Co-expression of tumor suppressor p53 (TP53) and cancer testis antigens (CTAs) as the possible indicator of “cancer-free” status

Objective: Biomarkers are biological substances that can be measured and objectively evaluated as indicators of concrete processes at different levels. Advances in biomedicine facilitated the use and importance of biomarkers for healthcare purposes. Several biomarkers that are used in the field of oncology are already identified and used in clinical practice, although their sensitivity is not sufficient. To contribute to this issue, we aimed to determine the expression of total cancer-testis antigens (CTAs) in correlation with the expression levels of tumor suppressor proteins p53 (TP53) and p63 (TP63) as well as BRCA1 in a healthy cohort. Materials and Methods: We analyzed samples of 90 blood donors (28, 31.1% – females, 62, 68.9% – males) as they can be considered as an appropriate group for recruiting health cohorts. The age distribution of the subjects was between 20 and 60 years. The enzyme linked immunosorbent assay analysis was used for the determination of CTAs, TP53, TP63, and BRCA1 expression levels. Results: A strong correlation between CTAs and TP53 expression levels has been revealed. The expression variables of targeted biomarkers are not equally distributed. The data specific to CTAs, TP53, and TP63 expression levels are skewed to the left. In the case of BRCA1, the data may indicate the presence of 2 subgroups for study subjects. Conclusions: The co-expression of CTAs and TP53 may be considered as the indicator of “cancer-free” status. This parameter may be piloted for cancer screening and early diagnosis purposes. However, the role of CTAs for cellular process regulation and especially regulation of tumor suppressor gene p53 shall be investigated further

Variation of almond yield, biometry, α-tocopherol levels, and antioxidant properties with nitrogen fertilization

A two years’ experiment (2015–2016) was set in a factorial design in which the effect of two application forms of nitrogen (N) (soil and soil + foliar spray) in different doses (0, 25, 50, and 100 kg N ha-1) on almond (Prunus dulcis Mill. cv. “Masbovera”) was evaluated. Kernel yield, biometric properties, phytochemicals, and antioxidant activities were assessed. The results showed that almond kernel yield increases with an increment in N rate doses and was positively correlated with kernel weight and thickness, and negatively with fruit weight. The levels of α-tocopherol and total polyphenol content were higher with lower N doses (25 and 50 kg N ha–1). The antioxidant activities were positively correlated with polyphenol content. Based on our results, excessive N rates over 50 kg/ha depreciate the levels of α-tocopherol, total polyphenols, and antioxidant bioactivities of kernels. Practical applications Almond is an important nut (dry) fruit that contains high levels of α-tocopherol, moderate levels of polyphenols, and high antioxidant activities, all responsible for their claimed health-promoting properties. Almond trees are known by their alternate behavior in which kernel yield and levels of phytochemicals and other compounds are highly variable between years. This article studies the usage of a sustainable nitrogen fertilization program toward a reduction of their alternate behavior, preserving and promoting their antioxidant properties and their levels of phytochemicals, particularly α-tocopherol and polyphenols. Our findings may provide a useful guide for adequate nitrogen fertilization program toward a better almond kernel qualityinfo:eu-repo/semantics/publishedVersio

Association of BMI Category Change with TB Treatment Mortality in HIV-Positive Smear-Negative and Extrapulmonary TB Patients in Myanmar and Zimbabwe

OBJECTIVE: The HIV epidemic has increased the proportion of patients with smear-negative and extrapulmonary tuberculosis (TB) diagnoses, with related higher rates of poor TB treatment outcomes. Unlike in smear-positive pulmonary TB, no interim markers of TB treatment progress are systematically used to identify individuals most at risk of mortality. The objective of this study was to assess the association of body mass index (BMI) change at 1 month (±15 days) from TB treatment start with mortality among HIV-positive individuals with smear-negative and extrapulmonary TB. METHODS AND FINDINGS: A retrospective cohort study of adult HIV-positive new TB patients in Médecins Sans Frontières (MSF) treatment programmes in Myanmar and Zimbabwe was conducted using Cox proportional hazards regression to estimate the association between BMI category change and mortality. A cohort of 1090 TB patients (605 smear-negative and 485 extrapulmonary) was followed during TB treatment with mortality rate of 28.9 per 100 person-years. In multivariable analyses, remaining severely underweight or moving to a lower BMI category increased mortality (adjusted hazard ratio 4.05, 95% confidence interval 2.77-5.91, p<0.001) compared with remaining in the same or moving to a higher BMI category. CONCLUSIONS: We found a strong association between BMI category change during the first month of TB treatment and mortality. BMI category change could be used to identify individuals most at risk of mortality during TB treatment among smear-negative and extrapulmonary patients

