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Objectives: This study compared the effects of leukocyte platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF) on patients' quality of life and the healing of palatal wounds after free gingival graft harvesting. Method and materials: After free gingival graft harvesting, palatal donor sites of 36 patients were assigned to one of three groups: L-PRF group, A-PRF group, or palatal stent + periodontal pack group (control group). Wound healing was evaluated by H2O2 test. Pain was evaluated by visual analog scale and number of analgesics consumed. For patient quality of life, the Oral Health Impact Profile-14 (OHIP-14) questionnaire was utilized. Results: Complete epithelialization was higher in the control group on day 7 than in the test groups (P < .05). Complete epithelialization was achieved in all groups 14 days postoperatively. Visual analog scale scores for pain and the number of analgesic tablets consumed were similar in all groups (P > .05). OHIP-14 total scores were similar in all study groups at 7 days postoperatively (P > .05). OHIP-14 total and physical pain score was lower in the L-PRF group than the A-PRF group at 14 days postoperatively (P < .05). Conclusion: Aside from the slight superiority of L-PRF over A-PRF, it can be concluded that both PRF procedures have similar effects on palatal wound healing and quality of life. [ABSTRACT FROM AUTHOR]

White blood cells (WBCs) are crucial microscopic defenders of the human immune system in combating transmittable conditions triggered by germs, infections, and various other human pathogens. Timely and appropriate WBC detection and classification are decisive for comprehending the immune system's standing and its feedback to various pathologies, assisting in diagnosing and monitoring illness. Nevertheless, the manual classification of WBCs is strenuous, extensive, and prone to errors, while automated approaches can be cost-prohibitive. Within artificial intelligence, deep learning (DL) approaches have become an appealing option for automating WBC recognition. The existing DL techniques for WBC classification face several limitations and computational difficulties, such as overfitting, limited scalability, and design complexity, often battling with function variety in WBC images and requiring considerable computational resources. This research study recommends an ingenious hybrid inception-xception Convolutional Semantic network (CNN) designed to deal with constraints in existing DL versions. The proposed network incorporates inception and depth-separable convolution layers to successfully catch attributes across many ranges, therefore minimizing concerns related to model complexity and overfitting. In contrast to traditional CNN designs, the proposed network lessens the layers made use of and increases their function removal capacities, hence enhancing the performance of WBC classification, which needs a wide variety of attribute abilities. Furthermore, the proposed model was trained, validated and tested on three popular and widely recognized datasets, namely, Leukocyte Images for Segmentation and Classification (LISC), Blood Cell Count and Detection (BCCD), and Microscopic PBS (PBS-HCB), where it demonstrates the generalization and robustness and superiority of our proposed model. The model depicted an outstanding average accuracy rate of 99.25%, 99.65%, and 98.6% on a five-fold cross-validation test for the respective datasets, surpassing existing models as detailed. The model's robustness and superior performance, validated across diverse datasets, underscore its potential as an advanced tool for accurate and efficient WBC classification in medical diagnostics. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota may be involved in neuropathic pain. However, the causal association between gut microbiota and neuropathic pain remains unclear. Whether immune cells and inflammatory factors mediate the pathway from gut microbiota to neuropathic pain has not been elucidated. Methods: We obtained the summary data of 412 gut microbiota, 731 immune cells, 91 inflammatory factors, and five types of neuropathic pain (drug-induced neuropathy, postherpetic neuralgia, sciatica, trigeminal neuralgia, and unspecified neuralgia) from large-scale genome-wide association study (GWAS) datasets and the FinnGen database. We used bidirectional Mendelian randomization (MR) analysis to explore the causal association between gut microbiota and neuropathic pain. Additionally, we conducted a mediation analysis to identify whether immune cells and inflammatory factors act as mediators within these causal relationships. Results: Our study revealed 30 causal relationships between 26 gut bacterial taxa and five types of neuropathic pain, including four associated with drug-induced neuropathy, six with postherpetic neuralgia, five with sciatica, eight with trigeminal neuralgia, and seven with unspecified neuralgia. Moreover, we identified 35 gut bacterial pathway abundances causally involved in neuropathic pain. The reverse MR analysis showed no evidence of reverse causality from gut microbiota to neuropathic pain. Mediation analysis demonstrated that the immune cell phenotype "HLA-DR++ monocyte % leukocyte" mediated the causal relationship between p_Proteobacteria and sciatica with a mediation proportion of 36.15% (P = 0.038), whereas "CD11c on CD62L+ myeloid dendritic cell" mediated the causal pathway from assimilatory sulfate reduction to trigeminal neuralgia with a mediation proportion of 27.90% (P = 0.041). Conclusion: This study identified the causal relationships between several specific gut microbiota and various neuropathic pain subtypes. Additionally, two immune cells may act as potential mediators in the pathways from gut microbiota to neuropathic pain. [ABSTRACT FROM AUTHOR]

Bisphenol F (BPF) is an emerging contaminant extensively used in the pharmaceutical, chemical, and food industries, exerting deleterious effects on human and wildlife health. Therefore, the current study was conducted to assess the toxicity induced by BPF in rohu Labeo rohita using multiple biomarkers such as oxidative stress, activity of antioxidant enzymes, biochemical parameters, histology, and genotoxicity. Fish were separated into four groups (T1–T4). Group T1 served as a control (0 μg/L), while Groups T2, T3, and T4 were exposed to BPF concentrations of 600 μg/L, 1200 μg/L, and 1800 μg/L, respectively, for 21 days. Results showed a significant (p < 0.05) increase in oxidative biomarkers (thiobarbituric acid reactive substance [TBARS] and reactive oxygen species [ROS]), while the concentration of antioxidant biomarkers (peroxidase [POD], superoxide dismutase [SOD], reduced glutathione [GSH], and catalase) was significantly (p < 0.05) decreased with the rising concentration of BPF in the liver, gills, and kidney of fish. Significant reduction (p < 0.05) in biochemical parameters was measured from collected whole blood, including red blood cells (RBCs), hemoglobin (HGB), mean corpuscular HGB (MCH), MC volume (MCV), hematocrit (HCT), MC HGB concentration (MCHC), platelets, low‐density lipoprotein (LDL), cholesterol, high‐density lipoprotein (HDL), total proteins, very LDL (VLDL), albumin and globulin, while white blood cells (WBCs), neutrophils, triglycerides, aspartate aminotransferase (AST), blood glucose, and alanine transaminase (ALT) levels were increased significantly (p < 0.05). Comet assay showed the DNA damage potential of BPF in erythrocytes. Histological examination showed that exposure to BPF causes several degenerative effects in the soft tissues (gills, liver, and kidney) of treated fish. It is concluded that BPF induces deleterious effects via disruptions in histological, genotoxic, and biochemical alterations in several organs of exposed fish. [ABSTRACT FROM AUTHOR]

A 60-day feeding trial was conducted to evaluate the effects of dietary Anabaena blue-green algae (ABGA) meal on the growth performance, digestibility, and physio-metabolic responses of Catla catla fingerlings (initial average weight 9.45 ± 0.15 g). Six iso-nitrogenous (30% crude protein) and iso-caloric (378.09 Kcal. digestible energy/100 g) diets were formulated: a control diet (A0, 0% ABGA) and five experimental diets with varying ABGA inclusion levels (A3: 3%, A6: 6%, A9: 9%, A12: 12%, A15: 15%). The results demonstrated that there were no significant differences (P > 0.05) in percentage weight gain (PWG), specific growth rate (SGR), protein efficiency ratio (PER), and feed conversion ratio (FCR) among the experimental groups. Additionally, dietary ABGA did not significantly affect (P > 0.05) body carcass composition among different groups. However, amylase activity significantly decreased (P < 0.05) in the A12 and A15 fed groups, whereas lipase and protease activities remained insignificant (P > 0.05) across all groups. Notably, oxidative stress responses (SOD; superoxide dismutase and CAT; catalase), carbohydrate metabolic enzymes (LDH; lactate dehydrogenase and MDH; malate dehydrogenase), and serum glucose levels increased significantly (P < 0.05) with higher ABGA inclusion. Conversely, serum albumin content significantly decreased (P < 0.05) in the ABGA-fed groups. There were no significant differences (P > 0.05) observed in serum total protein, albumin/globulin (A/G) ratio, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activities among the experimental groups. Hematological parameters revealed that RBC (red blood cell) count, hemoglobin (Hb) concentration, and packed cell volume (PCV) significantly decreased (P < 0.05), while WBC (white blood cell) count significantly (P < 0.05) increased with higher dietary ABGA inclusion. In conclusion, the inclusion of dietary ABGA up to 15% did not impair nutrient utilization and supported normal growth performance in C. catla fingerlings. However, higher inclusion levels may have a detrimental effect on their growth, nutrient utilization, and physio-metabolic responses. [ABSTRACT FROM AUTHOR]

The article discusses cases of spurious lymphocyte differential counts caused by the presence of target cells in automated hematology analyzers. The study highlights discrepancies between different analyzers and manual counts, with target cells identified in all cases. The presence of unlysed target cells interfered with the differential analysis, leading to inaccurate results. The study emphasizes the importance of understanding analyzer technology to identify and address spurious results effectively. [Extracted from the article]

Background: Intervertebral disc degeneration (IDD) was the most common cause of low back pain. Platelet rich plasma (PRP) has the potential to repair IDD, however, there is still no conclusion on whether Leukocyte-poor platelet rich plasma (Lp-PRP) or Leukocyte-rich platelet rich plasma (Lr-PRP) is better for the treatment of IDD. Methods: First, we conducted an in vitro study to compare the effects of autologous Lp-PRP and Lr-PRP on human degenerated nucleus pulposus (NP) cells. Then we verified the in vivo effects of autologous Lp-PRP and Lr-PRP in treating disc degeneration through a rabbit IDD model. Results: The in vitro study showed both autologous Lp-PRP and Lr-PRP can promote the cell proliferation, the synthesis of COL II and Aggrecan of human degenerated NP cells, while Lp-PRP are better than Lr-PRP (P<0.05). In addition, only Lp-PRP can inhibit the apoptosis of human degenerated NP cells (P<0.05), whereas Lr-PRP activates the catabolism on the contrary (P<0.05). Further, the in vivo study through the rabbit IDD model verified that autologous Lp-PRP has better effects than autologous Lr-PRP in repairing IDD according to X-ray, MRI, histological, and immunohistochemical assessment (P<0.05, respectively). And the caspase-3 IHC results also showed that only autologous Lp-PRP treatment could inhibit apoptosis of NP cells in the rabbit IDD model (P<0.05). Conclusion: Combining in vivo and in vitro studies, the present study confirmed that autologous Lp-PRP has a better effect than autologous Lr-PRP in repairing IDD, which may be due to the inflammatory factors (TNFα, IL-1β, etc.) in Lr-PRP antagonizing part of the repair effects and promoting the catabolism additionally. Therefore, our findings suggest that Lp-PRP may provide better results than Lr-PRP for treating IDD. Further randomized clinical trials will provide evidence to guide practice. [ABSTRACT FROM AUTHOR]

