥10/µL, the potential missed cases reduced to 6/278 (2.2%), with an estimated increase in 419 urine cultures annually. Conclusion: A urine microscopy WBC threshold of ≥100/µL results in a clinically significant number of missed UTIs. Implementation of various thresholds should consider both the potential missed UTI rate and the required resource utilisation.

CAE-ResVGG FusionNet: A Feature Extraction Framework Integrating Convolutional Autoencoders and Transfer Learning for Immature White Blood Cells in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a highly aggressive cancer form that affects myeloid cells, leading to the excessive growth of immature white blood cells (WBCs) in both bone marrow and peripheral blood. Timely AML detection is crucial for effective treatment and patient well-being. Currently, AML diagnosis relies on the manual recognition of immature WBCs through peripheral blood smear analysis, which is time-consuming, prone to errors, and subject to inter-observers' variation. This study aimed to develop a computer-aided diagnostic framework for AML, called "CAE-ResVGG FusionNet", that precisely identifies and classifies immature WBCs into their respective subtypes. The proposed framework leverages an integrated approach, by combining a convolutional autoencoder (CAE) with finely tuned adaptations of the VGG19 and ResNet50 architectures to extract features from CAE-derived embeddings. The process begins with a binary classification model distinguishing between mature and immature WBCs followed by a multiclassifier further classifying immature cells into four subtypes: myeloblasts, monoblasts, erythroblasts, and promyelocytes. The CAE-ResVGG FusionNet workflow comprises four primary stages, including data preprocessing, feature extraction, classification, and validation. The preprocessing phase involves applying data augmentation methods using geometric transformations and synthetic image generation using the CAE to address imbalance in the WBC distribution. Feature extraction involves image embedding and transfer learning, where CAE-derived image representations are used by a custom integrated model of VGG19 and ResNet50 pretrained models. The classification phase employs a weighted ensemble approach that leverages VGG19 and ResNet50, where the optimal weighting parameters are selected using a grid search. The model performance was assessed during the validation phase using the overall accuracy, precision, and sensitivity, while the area under the receiver characteristic curve (AUC) was used to evaluate the model's discriminatory capability. The proposed framework exhibited notable results, achieving an average accuracy of 99.9%, sensitivity of 91.7%, and precision of 98.8%. The model demonstrated exceptional discriminatory ability, as evidenced by an AUC of 99.6%. Significantly, the proposed system outperformed previous methods, indicating its superior diagnostic ability.

Trajectories of peripheral white blood cells count around the menopause: a prospective cohort study.

BACKGROUND: Menopause significantly impacts the immune system. Postmenopausal women are more susceptible to infection. Nonetheless, the pattern of change in peripheral white blood cell counts around the menopause remains poorly understood. METHODS: We conducted a prospective longitudinal cohort study with repeated measurements using Kailuan cohort study of 3632 Chinese women who participated in the first checkup (2006-2007) and reached their final menstrual period (FMP) by the end of the seventh checkup (2018-2020). Peripheral WBC count indicators included total white blood cells (TWBC), neutrophils (NEUT), lymphocytes (LYM), and monocytes (MON). Multivariable mixed effects regressions fitted piece-wise linear models to repeated measures of WBC count indicators as a function of time before or after the final menstrual period (FMP). Interaction and subgroup analysis were used to explore the effects of age and body mass index (BMI) on changes in WBC indicators around FMP. RESULTS: WBC count indicators decreased before the FMP, and the reduction in TWBC, NEUT, and MON continued for 2 years following the FMP. LYM and NEUT declined during < -1 years and - 4 ∼ + 2 years relative to FMP, respectively. A reduction in MON was observed pre-FMP, extending continuously through the two-year period post-FMP. TWBC declined from - 3 to + 2 years relative to FMP, but both MON and TWBC increased during > + 2 years. The baseline age had an interaction effect on changes in WBC indicators during specific menopausal stages, except for TWBC. Individuals in different age subgroups showed distinct trajectories for NEUT, LYM and MON around the FMP. High baseline BMI had a synergistic effect on changes in specific menopause segments for TWBC, LYM, and MON. The impact of menopause on TWBC and LYM was postponed or counterbalanced in high BMI individuals. Individuals in three BMI subgroups experienced similar MON changes around FMP, and there were slight variations during < -4 years. CONCLUSIONS: Menopause was associated with count changes of peripheral WBC. The trajectories of various WBC types differ around menopause. Age and BMI affected WBC trajectory around menopause. The menopause period may represent a window of opportunity to promote immune health in middle-aged women.

