Collected Blood Samples Research Articles

Recognition of HLA-DPB1 alleles and their associated HLA haplotypes in 55 randomized unrelated Taiwanese individuals.

Here, we report the distribution of HLA-DPB1 alleles studied in a cohort of 55 randomly collected blood samples from unrelated Taiwanese individuals and the deduced most likely HLA haplotypes associated with the defined DPB1 alleles in the cohort. Our aim is to reveal the unprecedented data on the distribution of HLA-DPB1 alleles in the Taiwanese population and to find out the most probable HLA haplotypes associated with the HLA-DPB1 alleles detected. The material for this study was blood samples, preserved in K2EDTA and/or acid citrate dextrose anticoagulants. The blood donors were voluntary individuals of Tzu Chi Bone Marrow Donor Registry, Tzu Chi Stem Cells Center, Hualien Tzu Chi Hospital. Sequence-based typing of the Sanger's sequencing method was performed for the HLA allelic typing. To discern the HLA-DPB1 alleles, exons 2 and 3 of the HLA-DPB1 locus were sequenced. Target exon sequence amplifications were achieved by polymerase chain reaction, and the resulting amplicons were sequenced by BigDye Terminator Cycle Sequencing Ready Reaction Kit according to the manufacturer's protocols. In the total number of 55 randomized unrelated Taiwanese individuals studied, we detected 11 different HLA-DPB1 alleles. DPB1*05:01 (44.54%) was the allele with the highest frequency observed and the next highest frequency allele found was DPB1*02:01 (17.27%), while DPB1*38:01 (0.90%) and DPB1*700:01N (0.90%) ranked the least observed DPB1 alleles. Our findings in this study may be useful in researches reinforcing the comprehensive understanding on the distribution of DPB1 alleles and their associated HLA haplotypes and their clinical applications in Taiwanese.

Preliminary results of anti-inflammatory cytokine concentrations predicting therapy outcome in panic disorder

BackgroundPatients with panic disorder (PD) show alterations of the immune reactivity to acute stress, which could serve as a marker for effective treatment. Nevertheless, the effect of immune reactivity under acute stress before treatment on therapy outcome remains unclear. MethodsA total of N = 16 PD patients performed the Trier Social Test. Blood sample collection of anti-inflammatory cytokine IL-10 accompanied the TSST. The Mobility Inventory was handed out for the assessment of avoidance behavior before and after treatment. Area under the curve with respect to the ground (AUCG) and increase (AUCI) were calculated for assessed cytokine levels and were used as predictors for therapy outcome in regression analyses. ResultsAUCG significantly predicts avoidance behavior in company after treatment (β = −0.007, p = .033) but not avoidance behavior alone (β = −0.003, p = .264). AUCI does not significantly predict therapy outcome. ConclusionHigher concentrations of anti-inflammatory cytokine IL-10 under acute stress before treatment predicts less avoidance behavior in company after therapy. Immune markers seem to play a crucial role in the maintenance of mental disorders such as PD. Underlying mechanisms and IL-10 as a marker for individualized treatments should be investigated in future studies.

Analytical Validation of a Volumetric Absorptive Microsampling Method for Therapeutic Drug Monitoring of the Oral Targeted Anticancer Agents, Abiraterone, Alectinib, Cabozantinib, Imatinib, Olaparib, and Sunitinib, and Metabolites.

Volumetric Absorptive Microsampling (VAMS) is a useful tool for therapeutic drug monitoring (TDM) of oral targeted anticancer agents. VAMS aims to improve safety and efficacy by enabling at-home blood sample collection by patients. This study aimed to develop and validate an ultra-high performance liquid chromatography-tandem mass spectrometry method for the quantitative determination of abiraterone, alectinib, cabozantinib, imatinib, olaparib, sunitinib, and the metabolites, Δ(4)-abiraterone (D4A), alectinib-M4, imatinib-M1, and N -desethyl sunitinib, in dried whole blood samples using VAMS to support TDM. After the collection of 10 μL of whole blood sample using the VAMS device, the analytes were extracted from the tip using methanol with shaking, evaporated, and reconstituted in acetonitrile:0.1 mol/L ammonium hydroxide in water (1:1, vol/vol). The extracts were then analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry. Validation experiments based on the ICH M10 guideline were carried out, and stability was evaluated under shipping and storage conditions. VAMS specimens were collected in the outpatient clinic to demonstrate the applicability of the assay. The validated range of the method was considered accurate and precise for all analytes. Accordingly, the validation experiments met the relevant requirements, except for cross-analyte interference. Based on the stability data, shipment can be performed at room temperature within 14 days after sample collection and the VAMS specimen can be stored up to 9 months at -20 and -70°C. Samples from 59 patients were collected at the hospital. The developed method could be used to successfully quantify the concentrations of abiraterone, D4A, alectinib, alectinib-M4, cabozantinib, imatinib, imatinib-M1, olaparib, sunitinib, and N -desethyl sunitinib within the validated range using VAMS. Therefore, the method can be used to estimate the dried whole blood-to-plasma ratios for TDM in the clinic.

