Efeito do probiótico lactobacilus casei adjunto a terapia periodontal em modelo experimental de periodontite: uma relação entre periodonto e intestino / Effect of the probiotic lactobacilus casei as an adjunct to periodontal therapy in an experimental model of periodontitis: a relationship between periodontium and intestine

A periodontite é uma condição crônica inflamatória que pode influenciar a microbiota intestinal. O tratamento padrão ouro para a periodontite inclui a raspagem e o alisamento corono-radicular (RACR), porém em casos complexos pode-se utilizar terapias adjuvantes, como os probióticos. A utilização deste tratamento adjuvante poderá contribuir para a melhoria da condição periodontal e a simbiose intestinal. O objetivo deste estudo foi avaliar o efeito na inflamação periodontal e intestinal da utilização do Lactobacillus casei (LC) adjunto a RACR em camundongos Balb/c com periodontite, induzida por ligadura. Este estudo é um ensaio pré-clínico, in vivo, randomizado, cego e controlado por placebo, constituído por 36 camundongos Balb/c machos. Os animais foram submetidos a indução da periodontite por colocação de ligadura com fio de seda 4.0 ao redor do segundo molar superior direito, sendo divididos em 4 grupos,o grupo controle: Sem Periodontite e sem RACR (n=8); Grupo Ligadura: Com Periodondite e sem RACR (n=10); Grupo raspagem: Com Periodontite e com RACR (n=10) ; Grupo raspagem + L.casei (n=8): Com Periodontite e com RACR + administração de LC, por gavagem, durante 30 dias. Foram realizadas análises de citocinas pelo método ELISA no tecido gengival (IL-6), intestinal (IL-1ß, IL-6 e IL-10) e sanguíneo (IL-1ß e IL-6), além de análises bioquímicas (TGO, TGP, ureia e creatinina) e contagem diferencial de leucócitos do sangue. Foram coletados fragmentos do intestino grosso desses animais e analisados quanto a biomarcadores do estresse oxidativo (SOD, GSH e MDA), atividade da acetilcolinesterase (AChE) e foi realizada contagem da população de Bactérias Produtoras de Ácido Láctico das fezes dos animais. A utilização do LC adjunto a RACR resultou em uma redução na expressão da IL-6 no tecido gengival de camundogos com Periodontite (p < 0,05). Para as inteleucinas séricas (IL-1ß e IL-6), não houve diferenças entre os grupos (p > 0,05). Já para as citocinas intestinais houve uma redução na expressão de IL-10 (p < 0,05), para os grupos em que foi induzida a Periodontite. Com relação ao estresse oxidativo intestinal os animais do Grupo raspagem e raspagem + LC tiveram uma redução dos níveis de MDA (p < 0,05), para a SOD e o GSH, não houve diferenças significativas entre os 4 grupos pesquisados (p < 0,05). Conclui-se que o uso de LC adjunto a RACR em camungongos com periodontite induzida por ligadura pode reduzir a liberação de IL-6 no tecido gengival. Com relação aos efeitos intestinais foi observada a modulação da resposta inflamatória, com a redução de MDA, nos animais que receberam o tratamento periodontal. E a redução da expressão da IL-10, nos animais com Periodontite (AU).