[Factors associated with normal leukocyte count and C-reactive protein in adults with acute appendicitis: a retrospective cohort study]. / Faktory, svyazannye s normal'nym kolichestvom leikotsitov i urovnem S-reaktivnogo belka u vzroslykh bol'nykh s ostrym appenditsitom: retrospektivnoe kogortnoe issledovanie.

OBJECTIVE: To identify the factors associated with normal leukocyte count and C-reactive protein (CRP) in adults with acute appendicitis. MATERIAL AND METHODS: A retrospective cohort study included patients aged 18-60 years after surgeries for acute appendicitis. Convenience sampling was used to select medical records, and variables such as age, sex, weight, height, origin, self-medication, diabetes (DM2), high blood pressure (HBP), type of appendicitis, duration of illness, preoperative time, type of appendectomy, operative time, and hospital stay were analyzed. Patients were categorized into those with normal and abnormal inflammatory parameters. The SPSS version 28 software was used for analysis. RESULTS: We included 333 patients; 11.11% ones had normal inflammatory parameters. Both groups had mean age of approximately 33 years. Men comprised 56.76% and 57.43%in both groups, respectively. The abnormal group had shorter mean preoperative time, and catarrhal appendicitis was more common in the normal group. Multivariate analysis revealed that rural origin and self-medication were significantly associated with normal inflammatory parameters. CONCLUSION: The prevalence of normal inflammatory parameters in acute appendicitis patients was 11.11%. Rural origin, self-medication, shorter preoperative time, and catarrhal appendicitis were significantly associated with normal inflammatory parameters in this context.

Systemic C-Reactive Protein Predicts Cerebral Vasospasm and Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Retrospective Observational Study.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is often complicated by cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI), which significantly impact patient outcomes. The study aimed to investigate the predictive value of systemic serum biomarker levels for CVS and DCI following aSAH. METHODS: We retrospectively analyzed data for 450 aSAH patients admitted to University Hospital Düsseldorf between January 2011 and October 2021. Serum biomarkers were measured on admission. The occurrence of CVS and DCI was assessed based on clinical and radiological criteria. Multivariate logistic regression analysis was performed to determine the independent association of serum biomarkers with CVS and DCI. We compared the predictive values of various models using the area under the receiver operating characteristic curve. RESULTS: Of the 450 patients, 126 (28.0%) developed CVS, 123 (27.3%) developed DCI, and 62 (13.8%) developed co-occurring CVS and DCI. Patients with CVS, DCI, or both had significantly higher admission C-reactive protein (CRP) levels than those without these complications (P < 0.001). Elevated CRP levels were independently associated with an increased risk of CVS, DCI, and co-occurring CVS and DCI (P < 0.05). CRP demonstrated a higher predictive value for CVS (area under the curve [AUC]: 0.811) and co-occurring CVS and DCI (AUC: 0.802) compared to DCI alone (AUC: 0.690). CONCLUSIONS: Our findings suggest that admission systemic CRP levels can serve as a more valuable predictor for developing CVS than DCI following aSAH. Incorporating CRP into clinical assessments may aid in risk stratification and early intervention strategies for patients at high risk of these complications.

An explainable AI-based blood cell classification using optimized convolutional neural network.