Background: Iron-deficiency is associated with increased morbidity and mortality in non-communicable diseases. However, iron parameters are rarely assessed in dogs. Here, we aimed to assess and correlate iron parameters in dogs suffering from Canine Atopic Dermatitis (CAD) compared to non-atopic, healthy dogs. Results: For this retrospective study, blood values and sera of 34 dogs with confirmed CAD were compared with 94 healthy non-atopic dogs. In our cohort, dogs with CAD had significantly lower mean corpuscular volume (MCV,) mean corpuscular hemoglobin (MCH) but higher white blood cell counts due to increased levels of circulating neutrophils and monocytes. CAD patients also had elevated total protein and c-reactive protein (CRP), but lower albumin levels compared to our healthy control dogs, indicated low-grade inflammation in the CAD cohort. Spearman correlations associated negatively clinical symptom (CADESI-4/PVAS) with MCV; ceruloplasmin and hepcidin, but positively with serum iron. Only in the CAD-cohort, MCV, CRP and albumin-levels negatively affected serum iron-levels and were positively associated with ceruloplasmin. Linear regression analysis revealed that serum iron-levels in CAD subjects, were positively dependent on hematocrit (packed cell volume, PCV) and albumin, and negatively dependent with white blood cells and neutrophils numbers. In contrast, in the healthy cohort, hepcidin was the sole factor associated with serum iron. Conclusions: A decreased iron status was associated with a higher symptom burden. Iron homeostasis differed markedly in healthy and atopic dermatitis dogs. CAD patients had depleted iron-stores and presented themselves with subclinical inflammation. [ABSTRACT FROM AUTHOR]

Rapid neutrophil recruitment is critical for controlling infection, with dysfunctional neutrophil responses in diseases like diabetes associated with greater morbidity and mortality. We have shown that the leukocyte protein ECRG4 enhances early neutrophil recruitment to cutaneous wounds and hypothesized that ECRG4 regulates the early host response to infection. Using a cutaneous infection model, we found that ECRG4 KO mice had decreased early neutrophil recruitment with persistent larger lesions, increased bacterial proliferation and systemic dissemination. Although previous work identified ECRG4 as a negative regulator of CD44 on neutrophils, the mechanism regulating neutrophil recruitment remained unknown. We demonstrated that pro-inflammatory responses were intact in ECRG4 KO mice, but found decreased neutrophil mobilization from bone marrow and decreased migration to chemokines. ECRG4 KO mouse neutrophils demonstrated an increase in adhesion molecules that regulate recruitment, including enhanced induction of integrin CD11b and increased L-selectin and CD44 on bone marrow neutrophils. Analysis of gene expression in leukocytes from diabetic patients found decreased ECRG4 expression with similar increased L-selectin and CD44. We propose a previously unrecognized mechanism governing neutrophil recruitment, whereby ECRG4 mediates neutrophil surface adhesion molecules that determine both recruitment and outside-in signaling that modulates neutrophil response to pro-inflammatory stimuli. [ABSTRACT FROM AUTHOR]

Background Study Design and Methods Results Discussion Splitting apheresis platelet (PLT) units increase available inventory during shortages. The impact of prolonged storage in gas‐impermeable aliquot bags on PLT quality in vitro and transfusion outcomes in patients remains uncertain.We assessed in vitro PLT quality and thromboelastography (TEG) in PLTs stored for 8 or 24 h in aliquot bags compared with baseline (T0). Retrospective assessment of response (PLT increment and corrected count increment (CCI)) was conducted among adults (≥18 years) transfused with split platelet units from January 2021 to June 2022.No differences were observed in PLT and white blood cell (WBC) counts, mean platelet volume, or TEG parameters during storage, except for an increase in TEG R time (mean ± SD) at 24 h (6.1 ± 0.5 min) compared to T0 (4.4 ± 0.8 min), p = 0.0031 one‐way ANOVA. Eighty‐one patients were transfused 119 split units with a median [IQR] PLT yield of 2.1 × 1011[1.9 × 1011 to 2.3 × 1011] and storage duration of 1.6[0.7–9.1] h. The overall median PLT count increment was 6.0 × 103/uL and CCI was 5.0 × 103, correlating negatively with split unit storage duration (Spearman rho = −0.218, p = 0.017). Compared with split transfusions of pathogen‐reduced (PR) PLTs, non‐PR splits were associated with higher median platelet count increments (7.0 × 103/μL vs. 4.0 × 103/μL, p = 0.0263 Mann–Whitney U) and higher CCIs (6.5 × 103 vs. 3.9 × 103, p = 0.0116 Mann–Whitney U) despite no differences in PLT yields (2.1 × 1011/μL vs. 2.1 × 1011/μL).Storing PLTs in aliquot bags for 8 or 24 h does not adversely affect their quality in vitro. Splitting apheresis PLTs are feasible for adult transfusions during shortages. It may be advisable to prioritize non‐PR PLTs for splitting given improved patient responses. [ABSTRACT FROM AUTHOR]

Heterogeneous particles co-focusing to a single stream is a vital prerequisite for cell counting and enumeration, playing an essential role in flow cytometry and single-cell analysis. Microfluidics-based inertial focusing holds great research prospects due to its simplicity of devices, ease of operation, high throughput, and freedom from external fields. Combining microfluidic channels with two or more different geometries has become a powerful tool for high-efficiency particle focusing. Here, we explored hybrid microfluidic channels for heterogeneous particle co-focusing. Four different annular channels with obstacles distributed on the inner wall were constructed and simulated, obtaining constantly variable secondary flows. Then we used four different fluorescent particles with the size of 10 μm, 12 μm 15 μm, and 20 μm as well as their mixture to perform the inertial focusing experiments of multi-sized particles. Theoretical simulation and experimental results demonstrated a focusing efficiency of >99%. Finally, we further utilized human white blood cells to estimate the co-focusing performance of our hybrid microfluidic channel, resulting in a high focusing efficiency of >92% and a high throughput of ≈8000 cell s−1. The hybrid microfluidic channels, capable of high-precision heterogeneous particle co-focusing, could pave a broad avenue for microfluidic flow cytometry and single-cell analysis. [ABSTRACT FROM AUTHOR]

Nowadays, there is growing interest in new compositions and drugs that can preserve and maintain human health. There are many studies on both known probiotics and new sources of biologically active substances which may potentially be new avenues for human longevity. Here, we describe the protective effect of cell lysates of the relict bacteria Bacillus sp. F (Bacilus Lyuba), isolated from the ancient permafrost of Central Yakutia, upon DNA damage, induced by hydrogen peroxide. The DNA damage was monitored by a comet assay in leukocytes isolated from the peripheral blood of experimental animals (BALB/c mice). Cell lysates were prepared using the French Press and ultrasonic treatment. The levels of DNA damage in the presence of bacterial lysates upon the stress test (20 μM hydrogen peroxide for 10 min at 37°C) were almost twice lower, compared with the buffer control. Of note, the maximal protective effect was observed in the temperature range of 50°C–60°C; with the increase of the temperature, this effect vanished. The obtained results do not give a clear answer on the mechanism of the protective properties of Bacillus sp. F. (Bacilus Lyuba) lysates. To answer this question, a detailed analysis of the protein composition of bacterial lysate at different temperatures should be performed. [ABSTRACT FROM AUTHOR]

C-terminal Src kinase (Csk) targets Src family kinases (SFKs) and thereby inactivates them. We have previously shown that Csk binds to phosphorylated tyrosine 685 of VE-cadherin, an adhesion molecule of major importance for the regulation of endothelial junctions. This tyrosine residue is an SFK target, and its mutation (VE-cadherin-Y685F) inhibits the induction of vascular permeability in various inflammation models. Nevertheless, surprisingly, it increases leukocyte extravasation. Here, we investigated whether endothelial Csk is involved in these effects. We found that the deficiency of Csk in endothelial cells augments SFK activation and the phosphorylation of VE-cadherin-Y685 but had no net effect on vascular leak formation. In contrast, the lack of endothelial Csk enhanced leukocyte adhesion and transmigration in vitro and in vivo. Furthermore, the silencing of Csk increased tyrosine phosphorylation of the SFK substrate cortactin. Importantly, the effects of Csk silencing on the increase in SFK activation, cortactin phosphorylation, and neutrophil diapedesis were all dependent on Y685 of VE-cadherin. Deletion of cortactin, in turn, erased the supporting effect of Csk silencing on leukocyte transmigration. We have previously shown that leukocyte transmigration is regulated by endothelial cortactin in an ICAM-1-dependent manner. In line with this, blocking of ICAM-1 erased the supporting effect of Csk silencing on leukocyte transmigration. Collectively, our results establish a negative feedback loop that depends on the phosphorylation of VE-cadherin-Y685, which recruits Csk, which in turn dampens the activation of SFK and cortactin and thereby the clustering of ICAM-1 and the extravasation of neutrophils. [ABSTRACT FROM AUTHOR]

