Green synthesis and two-step chromatographic separation of thiocanthal and thiocanthol: Two novel biologically active sulfur derivatives of oleocanthal and oleacein from extra virgin olive oil.

Oleocanthal and oleacein are the two major secoiridoids exclusively present in extra virgin olive oil (EVOO). Both compounds exert important pharmacological activities, including anti-inflammatory, anti-tumoral, neuro- and cardiovascular protective effects. Due to their enormous potential as possible drugs the extraction of these two bioactive natural products from EVOO has been extensively investigated in the last years and is generally supported by the use of organic chemistry. It is quite difficult to produce large quantities of these two compounds, either by organic solvent extraction and purification or by chemical synthesis, and furthermore organic processes such as cleaning, defatting, and extraction of EVOO pose a threat to the environment and are potentially harmful to workers. In this work we set up a novel aqueous extraction and isolation method from EVOO by transforming oleocanthal and oleacein into two water-soluble sulfonated products. The two derived compounds, here named thiocanthal and thiocanthol, were isolated by a two-step organic free chromatographic strategy, chemically characterized, and evaluated for their inhibitory activity on cyclooxygenase (COX). The results demonstrate that thiocanthal and thiocanthol possess anti-inflammatory effect, which is comparable to their precursors and higher than the well-known non-steroidal anti-inflammatory drug ibuprofen. Computational docking studies were performed to obtain and analyse putative models of the interaction of thiocanthal and thiocanthol with COX-1 and COX-2 binding sites. Predicted binding energy values suggested that both compounds might preferentially bind COX-2, which may have a significant pharmacological impact. Therefore, thiocanthal and thiocanthol, obtained by this novel green process, are extremely interesting both as new bioactive compounds per se and as lead compounds for the development of novel non-steroidal anti-inflammatory drugs (NSAIDs).

Association between changes in high-density lipoprotein cholesterol and risk of cardiovascular disease.

BACKGROUND: The present study was performed to determine the association between changes in the HDL-C concentration and incident CVD. METHODS: Time-dependent Cox regression models were used to evaluate the association between changes in the HDL-C concentration and the risk of incident CVD. Participants were followed up from 2015 to 2021. RESULTS: In total, 24,123 participants with a median follow-up of 4.26 years were analyzed, and the mean age of the cohort was 56.24 years, 57.8 % were female, 24.3 % were current smokers, and 12.8 % had a history of alcohol use. Low, normal, and high HDL-C was defined as <40, 40-80, and >80 mg/dL, respectively. The average time for the two HDL-C measurements was 2.8 years,compared with participants whose HDL-C was maintained at a normal level, the risk of CVD was higher in those whose HDL-C changed to a low level, remained unchanged at a low level(HR, 1.24; 95 % CI, 1.01-1.40,P < 0.001), similarly, the risk of CVD was higher in those whose HDL-C changed from very high level to normal level(HR, 0.81; 95 % CI, 0.67-0.99,P = 0.039). Also compared with participants whose HDL-C was maintained at a normal level, the risk of CVD was lower in those whose HDL-C increased from low to normal and high(HR, 0.80; 95 % CI, 0.66-0.98,P = 0.029). CONCLUSIONS: Participants whose HDL-C changed to a low level and whose low HDL-C level was maintained had a higher risk of CVD, whereas participants whose HDL-C changed from low to high had a lower risk of CVD.

Factors associated with time to death among HIV/TB co-infected patients on ART in Dire Dawa, Ethiopia: A retrospective study.