White blood cells (WBCs) are a vital component of the immune system. The efficient and precise classification of WBCs is crucial for medical professionals to diagnose diseases accurately. This study presents an enhanced convolutional neural network (CNN) for detecting blood cells with the help of various image pre-processing techniques. Various image pre-processing techniques, such as padding, thresholding, erosion, dilation, and masking, are utilized to minimize noise and improve feature enhancement. Additionally, performance is further enhanced by experimenting with various architectural structures and hyperparameters to optimize the proposed model. A comparative evaluation is conducted to compare the performance of the proposed model with three transfer learning models, including Inception V3, MobileNetV2, and DenseNet201.The results indicate that the proposed model outperforms existing models, achieving a testing accuracy of 99.12%, precision of 99%, and F1-score of 99%. In addition, We utilized SHAP (Shapley Additive explanations) and LIME (Local Interpretable Model-agnostic Explanations) techniques in our study to improve the interpretability of the proposed model, providing valuable insights into how the model makes decisions. Furthermore, the proposed model has been further explained using the Grad-CAM and Grad-CAM++ techniques, which is a class-discriminative localization approach, to improve trust and transparency. Grad-CAM++ performed slightly better than Grad-CAM in identifying the predicted area's location. Finally, the most efficient model has been integrated into an end-to-end (E2E) system, accessible through both web and Android platforms for medical professionals to classify blood cell.

Improving Interpretability of Leucocyte Classification with Multimodal Network.

White blood cell classification plays a key role in the diagnosis of hematologic diseases. Models can perform classification either from images or based on morphological features. Image-based classification generally yields higher performance, but feature-based classification is more interpretable for clinicians. In this study, we employed a Multimodal neural network to classify white blood cells, utilizing a combination of images and morphological features. We compared this approach with image-only and feature-only training. While the highest performance was achieved with image-only training, the Multimodal model provided enhanced interpretability by the computation of SHAP values, and revealed crucial morphological features for biological characterization of the cells.

High-Resolution Ultrasound Platform for Infant Meningitis Detection: An In Vitro Demonstration.

Infant meningitis remains a severe burden on global health, particularly for young infants. Traditional ultrasound imaging techniques are limited in spatial resolution to visualize white blood cells (WBCs) in the cerebrospinal fluid (CSF), which is considered a well-established marker for meningitis detection. This work presents a novel platform that uses high-resolution ultrasound to detect the backscatter signals from microscopic CSF WBCs through the anterior fontanelle of neonates and young infants. The whole system was built around a custom probe that allows for a 20 MHz focused transducer to be mechanically controlled to map the area of interest in the CSF. Data processing can be performed internally in the device without the need to extract the images for further analysis. The in vitro feasibility of the proposed solution was evaluated in imaging 7 µm particle suspensions at different concentrations relevant to meningitis diagnosis ranging from 7- to 646-particles (pp)/µL. The experimental tests were conducted from a simple setup using a sample container to a more realistic setup based on an anatomical phantom of the neonatal head. The results show high-quality images, where 7 µm particles can be resolved for the different concentrations.

Robustness assessment of an automated AI-based white blood cell morphometric analysis system using different smear preparation methods.

INTRODUCTION: Numerous AI-based systems are being developed to evaluate peripheral blood (PB) smears, but the feasibility of these systems on different smear preparation methods has not been fully understood. In this study, we assessed the impact of different smear preparation methods on the robustness of the deep learning system (DLS). METHODS: We collected 193 PB samples from patients, preparing a pair of smears for each sample using two systems: (1) SP50 smears, prepared by the DLS recommended fully automated slide preparation with double fan drying and staining (May-Grunwald Giemsa, M-G) system using SP50 (Sysmex) and (2) SP1000i smears, prepared by automated smear preparation with single fan drying by SP1000i (Sysmex) and manually stained with M-G. Digital images of PB cells were captured using DI-60 (Sysmex), and the DLS performed cell classification. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to evaluate the performance of the DLS. RESULTS: The specificity and NPV for all cell types were 97.4%-100% in both smear sets. The average sensitivity and PPV were 88.9% and 90.1% on SP50 smears, and 87.0% and 83.2% on SP1000i smears, respectively. The lower performance on SP1000i smears was attributed to the intra-lineage misclassification of neutrophil precursors and inter-lineage misclassification of lymphocytes. CONCLUSION: The DLS demonstrated consistent performance in specificity and NPV for smears prepared by a system different from the recommended method. Our results suggest that applying an automated smear preparation system optimized for the DLS system may be important.