Background: Alemtuzumab is administered intravenously (IV) for relapsing-remitting multiple sclerosis (RRMS), with limited studies of subcutaneous (SC) treatment. Objectives: We sought to evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety profile of SC-administered alemtuzumab in people with progressive multiple sclerosis (PMS). Design: SCALA was a phase I, open-label, randomized, parallel-group study with two 12-month periods and a safety monitoring phase to 60 months. Methods: Of 29 screened participants, 24 were enrolled and randomized 2:1 to two 12 mg/day alemtuzumab treatments (60 and 36 mg total; SC:IV). Key inclusion criteria: ⩾18 years with a PMS diagnosis. Key exclusion criteria included RRMS diagnosis and prior treatment with anti-CD52 antibodies. Primary endpoint: CD3+ lymphocyte count. Secondary endpoints: PD and PK parameters. Results: Demographics were broadly similar for participants in the SC (16) and IV (8) arms; more participants with primary PMS received SC (44%) versus IV (25%) treatment. After the first course, the mean CD3+ cell count/µL was reduced at month 1 in both arms (SC: baseline (BL) 1326 to 48 vs IV: BL 1155 to 84). Lymphocyte counts partially repopulated by month 12, with mean CD3+ cell counts/µL of SC 599 versus IV 528. The mean lymphocyte counts/µL decreased again after the second course at month 13 in both arms (SC: 90 vs IV: 129), with partial repopulation by month 24. Alemtuzumab serum concentrations were lower following SC administration relative to IV, with 32% bioavailability. There were no adverse events leading to permanent treatment discontinuation or death. Conclusion: In SCALA, there were similar patterns of lymphocyte depletion and repopulation for participants receiving SC or IV alemtuzumab. In both arms, alemtuzumab had a manageable safety profile, with no emerging safety concerns. The general stabilization of neurological outcomes observed over 60 months underscores the potential long-term benefits of alemtuzumab treatment. Trial registration: Clinicaltrials.gov identifier: NCT02583594. [ABSTRACT FROM AUTHOR]

Background: With the application of PCR testing and Metagenomic Next-Generation Sequencing(mNGS), the detection rate of causative organisms in paediatric bone and joint infections has been greatly improved. The aim of our study is to identify some indicators that could be used to distinguish the culture results to optimize the use of PCR and mNGS. Methods: In this study, a total of 117 cases of acute osteomyelitis of long bones in children who underwent pus culture were included. Patients were grouped as culture-negative (n:21) and culture-positive (n:96) groups according to the results of pus culture. Age, sex, duration of onset, maximum body temperature at onset, inflammatory indicators and D-dimer after admission were systematically collected for all patients and were compared for both groups. ROC curve (ROC) was used to evaluate the diagnostic efficiency of culture-negative. Logistic regression analysis was conducted to determine independent risk factors for culture-negative. Results: There was no significant difference in age, sex and erythrocyte sedimentation rate between culture-negative group and culture-positive group (P > 0.05). The duration of onset was longer, and the temperature, white blood cells, neutrophils count, C-reactive protein and D-dimer were less elevated in culture-negative acute osteomyelitis (P < 0.05). Duration of onset, maximum body temperature at onset, white blood cell count, neutrophil count, C-reactive protein, and D-dimer have certain diagnostic efficacy in judging the efficacy of negative culture. Logistic regression analysis indicated that the duration of onset more than 6.5 days, the maximum body temperature at onset lower than 38.35℃ and C-reactive protein lower than 78.40 mg/L were independent risk factors for negative culture (P < 0.05). Conclusions: Our study revealed that duration of onset more than 6.5 days, maximum body temperature at onset lower than 38.35℃ and C-reactive protein lower than 78.40 mg/L were independent risk factors for predicting negative culture. In children with this type of acute osteomyelitis, we recommend that the pus be tested by PCR or mNGS as a priority. [ABSTRACT FROM AUTHOR]

Background: This study utilized large-scale population data from the National Health and Nutrition Examination Survey (NHANES) to elucidate the relationship between the Klotho protein and metabolic syndrome along with its components. We further investigated the possible mediating effect of inflammation on these relationships. Our objective was to identify biomarkers for risk stratification and potential therapeutic targets for metabolic syndrome. Methods: This study enrolled 13,119 participants aged 40–79 years, spanning five NHANES cycles from 2007 to 2016, with complete information on metabolic syndrome and the Klotho protein. The definition of metabolic syndrome followed the criteria of the National Cholesterol Education Program-Adult Treatment Panel III. Survey-weighted logistic regression and subgroup analysis were used to explore the associations between serum Klotho protein levels and metabolic syndrome, along with its components. Mediation analysis was performed to investigate the mediating effects of inflammation-related markers, including white blood cells, neutrophils, lymphocytes, monocytes, the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic immune-inflammation index (SII) and the monocyte-to-HDL ratio (MHR), with the aim of elucidating how the Klotho protein influences the onset and progression of metabolic syndrome. Results: The study participants had an average age of 56.06 years (95% CI: 55.76–56.37), with a Klotho protein concentration of 798.10 pg/ml (95% CI: 656.50–980.50) and a 43.77% prevalence of metabolic syndrome (n = 5742). In the crude model, Klotho was negatively correlated with metabolic syndrome and its components, including central obesity, hypertension, and hypertriglyceridemia. After adjusting for all confounding factors, Klotho was demonstrated to be negatively associated only with metabolic syndrome (OR: 0.82, 95% CI: 0.70–0.97), hypertension (OR: 0.83, 95% CI: 0.70–0.98), and hypertriglyceridemia (OR: 0.78, 95% CI: 0.67–0.91). Subgroup and interaction analyses revealed significant interactions between age, sex, race/ethnicity, body mass index, and Klotho. Additionally, mediation analysis demonstrated that leukocytes, neutrophils and monocytes accounted for 34.78%, 31.91% and 7.13%, respectively, of the associations between Klotho and metabolic syndrome. Conclusion: The serum concentration of Klotho protein was negatively associated with metabolic syndrome, with the relationship being partly mediated by systemic immune inflammation. The findings of this research revealed that the Klotho protein may be a valuable biomarker for risk stratification and a potential therapeutic target for metabolic syndrome. [ABSTRACT FROM AUTHOR]

Thromboembolism, a serious complication in patients with liver abscesses, can lead to organ deterioration if left untreated. However, factors associated with thromboembolism in these patients remain poorly understood. We aimed to identify the factors associated with liver abscess complications, with a focus on thromboembolism and metastatic infection. Data from 325 patients diagnosed with liver abscesses between March 2019 and June 2023 were retrospectively collected. Baseline clinical and laboratory variables associated with thromboembolic events and metastatic infections were analyzed using logistic regression. A nomogram for predicting thromboembolism was constructed using significant predictors. Among the 325 patients, the median age was 68.0 years, and included 129 women. Fifty patients experienced thromboembolic events and 44 had metastatic infections. Significant predictors for thromboembolic events included white blood cell (WBC) ≥ 20,000/µL (odds ratio [OR] 3.401, p = 0.002), platelet count < 100,000/µL (OR 3.291, p = 0.004), and abscess septation (OR 2.704, p = 0.007). Age ≥ 65 years (OR 0.457, p = 0.040), WBC ≥ 20,000/µL (OR 3.340, p = 0.005), and abscess septation (OR 2.909, p = 0.008) were identified as factors associated with metastatic infections. A nomogram was constructed to predict thromboembolism using the following four variables: WBC ≥ 20,000/µL platelet count < 100,000/µL, albumin < 2.8 g/dL, and abscess septation, and demonstrated an AUROC of 0.755. Our study is the first to develop a reliable nomogram for thromboembolism prediction, utilizing easily accessible clinical parameters. This innovative model enables clinicians to efficiently identify high-risk patients, facilitating the implementation of additional studies to mitigate the risk of overlooked thromboembolic events in these at-risk individuals. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) continues to be a major health concern in today's world. Despite conflictive findings, evidence supports systemic inflammation's impact on CRC patients' survival rates. Therefore, this study aims to assess the prognostic role of the innate immune system in patients with CRC. Method: A total of 449 patients were included, with a 5-year follow-up period, and absolute neutrophil counts and their related ratios were measured. Results: The non-survival group had increased levels of white blood cells, neutrophils (both p <0.001), and monocytes (p=0.038), compared to the survival group, along with other neutrophil-related ratios. We observed increased mortality risk in patients in the highest tertile of white blood cells [HR=1.85 (1.09-3.13), p<0.05], neutrophils [HR=1.78 (95% CI: 1.07-2.96), p<0.05], and monocytes [HR=2.11 (95% CI: 1.22-3.63)], compared to the lowest tertile, after adjusting for all clinicopathological variables. Random forest analysis identified neutrophils as the most crucial variable in predicting survival rates, having an AUC of 0.712, considering all clinicopathological variables. A positive relationship between neutrophil counts and metastasis was observed when neutrophil counts are considered continuous (β=0.92 (0.41), p<0.05) and tumor size (width) when neutrophils were considered as logistic variable (T1 vs T3) [OR=1.42, (95% CI: 1.05-1.98), p<0.05]. Conclusion: This study offers comprehensive insights into the immune factors that impact the prognosis of CRC, emphasizing the need for personalized prognostic tools. [ABSTRACT FROM AUTHOR]

Background: Bovine colostrum (COL) is assumed to be one of the strongest natural immune stimulants. Regular ingestion of COL may contribute to improved immune response in athletes exposed to high training loads. Methods: Twenty-eight endurance-trained males aged 31.1 ± 10.2 years (body mass 81.9 ± 9.0 kg; height 1.82 ± 0.06 m) completed this randomized doubleblind placebo(PLA)-controlled crossover study aimed at investigating the effect of 12-week COL supplementation (25gCOL·day-1) on resting (REST), exerciseinduced (POST-EX), and short-term post-exercise recovery (REC; 1 h after test exercise) changes in selected saliva and blood immunoglobulins (Ig), white blood cell (WBC) count and differential; as well as blood hematological, nutritional status and muscle damage indices. The protocol assumed 4 study visits - before/after supplementation with COL (COLPRE and COLPOST) and PLA (PLAPRE and PLAPOST). During testing sessions, incremental rowing test to exhaustion and swimming-specific performance test were introduced as exercise stimuli. Results: At COLPOST visit the secretory IgA (SIgA) concentration in saliva was significantly higher at POST-EX and REC compared to REST (p<0.05). COL supplementation had no effect on blood IgA, IgE, IgD, IgG, and IgM concentrations. Furthermore, after COL supplementation decrease of hematocrit at REC (p<0.05) was revealed. Conclusions: 12-week supplementation with 25 gCOL·day-1 in endurance-trained male athletes resulted in a favorable increase in post-exercise concentration of salivary SIgA. COL seems to be a potential stimulator of local immune defense after exercise-induced homeostasis disturbances. Nevertheless, the lack of effect on blood markers indicates the need for further research in the area of mechanisms underlying the effect of the supposed COL immunological capacity. [ABSTRACT FROM AUTHOR]