Long-Term Kinetics of SARS-CoV-2 Neutralizing and Anti-Receptor Binding Domain Antibodies among Laboratory-Confirmed COVID-19 Cases in Delhi National Capital Region, India: A Prospective, One-Year Follow-Up Study.

Background: This study was conducted with the objective of measuring the neutralizing and anti-receptor binding domain antibody levels against SARS-CoV-2 among laboratory-confirmed COVID-19 cases and exploring its long-term kinetics over a period of 1 year. Methods: One hundred laboratory-confirmed COVID-19 cases were recruited. Serum samples of the participants were collected within three months from the date of the positive COVID-19 report. The participants were prospectively followed up every three months for symptoms and the collection of blood samples for three additional rounds. The presence of anti-SARS-CoV-2 antibodies (IgA, IgG, and IgM antibodies), anti-receptor binding domain antibodies (anti-RBD), and neutralizing antibodies were measured. Findings: Median plaque reduction neutralization test (PRNT) titers showed a rising trend in the first three rounds of follow-up. The quantitative anti-receptor binding domain ELISA (QRBD) values showed a declining trend in the initial three rounds. However, both the PRNT titers and QRBD values showed significantly higher values for the fourth round of follow-up. Total antibody (WANTAI) levels showed an increasing trend in the initial three rounds (statistically significant). Interpretation: Neutralizing antibodies showed an increasing trend. The anti-receptor binding domain antibodies showed a decreasing trend. Neutralizing antibodies and anti-RBD antibodies persisted in the majority.

Biosorption and Bioprotective Potential of Levilactobacillus brevis in Mice Challenged by Lead-Induced Oxidative Stress.

Lead (Pb) poisoning is a widespread issue in both developed and developing countries that poses a significant public health challenge. Our study aimed to explore the impact of Levilactobacillus brevis strains on inflammatory and antioxidant gene expression in the liver and brain of mice exposed to oxidative stress caused by Pb. We began by evaluating Pb absorption by Levilactobacillus brevis strains (ARKA-CH-1 (A1) and ARKA-CH-6 (A6)) using the inductively coupled plasma mass spectrometry (ICP-MS) in vitro to identify the most effective strain. We then divided four groups of BALB/c mice into control and experimental groups and treated them for 30days. The control group received a normal diet, while the experimental groups consumed lead-containing water (0.6g/L) with or without Levilactobacillus brevis strains. Following the experiments, we collected blood samples to test liver markers, antioxidant enzymes, and immunoglobulins. We also used real-time PCR to examine the expression of superoxide dismutase (SOD) and inducible nitric oxide synthase (iNOS) genes. The results showed that the A1 strain was the most effective in absorbing Pb. The Pb exposure led to an increase in liver enzyme values and a decrease in antioxidant enzyme activity and immunoglobulin factors. However, the combination of A1 and A6 strains had a greater effect in reducing inflammatory enzymes and increasing antioxidant enzymes. Furthermore, we observed a significant increase in iNOS gene expression and a notable decrease in SOD gene expression with Pb consumption. However, the combination of A1 and A6 strains had a synergistic effect in reducing iNOS and increasing SOD gene expression. In conclusion, Levilactobacillus brevis A1 strain alone or in combination with the A6 strain could be a promising strategy to mitigate the oxidative stress symptoms in mice challenged by lead-induced toxicity.