Assessing the impact of severe acute respiratory syndrome coronavirus 2 infection on hematological parameters.

BACKGROUND: The current study is a retrospective study designed to evaluate changes in complete blood count and coagulation parameters in adult coronavirus disease 2019 (COVID-19) patients at a prominent Saudi tertiary center to predict disease severity and mortality. METHODS: The cohort consisted of 74 800 adult patients divided into four groups based on a COVID-19 test and the patient's sex: 35 985 in the female negative COVID-19 group, 23 278 in the male negative COVID-19 group, 8846 in the female positive COVID-19 group and 6691 in the male positive COVID-19 group. RESULTS: Patients with COVID-19 demonstrated decreased white blood cell counts and increased red blood cell counts. Also, COVID-19-positive participants exhibited more prolonged partial thromboplastin time and lower D-dimer levels than those of COVID-19-negative subjects (p<0.05). The study also revealed gender-dependent impacts on platelet counts, implying a possible relationship with the greater infection mortality rate in men than in women (p<0.001). In addition, the study found a link between changes in coagulation test results and death in COVID-19 patients (p<0.001). The evidence regarding the effects of COVID-19 on blood cell counts and coagulation, on the other hand, is conflicting, most likely due to variances in study populations and the timing of testing postinfection. CONCLUSIONS: According to the findings, COVID-19-related alterations in blood cell count and clotting ability may be risk factors for death.

CRP, Fibrinogen, White Blood Cells, and Blood Cell Indices as Prognostic Biomarkers of Future COPD Exacerbation Frequency: The TIE Cohort Study.

Background/Objective: Systemic inflammation is common in chronic obstructive pulmonary disease (COPD), and evidence suggests that inflammatory biomarkers can predict acute exacerbations (AECOPDs). The aim of this study was to analyse whether C-reactive protein (CRP), fibrinogen, white blood cell count (WBC), or the blood cell indices PLR (platelet-to-lymphocyte ratio), SII (systemic immune inflammation index), SIRI (systemic inflammation response index), and AISI (aggregate index of systemic inflammation) can predict future AECOPDs. Methods: In the Tools Identifying Exacerbations (TIE) cohort study, participants with spirometry-confirmed COPD were recruited from primary and secondary care in three Swedish regions and assessed during a stable phase of COPD. AECOPD frequency during the three-year follow-up was reviewed in medical records. Associations were analysed via ordinal logistic regressions. Results: Of the 571 participants, 46% had ≥1 AECOPD during follow-up, and the mean ± SD AECOPD frequency was 0.63 ± 1.2/year. In unadjusted analyses, high levels of CRP (odds ratio 1.86, 95% CI 1.29-2.67), fibrinogen (2.09, 1.38-3.16), WBCs (2.18, 1.52-3.13), SII (1.52, 1.05-2.19), SIRI (1.76, 1.23-2.52), and AISI (1.99, 1.38-2.87) were associated with a higher AECOPD frequency. After adjustment for AECOPD history, age, sex, smoking, body mass index, COPD Assessment Test score, lung function, and inhaled corticosteroid use, associations remained for high levels of CRP (adjusted odds ratio of 1.64; 95% CI of 1.08-2.49), fibrinogen (1.55; 1.07-2.24), and WBC (1.65; 1.10-2.47). Conclusions: CRP, fibrinogen, and WBC, assessed during stable-phase COPD, enhanced AECOPD prediction, whereas PLR, SII, SIRI, and AISI did not.

Association of Bovine Respiratory Disease during the Pre-Weaning Period with Blood Cell Counts and Circulating Concentration of Metabolites, Minerals, and Acute Phase Proteins in Dairy Calves Transported to a Calf Raising Facility.