Introduction: One-lung ventilation (OLV) is a prevalently used technique to sustain intraoperative pulmonary function. Resolvin E1 (RvE1), a specialized pro-resolving lipid mediator, accelerates the resolution of inflammation in the lungs. However, its therapeutic effects on OLV-induced lung injury remain unclear. Methods: We initially developed an OLV rat model and treated it with RvE1. Subsequently, we assessed the wet/dry ratio of the lung tissue, performed hematoxylin and eosin staining, and calculated the ratio of polymorphonuclear cells to white blood cells in the bronchoalveolar lavage fluid. Additionally, we assessed apoptosis, inflammatory factor levels, and lung permeability in the rat lung tissues in the RvE1 treated and untreated groups and explored the molecular mechanisms mediated by RvE1. Results: Our results indicated that RvE1 alleviated lung injury and inflammation and improved lung tissue apoptosis and permeability in OLV rats. Moreover, RvE1 suppressed the expression of the BLT1/2 signaling pathway and its ligands. The use of BLT2 and BLT1 inhibitors (LY255283 and U-75302, respectively) enhanced RvE1's anti-inflammatory effects and reduced lung injury. Furthermore, synergistic treatment with the BLT2 inhibitor and RvE1 provided grater benefits by more effectively inhibiting the NF-kB, p38 MAPK, and ERK pathways. Discussion: RvE1 and the inhibition of BLT2 signalling reduce the inflammatory response and mitigate OLV-induced lung injury. These findings suggest a novel therapeutic pathway for managing OLV-related complications. [ABSTRACT FROM AUTHOR]

Objective: Cyclophosphamide (CTX) is an effective anticancer drug, but toxic effects against normal human tissues are its dose-limiting drawback. The aim of this research was to investigate the in vivo immunomodulatory activities of Allium ampeloprasum Subsp Iranicum against CTX-induced toxicity in mice. Materials and Methods: Extract of the whole plant of A. ampeloprasum Subsp Iranicum was obtained using the maceration technique, and its total phenolic and flavonoid contents were quantified through spectrophotometric analysis. Mice received daily oral administration (PO) of the extract (150 mg/kg) for a duration of 14 days, either as a standalone treatment or in conjunction with an intraperitoneal (IP) injection of 20 mg/kg CTX. The effects of the extract on body weight, spleen weight, white blood cell (WBC), serum antibody titer hemagglutination (HA), delayed-type hypersensitivity response (DTH), lymphocyte proliferation, cytokine production, and histopathological examinations were evaluated. Results: A. ampeloprasum Subsp Iranicum restored several parameters including spleen weight (p<0.001), WBC (p<0.001), lymphocytes (p<0.05), and monocytes (p<0.01), HA titer (p<0.05), and DTH response (p<0.01). A. ampeloprasum Subsp Iranicum notably stimulated lymphocyte proliferation to PHA (p<0.01) and LPS (p<0.05) and recovered interferon (IFN)-γ (p<0.001) and interleukin (IL)-4 (p<0.001) levels in the immunosuppressed mice. Also, CTX-induced histopathological changes were reversed by A. ampeloprasum Subsp Iranicum . Conclusion: Analyses revealed A. ampeloprasum Subsp Iranicum could regulate immunity and increase host immune responses. The observed strengthening effect can be attributed to the high amount of flavonoids and dipropyl trisulfide compounds present in A. ampeloprasum Subsp Iranicum. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer treatments like radiotherapy can sometimes cause tumors to shrink not only in the treated area but also in other parts of the body. This phenomenon, called the abscopal effect, happens when the immune system is triggered to attack tumors at distant sites. This review explores how heating the body (hyperthermia) alongside radiotherapy may improve the likelihood of this effect. Both treatments work by sending "danger" signals to the immune system, helping it recognize and attack cancer cells. Radiotherapy and hyperthermia together increase immune activity by releasing specific proteins and improving blood flow to the tumor, making it easier for immune cells to reach and attack cancer cells. This combination may offer a promising way to boost the body's natural defenses against cancer, helping more people experience widespread tumor shrinkage and potentially improving cancer treatment outcomes. Introduction: The abscopal effect is a systemic immune response characterized by metastases regression at sites distant from the irradiated lesion. This systematic review aims to explore the immunological mechanisms of action underlying the abscopal effect and to investigate how hyperthermia (HT) can increase the chances of radiotherapy (RT) triggering systemic anti-tumor immune responses. Methods: This review is created in accordance with the PRISMA guidelines. Results and Conclusion: HT and RT have both complementary and synergistic immunological effects. Both methods trigger danger signal release, promoting cytokine and chemokine secretion, which increases T-cell infiltration and facilitates cell death. Both treatments upregulate extracellular tumor HSP70, which could amplify DAMP recognition by macrophages and DCs, leading to stronger tumor antigen presentation and CTL-mediated immune responses. Additionally, the combined increase in cell adhesion molecules (VCAM-1, ICAM-1, E-selectin, L-selectin) could enhance leukocyte adhesion to tumors, improving lymphocyte trafficking and boosting systemic anti-tumor effects. Lastly, HT causes vasodilation and improves blood flow, which might exacerbate those distant effects. We suggest the combination of local radiotherapy with fever-range whole-body hyperthermia to optimally enhance the chances of triggering the abscopal effect mediated by the immune system. [ABSTRACT FROM AUTHOR]

Background: Platelet-rich plasma (PRP) is increasingly used for the injection treatment of knee osteoarthritis (OA). However, the role of leukocytes contained in PRP is controversial, with some preclinical studies suggesting detrimental effects and others emphasizing their contribution in secreting bioactive molecules. Purpose: To compare the safety and effectiveness of leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP) for the treatment of knee OA. Hypothesis: That leukocytes could influence results both in terms of adverse events and clinical outcomes. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This double-blind randomized controlled trial included 132 patients with Kellgren-Lawrence grade 1-3 knee OA who were randomized to a 3-injection cycle of either LR-PRP or LP-PRP. Patients were prospectively assessed at baseline and at 2, 6, and 12 months with subjective evaluations comprising the International Knee Documentation Committee (IKDC) subjective score, the KOOS (Knee injury and Osteoarthritis Outcome Score), the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index), the visual analog scale for pain, the EuroQol–visual analog scale, the EuroQol–5 dimensions, and the Tegner activity scale. Objective evaluations consisted of the IKDC objective score, active/passive range of motion, and circumference of the index and contralateral knees. Patient judgment of the treatment was recorded as well as adverse reactions and failures. Results: An overall improvement in subjective and objective outcomes was documented, with no differences between the 2 groups, except for the improvement in the IKDC subjective score at 2 months, which was greater for the LR-PRP group compared with the LP-PRP group (14.8 ± 14.8 vs 8.6 ± 13.3, respectively; P =.046), as well as for active (P =.021) and passive (P =.040) ROM of the index knee at 6 months, showing statistically significant higher values in the LP-PRP group; and for quadriceps circumference of the index (P =.042) and contralateral (P =.045) knees at 12 months, which were significantly greater in the LR-PRP group. The IKDC subjective score improved from 42.5 ± 17.6 at baseline to 55.6 ± 21.4 at 12 months for the LR-PRP group (P <.0005) and from 45.7 ± 16.4 to 55.3 ± 20.4 for the LP-PRP group (P =.001). No differences in terms of patient treatment judgment were observed at all follow-up time points. No severe adverse events related to the treatment were reported, but some mild adverse events related to the treatment were observed: 16 in the LR-PRP group and 17 in the LP-PRP group. Treatment failed in 5 patients in the LR-PRP group and 2 in the LP-PRP group. Conclusion: This double-blind randomized controlled trial demonstrated that leukocytes did not affect the safety and efficacy of intra-articular PRP injections for the treatment of patients with knee OA. Both LR-PRP and LP-PRP demonstrated comparable clinical outcomes at all follow-up time points, without showing differences in subjective and objective outcomes or in adverse events and treatment failures. Registration: NCT04187183 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

Background: Platelet-rich plasma (PRP) is one of the most frequently used orthobiologic products for the injection treatment of patients affected by knee osteoarthritis (OA). Some preliminary evidence supports the influence of platelet concentration on patients' clinical outcomes. Purpose: To analyze if platelet concentration can influence the safety and clinical efficacy of PRP injections for the treatment of patients with knee OA. Study Design: Cohort study; Level of evidence, 3. Methods: This study consisted of 253 patients with knee OA (142 men, 111 women; mean ± SD age, 54.8 ± 11.4 years; Kellgren-Lawrence grades 1-3) who were treated with 3 intra-articular injections of 5 mL of autologous leukocyte-rich or leukocyte-poor PRP. All patients were prospectively evaluated at baseline and at 2, 6, and 12 months. Patients were clinically assessed thorough the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales and the International Knee Documentation Committee (IKDC) Subjective score. Platelet concentration was correlated with clinical outcome. Further analysis was performed by stratifying patients into 3 groups (homogeneous for OA severity) based on platelet concentration (high, medium, and low). All complications and adverse events were reported, as well as failures. Results: An overall statistically significant improvement in all clinical scores was documented from baseline to each follow-up evaluation. Platelet concentration positively correlated with clinical outcome. KOOS Pain improved more with higher platelet concentration at 2 months (P =.036; rho = 0.132), 6 months (P =.009; rho = 0.165), and 12 months (P =.014; rho = 0.155). The same trend was shown by the other KOOS subscales and by the IKDC Subjective score, as well as by the comparison of the groups of high-, medium-, and low-platelet PRP. The highest failure rate (15.0%) was found in the low-platelet group as compared with the medium-platelet group (3.3%) and the high-platelet group (3.3%). No differences were observed among the 3 groups in terms of adverse events. Conclusion: This study demonstrated that platelet concentration influences the clinical outcome of PRP injections in knee OA treatment. PRP with a higher platelet concentration provides a lower failure rate and higher clinical improvement as compared with PRP with a lower platelet concentration, with overall better results up to 12 months of follow-up in patients with knee OA. [ABSTRACT FROM AUTHOR]