Periodontitis is a chronic inflammatory condition that can influence the gut microbiota. The gold standard treatment for periodontitis includes scaling and crown-root planing, but in complex cases adjuvant therapies such as probiotics can be used. The use of this adjuvant treatment may contribute to the improvement of periodontal condition and intestinal symbiosis. The aim of this study was to evaluate the effect on periodontal and intestinal inflammation of the use of Lactobacillus casei (LC) adjunct to scaling and root planing (RACR) in Balb/c mice with ligature-induced periodontitis. This study is a preclinical, in vivo, randomized, blinded, placebo-controlled trial consisting of 40 male Balb/c mice. The animals were submitted to periodontitis induction by placing a 4.0 silk suture ligature around the upper right second molar. The sample was divided into 4 groups, each with 10 animals: Group I: Without Periodontitis and without RACR; Group II: With Periodontitis and without RACR; Group III: With Periodontitis and with RACR; Group IV: With Periodontitis and with RACR + gavage of LC, for 30 days. Cytokine analyzes were performed by the ELISA method in gingival tissue (IL-6), intestinal tissue (IL-1ß, IL-6 and IL-10) and blood (IL-1ß and IL-6), the blood was also subjected to analysis biochemical (TGO, TGP, urea and creatinine) and differential leukocyte count. Fragments of the large intestine of these animals were collected and analyzed for biomarkers of oxidative stress (SOD, GSH and MDA), acetylcholinesterase (AChE) activity, and the population of Lactic Acid-Producing Bacteria in the animals' feces was counted. The use of LC adjunct to RACR resulted in a reduction in the expression of IL-6 in the gingival tissue of mice with Periodontitis (p < 0.05), for the blood inteleukins (IL-1ß and IL-6), there were no differences between the groups (p > 0.05). As for intestinal cytokines, there was a reduction in the expression of IL-10 (p < 0.05), for the groups that presented Periodontitis. Regarding intestinal oxidative stress, the animals in Groups III and IV had a reduction in MDA levels (p < 0.05), for SOD and GSH, there were no significant differences between the 4 groups studied (p < 0.05 ). It is concluded that the use of LC adjunct to RACR in mice with ligation-induced periodontitis can reduce the release of IL-6 in the gingival tissue. Regarding the intestinal effects, two effects were found: The first related to the modulation of the inflammatory response, with the reduction of MDA, in the animals that received periodontal treatment. And the second related to a pro-inflammatory effect, with the reduction of IL-10 expression (AU).

Increasing a microscope's effective field of view via overlapped imaging and machine learning.

This work demonstrates a multi-lens microscopic imaging system that overlaps multiple independent fields of view on a single sensor for high-efficiency automated specimen analysis. Automatic detection, classification and counting of various morphological features of interest is now a crucial component of both biomedical research and disease diagnosis. While convolutional neural networks (CNNs) have dramatically improved the accuracy of counting cells and sub-cellular features from acquired digital image data, the overall throughput is still typically hindered by the limited space-bandwidth product (SBP) of conventional microscopes. Here, we show both in simulation and experiment that overlapped imaging and co-designed analysis software can achieve accurate detection of diagnostically-relevant features for several applications, including counting of white blood cells and the malaria parasite, leading to multi-fold increase in detection and processing throughput with minimal reduction in accuracy.

New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation.

The contemporary strategy for spinal cord injury (SCI) therapy aims to combine multiple approaches to control pathogenic mechanisms of neurodegeneration and stimulate neuroregeneration. In this study, a novel regenerative approach using an autologous leucoconcentrate enriched with transgenes encoding vascular endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) combined with supra- and sub-lesional epidural electrical stimulation (EES) was tested on mini-pigs similar in morpho-physiological scale to humans. The complex analysis of the spinal cord recovery after a moderate contusion injury in treated mini-pigs compared to control animals revealed: better performance in behavioural and joint kinematics, restoration of electromyography characteristics, and improvement in selected immunohistology features related to cell survivability, synaptic protein expression, and glial reorganization above and below the injury. These results for the first time demonstrate the positive effect of intravenous infusion of autologous genetically-enriched leucoconcentrate producing recombinant molecules stimulating neuroregeneration combined with neuromodulation by translesional multisite EES on the restoration of the post-traumatic spinal cord in mini-pigs and suggest the high translational potential of this novel regenerative therapy for SCI patients.

Xuanfei Baidu Decoction reduces acute lung injury by regulating infiltration of neutrophils and macrophages via PD-1/IL17A pathway.

The pathogenic hyper-inflammatory response has been revealed as the major cause of the severity and death of the Corona Virus Disease 2019 (COVID-19). Xuanfei Baidu Decoction (XFBD) as one of the "three medicines and three prescriptions" for the clinically effective treatment of COVID-19 in China, shows unique advantages in the control of symptomatic transition from moderate to severe disease states. However, the roles of XFBD to against hyper-inflammatory response and its mechanism remain unclear. Here, we established acute lung injury (ALI) model induced by lipopolysaccharide (LPS), presenting a hyperinflammatory process to explore the pharmacodynamic effect and molecular mechanism of XFBD on ALI. The in vitro experiments demonstrated that XFBD inhibited the secretion of IL-6 and TNF-α and iNOS activity in LPS-stimulated RAW264.7 macrophages. In vivo, we confirmed that XFBD improved pulmonary injury via down-regulating the expression of proinflammatory cytokines such as IL-6, TNF-α and IL1-ß as well as macrophages and neutrophils infiltration in LPS-induced ALI mice. Mechanically, we revealed that XFBD treated LPS-induced acute lung injury through PD-1/IL17A pathway which regulates the infiltration of neutrophils and macrophages. Additionally, one major compound from XFBD, i.e. glycyrrhizic acid, shows a high binding affinity with IL17A. In conclusion, we demonstrated the therapeutic effects of XFBD, which provides the immune foundations of XFBD and fatherly support its clinical applications.