Our objective was to investigate the association of bovine respiratory disease (BRD) occurring within the first 56 days of life with blood cell counts and the circulating concentration of metabolites, minerals, and acute phase proteins throughout the pre-weaning period in dairy calves transported to a heifer raising facility within their first week of life. Data from 305 calves transported from dairies in Minnesota to a calf raising facility in New Mexico within their first four days of life were used in this retrospective cohort study. Blood samples were collected at 7, 17, 34, and 56 days of life for the analysis of blood cell counts, biochemistry, and the concentration of acute phase proteins. Blood urea nitrogen, albumin, GLDH, CK, P, Na, K, Cl, Zn, Hp, SAA, and monocyte counts were associated with BRD status throughout or at least at one of the time points evaluated in this study. In conclusion, several hematological variables were associated with BRD status in dairy calves that underwent transportation stress in early life.

A mystery revealed: an update on eosinophil and other blood cell morphology of the Argentine black and white tegu (Salvator merianae).

Reptile white blood cell (WBC) morphological features are strikingly variable across species. In the Argentine black and white tegu (Salvator merianae), red tegu (Salvator rufescens), and Savannah monitor (Varanus exanthematicus), previous reports described a WBC type with a single distinct, clear, linear- to ovoid- to crescent-shaped inclusion of presumptive monocytic origin. The objective of this study was to further investigate the origin of this unique WBC type with crescent-shaped inclusions. Blood samples from two Argentine black and white tegus, tegu 1, a 4-year-old female, and tegu 2, a 2-year-old presumed male, were submitted for routine hematological evaluation. Additional blood films were prepared and stained with these cytochemical stains: alkaline phosphatase (ALP; naphthol AS-MX phosphate substrate), alpha-naphthyl butyrate esterase, alpha-chloroacetate esterase, myeloperoxidase, Periodic acid-Schiff, and Sudan black B. Blood films from tegu 1 were also stained with a second ALP stain (5-bromo-4-chloro-3-indoxyl-phosphate and nitroblue tetrazolium substrate), Luna, luxol fast blue, and toluidine blue. The blood from tegu 1 was cytocentrifuged to isolate and fix the buffy coat in glutaraldehyde 2.5% aqueous solution for transmission electron microscopy. Six morphologically distinct WBC types were identified from tegu 1, including heterophils, basophils, monocytes, azurophils, lymphocytes, and the unique WBC type, which were identified as eosinophils with inclusions. WBC types in tegu 2 were similar; however, eosinophils lacked a discernable inclusion. Proper WBC identification will be useful in obtaining accurate hemogram data for this species.

Altered counts and mitochondrial mass of peripheral blood leucocytes in patients with chronic hepatitis B virus infection.

Hepatitis B virus (HBV) damages liver cells through abnormal immune responses. Mitochondrial metabolism is necessary for effector functions of white blood cells (WBCs). The aim was to investigate the altered counts and mitochondrial mass (MM) of WBCs by two novel indicators of mitochondrial mass, MM and percentage of low mitochondrial membrane potential, MMPlow%, due to chronic HBV infection. The counts of lymphocytes, neutrophils and monocytes in the HBV infection group were in decline, especially for lymphocyte (p = 0.034) and monocyte counts (p = 0.003). The degraded MM (p = 0.003) and MMPlow% (p = 0.002) of lymphocytes and MM (p = 0.005) of monocytes suggested mitochondrial dysfunction of WBCs. HBV DNA within WBCs showed an extensive effect on mitochondria metabolic potential of lymphocytes, neutrophils and monocytes indicated by MM; hepatitis B e antigen was associated with instant mitochondrial energy supply indicated by MMPlow% of neutrophils; hepatitis B surface antigen, antiviral therapy by nucleos(t)ide analogues and prolonged infection were also vital factors contributing to WBC alterations. Moreover, degraded neutrophils and monocytes could be used to monitor immune responses reflecting chronic liver fibrosis and inflammatory damage. In conclusion, MM combined with cell counts of WBCs could profoundly reflect WBC alterations for monitoring chronic HBV infection. Moreover, HBV DNA within WBCs may be a vital factor in injuring mitochondria metabolic potential.