Objective: This study investigates the practicability of serum kallistatin as a biomarker in the diagnosis of tubo-ovarian abscess (TOA) because C-reactive protein (CRP) is insufficiently specific for diagnosis. Methods: Thirty patients (control group) who presented for elective gynecological surgeries and 30 who were hospitalized due to TOA (study group) at the Antalya Training and Research Hospital Gynecology Clinic, Türkiye, between January 1 and December 31, 2022, were included in the study. Blood samples were collected for the calculation of complete blood count, biochemistry, CRP, and serum kallistatin values, and the results were recorded in a database. Results: Although no significant differences were observed between the control and study groups in terms of age or body mass index, significant differences were observed in terms of marital status, number of pregnancies, parity number, intrauterine device history, and previous surgical history (p > 0.05). Serum hemoglobin levels (12.61 ± 1.30 vs. 11.47 ± 1.77; p = 0.008), white blood cell (7.9 [6.15 ± 9.7] vs. 17.0 [11.6–19.6]; p < 0.001), neutrophil (4.6 [3.6–6.12] vs. 13.6 [9.25–16.1]; p < 0.001), lymphocyte (2.51 ± 0.71 vs. 2.33 ± 0.69; p = 0.307), and platelet counts (285.63 ± 78.0 vs. 407.03 ± 131.96; p < 0.001), neutrophil–lymphocyte ratio (2.11 ± 0.93 vs. 6.18 ± 2.20; p < 0.001), neutrophil–lymphocyte ratio (123.16 ± 52.63 vs. 184.39 ± 63.90; p < 0.001), hs-CRP (1.20 [5.55–1.92] vs. 240 [138.25–291.0]; p < 0.001), kallistatin (7.18 ± 3.15 vs. 3.83 ± 3.69; p = 0.006), and urine leukocyte values (1 [0.75–3] vs. 3 [1–6.5]; p = 0.038) also differed significantly between the control and study groups. Conclusion: The study findings show that serum kallistatin levels can be used as a biomarker in the diagnosis of TOA. Further studies involving more participants are now needed to test the accuracy of our results. [ABSTRACT FROM AUTHOR]

Background: Recently, enhanced recovery after surgery (ERAS) protocols have attracted attention; they emphasize on avoiding intraoperative hypothermia while performing lumbar fusion surgery. However, none of the studies have reported the protocol for determining the temperature of saline irrigation during biportal endoscopic spine surgery (BESS) procedure. This study evaluated the effectiveness of warm saline irrigation during BESS in acute postoperative pain and inflammatory reactions. Materials and methods: Fifty-five patients who underwent BESS procedure were retrospectively analyzed for the incidence of perioperative hypothermia (< 36oC), postoperative inflammatory factors (white blood cells (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), serum amyloid A (SAA)), and clinical outcomes (back visual analog scale (VAS) score, postoperative shivering). The patients were divided into the warm and cold saline irrigation groups. Results: Hemoglobin, WBC, ESR, creatine kinase, and creatine kinase-muscle brain levels did not significantly differ between the warm and cold saline groups. The mean CRP, IL-6, and SAA levels were significantly higher in the cold saline group than in the warm saline group (p = 0.0058, 0.0028, and 0.0246, respectively); back VAS scores were also higher with a statistically significant difference until two days postoperatively (p < 0.001). During the entire procedure, the body temperature was significantly lower in the cold saline irrigation group, but the hypothermia incidence rate significantly differed 30 min after the operation was started. Conclusions: Using warm saline irrigation during BESS is beneficial for early recovery after surgery, as it is associated with reduced postoperative pain and complication rates. [ABSTRACT FROM AUTHOR]

• Oral acute and subchronic toxicities of Ziziphus jujuba were evaluated in rats. • No major signs of toxicity were observed in the liver and kidney. • Repeated oral administration is safe at up to 1000 mg kg-1 bw over a 28-day period. • Ziziphus jujuba bark is relatively safe at lower dose. Ziziphus jujuba is a medicinal botanical with various pharmacological properties against cardiovascular diseases, respiratory system diseases, gastrointestinal problems, dysentery, and diarrhea. Despite its exhaustive use for medicinal aims, no study has yet been directed to evaluate this plant's potentially toxic profile. The present work focused on the acute and subchronic toxicity of Z. jujuba bark extract. The acute oral toxicity was performed using the OECD guideline 425; Z. jujuba bark extract was administered to female rats at a single dose of 5000 mg kg-1 body weight. The subchronic acute oral toxicity was carried out according to OECD guidelines 407; Z. jujuba bark extract was administered to male and female rats at doses of 250, 500, and 1000 mg kg-1 bw; after 28 days of Z. jujuba bark extract daily administration, the animals were sacrificed. Hematological parameters, serum and urinary biochemical parameters, and histological sections of the liver and kidneys were assessed. Administration of the single-oral dose of Z. jujuba bark methanolic extract did not cause any death in rats, and the LD 50 was found to be greater than 5000 mg kg-1 bw. The repeated administration of Z. jujuba bark methanolic extract at 250, 500, and 1000 mg kg-1 bw did not induce any significant perturbation of the white blood cells, lymphocytes, red blood cells, hemoglobin, hematocrit, and platelets in rats as compared to the controls. For the lipid parameters, namely triglycerides and cholesterol, no significant difference was recorded between the profiles of the treated and untreated groups of animals. Likewise, we registered non-significant changes in renal parameters such as creatinine, urea, and proteins; this was confirmed by the histological sections, which showed a normal kidney structure. Besides, we did not observe any significant modification in the values of liver parameters, ALT and AST. This finding was further confirmed by the histological examination of the liver, which revealed the organ's normal structure. Finally, for single-oral administration, Z. jujuba bark extract is almost non-toxic. For repeated oral administration, Z. jujuba bark extract is safe at doses up to 1000 mg kg-1 bw over a 28-day period. [ABSTRACT FROM AUTHOR]

This study delves into the optimization of niosomal production for biological applications, focusing on their emerging role as amphiphilic nanoparticles derived from nonionic surfactants, poised at the forefront of biomedical research. We aimed to formulate and characterize a diverse array of niosomal nanoparticles, with particular emphasis on process‐related parameters and physicochemical characteristics. Critical thresholds for size, polydispersity, and zeta potential were established to identify parameters crucial for optimal niosomal formulations through a comprehensive investigation of concentrations, sonication times, ingredient ratios, and surfactant types. Leveraging MODDE software, we generated 10 optimized formulations from preliminary parameter screening. The proposed experimental model design by the software exhibited acceptable similarity to the obtained experimental results (F‐score: 0.83). The criteria for selection of the predicted experimental model formed based on targeted physicochemical considerations. To enhance half‐life and penetration, especially in higher electrostatic regions like the central nervous system (CNS), we proposed a neutralized surface charge (−10 to 10 mV) while maintaining size within 100–200 nm and polydispersity below 0.5. Extended stability screening revealed periodic and extended Gaussian distributions for size and zeta potential to minimize flocculation and coagulation caused by neutralized surface charge. Notably, the cellular response performance of optimized niosomes was assessed via cellular binding, uptake, and viability in comparison with liposomes. Glioblastoma cell line (U‐87) and granulocyte colony‐stimulating factor (G‐CSF) containing lymphoblastic leukemia cell line (NFS‐60) were chosen to represent tumors developed in the CNS region and white blood cells, respectively, enabling a comprehensive comparative analysis with liposomes. The meticulous comparison between niosomes and liposomes revealed comparable cellular viability profiles on both U‐87 and NFS‐60 cell lines, highlighting their similarities in cellular interactions. Moreover, selected niosomal formulations demonstrated exceptional cellular uptake, either equaling or surpassing observed liposomal uptake. One of the most promising niosomes was selected and optimized to evaluate drug encapsulation performance of niosomes for further drug delivery adaptations by one of the chemotherapy drugs, paclitaxel (PTX). Cytotoxicity study was established with the most efficiently encapsulated niosomal condition with human‐derived fibroblasts (HDFs) and U‐87 as the representation of healthy and cancerous cell lines. Results demonstrated 1:100 diluted PTX‐loaded niosome in the certain concentration demonstrated favorable toxicity in U‐87 than original PTX at the same concentration while not disturbing healthy HDFs. These findings underscore the potential of niosomes for reliable drug delivery, challenging the dominance of liposomal vehicles and presenting economically viable nanocarriers with significant implications for advancing biomedical research. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the clinical management and effectiveness of metagenomic next-generation sequencing (mNGS) in patients with pyogenic spinal infections. Methods: We conducted a retrospective review of 17 patients diagnosed with pyogenic spinal infections and treated at our institution between October 2022 and February 2024. The cohort included 8 males and 9 females, with a mean age of 63.59 ± 10.18 years (range: 41–71 years). The infections comprised 9 epidural abscesses, 6 intervertebral space infections, and 2 deep abscesses. All patients underwent open surgical procedures and mNGS-based bacterial identification using intraoperative pus or tissue specimens, in addition to conventional blood bacterial cultures. Clinical outcomes were assessed using CRP, PCT, WBC inflammatory markers, and VAS scores postoperatively. Results: All 17 patients with pyogenic spinal infections underwent open surgery and mNGS bacterial detection at our institution. Among the 17 patients, mNGS yielded positive results in 14 cases (82.4%), significantly higher than the 5.9% positivity rate of conventional bacterial cultures (p < 0.001). The mNGS test time was notably shorter than conventional cultures (1.0 vs. 5.88 days, p < 0.001). Postoperative antibiotic therapy was adjusted based on mNGS findings. There were significant reductions in postoperative VAS, WBC, PCT, and CRP values compared to preoperative levels (p < 0.01). Conclusion: Metagenomic next-generation sequencing is effective in managing pyogenic spinal infections by facilitating rapid and sensitive detection of pathogens. This technique improves the timeliness and accuracy of diagnosis, highlighting its potential for broader clinical use. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of 14-3-3β in acute asthma exacerbations in children and analyze the risk factors for asthma exacerbations. Methods: This study recruited 101 children with acute asthma exacerbations, 101 children with stable asthma, and 65 healthy children. Serum 14-3-3β was compared among the three groups. Factors such as asthma family history, skin prick test, serum-specific IgE test, coinfections, and clinical indicators (FeNO, FEV1, white blood cells, eosinophils, and serum IgE level) were compared between the asthma groups. Risk factors associated with acute asthma exacerbations were identified using multivariate logistic regression models. ROC curve was drawn to determine the diagnostic sensitivity and specificity of 14-3-3β. Results: Serum 14-3-3β was significantly greater in the acute asthma group than in the stable asthma and control groups. Serum 14-3-3β was higher in severe acute asthma group than in mild-moderate asthma group. There were no significant differences in serum 14-3-3β levels between stable asthma and control groups (p >.05). Multivariate logistic regression analysis revealed that serum 14-3-3β level, FeNO, coinfection, and FEV1 z-score significantly increased the odds of acute asthma exacerbations in children. The optimal 14-3-3β cutoff value (39.79 ng/mL), had a sensitivity of 69.3% and specificity of 94.1% for predicting acute asthma exacerbations. Conclusions: 14-3-3β is elevated in children with acute exacerbations of asthma, and increases with exacerbation severity. 14-3-3β, FeNO, FEV1, and coinfection could be independent risk factors for predicting asthma exacerbations. The optimal 14-3-3β cutoff value for predicting asthma exacerbations was 39.79 ng/mL. [ABSTRACT FROM AUTHOR]