Background: Tuberculosis is one of the leading causes of death, especially for people living with HIV. However, little is known about the time to death of HIV/TB co-infected patients and associated factors in the study area. This study focused on identifying factors associated with time to death among HIV/TB co-infected patients under antiretroviral therapy in Ethiopia. Methods: From January 2008 to January 2023, a hospital-based retrospective study was conducted on 434 HIV/TB co-infected patients attending the ART clinic at Dilchora Referral Hospital in Dire Dawa, Ethiopia. The medical records were reviewed using a structured data extraction tool. Data were entered with Epi Info version 7 and analyzed with Stata version 17. The Kaplan-Meier survival curve was used along with log-rank tests to estimate and compare survival times. Bi-variable and multivariable Cox regression were performed to identify factors associated with time to mortality in HIV/TB co-infected patients. The adjusted hazard ratio with its 95 % confidence interval was used to estimate the strength of the association and a P-value of 0.05 was considered statistically significant. Results: The study included 434 HIV/TB co-infected patients. The overall median survival time was 144 months (95 % CI: [132, 156]). One hundred thirty-four (30.88 %) deaths were observed during follow-up, resulting in an all-cause mortality rate of 5.1 (95 % CI: [4.29, 6.02]) per 1000 person-months of study follow-up. The independent determinants of mortality were underweight BMI (AHR: 4.52; 95 % CI: [1.30, 15.67]), poor ART adherence (AHR: 1.60; 95 % CI: [1.03, 2.50]), advanced WHO clinical stage (AHR: 1.69; 95 % CI: [1.1, 2.62]), bedridden functional status (AHR: 1.63; 95 % CI: [1.04, 2.57]), initial ART regimen (AHR: 2.68; 95 % CI: [1.74, 4.12]), and smoking status (AHR: 1.48; 95 % CI: [1.01, 2.16]). Conclusion: The mortality rate of HIV/TB co-infected patients in this study was very high. While implementing target improvements in the National Tuberculosis and HIV Program, healthcare providers and policymakers should give higher priority to these risk factors identified in the present study.

A nomogram and heat map based on LASSO-Cox regression for predicting the risk of early-stage severe fever with thrombocytopenia syndrome patients developing into critical illness at 7-day and 14-day.

Severe fever with thrombocytopenia syndrome (SFTS) represents an emerging infectious disease characterized by a substantial mortality risk. Early identification of patients is crucial for effective risk assessment and timely interventions. In the present study, least absolute shrinkage and selection operator (LASSO)-Cox regression analysis was conducted to identify key risk factors associated with progression to critical illness at 7-day and 14-day. A nomogram was constructed and subsequently assessed for its predictive accuracy through evaluation and validation processes. The risk stratification of patients was performed using X-tile software. The performance of this risk stratification system was assessed using the Kaplan-Meier method. Additionally, a heat map was generated to visualize the results of these analyses. A total of 262 SFTS patients were included in this study, and four predictive factors were included in the nomogram, namely viral copies, aspartate aminotransferase (AST) level, C-reactive protein (CRP), and neurological symptoms. The AUCs for 7-day and 14-day were 0.802 [95% confidence interval (CI): 0.707-0.897] and 0.859 (95% CI: 0.794-0.925), respectively. The nomogram demonstrated good discrimination among low, moderate, and high-risk groups. The heat map effectively illustrated the relationships between risk groups and predictive factors, providing valuable insights with high predictive and practical significance.

Mortality Risk Assessment Using Deep Learning-Based Frequency Analysis of EEG and EOG in Sleep.

