Advances in three-dimensional bioprinted stem cell-based tissue engineering for cardiovascular regeneration.

Three-dimensional (3D) bioprinting of cellular or biological components are an emerging field to develop tissue structures that mimic the spatial, mechanochemical and temporal characteristics of cardiovascular tissues. 3D multi-cellular and multi-domain organotypic biological constructs can better recapitulate in vivo physiology and can be utilized in a variety of applications. Such applications include in vitro cellular studies, high-throughput drug screening, disease modeling, biocompatibility analysis, drug testing and regenerative medicine. A major challenge of 3D bioprinting strategies is the inability of matrix molecules to reconstitute the complexity of the extracellular matrix and the intrinsic cellular morphologies and functions. An important factor is the inclusion of a vascular network to facilitate oxygen and nutrient perfusion in scalable and patterned 3D bioprinted tissues to promote cell viability and functionality. In this review, we summarize the new generation of 3D bioprinting techniques, the kinds of bioinks and printing materials employed for 3D bioprinting, along with the current state-of-the-art in engineered cardiovascular tissue models. We also highlight the translational applications of 3D bioprinting in engineering the myocardium cardiac valves, and vascular grafts. Finally, we discuss current challenges and perspectives of designing effective 3D bioprinted constructs with native vasculature, architecture and functionality for clinical translation and cardiovascular regeneration.

Anxiety and contradictory class position in the hierarchy of Brazilian firefighters.

BACKGROUND: Workers holding intermediate hierarchical positions in an institution may have a higher risk of occupational stress-related, ill health. This study examined the prevalence rates and odds ratios (ORs) of anxiety disorders among a hierarchical group of firefighters. METHODS: This cross-sectional study samples firefighters from Minas Gerais, Brazil, who answered a structured questionnaire in 2011 (survey completion rate = 89.5%). The outcome of interest was a medical diagnosis of anxiety disorder. Bivariate and multivariate analyses were conducted among five hierarchical occupational positions: privates (lowest position), corporals, sergeants (intermediate position), sub lieutenants, and officers (highest position). RESULTS: Overall, 8.4% of the sample reported an anxiety disorder, with the highest rate observed among intermediate workers (sergeants = 14.2%), followed by corporals (10%), privates (5.6%), sub lieutenants (5%), and officers (2.1%). Compared with privates, the unadjusted OR for sergeants was 2.49 (95% confidence interval, 1.35, 4.58). This finding remained statistically significant after adjustment for several control variables but was eliminated by age. CONCLUSION: The mental health of firefighters is affected by social class position. Mental health promotion efforts should focus on longitudinal research and work toward interventions aimed at modifying the hierarchical structure of workplaces.

Ethyl Butyrate Synthesis Catalyzed by Lipases A and B from Candida antarctica Immobilized onto Magnetic Nanoparticles. Improvement of Biocatalysts' Performance under Ultrasonic Irradiation.

The synthesis of ethyl butyrate catalyzed by lipases A (CALA) or B (CALB) from Candida antarctica immobilized onto magnetic nanoparticles (MNP), CALA-MNP and CALB-MNP, respectively, is hereby reported. MNPs were prepared by co-precipitation, functionalized with 3-aminopropyltriethoxysilane, activated with glutaraldehyde, and then used as support to immobilize either CALA or CALB (immobilization yield: 100 ± 1.2% and 57.6 ± 3.8%; biocatalysts activities: 198.3 ± 2.7 Up-NPB/g and 52.9 ± 1.7 Up-NPB/g for CALA-MNP and CALB-MNP, respectively). X-ray diffraction and Raman spectroscopy analysis indicated the production of a magnetic nanomaterial with a diameter of 13.0 nm, whereas Fourier-transform infrared spectroscopy indicated functionalization, activation and enzyme immobilization. To determine the optimum conditions for the synthesis, a four-variable Central Composite Design (CCD) (biocatalyst content, molar ratio, temperature and time) was performed. Under optimized conditions (1:1, 45 °C and 6 h), it was possible to achieve 99.2 ± 0.3% of conversion for CALA-MNP (10 mg) and 97.5 ± 0.8% for CALB-MNP (12.5 mg), which retained approximately 80% of their activity after 10 consecutive cycles of esterification. Under ultrasonic irradiation, similar conversions were achieved but at 4 h of incubation, demonstrating the efficiency of ultrasound technology in the enzymatic synthesis of esters.