Background Assessment for vitamin C deficiency (VCD) is rarely undertaken in an acute hospital setting in high-income countries. However, with growing interest in VCD in community settings, there is emerging evidence investigating the prevalence and impact of VCD during hospitalization. Objectives In this scoping review, the prevalence of VCD in adult hospitalized patients is explored, patient characteristics are described, and risk factors and clinical outcomes associated with VCD are identified. Methods A systematic scoping review was conducted in accordance with the PRISMA-ScR framework. The Ovid MEDLINE, Ovid Embase, Scopus, CINAHL Plus, Allied and Complementary Medicine Database, and the Cochrane Library databases were searched for interventional, comparative, and case-series studies that met eligibility criteria, including adult hospital inpatients in high-income countries, as defined by the Organization for Economic Co-operation and Development, that reported VCD prevalence using World Health Organization reference standards. These standards define VCD deficiency as plasma or serum vitamin C level <11.4 µmol/L, wholeblood level <17 µmol/L, or leukocytes <57 nmol/108 cells. Results Twenty-three articles were included, representing 22 studies. The cumulative prevalence of VCD was 27.7% (n = 2494; 95% confidence interval [CI], 21.3-34.0). High prevalence of VCD was observed in patients with severe acute illness and poor nutritional status. Scurvy was present in 48% to 62% of patients with VCD assessed in 2 studies (n = 71). Being retired (P  = 0.015) and using excessive amounts of alcohol and tobacco (P  = 0.0003) were independent risk factors for VCD (n = 184). Age was not conclusively associated with VCD (n = 631). Two studies examined nutrition associations (n = 309); results were inconsistent. Clinical outcomes for VCD included increased risk of frailty (adjusted odds ratio, 4.3; 95%CI, 1.33–13.86; P  = 0.015) and cognitive impairment (adjusted odds ratio, 2.93; 95%CI, 1.05–8.19, P  = 0.031) (n = 160). Conclusions VCD is a nutritional challenge facing the healthcare systems of high-income countries. Research focused on early identification and treatment of patients with VCD is warranted. Systematic Review Registration Open Science Framework (https://doi.org/10.17605/OSF.IO/AJGHX). [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the predictive value of discharge C-reactive protein (CRP) and white blood cell (WBC) levels for 90-day readmission after pancreatoduodenectomy (PD). A two-centre, retrospective study was performed between 2008 and 2022. Receiver operating characteristic (ROC) curve analysis was used to determine the predictive value of CRP level and WBC count at discharge. A conditional inference tree (CTREE) was constructed to identify combined risks within subgroups using variables associated with readmission. Of 438 patients, 54 (12%) were readmitted. The median WBC count at discharge was comparable between the readmitted and not readmitted groups (9.1 vs. 8.5 G/l). The CRP levels at discharge were predictive of 90-day readmission, with an area under the ROC curve (AUC) of 0.63 (95% CI: 0.55−0.63). A CRP concentration below 105 mg/l ruled out 90-day readmission, with a negative predictive value (NPV) of 90% (95% CI: 81%–95%). CTREE confirmed the diagnostic value of CRP at discharge (AUC = 0.68, 95% CI 0.60–0.68). CTREE additionally identified previous wound infection as a second risk factor for readmission in patients with CRP levels less than 101 mg/l (P = 0.003). CRP levels below 105 mg/l at discharge allow for a safe discharge with a low 90-day readmission rate. Wound infection, but not WBC count, was a positive predictor of 90-day readmission with moderate accuracy, suggesting the need for predischarge imaging for undetected complications in this patient cohort. Our retrospective analysis did not require registration with a publicly accessible registry. [ABSTRACT FROM AUTHOR]

Aim: To investigate the associations between oral health and depression, anxiety and their comorbidity in the UK Biobank cohort. Materials and Methods: Oral health problems were self‐reported at baseline. Symptoms of depression and anxiety were assessed using the Mental Health Questionnaire (PHQ‐4) in a cross‐sectional study. In the cohort study, diagnoses of depression and anxiety disorders were based on hospital records. Logistic regression and Cox regression models were used to analyse the association between oral health and depression/anxiety. Results: A total of 305,188 participants were included in the cross‐sectional study, and multivariate analysis showed that periodontal disease was associated with depression and/or anxiety (odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.73–1.86). In the prospective cohort study involving 264,706 participants, periodontal disease was significantly associated with an increased risk of depression and/or anxiety (hazard ratio [HR]: 1.14, 95% CI: 1.10–1.19), depression (HR: 1.19, 95% CI: 1.13–1.25) and anxiety (HR: 1.13, 95% CI: 1.07–1.19). Periodontal disease was also significantly associated with comorbid depression and anxiety (HR: 1.27, 95% CI: 1.16–1.38). Multiple mediation analysis using baseline inflammatory factors showed that white blood cell count and C‐reactive protein explained 3.07% and 3.15% of the association between periodontal disease and depression and anxiety, respectively. However, the results of longitudinal multiple mediation analysis of inflammatory factors at first follow‐up (N = 10,673) were not significant. Conclusions: Periodontal disease was found to be consistently associated with an increased risk of depression, anxiety and their comorbidity. [ABSTRACT FROM AUTHOR]

Objectives: Pneumocystis jirovecii pneumonia (PJP) is a serious complication of autoimmune and inflammatory diseases. This study aimed to describe the characteristics of PJP in patients with various systemic vasculitides and explore potential prognostic factors. Method: Data on 62 enrolled PJP patients with systemic vasculitis were analyzed. Patients were stratified based on the outcomes. Prognostic factors were investigated using Cox-regression models. Characteristics of patients with and without interstitial lung disease (ILD) were compared. Results: Among 62 vasculitis-PJP patients, 48 had anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), with microscopic polyangiitis (MPA) being the most common subtype (28 patients). MPA (HR 4.33, p = 0.001), concomitant aspergillosis (HR 2.68, p = 0.019), and higher D-dimer at PJP diagnosis (HR 1.07, p = 0.004) were independent adverse prognostic factors for overall survival. Stable disease activity of vasculitis was an independent favorable prognostic factor (HR 0.28, p = 0.027). Patients with MPA were older than non-MPA patients (median age: 69 vs. 58 years, p = 0.001); both ILD and fibrotic ILD were more prevalent in MPA patients (ILD: 78.6% vs. 35.3%, p = 0.001; fibrotic ILD: 57.1% vs. 11.8%, p < 0.001). At the diagnosis of PJP, patients with preexisting ILD had higher counts of white cells, lymphocytes, and neutrophils, as well as higher levels of immunoglobulin (Ig) G and IgA, than patients without preexisting ILD. Conclusions: MPA was associated with a higher risk of death in patients with vasculitis-PJP, possibly due to a higher prevalence of ILD. In clinical practice, we should pay more attention to the prophylaxis and management of PJP in patients with systemic vasculitis-associated ILD and/or MPA. Key Points • Data from this study showed that MPA was the most common subtype of vasculitis among vasculitis-PJP patients. • Compared with non-MPA patients in this study, patients with MPA were older, had more ILD and fibrotic ILD, and had a poorer prognosis. • In clinical practice, we should pay more attention to the prophylaxis and management of PJP in patients with systemic vasculitis-associated ILD and/or MPA. [ABSTRACT FROM AUTHOR]

Background: Ureteric stone is responsible for around 20% of urinary tract stones and among them 70% of these are located in distal portion of the ureter. Stone causing ureter obstruction produce inflammatory changes in ureteric wall and prevent spontaneous passage of stone. The objective of the study is to compare the predictive role of procalcitonin and Neutrophil-to-lymphocyte ratio (NLR) for spontaneous passage of stone. Materials and methodology: Total 150 participants having ureteric stone of 4–8 mm, were included in prospective observational study. The patients were followed up for 4 weeks. Spontaneous Stone Passage (SSP) was confirmed with either the patient collecting the stone during urination or by Non-Contrast CT performed at 4 weeks. Blood samples of the patients were analysed and White blood cells, sedimentation, Neutrophile to Lymphocyte (NLR), procalcitonin level compared to analyse predictors of future SSP. Result: The procalcitonin levels of the Spontaneous stone passing SSP (−ve) group (209.05 ± 78.45 pg/ml) were significantly higher than the not passing the SSP (+ve) group (130.76 ± 24.18) (p < 0.001). NLR is significantly higher in the SSP −ve (3.84 ± 0.41) than the SSP +ve (2.18 ± 0.38) group (p < 0.001). In single and multivariate analysis, significant activity was found for procalcitonin in SP +ve group. Conclusion: The findings of the study suggests that high level of procalcitonin, and high NLR have a negative effect on passage of stone. So early intervention can be planned to these patients to prevent complications. [ABSTRACT FROM AUTHOR]

Even in the current era of hematology analyzer automation and peripheral equipment, quality control sample measurement remains a manual task, leading to variability in quality control data and increased workload. In this study, we evaluated the performance of quality control measurement using the BT-50 Transportation Unit (BT-50, Sysmex, Kobe, Japan), equipped with a scheduled automatic quality control function, to ensure measurement accuracy and streamline the workflow of hematology testing. We evaluated the automatic measurement performance of quality control samples using the BT-50 for six representative blood test parameters: WBC (white blood cell), RBC (red blood cell), HGB (hemoglobin), HCT (hematocrit), PLT (platelet), and RET% (reticulocyte percent). We evaluated the equivalence and compared measurement accuracy between the BT-50 and the manual method. We then compared the variability to other laboratories and confirmed the stability of quality control samples. We also evaluated changes in workflow and staff resources before and after the introduction of the BT-50. The quality control measurement results for the BT-50 and the manual method were found to be equivalent for all six parameters. The variability measured by the BT-50 was lower for some parameters compared to the manual method. Furthermore, the workflow was streamlined by reducing manual processes, resulting in increased efficiency. We confirmed the performance of quality control measurements using the schedule function of the BT-50. Introducing the BT-50 reduced the operator's workload, improved operational efficiency, and promoted the standardization of quality control measurements. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 6-year-old girl experiencing recurrent Kawasaki disease (KD) accompanied by Kawasaki disease shock syndrome (KDSS). Topics discussed include the challenges in diagnosing KDSS, the elevated inflammatory markers indicating severity, and the management strategies implemented, including the use of intravenous immunoglobulin (IVIG) and antiplatelet therapy.