STUDY OBJECTIVES: To assess whether the frequency content of electroencephalography (EEG) and electrooculography (EOG) during nocturnal polysomnography (PSG) can predict all-cause mortality. METHODS: Power spectra from PSGs of 8,716 participants, included from the MrOS Sleep Study and the Sleep Heart Health Study (SHHS), were analyzed in deep learning-based survival models. The best-performing model was further examined using SHapley Additive Explanation (SHAP) for data-driven sleep-stage specific definitions of power bands, which were evaluated in predicting mortality using Cox Proportional Hazards models. RESULTS: Survival analyses, adjusted for known covariates, identified multiple EEG frequency bands across all sleep stages predicting all-cause mortality. For EEG, we found an all-cause mortality hazard ratio (HR) of 0.90 (CI95% 0.85-0.96) for 12-15 Hz in N2, 0.86 (CI95% 0.82-0.91) for 0.75-1.5 Hz in N3, and 0.87 (CI95% 0.83-0.92) for 14.75-33.5 Hz in REM sleep. For EOG, we found several low-frequency effects including an all-cause mortality HR of 1.19 (CI95% 1.11-1.28) for 0.25 Hz in N3, 1.11 (CI95% 1.03-1.21) for 0.75 Hz in N1, and 1.11 (CI95% 1.03-1.20) for 1.25-1.75 Hz in Wake. The gain in the concordance index (C-index) for all-cause mortality is minimal, with only a 0.24% increase: The best single mortality predictor was EEG N3 (0-0.5 Hz) with C-index of 77.78% compared to 77.54% for confounders alone. CONCLUSION: Spectral power features, possibly reflecting abnormal sleep microstructure, are associated with mortality risk. These findings add to a growing literature suggesting that sleep contains incipient predictors of health and mortality.

Identification of Sweetness Preference-Related Single-Nucleotide Polymorphisms for Polygenic Risk Scores Associated with Obesity.

Our study aimed to identify sweetness preference-associated single-nucleotide polymorphisms (SNPs), characterize the related genetic loci, and develop SNP-based polygenic risk scores (PRS) to analyze their associations with obesity. For genotyping, we utilized a pooled genome-wide association study (GWAS) dataset of 18,499 females and 10,878 males. We conducted genome-wide association analyses, functional annotation, and employed the weighted method to calculate the levels of PRS from 677 sweetness preference-related SNPs. We used Cox proportional hazards modeling with time-varying covariates to estimate age-adjusted and multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for obesity incidence. We also tested the correlation between PRS and environmental factors, including smoking and dietary components, on obesity. Our results showed that in males, the TT genotype of rs4861982 significantly increased obesity risk compared to the GG genotype in the Health Professionals Follow-up Study (HPFS) cohort (HR = 1.565; 95% CI, 1.122-2.184; p = 0.008) and in the pooled analysis (HR = 1.259; 95% CI, 1.030-1.540; p = 0.025). Protein tyrosine phosphatase receptor type O (PTPRO) was identified as strongly associated with sweetness preference, indicating a positive correlation between sweetness preference and obesity risk. Moreover, each 10 pack-year increment in smoking was significantly associated with an increased risk of obesity in the HPFS cohort (HR = 1.024; 95% CI, 1.000-1.048) in males but not in females. In conclusion, significant associations between rs4861982, sweetness preference, and obesity were identified, particularly among males, where environmental factors like smoking are also correlated with obesity risk.

Development of a highly specific LAMP assay for detection of Sarcocystis tenella and Sarcocystis gigantea in sheep.

Sarcocystis infection in sheep has caused significant economic losses in the livestock industry, and the genetic similarity among Sarcocystis species highlights the need for precise diagnostic methods in sheep. This study developed a loop-mediated isothermal amplification (LAMP) method targeting COX-1 and 28S rRNA genes to detect Sarcocystis tenella and Sarcocystis gigantea, respectively. The LAMP method exhibited high specificity, selectively amplifying target DNA sequences without cross-reactivity with closely related protozoa, such as Toxoplasma gondii and Neospora caninum. Detection limits were determined as 3 × 105 copies/L for S. tenella and 6 × 104 copies/L for S. gigantea, enabling sensitive identification of low-level infections. Comparative analysis with conventional PCR on sheep cardiac tissues demonstrated a higher LAMP detection rate (80.0% vs 66.7%). In conclusion, the LAMP method offers superior sensitivity to conventional PCR, allows visual confirmation of results, and provides a rapid diagnostic tool for identifying S. tenella and S. gigantea infection in sheep. However, due to the limitation of sample availability, we were unable to assess all Sarcocystis species that use sheep as intermediate hosts, which warrants further research.

Inferring Diagnostic and Prognostic Gene Expression Signatures Across WHO Glioma Classifications: A Network-Based Approach.