Distribution of ABO-Rh Blood Group System Among the Students at Shah Abdul Latif University Khairpur, Pakistan

Background: The distribution of ABO and Rh blood groups significantly varies across different populations and is crucial for effective blood bank management and transfusion services. Previous studies have shown diverse patterns in blood group distribution globally, influenced by regional, ethnic, and demographic factors. Objective: This study aimed to analyze the distribution of ABO and Rh blood groups among the student population at Shah Abdul Latif University (SALU), Sindh, Pakistan, and to understand its implications for local healthcare services. Methods: A cross-sectional study was conducted involving 253 students (133 males and 120 females) aged 18 to 24 years. Informed consent was obtained from all participants. The study employed a sterile lancet for blood sample collection via a finger prick. Blood group phenotyping was done using the slide method with monoclonal antiserum A, B, and D. Agglutination results were recorded to determine the ABO blood group and Rh factor. Data analysis was conducted using the Statistical Package for the Social Sciences (SPSS) version 25. Results: The study found that 21.7% of students belonged to blood group A (49.1% Rh positive and 5.5% Rh negative in males, 40% Rh positive and 5.5% Rh negative in females), 35.2% to blood group B (38.2% Rh positive and 6.7% Rh negative in males, 52.8% Rh positive and 2.3% Rh negative in females), 11.1% to blood group AB (57.1% Rh positive in males, 39.3% Rh positive in females), and 32.0% to blood group O (54.3% Rh positive and 2.5% Rh negative in males, 38.3% Rh positive and 4.9% Rh negative in females). Conclusion: The distribution of ABO and Rh blood groups in the student population at SALU exhibits a distinct pattern, emphasizing the importance of regional studies in blood group distribution. These findings have significant implications for blood bank management, transfusion services, and healthcare planning in the region.

Use of Home-Based Self-Collected Dried Blood Spots to Test for Syphilis, Human Immunodeficiency Virus, Hepatitis C and B Virus Infections and Measuring Creatinine Concentration.

Home-based self-collected dried blood spot (DBS) sampling could simplify sexual health and preexposure prophylaxis care and reduce sexually transmitted infections (STIs) clinic visits for men who have sex with men (MSM). We compared the performance of DBS to venipuncture collected blood samples to test four STIs and creatinine concentration. We invited MSM clients of the Amsterdam STI clinic to participate. Routinely collected peripheral blood was tested for syphilis treponemal antibody, HIV (HIV Ag/Ab), HCV (antibodies), HBV (HBsAg) and creatinine concentration. Participants received a home kit for DBS sampling, a return envelope and a questionnaire to evaluate the acceptability, feasibility and usability of DBS, measured on 5-point Likert scales, 1 representing complete disagreement and 5 complete agreement. We assessed sensitivity and specificity of DBS versus peripheral blood-based testing. In 2020 to 2021, we included 410 participants; 211 (51.5%) returned a completed DBS card, 117 (28.5%) returned a partially filled card and 82 (20.0%) did not return a card. The sensitivity for syphilis was 90.8% and the specificity 84.3%. For both HIV Ag/Ab and HBsAg, the sensitivity and specificity were 100.0%. The sensitivity for HCV antibody was 80.0%, and the specificity was 99.2%. The DBS creatinine concentration was a mean of 5.3 μmol/L higher than in venipuncture obtained plasma. Participants' median willingness to take a future DBS was 4 (interquartile range, 3-5). Dried blood spot may be an acceptable method among MSM for STI testing and creatinine follow-up during preexposure prophylaxis use. However, collecting enough blood on DBS cards was a challenge, and sensitivities for syphilis and HCV serology were too low.

The role of moesin in diagnosing and assessing severity of lymphangioleiomyomatosis

BackgroundLymphangioleiomyomatosis (LAM) is a rare disease which is easily misdiagnosed. Vascular endothelial growth factor D (VEGF-D), as the most common biomarker, however, is not so perfect for the diagnosis and severity assessment of LAM.Materials and methodsThe isobaric tags for relative and absolute quantitation (iTRAQ)-based method was used to identify a cytoskeleton protein, moesin. 84 patients with LAM, 44 patients with other cystic lung diseases (OCLDs), and 37 healthy control subjects were recruited for collecting blood samples and clinical data. The levels of moesin in serum were evaluated by ELISA. The relationships of moesin with lymphatic involvement, lung function, and treatment decision were explored in patients with LAM.ResultsThe candidate protein moesin was identified by the proteomics-based bioinformatic analysis. The serum levels of moesin were higher in patients with LAM [219.0 (118.7–260.5) pg/mL] than in patients with OCLDs (125.8 ± 59.9 pg/mL, P < 0.0001) and healthy women [49.6 (35.5–78.9) ng/mL, P < 0.0001]. Moesin had an area under the receiver operator characteristic curve (AUC) of 0.929 for predicting LAM diagnosis compared to healthy women (sensitivity 81.0%, specificity 94.6%). The combination of moesin and VEGF-D made a better prediction in differentiating LAM from OCLDs than moesin or VEGF-D alone. Moreover, elevated levels of moesin were related to lymphatic involvement in patients with LAM. Moesin was found negatively correlated with FEV1%pred, FEV1/FVC, and DLCO%pred (P = 0.0181, r = − 0.3398; P = 0.0067, r = − 0.3863; P = 0.0010, r = − 0.4744). A composite score combining moesin and VEGF-D improved prediction for sirolimus treatment, compared with each biomarker alone.ConclusionHigher levels of moesin in serum may indicate impaired lung function and lymphatic involvement in patients with LAM, suggest a more serious condition, and provide clinical guidance for sirolimus treatment.