• Higher leukocytes, neutrophils, monocytes, LLR, NLR, MLR, and CRP at SSD diagnosis are linked to higher mortality. • Higher lymphocytes, platelets, and PLR are linked to lower mortality. • CRP has the highest predictive value for mortality. • Higher leukocytes, neutrophils, monocytes, LLR, NLR, and MLR are linked with treatment resistance. • Higher platelets decrease the risk of psychiatric readmissions, while elevated LLR increases this risk. Immune mechanisms are associated with adverse outcomes in schizophrenia; however, the predictive value of various peripheral immune biomarkers has not been collectively investigated in a large cohort before. To investigate how white blood cell (WBC) counts, ratios, and C-Reactive Protein (CRP) levels influence the long-term outcomes of individuals with schizophrenia spectrum disorder (SSD). We identified all adults in the Central Denmark Region during 1994–2013 with a measurement of WBC counts and/or CRP at first diagnosis of SSD. WBC ratios were calculated, and both WBC counts and ratios were quartile-categorized (Q4 upper quartile). We followed these individuals from first diagnosis until outcome of interest (death, treatment resistance and psychiatric readmissions), emigration or December 31, 2016, using Cox regression analysis to estimate adjusted hazard ratios (aHRs). Among 6,845 participants, 375 (5.5 %) died, 477 (6.9 %) exhibited treatment resistance, and 1470 (21.5 %) were readmitted during follow-up. Elevated baseline levels of leukocytes, neutrophils, monocytes, LLR, NLR, MLR, and CRP increased the risk of death, whereas higher levels of lymphocytes, platelets, and PLR were associated with lower risk. ROC analysis identified CRP as the strongest predictor for mortality (AUC=0.84). Moreover, elevated levels of leukocytes, neutrophils, monocytes, LLR, NLR and MLR were associated with treatment resistance. Lastly, higher platelet counts decreased the risk of psychiatric readmissions, while elevated LLR increased this risk. Elevated levels of WBC counts, ratios, and CRP at the initial diagnosis of SSD are associated with mortality, with CRP demonstrating the highest predictive value. Additionally, certain WBC counts and ratios are associated with treatment resistance and psychiatric readmissions. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effect of bovine leukemia virus (BLV) on the systemic profile of naturally infected dairy heifers during the transition period. Pregnant Holstein and Jersey heifers (n=24) were distributed in pairs into two experimental groups: (BLV+) and (BLV–). Animals in the BLV+ group were divided into two subgroups based on the median BLV proviral load (high and low). The animals were then assessed at weeks –3, –2, –1, calving time (0), +1, +2, and +3. Blood samples were obtained for hematological and biochemical analyses, as well as haptoglobin measurements. Farm BLV screening revealed a herd BLV prevalence of 57.25% and heifer BLV prevalence of 38.7%. Mean corpuscular hemoglobin concentration was the only hematological variable for which group interaction was observed, with BLV+ cattle having higher values (33.29 ± 3.39%) than BLV– cattle (31.08 ± 2.31%). Aspartate aminotransferase activity was higher in the BLV+ heifers. The BLV+ group had greater incidence of inflammation (haptoglobin ≥ 2.0 mg/dL). Fibrinogen concentrations were also higher at weeks 0 and +1 in BLV+ heifers than in BLV– heifers. A high proviral load affected total leukocyte and lymphocyte count; however, this profile was not observed in the low proviral load and paired BLV– heifers. To our knowledge, this is the first study to report the impact of BLV infection on the health of dairy heifers during the transition period, demonstrating the effect of proviral load on white blood cell changes and early inflammation in infected animals. [ABSTRACT FROM AUTHOR]

Introduction: The complex and unresolved pathogenesis of schizophrenia has posed significant challenges to its diagnosis and treatment. While recent research has established a clear association between immune function and schizophrenia, the causal relationship between the two remains elusive. Methods: We employed a bidirectional two-sample Mendelian randomization approach to investigate the causal relationship between schizophrenia and 731 immune cell traits by utilizing public GWAS data. We further validated the causal relationship between schizophrenia and six types of white cell measures. Results: We found the overall causal effects of schizophrenia on immune cell traits were significantly higher than the reverse ones (0.011 ± 0.049 vs 0.001 ± 0.016, p < 0.001), implying that disease may lead to an increase in immune cells by itself. We also identified four immune cell traits that may increase the risk of schizophrenia: CD11c+ monocyte %monocyte (odds ratio (OR): 1.06, 95% confidence interval (CI): 1.03~1.09, FDR = 0.027), CD11c+ CD62L-monocyte %monocyte (OR:1.06, 95% CI: 1.03~1.09, FDR = 0.027), CD25 on IgD+ CD38-naive B cell (OR:1.03, 95% CI:1.01~1.06, FDR = 0.042), and CD86 on monocyte (OR = 1.04, 95% CI:1.01~1.06, FDR = 0.042). However, we did not detect any significant causal effects of schizophrenia on immune cell traits. Using the white blood cell traits data, we identified that schizophrenia increases the lymphocyte counts (OR:1.03, 95%CI: 1.01-1.04, FDR = 0.007), total white blood cell counts (OR:1.02, 95%CI: 1.01-1.04, FDR = 0.021) and monocyte counts (OR:1.02, 95%CI: 1.00-1.03, FDR = 0.034). The lymphocyte counts were nominally associated with the risk of schizophrenia (OR:1.08,95%CI:1.01-1.16, P=0.019). Discussion: Our study found that the causal relationship between schizophrenia and the immune system is complex, enhancing our understanding of the role of immune regulation in the development of this disorder. These findings offer new insights for exploring diagnostic and therapeutic options for schizophrenia. [ABSTRACT FROM AUTHOR]

Background:The relationship between serum calcium levels and the prognosis of cerebral infarction remains controversial. Purpose: This study aims to investigate the correlation between serum calcium levels and in-hospital mortality in critically ill patients with ischemic stroke admitted to the intensive care unit (ICU). Methods: A retrospective cohort study was conducted using data from the MIMIC-IV database. Demographic and clinical data of all participants were collected including gender, age, hypertension, diabetes, myocardial infarction, heart failure, chronic obstructive pulmonary disease, hemoglobin, potassium, sodium, anion gap, platelets, white blood cells, glucose, creatinine, Glasgow coma score (GCS), IV-tPA administration (rt-PA), and mechanical thrombectomy (MT). The outcome measure was in-hospital death. Multivariable-adjusted logistic regression analysis, curve fitting, interaction analysis, and threshold eect analysis were employed to evaluate the relationship between serum calcium levels and in-hospital mortality among ICU patients with cerebral infarction. Results: A total of 2,680 critically ill patients with cerebral infarction were enrolled, with a mean serum calcium level of 8.6 ± 0.8 mg/dL. The overall inhospital mortality rate was 19.5%, where Group 1 (serum calcium < 8.0 mg/dL) had a mortality rate of 27.7%, Group 2 (serum calcium 8–9 mg/dL) had a rate of 19.8%, and Group 3 (serum calcium ≥ 9 mg/dL) had a rate of 13.9%. There was a non-linear, S-shaped relationship between serum calcium levels and inhospital mortality. Serum calcium levels within the range of 7.70–9.50 mg/dL were found to be independently associated with increased in-hospital mortality in ICU patients with cerebral infarction. No significant interactions were detected in subgroup analyses, and the results of sensitivity analyses remained stable. Conclusion: Serum calcium levels are independently associated with in-hospital mortality in critically ill patients with cerebral infarction in the ICU setting. Within the range of 7.70–9.50 mg/dL, lower serum calcium levels increase the risk of in-hospital death among these patients, emphasizing the importance of close monitoring by ICU physicians [ABSTRACT FROM AUTHOR]

Gliomas, the most prevalent type of neurological tumor, pose a challenging prognosis for patients. Recent studies have underscored the importance of inflammatory markers such as the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR) in predicting the prognosis of gliomas. We undertook a thorough meta-analysis to elucidate the role of these inflammatory markers in forecasting the prognosis of glioma patients. We extracted hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI) from each study for analysis. To assess heterogeneity and identify influential studies, we conducted sensitivity analysis. Subgroup analysis was performed to investigate sources of heterogeneity, and we employed Egger's test to evaluate publication bias in the meta-analysis. Higher NLR levels were associated with shorter overall survival (HR = 1.46, 95% CI: 1.33–1.60) and progression-free survival (HR = 1.24, 95% CI: 1.04–1.48). There was no significant correlation between PLR levels and overall survival (HR = 1.01, 95% CI: 1.00–1.01) or progression-free survival (HR = 1.00, 95% CI: 0.98–1.02) in glioma patients. Elevated MLR levels were associated with decreased overall survival in glioma patients (HR = 1.78, 95% CI: 1.36–2.34). SII levels did not show any significant association with overall or progression-free survival in glioma patients (HR = 1.00, 95% CI: 0.99–1.01).In the sensitivity analysis, two studies potentially contributed to the instability. Subgroup analyses showed patient population and area were identified as potential sources of heterogeneity. Egger's test showed that there was publication bias in the relationship between NLR and PLR and overall survival (P < 0.05).All randomized controlled models, except for these, were not affected by publication bias. NLR and MLR are two reliable indicators of inflammation in the prognosis of glioma patients; PLR and SII do not have significant value in the prognosis of glioma patients. [ABSTRACT FROM AUTHOR]