Tumor heterogeneity is a challenge to designing effective and targeted therapies. Glioma-type identification depends on specific molecular and histological features, which are defined by the official World Health Organization (WHO) classification of the central nervous system (CNS). These guidelines are constantly updated to support the diagnosis process, which affects all the successive clinical decisions. In this context, the search for new potential diagnostic and prognostic targets, characteristic of each glioma type, is crucial to support the development of novel therapies. Based on The Cancer Genome Atlas (TCGA) glioma RNA-sequencing data set updated according to the 2016 and 2021 WHO guidelines, we proposed a 2-step variable selection approach for biomarker discovery. Our framework encompasses the graphical lasso algorithm to estimate sparse networks of genes carrying diagnostic information. These networks are then used as input for regularized Cox survival regression model, allowing the identification of a smaller subset of genes with prognostic value. In each step, the results derived from the 2016 and 2021 classes were discussed and compared. For both WHO glioma classifications, our analysis identifies potential biomarkers, characteristic of each glioma type. Yet, better results were obtained for the WHO CNS classification in 2021, thereby supporting recent efforts to include molecular data on glioma classification.

An MRI-based radiomics nomogram to predict progression-free survival in patients with endometrial cancer.

Aim: This study aimed to explore the importance of an MRI-based radiomics nomogram in predicting the progression-free survival (PFS) of endometrial cancer.Methods: Based on clinicopathological and radiomic characteristics, we established three models (clinical, radiomics and combined model) and developed a nomogram for the combined model. The Kaplan-Meier method was utilized to evaluate the association between nomogram-based risk scores and PFS.Results: The nomogram had a strong predictive ability in calculating PFS with areas under the curve (ROC) of 0.905 and 0.901 at 1 and 3 years, respectively. The high-risk groups identified by the nomogram-based scores had shorter PFS compared with the low-risk groups.Conclusion: The radiomics nomogram has the potential to serve as a noninvasive imaging biomarker for predicting individual PFS of endometrial cancer.

[Box: see text].

Prevalence and molecular identification of hypodermosis from slaughtered cattle in Sulaymaniyah province, Iraq.

INTRODUCTION: Hypodermosis is a subcutaneous infestation in cattle that is caused by larvae of Hypoderma spp. and it is an economically important disease in the cattle industry. This study aimed to find the prevalence rate of hypodermosis and identify variations in the COX1 gene among isolates present in Sulaymaniyah, in the Kurdistan region of Iraq. METHODOLOGY: The study was conducted in a Sulaymaniyah slaughterhouse from March to July 2021. The carcasses of 867 cattle were carefully checked before and after skinning them to record the presence of boils containing the larvae of Hypoderma spp. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using TaqI enzyme, and sequencing of the COX1 gene were used for diagnosis and molecular characterization of Hypoderma spp. RESULTS: The rate of infestation with Hypoderma bovis was 1.61% and the highest rate (3.57%) was detected in April. The disease was significantly (p < 0.05) higher in local breeds at 2.79%. PCR-RFLP confirmed that all recorded species were H. bovis. The result was further confirmed by Sanger sequencing of the COX1 gene of the isolated species. Comparison of the sequences of the conserved COX1 gene of the parasite led to identification of six different haplotypes in the research area. Two of the haplotypes were previously recorded internationally, while four new haplotypes associated with four novel mutations were recorded for the first time in the study region. CONCLUSIONS: Based on these results we can conclude that H. bovis is a widespread species in the research region.

Acarbose might be associated with reduced risk of gastric cancer in patients with diabetes mellitus: A nationwide population-based cohort study.