P468 Relevance of anti-drug antibodies in context of supra-therapeutic anti-TNF concentrations

Abstract Background The low serum concentration of anti-tumor necrosis factor-alpha (anti-TNFα) agents and the presence of anti-drug antibodies are related to poor therapeutic outcomes in inflammatory bowel disease (IBD). We aimed to evaluate the prognosis of patients having both antidrug antibodies and supratherapeutic drug concentrations. Methods IBD patients on maintenance infliximab (IFX) or adalimumab (ADA) therapy were prospectively recruited. Serum drug concentrations and antidrug antibodies were measured (Anser, Prometheus). The drug concentrations were classified as subtherapeutic (IFX: &amp;lt;3 µg/mL; ADA: &amp;lt;5 µg/mL), therapeutic (IFX: 3-8 µg/mL; ADA 5-10 µg/mL), and supratherapeutic (IFX &amp;gt; 8 µg/mL; ADA &amp;gt; 10 µg/mL) concentrations regardless of the timing of blood sample collection. We analysed the relationship between i) drug concentrations and ii) the presence and absence of anti-drug antibodies with use of systemic corticosteroids and anti-TNF discontinuation. Results Of 172 patients (122 CD [70.9%], 44 UC [25.6%], 3 IBD-U [1.7%], and 3 IBD-pouch [1.7%]), the median age was 32.3 years (range, 24.8-42.5), and the median duration of IBD was 9.7 years (range 5.3-15.6). IFX and ADA were used in 81 (47.1%) and 91 (52.9%) patients, respectively, and concurrent usage of immunomodulators and systemic corticosteroids was observed in 39 (22.7%) and 23 (13.4%) patients, respectively. Supratherapeutic, therapeutic, and subtherapeutic concentrations were observed in 74 (43.0%), 32 (18.6%), and 66 (38.4%), respectively. The patients with antidrug antibodies (n = 79, 45.9%) showed a higher frequency of having subtherapeutic drug concentrations (68.4% vs 12.9%, P &amp;lt; 0.001) compared to those without antibodies, and the presence of antibodies was an independent predictor of discontinuation of anti-TNFα agents (hazard ratio 3.50, 95% confidence interval 1.88-6.51, P &amp;lt; 0.001, Fig. 1A). In subgroup analysis, patients with antidrug antibodies and supratherapeutic drug concentration exhibited a tendency to have improved drug persistence compared to those with subtherapeutic drug concentration, albeit insignificantly (P = 0.099, Fig. 1B). However, the persistence in this group was still poorer than that observed in patients without antibodies (P = 0.003). Finally, neither anti-TNFα concentrations nor the presence of antidrug antibodies were associated with the need for additional systemic corticosteroid use within 6 months. Conclusion The presence of antidrug antibodies can predict the discontinuation of anti-TNFα agents despite supratherapeutic drug levels. While supratherapeutic drug concentration may improve the treatment persistence of anti-TNFα agents in patients with anti-drug antibodies, it does not last as long as in those without antibodies.

Effect of Resveratrol as an adjunct to Scaling and Root Planing in Chronic Periodontitis Patients with Type 2 Diabetes

Resveratrol is a polyphenol stilbene found in red wine, red grape skins and other plants such as mulberries and peanuts. Resveratrol exhibits a wide range of beneficial properties such as anticarcinogenic agent, platelet antiaggregation agent, antiallergenic, antioxidant, and anti- inflammatory agent. Material and Methods A total of 30 patients diagnosed as chronic periodontitis with diabetes were included in this study. and divided into 2 groups, Group-I(SRP+ resveratrol, n=15) &amp; Group-II (SRP alone, n=15). Resveratrol capsules once daily were prescribed for 3 weeks. Plaque index(PI), Gingival index (MSBI), probing pocket depth (PPD), clinical attachment level (CAL) and serum venous blood sample collection for HbA1c levels. All the parameters were recorded at baseline and at 3 months post-operative. Results All the parameters in both Group I and Group II showed statistically significant (P≤0.001) reduction from baseline to 3 months. improvement from baseline to 3 months. When compared between the two groups, a significant difference was observed in Group I in relation with PI and HbA1c levels at 3 months post-operatively. Conclusion Resveratrol as adjunctive to SRP has shown reduction in periodontal parameters in chronic periodontitis along with improved glycemic control in diabetes patients. Key Words: Diabetes, Glycated hemoglobin levels, Resveratrol, Scaling and root planing

The Aquaporin 3 Polymorphism (rs17553719) Is Associated with Sepsis Survival and Correlated with IL-33 Secretion.