Nanoscale insights into hematology: super-resolved imaging on blood cell structure, function, and pathology.

Fluorescence nanoscopy, also known as super-resolution microscopy, has transcended the conventional resolution barriers and enabled visualization of biological samples at nanometric resolutions. A series of super-resolution techniques have been developed and applied to investigate the molecular distribution, organization, and interactions in blood cells, as well as the underlying mechanisms of blood-cell-associated diseases. In this review, we provide an overview of various fluorescence nanoscopy technologies, outlining their current development stage and the challenges they are facing in terms of functionality and practicality. We specifically explore how these innovations have propelled forward the analysis of thrombocytes (platelets), erythrocytes (red blood cells) and leukocytes (white blood cells), shedding light on the nanoscale arrangement of subcellular components and molecular interactions. We spotlight novel biomarkers uncovered by fluorescence nanoscopy for disease diagnosis, such as thrombocytopathies, malignancies, and infectious diseases. Furthermore, we discuss the technological hurdles and chart out prospective avenues for future research directions. This review aims to underscore the significant contributions of fluorescence nanoscopy to the field of blood cell analysis and disease diagnosis, poised to revolutionize our approach to exploring, understanding, and managing disease at the molecular level.

Survivin: A key apoptosis inhibitor in COVID-19 infection and its implication for treatment protocol.

While the relationship between cellular apoptosis and proliferation rates in COVID patients remains underexplored in existing literature, various viruses are known to impact these fundamental process to modulate response to infection. This paper aims to assess apoptosis and proliferation rates in individuals recently infected with Coronavirus, both before and after vaccination, comparing them with healthy controls. Peripheral blood cells from newly diagnosed COVID-19 patients revealed a significant increase in proliferation and apoptosis levels in fresh lymphocytes and granulocytes compared to healthy donors. Notably, as none of the patients were under corticosteroid therapy or cytotoxic drugs, the study underscores the critical role of white blood (WBC) apoptosis in viral pathogenesis, potentially contributing significantly to COVID-19's pathogenicity. Elevated levels of soluble Fas ligand (FaSL) and the pro-inflatmmatory cytokine IL-38 were identified in COVID-19 patients, indicating potential immune dysregulation. Furthermore, individual who received the vaccine or recovered from COVID-19 exhibited higher survivin rates, suggesting a protective role for survivin in migitating lung damage. These findings suggest the prospect of developing a strategy to prevent WBC apoptosis, offering potential benefits in averting lymphopenia associated with severe COVID-19 ouctomes.

Enterovirus A71 crosses a human blood-brain barrier model through infected immune cells.

Enterovirus A71 (EV-A71) is associated with neurological conditions such as acute meningitis and encephalitis. The virus is detected in the bloodstream, and high blood viral loads are associated with central nervous system (CNS) manifestations. We used an in vitro blood-brain barrier (BBB) model made up of human brain-like endothelial cells (hBLECs) and brain pericytes grown in transwell systems to investigate whether three genetically distinct EV-A71 strains (subgenogroups C1, C1-like, and C4) can cross the human BBB. EV-A71 poorly replicated in hBLECs, which released moderate amounts of infectious viruses from their luminal side and trace amounts of infectious viruses from their basolateral side. The barrier properties of hBLECs were not impaired by EV-A71 infection. We investigated the passage through hBLECs of EV-A71-infected white blood cells. EV-A71 strains efficiently replicated in immune cells, including monocytes, neutrophils, and NK/T cells. Attachment to hBLECs of immune cells infected with the C1-like virus was higher than attachment of cells infected with C1-06. EV-A71 infection did not impair the transmigration of immune cells through hBLECs. Overall, EV-A71 targets different white blood cell populations that have the potential to be used as a Trojan horse to cross hBLECs more efficiently than cell-free EV-A71 particles.IMPORTANCEEnterovirus A71 (EV-A71) was first reported in the USA, and numerous outbreaks have since occurred in Asia and Europe. EV-A71 re-emerged as a new multirecombinant strain in 2015 in Europe and is now widespread. The virus causes hand-foot-and-mouth disease in young children and is involved in nervous system infections. How the virus spreads to the nervous system is unclear. We investigated whether white blood cells could be infected by EV-A71 and transmit it across human endothelial cells mimicking the blood-brain barrier protecting the brain from adverse effects. We found that endothelial cells provide a strong roadblock to prevent the passage of free virus particles but allow the migration of infected immune cells, including monocytes, neutrophils, and NK/T cells. Our data are consistent with the potential role of immune cells in the pathogenesis of EV-A71 infections by spreading the virus in the blood and across the human blood-brain barrier.