BACKGROUND: Several epidemiologic studies have revealed a higher risk of cancer in patients with diabetes mellitus (DM) relative to the general population. To investigate whether the use of acarbose was associated with higher/lower risk of new-onset cancers. METHOD: We conducted a retrospective cohort study, using a population-based National Health Insurance Research Database of Taiwan. Both inpatients and outpatients with newly onset DM diagnosed between 2000 and 2012 were collected. The Adapted Diabetes Complications Severity Index (aDCSI) was used to adjust the severity of DM. The Cox proportional hazards regression model was used to estimate the hazard ratio (HR) of disease. RESULTS: A total of 22 502 patients with newly diagnosed DM were enrolled. The Cox proportional hazards regression model indicating acarbose was neutral for risk for gastroenterological malignancies, when compared to the acarbose non-acarbose users group. However, when gastric cancer was focused, acarbose-user group had significantly lowered HR than non-acarbose users group (p = 0.003). After adjusted for age, sex, cancer-related comorbidity, severity of DM, and co-administered drugs, the HR of gastric cancer risk was 0.43 (95% CI = 0.25-0.74) for acarbose-user patients. CONCLUSION: This long-term population-based study demonstrated that acarbose might be associated with lowered risk of new-onset gastric cancer in diabetic patients after adjusting the severity of DM.

Explore on screening COX-2 inhibitors from the essential oil of Solanum lyratum Thunb. By molecular docking and molecular dynamics simulation.

This study aimed to investigate Solanum lyratum Thunb. with respect to the potential ingredients with anti-inflammatory activity from its essential oil by silico study. To this regard, the essential oil of Solanum lyratum Thunb. was extracted by hydrodistillation. 25 compounds were identified by GC-MS. Using virtual screening, molecular docking and molecular dynamics simulation of the 25 identified compounds, the ones showing anti-inflammatory activity on COX-2 were identified. According to the drug-like principle and the prediction of ADEMT properties, the six compounds of Spathulenol, Cedrol, Juniper camphor, Santalol, Nootkatone and 7,9-Di-tert-butyl-1-oxaspiro[4.5]deca-6,9-diene-2,8-dione were identified and then studied for molecular docking, and based on which the top two compounds of binding free energy were studied by the molecular dynamics simulation. The molecular docking data indicated that the binding free energies of Spathulenol, Cedrol, Juniper camphor, Santalol, Nootkatone and 7,9-Di-tert-butyl-1-oxaspiro[4.5]deca-6,9-diene-2,8-dione to COX-2 protein were -5.65, -7.19, -6.35, -4.94, -5.82 and -5.14 kcal/mol, respectively. The findings showed the steady interactions of hydrogen bonds and hydrophobic bonds between both the top two compounds of binding free energy and the active site residues of COX-2 (4M11) throughout the simulation via hydrogen bonds and hydrophobic bonds. The very study shall be supportive for in vitro and in vivo studies in developing drug products using the lead bioactive ingredients for anti-inflammatory in the future.

Treatment of metastatic apocrine sweat gland adenocarcinoma in a cat with association of surgical resection and angular oris reconstruction, extensive lymphadenectomy, electrochemotherapy and systemic chemotherapy.

Apocrine sweat gland adenocarcinoma (ASGAC) is a rare skin carcinoma in cats. In some cases, this tumor occurs in anatomical sites of challenging wide surgical resection, which increases the need for adjuvant therapies for residual disease. These include radiotherapy or electrochemotherapy (ECT), local treatments for invasive tumors in companion animals often associated with surgery. However, the current literature for ASGAC treatment is limited and there are no reports of ECT as an adjuvant therapy. In this case report, we account for the case of an 11-year-old cat with a history of a non-ulcerated recurrent ASGAC, measuring 1.3 × 1.0 cm, located by the rostral mandibular region. Surgical resection included the angularis oris axial flap for facial reconstruction associated with electroporation of the surgical bed and, post-operatively, in the surgical scar. Histopathological results confirmed the presence of a recurrent ASGAC. Immunostaining revealed cyclooxygenase 2 (COX-2) expression with a score of 6, 50 % positivity in Ki-67, and positive for pan-cytokeratin (PCK AE-1/ AE-3). A selective COX-2 inhibitor was initiated along with systemic chemotherapy with chlorambucil. The local approach including surgery and ECT was chosen due to the unfavorable anatomical site for extensive resection and the unavailability of radiotherapy. Subsequently, carboplatin chemotherapy was required due to metastasis in the mandibular lymph node. This case report supports the effectiveness of a multimodal treatment including surgery, ECT, and chemotherapy in a cat with recurrent ASGAC.