Sepsis is a common life-threatening disease caused by dysregulated immune response and metabolic acidosis which lead to organ failure. An abnormal expression of aquaporins plays an important role in organ failure. Additionally, genetic variants in aquaporins impact on the outcome in sepsis. Thus, we investigated the polymorphism (rs17553719) and expression of aquaporin-3 (AQP3) and correlated these measurements with the survival of sepsis patients. Accordingly, we collected blood samples on several days (plus clinical data) from 265 sepsis patients who stayed in different ICUs in Germany. Serum plasma, DNA, and RNA were then separated to detect the promotor genotypes of AQP3 mRNA expression of AQP3 and several cytokines. The results showed that the homozygote CC genotype exhibited a significant decrease in 30-day survival (38.9%) compared to the CT (66.15%) and TT genotypes (76.3%) (p = 0.003). Moreover, AQP3 mRNA expression was significantly higher and nearly doubled in the CC compared to the CT (p = 0.0044) and TT genotypes (p = 0.018) on the day of study inclusion. This was accompanied by an increased IL-33 concentration in the CC genotype (day 0: p = 0.0026 and day 3: p = 0.008). In summary, the C allele of the AQP3 polymorphism (rs17553719) shows an association with increased AQP3 expression and IL-33 concentration accompanied by decreased survival in patients with sepsis.

Ovarian cancer is detectable from peripheral blood using machine learning over T-cell receptor repertoires.

The extraordinary diversity of T cells and B cells is critical for body maintenance. This diversity has an important role in protecting against tumor formation. In humans, the T-cell receptor (TCR) repertoire is generated through a striking stochastic process called V(D)J recombination, in which different gene segments are assembled and modified, leading to extensive variety. In ovarian cancer (OC), an unfortunate 80% of cases are detected late, leading to poor survival outcomes. However, when detected early, approximately 94% of patients live longer than 5 years after diagnosis. Thus, early detection is critical for patient survival. To determine whether the TCR repertoire obtained from peripheral blood is associated with tumor status, we collected blood samples from 85 women with or without OC and obtained TCR information. We then used machine learning to learn the characteristics of samples and to finally predict, over a set of unseen samples, whether the person is with or without OC. We successfully stratified the two groups, thereby associating the peripheral blood TCR repertoire with the formation of OC tumors. A careful study of the origin of the set of T cells most informative for the signature indicated the involvement of a specific invariant natural killer T (iNKT) clone and a specific mucosal-associated invariant T (MAIT) clone. Our findings here support the proposition that tumor-relevant signal is maintained by the immune system and is coded in the T-cell repertoire available in peripheral blood. It is also possible that the immune system detects tumors early enough for repertoire technologies to inform us near the beginning of tumor formation. Although such detection is made by the immune system, we might be able to identify it, using repertoire data from peripheral blood, to offer a pragmatic way to search for early signs of cancer with minimal patient burden, possibly with enhanced sensitivity.

Challenges and epidemiological implications of the first outbreak of dengue and chikungunya in Sudan.

Dengue and chikungunya are mosquito-borne infections that are spreading rapidly worldwide. The highest burden lies in tropical and subtropical countries. In 2022 Sudan encountered the most widespread infection of both diseases. To describe the magnitude of the first outbreak of dengue and chikungunya infections in Tandalti Town, White Nile State, southern part of Sudan. Following the report of a high number of undifferentiated febrile illnesses in 32 health clinics in Tandalti Town, an area with high densities of Aedes aegypti, we collected blood samples from symptomatic suspected cases. The samples were tested for major arboviral infections using arboviral-specific enzyme-linked immunosorbent assays (IgM capture ELISA), and serologically positive samples were confirmed using commercially available Real Time RT-PCR Kits. Out of 773 suspected cases, 63 (8.15%) were confirmed. Eleven (17.46%) of the confirmed cases were DENV, 49 (77.77%) were CHIKV, and 3 (4.76%) were DENV and CHIKV co-infections. The outbreak started at the beginning of October and ended by mid December 2022. Both dengue and chikungunya infection was higher (41(65.08%)) among young females than males (22 (34.92%)). White Nile State may experience larger outbreaks of dengue and chikungunya in the future, there is, therefore, an urgent need for proper vector control interventions in the state and nearby states.