Prognostic factors to predict the survival in patients with advanced gastric cancer who receive later-line nivolumab monotherapy-The Asahikawa Gastric Cancer Cohort Study (AGCC).

BACKGROUND: Chemotherapy for advanced gastric cancer is recommended in the guidelines; however, later-line treatment remains controversial. Since immune checkpoint inhibitors have been used for the treatment of various malignancies, trials have been performed for gastric cancer. A phase 3 trial indicated the survival benefit of nivolumab monotherapy for gastric cancer patients treated with prior chemotherapy regimens. PATIENTS AND METHODS: A regional cohort study was undertaken to determine the real-world data of nivolumab treatment for patients with advanced or recurrent gastric cancer. The patients were enrolled for 2 years from October 2017 to October 2019 and were prospectively followed for 1 year to examine the overall survival (OS). The patient characteristics were analyzed in a multivariate analysis and a nomogram to predict the probability of survival was generated. RESULTS: In total, 70 patients who received nivolumab as ≥third-line chemotherapy were included in the Asahikawa Gastric Cancer Cohort. The median OS was 7.5 (95% CI, 4.8-10.2) months and the response rate was 18.6%. Diffuse type classification, bone metastasis, high neutrophil/lymphocyte ratio, and high CRP were associated with poor OS/prognosis in the multivariate analysis. A nomogram was developed based on these clinical parameters and the concordance index was 0.80 (95% CI, 0.68-0.91). The responders were aged and were frequently diagnosed with intestinal type gastric cancer, including patients with a HER2-positive status (27.3%) or microsatellite instability-high (27.3%) status. CONCLUSIONS: The regional cohort study of nivolumab monotherapy for gastric cancer patients revealed prognostic factors and a nomogram was developed that could predict the probability of survival.

White blood cell count and clinical outcomes after left main coronary artery revascularization: insights from the EXCEL trial.

BACKGROUND: Prior studies have reported an association between elevated white blood cell count (WBCc) and worse clinical outcomes after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). We assessed the prognostic impact of WBCc in patients undergoing revascularization for left main coronary artery disease (LMCAD). METHODS: In Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL), 1905 patients with LMCAD and low or intermediate SYNTAX scores were randomized to PCI with everolimus-eluting stents versus CABG. The 1895 patients with baseline WBCc available were grouped in tertiles of WBCc (mean 5.6 ± 0.8, 7.5 ± 0.5, and 10.1 ± 1.6 × 109/L). RESULTS: Five-year rates of the primary endpoint (death, myocardial infarction or stroke) were similar across increasing WBCc tertiles (21.2, 18.9, and 21.6%; P = 0.46). Individual components of the primary endpoint, Bleeding Academic Research Consortium (BARC) 3-5 bleeding, stent thrombosis or graft occlusion and ischemia-driven revascularization were all similar across WBCc tertiles. By multivariable analysis, WBCc as a continuous variable was not an independent predictor of adverse events (hazard radio per 1 × 109/L: 1.02; 95% CI, 0.97-1.08; P = 0.43). Results were consistent in the PCI and CABG arms individually. CONCLUSION: There was no association between baseline WBCc and 30-day or 5-year clinical outcomes after PCI or CABG. The absence of a clear incremental increase in events with increasing WBCc in the current analysis indicates that WBCc should not routinely be used as a prognostic marker or to guide revascularization decisions in patients with LMCAD.

Differential effect of clopidogrel and ticagrelor on leukocyte count in relation to patient characteristics, biomarkers and genotype: a PLATO substudy.