Background: Immuno-hematological abnormalities are common among HIV infected individuals as well as patients with highly active antiretroviral therapy (HAART). However, the immuno-hematological outcome of Dolutegravir based antiretroviral therapy (ART) usage is not well investigated. Objectives: To assess hematological and immunological parameters among adult HIV patients before and after initiation of Dolutegravir based ART regimen at St. Peter Specialized Hospital, Addis Ababa, Ethiopia. Methods: A cross-sectional study was conducted from May to July 2021 at St. Peter Specialized Hospital among adult HIV patients. A total of 422 HIV patients on Dolutegravir based ART (combination of Dolutegravir/lamivudine/tenofovir disoproxil fumarate (DTG/3TC/TDF)) for a minimum of 3 months were selected using convenient sampling methods. Socio-demographic as well as clinical data of the participants was obtained using pre-tested structured questionnaires and a review of medical records. Hematological parameters such as CBC was obtained using Beckman coulter automated hematology analyzer and immunological parameters such as CD4 count were determined using BD FACS presto. Statistical analysis of the data was done using SPSS version 21. Paired t-test was used to compare dependent variables before and after initiation of the new HAART and binary logistic regression was used to determine predictors of immuno-hematological abnormalities. P-value < 0.05 was considered as statistically significant. Results: Of 422 adult HIV patients, about 273(64.7%) were females. The mean age of study participants was 42.2 years (±10.4SD). The mean white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (Hb), platelet distribution width (PDW), CD4 count, as well as lymphocyte percentage, neutrophil percentage, and platelet counts (PLT) were increased significantly(P<0.05) after 3 months of the Dolutegravir based therapy. While, red cell distribution width (RDW) and mean cell hemoglobin (MCH) were decreased (P<0.05) after the treatment. Other hematological parameters such as mean cell volume (MCV), hematocrit (HCT), mean cell hemoglobin concentration (MCHC), mean platelet volume (MPV) and platelet distribution width (PDW) showed no significant change. On the other hand, the most common hematological abnormalities identified after the new HAART were anemia (12.1%); followed by Leucopenia (11.3%), neutropenia (6%), and thrombocytopenia (4%). Anemia was associated with female sex (AOR = 7.8, 95% CI: 1.9–32.2, P<0.005) and WHO clinical stage III/IV (AOR = 16, 95% CI: 10.63–66.46, P<0.01). Conclusion: There was a significant change in certain immuno-hematological parameters such as WBC count, RBC count, PLT count, Hb, PDW, CD4 count, lymphocyte and neutrophil percentage after initiation of the Dolutegravir based therapy. Anemia was the most common hematological abnormality. Further studies are required to fully comprehend the outcome of the new treatment regimen on immuno-hematological parameters. [ABSTRACT FROM AUTHOR]

Background: Airway mucus hypersecretion (AMH) can occur in children with acute respiratory diseases, but its underlying mechanisms and relationship with the lower respiratory tract microbiota (LRTM) are not yet fully understood. This study investigates the characteristics of LRTM in children with Mycoplasma pneumoniae pneumonia (MPP) and its impact on AMH. Methods: We collected bronchoalveolar lavage fluid and related clinical indicators from 202 children with MPP. 16S rRNA gene amplicon sequencing was used for detection and identification. Microbial diversity and characteristic genera were compared, and their abundance was analyzed for correlations with clinical factors. Results: As the disease course (days from onset to bronchoscopy, grouped into T1, T2, T3) extended, α-diversity of the LRTM gradually increased, particularly in the T3 hypersecretion group. Moreover, significant differences were observed in the incidence of AMH, co-infection rates, peripheral white blood cell (WBC) count, and C-reactive protein levels. In AMH, Mycoplasmoides and Veillonella abundance and peripheral neutrophils were risk factors for increased secretions. In addition, in the T3 co-infection group, Streptococcus and Prevotella increased, replacing Stenotrophomonas as the dominant genus, possibly due to β-lactam antibiotic use. Prevotella abundance was strongly correlated with WBC. Conclusion: The composition and structure of LRTM in children with MPP played a crucial role in AMH and disease progression. [ABSTRACT FROM AUTHOR]

Introduction: Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is characterized by abrupt onset of obsessive-compulsive disorder or eating restriction along with the abrupt onset of other co-occurring symptoms (tics, behavioral and cognitive regression, etc.). PANS is thought to be a postinfectious immunopsychiatric disorder, although as with most post-infectious disorders, it is challenging to establish a causal relationship with proposed infectious triggers. Intravenous immunoglobulin (IVIG) can modulate inflammation and support the elimination of infection and has been used for treatment of many post-infectious inflammatory disorders and autoimmune conditions. The aim of the study is to explore the pro-inflammatory state in PANS before and after administration of IVIG. Methods: Children with moderate-to-severe PANS received six infusions of IVIG (Octagam 5%, Octapharma) every 3 weeks with post treatment follow-up. Blood samples and psychiatric measures were obtained at Visits 1 (pre-treatment), 7 and 8 (4 and 11 weeks after last infusion, respectively). Myeloid cell activation was assessed via flow cytometry. Results: All ten patients included in the study were male, White, with mean age 12.4 years (range 6–16). Statistically significant improvements following IVIG treatment were demonstrated in all psychometric assessments and parent questionnaires including CY-BOCS (obsessive compulsive scale), YGTSS (tic scale) and a parent PANS rating scale (for all scales p<0.001). The fraction of pro-inflammatory monocytes and dendritic cells decreased from pre-IVIG treatment levels. The proportional reductions were not compensated by increases in total white blood cells; pro-inflammatory monocytes post-IVIG were decreased as a proportion of CD14+ myeloid cells and in absolute number. Conclusions: The results of this study suggest that active PANS is associated with a pro-inflammatory state. This pro-inflammatory profile and psychometric scores improved following IVIG treatment. Future work will aim to further elucidate the roles of innate and adaptive immune responses in PANS and the regulatory mechanism(s) of IVIG in PANS treatment. [ABSTRACT FROM AUTHOR]

Objective: Rare disease. Background: Superior mesenteric artery syndrome, also known as Wilkie's syndrome, is a rare etiology of obstruction of the lower duodenum between the superior mesenteric artery and aorta. It often presents with unspecific abdominal pain and laboratory findings, resulting in difficult diagnosis and treatment. Case Report: A 21-year-old male patient was admitted to our clinic with a 13-month history of coughing, ill feeling, night sweats, vomiting, unintentional weight loss, and epigastric pain. Despite recurrent referral, the diagnostic panels, including a full abdominal laboratory workup, were unremarkable, with the following results: pancreatic amylase: 34.6 U/L, pancreatic lipase: 22 U/L, bilirubin: 0.66 mg/dL, aspartate aminotransferase: 21 U/L, alanine aminotransferase: 40 U/L, white blood cells: 12.59×109/L, plasma total protein: 8.4 g/dL, and hemoglobin: 14.7 g/dL. An abdominal computed tomography scan revealed a paucity of the mesenteric artery and subcutaneous fat, the dilation of the stomach and compression of the duodenum between the superior mesenteric artery and aorta, and an aorto-mesenteric distance of 5.1 mm, resembling superior mesenteric artery syndrome (Wilkie's syndrome). Conservative therapy, including high caloric nutritional support, was administered. A gastroscopy was performed to dilate the distal portion of the duodenum, to enable a physiological passage. The patient was discharged 5 days after diagnosis in good condition, with weight gain, and continued to receive regular follow-up with our outpatient department. Conclusions: This case underlines the importance of considering rare etiologies of abdominal symptoms for concise diagnosis, along with the importance of considering nonsurgical treatment, especially in young patients. [ABSTRACT FROM AUTHOR]

Background and Objectives Materials and Methods Results Conclusion Platelet transfusions carry an important risk of infection transmission. The Mirasol Pathogen Reduction Technology system for platelets uses riboflavin and UV light to introduce irreparable lesions into nucleic acids, thereby inhibiting pathogen replication and inactivating white blood cells. The objective of this study is to evaluate the safety of pathogen‐reduced platelet transfusions (PRPTs) in critically ill infants in a neonatal intensive care unit (NICU) in the Caribbean.We conducted a descriptive retrospective study of the use of Mirasol PRPTs in patients admitted to the NICU of the general hospital in Curaçao from February 2016 to April 2023.A total of 208 PRPTs were administered to 46 patients (median [range] transfusions per patient: 3 [1–24]). Three patients were born term, and 43 were born preterm (median [range] gestational age: 27 4/7 weeks [24 6/7–36 6/7]). PRPTs were well‐tolerated and no complications occurred, especially no signs of haemolysis nor any signs of new infection within 24 h after transfusion. Twenty‐one of 46 patients (46%) died during their admittance. None of the deaths were deemed related to PRPT.Mirasol PRPT appears to be safe for use in critically ill neonates, including extremely preterm neonates. [ABSTRACT FROM AUTHOR]

Chemerin is an adipokine with chemotactic activity to a subset of leukocytes. Chemerin binds to 3 G protein-coupled receptors, including chemokine-like receptor 1 (CMKLR1), G protein-coupled receptor 1 (GPR1), and C-C chemokine receptor-like 2 (CCRL2). Here, we report that GPR1 is capable of Gi signaling when stimulated with full-length chemerin or its C-terminal nonapeptide (C9, YFPGQFAFS). We present high-resolution cryo-EM structures of Gi-coupled GPR1 bound to full-length chemerin and to the C9 peptide, respectively. C9 insertion into the transmembrane (TM) binding pocket is both necessary and sufficient for GPR1 signaling, whereas the full-length chemerin uses its bulky N-terminal core for interaction with a β-strand located at the N-terminus of GPR1. This interaction involves multiple β-strands of full-length chemerin, forming a β-sheet that serves as a "lid" for the TM binding pocket and is energetically expensive to remove as indicated by molecular dynamics simulations with free energy landscape analysis. Combining results from functional assays, our structural model explains why C9 is an activating peptide at GPR1 and how the full-length chemerin uses a "two-site" model for enhanced interaction with GPR1. GPR1 is a chemerin receptor, but whether Gi signaling is elicited upon binding to the chemerin adipokine remains unclear. This study reports a cryo-EM structural analysis of the GPR1-Gi complex bound to chemerin, confirming Gi signaling and a 'two-site' activation mechanism. [ABSTRACT FROM AUTHOR]

Massive transfusion of blood products poses challenges in determining the need for transfusion and the appropriate volume of blood products. This review explores the use of machine learning (ML) models to predict transfusion risk during surgical procedure, focusing on the methodology, variables, and software employed to predict transfusion. This scoping review investigates the development and current state of machine learning models for predicting transfusion risk during surgical procedure, aiming to inform physicians about the field's progress and potential directions. The review was conducted using the databases Cochrane, Embase, and PubMed. The search included keywords related to blood transfusion, statistical models, and surgical procedures. Peer-reviewed articles were included, while literature reviews, case reports, and non-human studies were excluded. A total of 40 studies met the inclusion criteria. The most frequently studied biological variables included haemoglobin, platelet count, international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, creatinine, white blood cells, and albumin. Clinical variables of importance included age, sex, surgery type, blood pressure, weight, surgery duration, american society of anesthesiology (ASA) status, blood loss, and body mass index (BMI). The software employed varied, with Python, R, SPSS, and SAS being the most commonly used. Logistic regression was the predominant methodology used in 20 studies. Our scoping review highlights the need for improved reporting and transparency in methodology, variables, and software used. Future research should focus on providing detailed descriptions and open access to codes of respective models, promoting reproducibility, and enhancing the clinical relevance of transfusion risk prediction models. [ABSTRACT FROM AUTHOR]