Serum Levels of Fetuin-A, Ischemia-modified Albumin (IMA), and Ferritin in Hospitalized patients with severe COVID-19. A Case-control Study

Objective: To measure the serum levels of Fetuin-A, ischemia-modified albumin (IMA), and ferritin in hospitalized patients with severe COVID-19in Baghdad, Iraq. Moreover, to determine these biomarkers' cut-off valuesthat differentiate between severely ill patients and control subjects. Methods: This case-control study was done from 15 September to the end of December 2021 and involved a review of the files and collectionof blood samples from patients (n=45, group1) hospitalized in COVID-19 treatment centersbecause of severe symptoms compared tohealthy subjects as controls (n=44, group2). Results: Fetuin-A serum levels were not statistically different between patients and controls. In contrast, IMA and ferritin levels were significantly different between the 2 groups, with patients' levelsbeing greater than control participants' (p 0.05). The critical values for the Fetuin-A, IMA, and ferritin tests were 393.78 mg/L, 59.22 ng/ml, and 126 µg/L, respectively, with concentration curves of 0.58, 0.70, and 0.93 for each. Conclusions: Patients and controls showed no significant difference in Fetuin-A levels in the blood. However, IMA and ferritin levels werehigher in people suffering from acute COVID-19 infection than in controls, with Fetuin-A values less than 393.78 mg/L andIMA and ferritin valueshigher than 59.22 ng/mland 126,000 μg/L, respectively.

SEROPREVALENCE OF TOXOPLASMA GONDII INFECTION IN PIGS FROM SOUTHWESTERN MISSISSIPPI.

Toxoplasma gondii infection of swine is a potential public health concern because it can be acquired by humans through the handling and consumption of contaminated raw meat. Infections in immunocompromised individuals and fetuses are the most severe and these individuals are most likely to develop clinical toxoplasmosis. Since Mississippians consume a lot of pork, there was a significant need to know the extent to which it poses a health problem in the State. This study focused on the southwestern region of Mississippi. Between July 2003 and March 2004, blood samples were collected from slaughterhouses in southwestern Mississippi and the Alcorn State University swine farm in Churchill, Mississippi. The collected blood samples were centrifuged and the sera were collected, labeled, and stored in a freezer at -20 C. The modified agglutination test was performed at dilutions of 1:25, 1:50, and 1:500. A titer of 25 was considered seropositive. Of a total of 302 samples tested, 48 (16%) were positive at a titer of 25; 29 (10%) were positive at 50; 11 (4%) were positive at 500. The seroprevalence of T. gondii in pigs in southwestern Mississippi is not as high as previous studies done in Mississippi. This could be attributed to the sample size. However, the potential for infection still exists.

The Smokers Health Multiple ACtions (SMAC-1) Trial: Study Design and Results of the Baseline Round.