Urban Movement and Alcohol Intake Strongly Predict Defaulting from Tuberculosis Treatment: An Operational Study

BACKGROUND: High levels of defaulting from treatment challenge tuberculosis control in many African cities. We assessed defaulting from tuberculosis treatment in an African urban setting. METHODS: An observational study among adult patients with smear-positive pulmonary tuberculosis receiving treatment at urban primary care clinics in Kampala, Uganda. Defaulting was defined as having missed two consecutive monthly clinic visits while not being reported to have died or continued treatment elsewhere. Defaulting patients were actively followed-up and interviewed. We assessed proportions of patients abandoning treatment with and without the information obtained through active follow-up and we examined associated factors through multivariable logistic regression. RESULTS: Between April 2007 and April 2008, 270 adults aged ≥15 years were included; 54 patients (20%) were recorded as treatment defaulters. On active follow-up vital status was established of 28/54 (52%) patients. Of these, 19 (68%) had completely stopped treatment, one (4%) had died and eight (29%) had continued treatment elsewhere. Extrapolating this to all defaulters meant that 14% rather than 20% of all patients had truly abandoned treatment. Daily consumption of alcohol, recorded at the start of treatment, predicted defaulting (adjusted odds ratio [OR(adj)] 4.4, 95%CI 1.8-13.5), as did change of residence during treatment (OR(adj) 8.7, 95%CI 1.8-41.5); 32% of patients abandoning treatment had changed residence. CONCLUSIONS: A high proportion of tuberculosis patients in primary care clinics in Kampala abandon treatment. Assessing change of residence during scheduled clinic appointments may serve as an early warning signal that the patient may default and needs adherence counseling

Nucleic Acid Amplification Tests for Diagnosis of Smear-Negative TB in a High HIV-Prevalence Setting: A Prospective Cohort Study

Nucleic acid amplification tests are sensitive for identifying Mycobacterium tuberculosis in populations with positive sputum smears for acid-fast bacilli, but less sensitive in sputum-smear-negative populations. Few studies have evaluated the clinical impact of these tests in low-income countries with high burdens of TB and HIV.We prospectively enrolled 211 consecutive adults with cough ≥2 weeks and negative sputum smears at Mulago Hospital in Kampala, Uganda. We tested a single early-morning sputum specimen for Mycobacterium tuberculosis DNA using two nucleic acid amplification tests: a novel in-house polymerase chain reaction targeting the mycobacterial secA1 gene, and the commercial Amplified® Mycobacterium tuberculosis Direct (MTD) test (Gen-Probe Inc, San Diego, CA). We calculated the diagnostic accuracy of these index tests in reference to a primary microbiologic gold standard (positive mycobacterial culture of sputum or bronchoalveolar lavage fluid), and measured their likely clinical impact on additional tuberculosis cases detected among those not prescribed initial TB treatment.Of 211 patients enrolled, 170 (81%) were HIV-seropositive, with median CD4+ T-cell count 78 cells/µL (interquartile range 29-203). Among HIV-seropositive patients, 94 (55%) reported taking co-trimoxazole prophylaxis and 29 (17%) reported taking antiretroviral therapy. Seventy-five patients (36%) had culture-confirmed TB. Sensitivity of MTD was 39% (95% CI 28-51) and that of secA1 was 24% (95% CI 15-35). Both tests had specificities of 95% (95% CI 90-98). The MTD test correctly identified 18 (24%) TB patients not treated at discharge and led to a 72% relative increase in the smear-negative case detection rate.The secA1 and MTD nucleic acid amplification tests had moderate sensitivity and high specificity for TB in a predominantly HIV-seropositive population with negative sputum smears. Although newer, more sensitive nucleic acid assays may enhance detection of Mycobacterium tuberculosis in sputum, even currently available tests can provide substantial clinical impact in smear-negative populations

Increased production of IL-4 and IL-12p40 from bronchoalveolar lavage cells are biomarkers of Mycobacterium tuberculosis in the sputum