Inflammation plays a key role in cardiovascular disease by contributing to atherothrombosis. The PLATelet inhibition and patient Outcomes (PLATO) study (NCT00391872) compared ticagrelor to clopidogrel in patients with acute coronary syndromes and demonstrated fewer cardiovascular events with ticagrelor but lower white blood cell counts (WBC) with clopidogrel. In this further analysis of the PLATO biomarker substudy, we assessed associations between WBC and clinical characteristics, biomarker levels, and CYP2C19 polymorphisms.On-treatment mean (SD) WBC in the clopidogrel group was mildly reduced at each stage of follow-up compared with either the ticagrelor group (1 month: 7.27 (2.1) and 7.67 (2.23) x109/L for clopidogrel and ticagrelor, respectively; p < .001) or following cessation of clopidogrel (7.23 (1.97) x109/L, at 6 months vs 7.56 (2.28) x109/L after treatment cessation; P < .001). This occurred independently of baseline biomarkers and CYP2C19 genotype (where known). Adjusting for clinical characteristics and other biomarkers, no significant interaction was detected between clinical risk factors and the observed effect of clopidogrel on WBC.Clopidogrel weakly suppresses WBC, independent of clinical characteristics, baseline inflammatory biomarker levels, and CYP2C19 genotype. Further work is required to determine the mechanism for this effect and whether it contributes to clopidogrel's efficacy as well as therapeutic interaction with anti-inflammatory drugs.

The prognostic value of neutrophil-to-lymphocyte ratio across all stages of coronary artery disease.

The natural history of coronary heart disease (CAD) commonly begins with atherosclerosis, progressing to chronic coronary syndrome (CCS), acute coronary syndrome (ACS), and eventually, heart failure. Despite advancements in preventive and therapeutic strategies, there is room for further cardiovascular risk reduction. Recently, inflammation has emerged as a potential therapeutic target. The neutrophil-to-lymphocyte ratio (NLR) is a novel inflammatory biomarker which predicts poor prognosis in several conditions such as metabolic syndrome, sepsis, malignancy and CAD. In atherosclerosis, a high NLR predicts plaque vulnerability and severe stenosis. This is consistent with observations in CCS, where an elevated NLR predicts long-term major adverse cardiac events (MACEs). In ACS patients, high NLR levels are associated with larger infarct sizes and poor long-term outcomes. Possible reasons for this include failure of fibrinolysis, ischemia-reperfusion injury and in-stent restenosis, all of which are associated with raised NLR levels. Following myocardial infarction, an elevated NLR correlates with pathological cardiac remodeling which propagates chronic heart failure. Finally, in heart failure patients, an elevated NLR predicts long-term MACEs, mortality, and poor left ventricular assist device and transplant outcomes. Further studies must evaluate whether the addition of NLR to current risk-stratification models can better identify high-risk CAD patients.

The role of inflammatory indices in the outcome of COVID-19 cancer patients.

To assess the prognostic role of different inflammatory indices on the outcome of cancer patients with COVID-19. Sixty-two adults and 22 pediatric cancer patients with COVID-19 infection were assessed for the prognostic value of certain inflammatory indices including the neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), derived NLR (dNLR), systemic inflammation index (SII), mean platelet volume to platelet ratio (MPR), C-reactive protein to lymphocyte ratio (CRP/L), aggregate index of systemic inflammation (AISI), systemic inflammation response index (SIRI), and neutrophil to lymphocyte, platelet ratio (NLPR). Data were correlated to patients' outcome regarding ICU admission, and incidence of mortality. Increased CRP/L ratio in adult COVID-19 cancer patients was significantly associated with inferior survival [152 (19-2253) in non-survivors, compared to 27.4 (0.8-681) in survivors (P = 0.033)]. It achieved a sensitivity (60%) and a specificity (90.2%) at a cut-off 152, while it achieved a sensitivity of 60% and specificity 95.1% at a cut-off 252 (AUC 0.795, P = 0.033). When combining both CRP/L and NLPR for the prediction of poor outcome in adult cancer patients with COVID19, the sensitivity increased to 80% and the specificity was 70.7% (AUC 0.805, P = 0.027). Increased incidence of ICU admission in pediatric cancer patients associated significantly with the severity of covid19 infection, decreased mean corpuscular hemoglobin (MCH) < 28.3, increased red cell distribution width (RDW) > 16, lymphopenia < 1.04, pseudo Pelger-Huet appearance, and PLR < 196.4 (P = 0.004, P = 0.040, P = 0.029, P = 0. 0.039, P = 0.050, and P = 0.040; respectively). The mean corpuscular volume (MCV), MCH, and RDW could be useful prognostic markers for poor outcome in COVID-19 pediatric cancer patients (P < 0.05 for all). Increased both CRP/L and NLPR associated significantly with poor survival in adult COVID-19 cancer patients, while PLR associated significantly with ICU admission in pediatric COVID-19 cancer patients.