Lung cancer screening with low-dose helical computed tomography (LDCT) reduces mortality in high-risk subjects. Cigarette smoking is linked to up to 90% of lung cancer deaths. Even more so, it is a key risk factor for many other cancers and cardiovascular and pulmonary diseases. The Smokers health Multiple ACtions (SMAC-1) trial aimed to demonstrate the feasibility and effectiveness of an integrated program based on the early detection of smoking-related thoraco-cardiovascular diseases in high-risk subjects, combined with primary prevention. A new multi-component screening design was utilized to strengthen the framework on conventional lung cancer screening programs. We report here the study design and the results from our baseline round, focusing on oncological findings. High-risk subjects were defined as being >55 years of age and active smokers or formers who had quit within 15 years (>30 pack/y). A PLCOm2012 threshold >2% was chosen. Subject outreach was streamlined through media campaign and general practitioners' engagement. Eligible subjects, upon written informed consent, underwent a psychology consultation, blood sample collection, self-evaluation questionnaire, spirometry, and LDCT scan. Blood samples were analyzed for pentraxin-3 protein levels, interleukins, microRNA, and circulating tumor cells. Cardiovascular risk assessment and coronary artery calcium (CAC) scoring were performed. Direct and indirect costs were analyzed focusing on the incremental cost-effectiveness ratio per quality-adjusted life years gained in different scenarios. Personalized screening time-intervals were determined using the "Maisonneuve risk re-calculation model", and a threshold <0.6% was chosen for the biennial round. In total, 3228 subjects were willing to be enrolled. Out of 1654 eligible subjects, 1112 participated. The mean age was 64 years (M/F 62/38%), with a mean PLCOm2012 of 5.6%. Former and active smokers represented 23% and 77% of the subjects, respectively. At least one nodule was identified in 348 subjects. LDCTs showed no clinically significant findings in 762 subjects (69%); thus, they were referred for annual/biennial LDCTs based on the Maisonneuve risk (mean value = 0.44%). Lung nodule active surveillance was indicated for 122 subjects (11%). Forty-four subjects with baseline suspicious nodules underwent a PET-FDG and twenty-seven a CT-guided lung biopsy. Finally, a total of 32 cancers were diagnosed, of which 30 were lung cancers (2.7%) and 2 were extrapulmonary cancers (malignant pleural mesothelioma and thymoma). Finally, 25 subjects underwent lung surgery (2.25%). Importantly, there were zero false positives and two false negatives with CT-guided biopsy, of which the patients were operated on with no stage shift. The final pathology included lung adenocarcinomas (69%), squamous cell carcinomas (10%), and others (21%). Pathological staging showed 14 stage I (47%) and 16 stage II-IV (53%) cancers. LDCTs continue to confirm their efficacy in safely detecting early-stage lung cancer in high-risk subjects, with a negligible risk of false-positive results. Re-calculating the risk of developing lung cancer after baseline LDCTs with the Maisonneuve model allows us to optimize time intervals to subsequent screening. The Smokers health Multiple ACtions (SMAC-1) trial offers solid support for policy assessments by policymakers. We trust that this will help in developing guidelines for the large-scale implementation of lung cancer screening, paving the way for better outcomes for lung cancer patients.

Measurement of Oxidative Stress Index (OSI) in Penile Corpora Cavernosa and Peripheral Blood of Peyronie's Disease Patients: A Report of 49 Cases.

Peyronie's disease (PD) is a chronic inflammatory disease affecting the penile albuginea. Oxidative stress (OS) is important for the development of the disease; therefore, it seemed interesting to us to directly measure OS at both the site of the disease and in peripheral blood. For a precise OS study, it is necessary to evaluate not only the single results of the total oxidant status (TOS) and total antioxidant status (TAS) but also their ratio: OS index (OSI) (arbitrary unit) = TOS/TAS × 100. This study included 49 PD patients examined and diagnosed in our Peyronie's care center and a control group of 50 cases. We collected blood samples from both the penis and a vein in the upper extremity; we used d-ROMs and PAT-test (FRAS kit) for OS measurement. Pearson's study found a statistical correlation between penile OSI values and PD plaque volumes: p-value = 0.002. No correlation was found between systemic OSI values and PD plaque volumes: p-value = 0.27. Penile OSI values were significantly reduced after the elimination of the PD plaque (p < 0.00001). The mean value of the penile OSI indices in the PD patients after plaque elimination corresponded to 0.090 ± 0.016 (p = 0.004). The comparison between the penile OSI values of the PD patients (with plaque elimination) and the control group revealed no statistically significant differences (p = 0.130). The absence of a correlation between Peyronie's plaque volume and systemic OSI values indicates that it is preferable to carry out the OS study by taking a sample directly from the site of the disease. By carrying out a penile OSI study, it would be possible to obtain a precise plaque-volume-dependent oxidative marker. Even if the study did not demonstrate any correlation between OSI indices and anxious-depressive state, we detected a high prevalence of anxiety (81.6%) and depression (59.1%) in PD patients.

Indication of Hyperhomocysteinemia in Type 2 Diabetes Mellitus Patients with Cardiovascular Complications

Introduction Cardiovascular disease (CVD) is one of the prominent causes of mortality in cases of chronic Type 2 diabetes mellitus (T2DM) patients and necessitates improving risk categorization. There are few available biomarkers that can assess preceding or current glycemic and cardiac status, but not prognosis. Serum homocysteine (Hcy) has been indicated and reported to be a likely biomarker that can detect cardiovascular complication in patients with T2DM. Methodology Present study details the comparative analysis of several biochemical and metabolic biomarkers including Hcy in T2DM patients with and without CVD complications. A total of eighty patients, n = 40 each in T2DM with CVD and T2DM without CVD, were included in the study. Patient’s preparation, blood sample collection and analyses of all biochemical, metabolic markers including Hcy were performed as per standard protocols. One way ANOVA was used for independent measures including Tukey HSD with level of significance at P&lt; 0.05. Results Indication of hyperhomocysteinemia, was significantly apparent in patients with T2DM who have CVD, as compared to those with T2DM without CVD. All other biochemical and metabolic parameters manifested marked significant (P&lt; 0.00001) elevations, which was more perceptible in T2DM CVD as compared to T2DM non CVD. Clinical relevance of high Hcy in blood in patients with T2DM CVD thus suggested being prominent risk factor for proceeding renal and cardiac complications.