Assessment of cell death in the liver of Labeo rohita on exposure to an emerging contaminant aspirin: an immunofluorescent, flow cytometric and biochemical investigation.

Aspirin is one of the most frequently detected non-steroidal anti-inflammatory drugs in aquatic environments. Despite its prevalence, toxicity possessed by aspirin to non-target organisms like fish is poorly explored. In the present study, cell death induced by different concentrations of aspirin (1, 10, and 100 µg/L) has been investigated in the liver of fish, Labeo rohita exposed for 28 days. A significant increase (p < 0.05) in the density of caspase-3 positive cells in a dose and duration-dependent manner assessed through immunofluorescent staining indicates caspase-dependent pathway of cell death which may be either through intrinsic or extrinsic pathway. The flow cytometric analysis, in addition, revealed a significant (p < 0.05) decline in the live cells and an increase in apoptotic cells in the liver of fish exposed to aspirin. Cell death due to apoptosis is further indicated by a significant increase (p < 0.05) in the Kupffer cells and tumor necrosis factor-α. The decrease in the activity of cyclooxygenase (COX) enzyme significantly (p < 0.05) in all three exposure concentrations of aspirin suggests COX-dependent pathway of cell death. The present study provides in-depth insights into aspirin-induced cell death in the liver of fish at environmentally realistic concentrations.

The spread of the invasive mosquito Aedes albopictus (Diptera: Culicidae) in Portugal: a first genetic analysis.

BACKGROUND: Aedes albopictus, commonly known as the Asian tiger mosquito, has become one of the most invasive mosquito species. Over the last 5 decades, it has been introduced and established in various tropical and temperate regions worldwide. First reported in Europe in 1979 in Albania and later in Italy in 1990, the species is now established in 13 European Union (EU)/European Economic Area (EEA) countries and 337 regions (2023). In Portugal, Ae. albopictus was first detected in the Algarve and Penafiel regions in 2017, followed by Alentejo in 2022 and Lisbon in 2023. This mosquito species poses a significant public health risk as a vector for numerous pathogenic viruses, including dengue, Zika, and chikungunya. METHODS: Aedes albopictus collected in Lisbon in 2023 were analyzed using cytochrome c oxidase I (COX) gene sequencing to understand their genetic relationships. RESULTS: Our data indicate that the Ae. albopictus mosquito populations detected in three locations in Lisbon in 2023 correspond to recent but distinct introduction events. CONCLUSIONS: Although there has been no local transmission of Aedes-transmitted viruses in mainland Portugal to date, the spread of the mosquito and increased international travel increase the risk of Aedes-borne disease outbreaks. The ongoing spread of Ae. albopictus in the country and the confirmed multiple introductions in new locations raise awareness of the need to monitor mosquito vectors to control and prevent autochthonous Aedes-borne disease outbreaks.

Prognostic Role of Clinicopathological Characteristics and Serum Markers in Metastatic Melanoma Patients Treated with BRAF and MEK Inhibitors.

Prognostic studies can provide important information about disease biology and improve the use of biomarkers to optimize treatment decisions. METHODS: A total of 199 patients with advanced melanoma treated with BRAF + MEK inhibitors were included in our single-center retrospective study. We analyzed the risk of progression and death using multivariate Cox proportional hazard models. The predictive effect of prognostic factors on progression-free survival (PFS) was evaluated in ROC analysis. RESULTS: We found that primary tumor localization, Clark level, pT category, baseline M stage and baseline serum S100B are independent and significant prognostic factors for PFS. The discriminative power of the combination of these factors was excellent for predicting 18 month PFS (AUC 0.822 [95% CI 0.727; 0.916], p < 0.001). Primary tumor localization on the extremities, Clark level V, baseline M1c stage or M1d stage, and elevated baseline serum S100B and LDH levels were independently and significantly associated with unfavorable overall survival (OS). CONCLUSION: Baseline M stage and serum S100B appear to be independent prognostic factors for both PFS and OS in melanoma patients treated with BRAF + MEK inhibitors. We newly identified significant and independent prognostic effects of primary tumor localization and Clark level on survival that warrant further investigation.