Epigenetic quantification of circulating immune cells in peripheral blood of triple-negative breast cancer patients.

BACKGROUND: A shift in the proportions of blood immune cells is a hallmark of cancer development. Here, we investigated whether methylation-derived immune cell type ratios and methylation-derived neutrophil-to-lymphocyte ratios (mdNLRs) are associated with triple-negative breast cancer (TNBC). METHODS: Leukocyte subtype-specific unmethylated/methylated CpG sites were selected, and methylation levels at these sites were used as proxies for immune cell type proportions and mdNLR estimation in 231 TNBC cases and 231 age-matched controls. Data were validated using the Houseman deconvolution method. Additionally, the natural killer (NK) cell ratio was measured in a prospective sample set of 146 TNBC cases and 146 age-matched controls. RESULTS: The mdNLRs were higher in TNBC cases compared with controls and associated with TNBC (odds ratio (OR) range (2.66-4.29), all Padj. < 1e-04). A higher neutrophil ratio and lower ratios of NK cells, CD4 + T cells, CD8 + T cells, monocytes, and B cells were associated with TNBC. The strongest association was observed with decreased NK cell ratio (OR range (1.28-1.42), all Padj. < 1e-04). The NK cell ratio was also significantly lower in pre-diagnostic samples of TNBC cases compared with controls (P = 0.019). CONCLUSION: This immunomethylomic study shows that a shift in the ratios/proportions of leukocyte subtypes is associated with TNBC, with decreased NK cell showing the strongest association. These findings improve our knowledge of the role of the immune system in TNBC and point to the possibility of using NK cell level as a non-invasive molecular marker for TNBC risk assessment, early detection, and prevention.

Profiling of inflammatory cytokines in patients with caustic gastrointestinal tract injury.

INTRODUCTION: Study of inflammatory cytokines in patients with caustic gastrointestinal tract injury is sketchy. This study investigated the cytokine profiling of patients with caustic substance ingestion, and analyzed the differences between patients with severe and mild injury. METHODS: This prospective, cross-sectional study enrolled 22 patients admitted to Chang Gung Memorial Hospital between March and October 2018. All patients underwent esophagogastroduodenoscopy in 24 hours. Patients were categorized into two subgroups, as mild (<2b, n = 11) or severe (≥2b, n = 11) group. RESULTS: The neutrophil count was higher in severe than mild group (P = 0.032). Patients in mild and severe groups exhibited significantly higher circulating inflammatory cytokines than healthy control, including interleukin (IL)-2, IL-5, IL-8, IL-9, IL-12, IL-13, interferon-gamma inducible protein-10, macrophage inflammatory protein-1 beta, regulated upon activation, normal T cell expressed and presumably secreted and tumor necrosis factor-alpha. Furthermore, the levels of IL-2 and tumor necrosis factor-alpha were significantly higher in patients with severe group than mild group. Although there was no difference in cumulative survival between both groups (P = 0.147), the severe group received more operations (P = 0.035) and suffered more gastrointestinal complications (P = 0.035) than mild group. CONCLUSION: Caustic substance ingestion produces mucosal damages and leads to excessive neutrophils and inflammatory cytokines in peripheral blood.

Complete blood cell count-derived ratios can be useful biomarkers for neurological diseases.

Complete blood cell count-derived parameters such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have recently shown to be highly sensitive biomarkers. Their usefulness has been proven as prognostic factors in several cancers, in the stratification of mortality in major cardiac events, as predictors and markers of infectious or inflammatory pathologies, and in many other conditions. Surprisingly, the study of these biomarkers in neurological diseases is somewhat limited. This paper aims to take stock of the data present in the literature regarding the complete blood cell count-derived ratios in this group of pathologies and to formulate a hypothesis, based on the most recent data concerning innate and acquired immunity, on which diseases of the nervous system could benefit in diagnostic and prognostic terms from the in-depth study of these new biomarkers.

Blood leukocyte count as a systemic inflammatory biomarker associated with a more rapid spirometric decline in a large cohort of iron and steel industry workers.