Seroprevalence, Blood Chemistry, and Patterns of Canine Parvovirus, Distemper Virus, Plague, and Tularemia in Free-Ranging Coyotes (Canis latrans) in Northern New Mexico, USA.

Wildlife diseases have implications for ecology, conservation, human health, and health of domestic animals. They may impact wildlife health and population dynamics. Exposure rates of coyotes (Canis latrans) to pathogens such as Yersinia pestis, the cause of plague, may reflect prevalence rates in both rodent prey and human populations. We captured coyotes in north-central New Mexico during 2005-2008 and collected blood samples for serologic surveys. We tested for antibodies against canine distemper virus (CDV, Canine morbillivirus), canine parvovirus (CPV, Carnivore protoparvovirus), plague, tularemia (Francisella tularensis), and for canine heartworm (Dirofilaria immitis) antigen. Serum biochemistry variables that fell outside reference ranges were probably related to capture stress. We detected antibodies to parvovirus in 32/32 samples (100%), and to Y. pestis in 26/31 (84%). More than half 19/32 (59%) had antibodies against CDV, and 5/31 (39%) had antibodies against F. tularensis. We did not detect any heartworm antigens (n = 9). Pathogen prevalence was similar between sexes and among the three coyote packs in the study area. Parvovirus exposure appeared to happen early in life, and prevalence of antibodies against CDV increased with increasing age class. Exposure to Y. pestis and F. tularensis occurred across all age classes. The high coyote seroprevalence rates observed for CPV, Y. pestis, and CDV may indicate high prevalence in sympatric vertebrate populations, with implications for regional wildlife conservation as well as risk to humans via zoonotic transmission.

Hypoglycemic, antidiabetic and toxicological evaluation of leaf extract of Xylopia parviflora (A. rich.) Benth

BackgroundAlmost all Xylopia species have a long history of being used therapeutically in China due to their potent antioxidant properties. Xylopia parviflora (X. parviflora) is a relatively novel plant comprised mainly of beta-pinene, which has a rich history in Chinese medicine and is a principal active constituent in numerous Chinese herbs such as Rakkyo, the Chinese onions, Huasi Baidu Fang and Ru Xiang which are all native to China. ObjectiveThe study evaluated the antidiabetic potentials of the methanol leaf extract of X. parviflora and its toxicity profile. MethodsA modified version of the OECD guidelines was used to conduct acute and sub-chronic toxicity tests on the plant extract. The extract's effects on glucose, haematological, and biochemical components were evaluated using standard procedures. Using glibenclamide (10 mg/kg) and distilled water as positive and negative controls, the extract was tested for its antidiabetic activity in diabetic rats with streptozotocin induction at 50, 150, and 300 mg/kg for 28 days. Furthermore, vital organs underwent histopathological examination. Analysis of Variance (ANOVA) and the Dunnett multiple comparison tests were used for the statistical analysis, with a significance level of p < 0.05 ResultsPreliminary phytochemical analysis of the leaf extract revealed the presence of tannins, flavonoids, saponins, alkaloids, terpenoids, deoxy-sugars, and anthraquinones. The extract's median lethal dose (LD50) was greater than 2000 mg/kg in mice. Although it significantly reduced blood glucose levels in normal rats at 150 and 300 mg/kg doses, it had no toxic effects on the haematological and biochemical components of the collected blood samples. The extract produced an antidiabetic, non-dose-dependent impact on day seven at all the tested doses in streptozotocin-induced rats. On days 14, 21, and 28, however, glibenclamide and extract activity at all tested doses were comparable. At 200 mg/kg, the extract did not affect the histology of the liver, brain, kidney, or pancreas, but at 400 and 800 mg/kg, it had a slight and severe impact on these organs, respectively. ConclusionAccording to the study's findings, X. parviflora has antihyperglycemic activity and is non-toxic at low doses but may be harmful at high doses.