TMT-based proteomics reveals methylprotodioscin alleviates oxidative stress and inflammation via COX6C in myocardial infraction.

The effect of methylprotodioscin (MPD), a steroidal saponin obtained from medicinal plants, on myocardial infarction (MI) remains elusive. In this study, HL-1 and AC16 cells were subjected to injury induced by hypoxic environment, and a mouse model of MI was established by ligating the left anterior descending. MPD significantly increased viabilities and proliferations, improved the stability of MMP, reduced ROS and inflammatory factor levels in hypoxia cardiomyocytes. Moreover, MPD significantly improved cardiac functions, increased the ventricular ejection fraction and short axis shortening rate of mice with MI, reduced the infarction area, alleviated oxidative stress and increased ATPase activities. Then, differentially expressed proteins (DEPs) were discovered and evaluated using tandem mass tag (TMT)-based proteomics and bioinformatics approaches. Compared with sham group, there were 420 DEPs in the cardiac tissue of MI group, likewise, 163 DEPs in MPD group were identified compared to MI group. By validating, the expression of COX6C was elevated in MI group and declined in MPD groups, consistent with the TMT-based proteomics results. Correspondingly, p-NF-κB expression was downregulated, while Nrf2 and SOD expressions were upregulated by MPD. Moreover, si-COX6C transfection blocked the regulatory effects of MPD on COX6C-mediated inflammation and oxidative stress in MI. Our findings indicate that MPD, a naturally occurring active ingredient, could effectively improve cardiac function. Its ability may result from regulating COX6C to reduce oxidative stress and suppress inflammation, suggesting that MPD is very attractive for the treatment of MI.

Inflammatory and immune variables as predictors of survival in dogs with myxomatous mitral valve disease.

BACKGROUND: We aimed to investigate the association between selected inflammatory and immune variables and survival of dogs with myxomatous mitral valve disease (MMVD). We evaluated data of 62 client-owned dogs with MMVD, grouped into preclinical, stable congestive heart failure (CHF) and unstable CHF. Univariate Cox proportional hazards regression analysis was used to quantify the association of white blood cell count, concentrations and percentages of T lymphocytes and their subtypes (T helper lymphocytes, cytotoxic T lymphocytes, double positive T lymphocytes, double negative T lymphocytes) and B lymphocytes with survival. P values < 0.1 in individual groups and P values < 0.05 in the group of all patients were considered significant. Spearman correlation coefficients between significant covariates were calculated to assess the relationships among variables and with survival. RESULTS: In the preclinical group, percentage of double positive T lymphocytes was negatively associated with survival (hazard ratio (HR) = 2.328; P = 0.051). In the unstable CHF, T lymphocyte (HR = 1.613; P = 0.085), cytotoxic T lymphocyte (HR = 1.562; P = 0.048), double positive (HR = 1.751; P = 0.042), and double negative T lymphocyte (HR = 1.613; P = 0.096) concentrations were negatively associated with survival, as well as cytotoxic T lymphocyte (HR = 1.502; P = 0.007) concentration in the group of all patients. The percentage of T helper lymphocytes was positively associated with survival in the unstable CHF (HR = 0.604; P = 0.053) and in the group of all patients (HR = 0.733; P = 0.044). The concentration of cytotoxic T lymphocytes positively correlated with left atrial to aortic ratio (LA/Ao) (rho = 0.259, P = 0.037), and peak velocity of early diastolic mitral flow (rho = 0.259, P = 0.039), whereas the percentage of T helper lymphocytes negatively correlated with left atrial to aortic ratio (LA/Ao) (rho = -0.212, P = 0.090) and early to late mitral flow ratio (rho = -0.232, P = 0.072). CONCLUSIONS: Cytotoxic T lymphocytes, T helper lymphocytes, double positive and double negative T lymphocytes as well as biomarkers cardiac troponin I, N-terminal pro-B-type natriuretic peptide, C-reactive protein are implicated in the progression of MMVD.