Sex-specific relationships of inflammatory biomarkers with blood pressure in older adults.

Emerging evidence indicates an association between blood pressure and inflammation, yet this relationship remains unclear in older adults, despite the elevated prevalence of hypertension. We investigated the association between blood pressure, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and white blood cell (WBC) count in a cohort of 3571 older adults aged 65 and above, and 587 middle-aged participants (55-59 years old). In women aged 65 and above, the relationship between inflammatory markers and blood pressure was consistent, with hs-CRP and WBC emerging as predictors of high blood pressure. For hs-CRP, the adjusted odds ratio (OR) was 1.5 (95% CI, 1.07 to 2.10, P = 0.02), and for WBC, the adjusted OR was 1.41 (95% CI, 1.02 to 1.94, P = 0.04), comparing the highest to the lowest quartiles. In men, only the WBC count was significantly associated with an increased OR for high BP (adjusted OR 1.49, 95% CI, 1.09 to 2.02, P = 0.01) across quartiles. Across the entire study population, in a fully adjusted model, all inflammatory markers were modestly associated with blood pressure levels, while the effect of being over 65 years was the most significant predictor of high blood pressure (OR 1.84, 95% CI, 1.50 to 2.25, P < 0.001). The link between key inflammation markers and blood pressure in older adults varies by sex and biomarker type and may differ from the relationship observed in younger individuals. These relationships are likely to be affected by factors linked to age.

The chronic leukocyte and inflammatory cytokine responses of older adults to resistance training in normobaric hypoxia; a randomized controlled trial.

TRIAL DESIGN: Older adults experience chronic dysregulation of leukocytes and inflammatory cytokines, both at rest and in response to resistance training. Systemic hypoxia modulates leukocytes and cytokines, therefore this study characterized the effects of normobaric hypoxia on the leukocyte and cytokine responses of older adults to resistance training. METHODS: 20 adults aged 60-70 years performed eight weeks of moderate-intensity resistance training in either normoxia or normobaric hypoxia (14.4% O2), consisting of two lower body and two upper body exercises. Venous blood was drawn before and after the training intervention and flow cytometry was used to quantify resting neutrophils, lymphocytes, monocytes, eosinophils and basophils, in addition to the subsets of lymphocytes (T, B and natural killer (NK) cells). Inflammatory cytokines were also quantified; interleukin 1 beta (IL-1ß), IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor alpha (TNF-α). Acute changes in leukocytes and cytokines were also measured in the 24 h following the last training session. RESULTS: After the intervention there was a greater concentration of resting white blood cells (p = 0.03; 20.3% higher) T cells (p = 0.008; 25.4% higher), B cells (p = 0.004; 32.6% higher), NK cells (p = 0.012; 43.9% higher) and eosinophils (p = 0.025; 30.8% higher) in hypoxia compared to normoxia, though the cytokines were unchanged. No acute effect of hypoxia was detected in the 24 h following the last training session for any leukocyte population or inflammatory cytokine (p < 0.05). CONCLUSIONS: Hypoxic training caused higher concentrations of resting lymphocytes and eosinophils, when compared to normoxic training. Hypoxia may have an additional beneficial effect on the immunological status of older adults. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR). TRIAL NUMBER: ACTRN12623001046695. Registered 27/9/2023. Retrospectively registered. All protocols adhere to the COSORT guidelines.