OBJECTIVE: Iron and steel industry workers are exposed to high levels of inhalable dust particles that contain various elements, including metals, and cause occupational lung diseases. We aim to assess the relationship between occupational dust exposure, systemic inflammation, and spirometric decline in a cohort of Chinese iron and steel workers. METHODS: We studied 7513 workers who participated in a Health Surveillance program at Wugang Institute for Occupational Health between 2008 and 2017. Time-weighted exposure intensity (TWEI) of dust was quantified based on self-reported dust exposure history, the experience of occupational hygienists, and historical data of dust exposure for workers with certain job titles. A linear mixed-effects model was used for association analyses. RESULTS: The average annual change of lung function was - 50.78 ml/year in forced expiratory volume in 1 s (FEV1) and - 34.36 ml/year in forced vital capacity (FVC) in males, and - 39.06 ml/year in FEV1 and - 26.66 ml/year in FVC in females. Higher TWEI prior to baseline was associated with lower longitudinal measurements of FEV1 and FVC but not with their decline rates. Higher WBC and its differential at baseline were associated with lower longitudinal measurements and a more rapid decline of FEV1 and FVC in a dose-dependent monotonically increasing manner. Moreover, the increase of WBC and its differential post-baseline was also associated with a more rapid decline of FEV1 and FVC. CONCLUSIONS: Our findings support the important role of systemic inflammation in affecting the temporal change of lung function in iron and steel industry workers.

Predictive value of the monocyte-to-lymphocyte ratio in the diagnosis of prostate cancer.

ABSTRACT: It has been reported that inflammation and immune system are related to prostate cancer. The neutrophil-to-lymphocyte ratio (NLR), as well as the platelet-to-lymphocyte ratio (PLR), have already been proposed as new indices to help diagnose prostate cancer (PCa). However, the monocyte-to-lymphocyte ratio (MLR) with regard to PCa has rarely been mentioned.To investigate the capability of the MLR to predict PCa.Patients who were pathologically diagnosed with PCa in our hospital and healthy control subjects who conformed to the inclusion criteria were enrolled. Patient data were recorded, including age, complete blood counts, blood biochemistry, and serum prostate-specific antigen (PSA) levels. The differences in these data between the groups were analyzed and the diagnostic value of the MLR was compared with PSA.Our study included a total of 100 patients with PCa and 103 healthy control subjects. Patients with PCa presented with a significantly higher NLR, MLR, and PLR compared to control subjects. However, the hemoglobin and lymphocyte levels were lower (P < .05) in PCa patients. The area under the curve (AUC) of PSA and ratio of free/total serum prostate-specific antigen were 0.899 (95% confidence interval [CI]: 0.857-0.942) and 0.872 (95% CI: 0.818-0.926), respectively, while the AUC of the MLR was 0.852 (95% CI: 0.798-0.906), which was higher than that of the NLR, PLR, and any other blood parameters. Additionally, the optimal cut-off value of the MLR for PCa was 0.264, with a specificity of 87.4% and a sensitivity of 72.0%. An evaluation of the diagnostic value of MLR + PSA gave an AUC of 0.936 (95% CI: 0.902-0.970). However, the AUC of MLR + PSA + f/tPSA was 0.996 (95% CI: 0.991-1.000). The diagnostic value of MLR + NLR + PSA gave an AUC of 0.945 (95% CI: 0.913-0.977), and the specificity is 0.971.PSA remains the most important diagnostic indicator. MLR combined with PSA and f/tPSA has the higher predictive value than PSA. It suggests that MLR may be another good predictive indicator of PCa. It can help reduce the clinical false positive rate.

The clinical significance of neutrophil-lymphocyte ratio in patients treated with hemodialysis complicated with lung infection.