Perceptions of Mental Health Among Hispanic Older Adults: Findings Among Immigrants from the Dominican Republic, Colombia, and Guatemala.

Disparities exist in the recognition and treatment of mental health issues among Hispanic community-dwelling older adults. Previous researchers have focused on accessing mental health services, with limited attention to older Hispanic immigrants' perceptions of mental health issues. A qualitative descriptive research design was used to understand older Hispanic immigrants' perceptions of mental health issues, especially those related to stress, anxiety, and depression. Seventeen older adults from the Dominican Republic, Colombia, and Guatemala were interviewed. Despite having experienced significant personal tragedies, participants did not initially describe emotional distress or any mental health issues. When specifically questioned, depression was the most recognized illness. Depression was commonly described as sadness, whereas stress and anxiety had multiple definitions among participants. Understanding older Hispanic immigrants' perceptions of mental health issues and establishing a therapeutic relationship between the health care provider and patient may be helpful in recognizing and treating individuals who may be at high risk for emotional distress, anxiety, and depression. [Journal of Gerontological Nursing, 44(11), 44-50.].

Long working hours in the healthcare system of the Belo Horizonte municipality, Brazil: a population-based cross-sectional survey.

BACKGROUND: Health personnel are key players in developing and improving healthcare systems, caring for individuals and their communities, and helping improve quality of life. However, these professionals are often exposed to long working hours because of the pressing need for their services at potentially any time of day. The long working hours they endure are a major risk factor for both acute and chronic health problems. The present study aimed to analyze occurrences of long working hours and their association with individual characteristics and employment factors among workers in the municipal healthcare system in Belo Horizonte, Brazil. METHODS: In this cross-sectional study, a ramdomly selected proportional sample of 1549 participants was analyzed from among the total of 13 602 workers in the Belo Horizonte municipal healthcare system in 2009. "Long" working hours were defined as >44 h/week. A self-administered questionnaire was used for accumulating data. Associations with outcomes were estimated using logistic regression, in univariate and multivariate models. RESULTS: The rate of occurrence of long working hours was 31.4% (95% CI 29.1-33.7). Lower educational level (high school, technical, or uncompleted undergraduate [OR 0.60, 95% CI 0.47-0.78 p < 0.001], or elementary [OR 0.33, 95% CI 0.19-0.55 p < 0.001]) was associated with a lower likelihood of self-reporting long working hours in relation to the group with the highest educational level (completed undergraduate or postgraduate). Male sex (OR 1.62, 95% CI 1.26-2.09 p < 0.001), having children (PR 1.54, 95% CI 1.20-1.97 p = 0.001), and being in the healthcare provider group (OR 1.82, 95% CI 1.40-2.35 p < 0.001) were factors associated with greater likelihood of long working hours. CONCLUSIONS: It was observed that number of long weekly working hours was related to individual characteristics and employment factors.

In vivo imaging of Nematostella vectensis embryogenesis and late development using fluorescent probes.

BACKGROUND: Cnidarians are the closest living relatives to bilaterians and have been instrumental to studying the evolution of bilaterian properties. The cnidarian model, Nematostella vectensis, is a unique system in which embryology and regeneration are both studied, making it an ideal candidate to develop in vivo imaging techniques. Live imaging is the most direct way for quantitative and qualitative assessment of biological phenomena. Actin and tubulin are cytoskeletal proteins universally important for regulating many embryological processes but so far studies in Nematostella primarily focused on the localization of these proteins in fixed embryos. RESULTS: We used fluorescent probes expressed in vivo to investigate the dynamics of Nematostella development. Lifeact-mTurquoise2, a fluorescent cyan F-actin probe, can be visualized within microvilli along the cellular surface throughout embryonic development and is stable for two months after injection. Co-expression of Lifeact-mTurquoise2 with End-Binding protein1 (EB1) fused to mVenus or tdTomato-NLS allows for the visualization of cell-cycle properties in real time. Utilizing fluorescent probes in vivo helped to identify a concentrated 'flash' of Lifeact-mTurquoise2 around the nucleus, immediately prior to cytokinesis in developing embryos. Moreover, Lifeact-mTurquoise2 expression in adult animals allowed the identification of various cell types as well as cellular boundaries. CONCLUSION: The methods developed in this manuscript provide an alternative protocol to investigate Nematostella development through in vivo cellular analysis. This study is the first to utilize the highly photo-stable florescent protein mTurquoise2 as a marker for live imaging. Finally, we present a clear methodology for the visualization of minute temporal events during cnidarian development.