BACKGROUND: Tuberculosis (TB) causes 1.45 million deaths annually world wide, the majority of which occur in the developing world. Active TB disease represents immune failure to control latent infection from airborne spread. Acid-fast bacillus (AFB) seen on sputum smear is a biomarker for contagiousness. METHODS: We enrolled 73 tuberculosis patients with extensive infiltrates into a research study using bronchoalveolar lavage (BAL) to sample lung immune cells and assay BAL cell cytokine production. All patients had sputum culture demonstrating Mycobacterium tuberculosis and 59/73 (81%) had AFB identified by microscopy of the sputum. Compared with smear negative patients, smear positive patients at presentation had a higher proportion with smoking history, a higher proportion with temperature >38.5 0 C, higher BAL cells/ml, lower percent lymphocytes in BAL, higher IL-4 and IL-12p40 in BAL cell supernatants. There was no correlation between AFB smear and other BAL or serum cytokines. Increasing IL-4 was associated with BAL PMN and negatively associated with BAL lymphocytes. Each 10-fold increase in BAL IL-4 and IL-12p40 increased the odds of AFB smear positivity by 7.4 and 2.2-fold, respectively, in a multi-variable logistic model. CONCLUSION: Increasing IL-4 and IL-12p40 production by BAL cells are biomarkers for AFB in sputum of patients who present with radiographically advanced TB. They likely reflect less effective immune control of pathways for controlling TB, leading to patients with increased infectiousness

Intensive Case Finding and Isoniazid Preventative Therapy in HIV Infected Individuals in Africa: Economic Model and Value of Information Analysis

Background: Tuberculosis (TB) accounts of much of the morbidity and mortality associated with HIV. We evaluate the costeffectiveness of different strategies to actively screen for TB disease in HIV positive individuals, where isoniazid preventative therapy (IPT) is given to those screening negative, and use value of information analysis (VOI) to identify future research priorities. Methodology / Principal Findings: We built an individual sampling model to investigate the costs (2010 US Dollars) and consequences of screening for TB, and providing TB treatment or IPT in adults testing HIV positive in Sub-Saharan Africa. A systematic review and meta-analysis was conducted to assess performance of the nine different TB screening strategies evaluated. Probabilistic sensitivity analysis was conducted to incorporate decision uncertainty, and expected value of perfect information for the entire model and for groups of parameters was calculated. Screening all HIV infected individuals with sputum microscopy was the least costly strategy, with other strategies not cost-effective at WHO recommended thresholds. Screening those with TB symptoms with sputum microscopy and CXR would be cost-effective at a threshold ICER of $7,800 per quality-adjusted life year (QALY), but associated with significant uncertainty. VOI analysis suggests further information would be of value. Conclusions / Significance: Resource-constrained countries in sub-Saharan Africa wishing to scale up TB preventativ

SUDOSCAN: A Simple, Rapid, and Objective Method with Potential for Screening for Diabetic Peripheral Neuropathy.

Clinical methods of detecting diabetic peripheral neuropathy (DPN) are not objective and reproducible. We therefore evaluated if SUDOSCAN, a new method developed to provide a quick, non-invasive and quantitative assessment of sudomotor function can reliably screen for DPN. 70 subjects (45 with type 1 diabetes and 25 healthy volunteers [HV]) underwent detailed assessments including clinical, neurophysiological and 5 standard cardiovascular reflex tests (CARTs). Using the American Academy of Neurology criteria subjects were classified into DPN and No-DPN groups. Based on CARTs subjects were also divided into CAN, subclinical-CAN and no-CAN. Sudomotor function was assessed with measurement of hand and foot Electrochemical Skin Conductance (ESC) and calculation of the CAN risk score. Foot ESC (μS) was significantly lower in subjects with DPN [n = 24; 53.5(25.1)] compared to the No-DPN [77.0(7.9)] and HV [77.1(14.3)] groups (ANCOVA p<0.001). Sensitivity and specificity of foot ESC for classifying DPN were 87.5% and 76.2%, respectively. The area under the ROC curve (AUC) was 0.85. Subjects with CAN had significantly lower foot [55.0(28.2)] and hand [53.5(19.6)] ESC compared to No-CAN [foot ESC, 72.1(12.2); hand ESC 64.9(14.4)] and HV groups (ANCOVA p<0.001 and 0.001, respectively). ROC analysis of CAN risk score to correctly classify CAN revealed a sensitivity of 65.0% and specificity of 80.0%. AUC was 0.75. Both foot and hand ESC demonstrated strong correlation with individual parameters and composite scores of nerve conduction and CAN. SUDOSCAN, a non-invasive and quick test, could be used as an objective screening test for DPN in busy diabetic clinics, insuring adherence to current recommendation of annual assessments for all diabetic patients that remains unfulfilled