ABSTRACT: The goal of this work was to investigate the potential significance of neutrophil-lymphocyte ratio (NLR) in patients treated with maintenance hemodialysis (MHD).Herein, we retrospectively reviewed the electronic medical records of 100 patients with end-stage renal failure who were treated with MHD. All patients enrolled in this study met the inclusion criteria and were followed. The differences in each indicator between the two groups were compared using the Wilcoxon rank-sum test. On the other hand, Spearman correlation and logistic regression analysis were used to explore the correlation and risk factors for pulmonary infection between NLR and other indicators. Finally, we determined the optimal cut-off values for NLR, hypersensitive c-reactive protein (hs-CRP), and procalcitonin (PCT) diagnosis of pulmonary infection using the receiver operating characteristic curve.We found that NLR was positively correlated with age, PCT, hs-CRP, and hospital stay, but negatively correlated with hemoglobin, red blood cell, and Albumin. The expression levels of PCT, hs-CRP, and NLR in the infected group decreased significantly than those before treatment. Multiple regression analysis revealed that NLR is an important independent risk factor for MHD patients with pulmonary infection. Additionally, receiver operating characteristic curve analysis showed that the sensitivity, specificity, and area under the curve were 87.76%, 100%, and 0.920 when using NLR combined with hs-CRP to predict pulmonary infection in MHD patients, whereas that of NLR combined with PCT were 87.76%, 96.08%, and 0.944, respectively.Findings from this study suggested that NLR is an independent risk factor for MHD patients with pulmonary infection, which can effectively predict pulmonary infection. Moreover, sensitivity and specificity were greatly enhanced when using NLR combined with PCT/hs-CRP to predict pulmonary infection in MHD patients.

A Polylobar Nucleus Identifying and Extracting Method for Leukocyte Counting.

Accurate counting of leukocytes is an important method for diagnosing human blood diseases. Because most nuclei of neutrophils and eosinophils are polylobar, it is easily confused with the unilobar nuclei in nucleus segmentation. Therefore, it is very essential to accurately identify and determine the polylobar leukocytes. In this paper, a polylobar nucleus identification and extracting method is proposed. Firstly, by using the Otsu threshold and area threshold method, the nuclei of leukocytes are accurately segmented. According to the morphological characteristics of polylobar leukocytes, the edges of the mitotic polylobar leukocytes are detected, and the numbers of polylobar leukocytes are determined according to the minimal distance rule. Therefore, the accurate counting of leukocytes can be realized. From the experimental results, we can see that using the Otsu method and the area threshold to segment the polylobar nuclear leukocytes, the segmentation ratio of the leukocyte nucleus reached 98.3%. After using the morphological features, the polylobar nuclear leukocytes can be accurately counted. The experimental results have verified the feasibility and practicability of the proposed method.

Randomized, placebo controlled, double blinded pilot superiority phase 2 trial to evaluate the effect of curcumin in moderate to severe asthmatics.

BACKGROUND: Curcumin, a derivative of the spice turmeric, has been adopted by Eastern medicine for centuries as an adjunct to treat several medical conditions (e.g., anorexia and arthritis) because of its well-established anti-inflammatory properties. Studies have shown that the use of curcumin in mice models has led to reduction in several inflammatory markers as well as key inflammatory pathway enzymes. As a result, studies in Western medicine have developed to determine if this recognized benefit can be utilized for patients with inflammatory lung diseases, such as asthma. This study will seek to better understand if curcumin can be used as an adjunctive therapy for improving asthma control of patients with moderate to severe asthma; a finding we hope will allow for a more affordable treatment. METHODS: This study will utilize a randomized, placebo controlled, double blinded pilot superiority phase 2 trial at an outpatient pulmonary clinic in Southern California, USA. Subjects will be receiving Curcumin 1500 mg or matching placebo by mouth twice daily for the study period of 12 weeks. Subjects will be randomized to either a placebo or intervention Curcumin. Subjects will have 6 clinic visits: screening visit, a baseline visit, monthly clinic visits (weeks 4, 8, and 12), at weeks 4, 8, and a follow-up clinic visit or phone-call (week 16). Changes in asthma control test scores, number of days missed from school/work, FEV1 (% predicted), FEV1/FVC ratio, FVC (% predicted), blood eosinophil count, blood total IgE, and FeNO levels will be compared by group over time. DISCUSSION: The therapeutic effects of curcumin have been studied on a limited basis in asthmatics and has shown mixed results thus far. Our study hopes to further establish the benefits of curcumin, however, there are potential issues that may arise from our study design that we will address within this paper. Moreover, the onset of the COVID-19 pandemic has resulted in safety concerns that have delayed initiation of our study. This study will contribute to existing literature on curcumin's role in reducing lung inflammation as it presents in asthmatics as well as patients suffering from COVID-19. TRIAL REGISTRATION: This study protocol has been approved by the Institutional Review Board at Loma Linda University Health, (NCT04353310). IND# 145101 Registered April 20th, 2020. https://clinicaltrials.gov/ct2/show/NCT04353310 .