Development and Validation of a Prognostic Nomogram Model for HER2-Positive Male Breast Cancer Patients.

BACKGROUND: HER2-positive male breast cancer (MBC) is a rare condition that has a poor prognosis. The purpose of this study was to establish a nomogram model for predicting the prognosis of HER2-positive MBC patients. METHODS: 240 HER2-positive MBC patients from 2004 to 2015 were retrieved from the surveillance, epidemiology, and end results (SEER) database. All HER2-positive MBC patients were divided randomly into training (n = 144) and validation cohorts (n = 96) according to a ratio of 6:4. Univariate and multivariate Cox regression analyses were used to determine the prognostic factors associated with HER2-positive MBC patients. A clinical prediction model was constructed to predict the overall survival of these patients. The nomogram model was assessed by using receiver operating characteristics (ROC) curves, calibration plots and decision curve analysis (DCA). RESULTS: The Cox regression analysis showed that T-stage, M-stage, surgery and chemotherapy were independent risk factors for the prognosis of HER2-positive MBC patients. The model could also accurately predict the Overall survival (OS) of the patients. In the training and validation cohorts, the C indexes of the OS nomograms were 0.746 (0.677-0.815) and 0.754 (0.679-0.829), respectively. Calibration curves and DCA verified the reliability and accuracy of the clinical prediction model. CONCLUSION: In conclusion, the predictive model constructed had good clinical utility and can help the clinician to select appropriate treatment strategies for HER2-positive MBC patients.

Genetic variation and population structure of Taenia multiceps (Coenurus cerebralis) based on mitochondrial cox1 gene: A comprehensive global analysis.

Taenia multiceps is a neglected parasite having veterinary and public health importance. The predilection sites of the parasite larva (Coenurus cerebralis) are brain (cerebral coenurosis) and subcutaneous (non-cerebral coenurosis). There is a dearth of data regarding molecular characterization of T. multiceps and even fewer population structure-based studies on T. multiceps. The current study was conducted to provide epidemiological information regarding the global population structure of the parasite. The NCBI GenBank database was accessed to download the sequences of cox1 gene, which were further subjected to PopArt software to construct median-joining networks. The DnaSp software was used to compute neutrality and diversity indices. Host and region-wise indices of neutrality and diversity were also computed. There were 166 gene sequences found in the NCBI database. Followed by removal of short gene sequences, 143 were considered to perform bioinformatic analyses. A total of 30 haplotypes with 46 mutations and 23 parsimony informative sites were found. High diversity (Hd = 0.889, π = 0.01186) and negative but statistically insignificant neutrality indices (Tajima's D = -1.57659, Fu's Fs = -10.552) were found. Region-wise results revealed highest haplotype diversities in isolates from KSA (Hd = 1.00) followed by Greece and Italy (Hd = 0.962), and China (Hd = 0.931). Host-wise data analysis showed an overall negative Tajima's D value and there exists highest haplotype diversity in cattle (Hd = 1.00) followed by dogs (Hd = 0.833), sheep (Hd = 0.795) and goats (Hd = 0.788). The findings of the study indicate that the population diversity of T. multiceps will increase worldwide as shown by high diversity and negative neutrality indices. The findings of the study significantly add-in to the existing bank of knowledge about population structure of T. multiceps. We recommend conducting more studies employing different genetic markers to better comprehend the epidemiology of the parasite.