"A man's gonna do what a man wants to do": African American and Hispanic women's perceptions about heterosexual relationships: a qualitative study.

BACKGROUND: HIV prevention efforts have given limited attention to the relational schemas and scripts of adult heterosexual women. These broader schemas and scripts of romantic and other sexual liaisons, partner selection, relationship dynamics, and power negotiations may help to better understand facilitators and barriers to HIV risk-reduction practices. METHODS: We conducted exploratory qualitative interviews with 60 HIV-uninfected heterosexual African-American women from rural counties in North Carolina and Alabama, and Hispanic women from an urban county in southern Florida. Data were collected for relationship expectations; relationship experiences, and relationship power and decision-making. Interview transcripts underwent computer-assisted thematic analysis. RESULTS: Participants had a median age of 34 years (range 18-59), 34% were married or living as married, 39% earned an annual income of $12,000 or less, 12% held less than a high school education, and 54% were employed. Among the Hispanic women, 95% were foreign born. We identified two overarching relationship themes: contradictions between relationship expectations and desires and life circumstances that negated such ideals, and relationship challenges. Within the contradictions theme, we discovered six subthemes: a good man is hard to find; sex can be currency used to secure desired outcomes; compromises and allowances for cheating, irresponsible, and disrespectful behavior; redefining dating; sex just happens; needing relationship validation. The challenges theme centered on two subthemes: uncertainties and miscommunication, and relationship power negotiation. Gender differences in relationship intentions and desires as well as communication styles, the importance of emotional and financial support, and the potential for relationships to provide disappointment were present in all subthemes. In examining HIV risk perceptions, participants largely held that risk for HIV-infection and the need to take precautions were problems of women who differed from them (i.e., abuse drugs, are promiscuous, exchange sex). CONCLUSION: Underlying women's relational schemas was a belief that relationship priorities differed for men and women. Consequently, expectations and allowances for partner infidelity and negligent behaviors were incorporated into their scripts. Moreover, scripts endorsed women's use of sex as currency in relationship formation and endurance, and did not emphasize HIV risk. Both couple- and gender-specific group-level interventions are needed to deconstruct (breakdown) and reconstruct (rewrite) relationship scripts.

Genetic variation in oxidative stress and DNA repair genes in a Mexican population.

BACKGROUND: Oxidative stress has been associated with several complex diseases. Effects generated as a result of oxidative stress may be modulated by various genes. Variation in these genes, particularly when located within coding or regulating regions, may be the primary cause of this modulation. The aim of this work was to determine the allelic and genotypic frequencies of CAT C-262T, SOD3 Ala58Thr, APEX1 Asp148Glu, XPD Lys751Gln and XRCC3 Thr241Met genetic markers in a northern Mexican population. SUBJECTS AND METHODS: This study analysed 250 unrelated individuals by RT-PCR. RESULTS: A high allele mutant frequency was found in SOD3 Ala58Thr and APEX1 Asp148Glu genetic markers (0.395 and 0.38, respectively). A correspondence analysis showed that northern Mexicans are close to European populations. A linkage disequilibrium test between XPD Lys751Gln and CAT C-262T and XPD Lys751Gln and SOD3 Ala58Thr genetic markers was significant (p = 0.000). CONCLUSION: The genetic markers described in this work will be a valuable resource for future functional studies in the northern Mexican population to explore comprehensively their role in the aetiology of human diseases. Furthermore, it will be necessary to replicate these studies in other regions of Mexico due to differences between Mexican sub-populations.

A developmental cascade model of adolescent peer relationships, substance use, and psychopathological symptoms from child maltreatment.

INTRODUCTION: Although previous studies have demonstrated high intercorrelations among deviant peer affiliation, substance use, externalizing and internalizing symptoms in adolescence, these studies have been limited because they did not examine 1) the associations over time by assuming one particular sequence; and 2) child maltreatment effects. METHODS: This study included 617 adolescents (54.3 % girls, 55.6 % Black) at-risk of maltreatment living in the U.S and primarily low-income. Deviant peer affiliation was assessed at ages 12, 14, and 16 using 13 items from the modified version of the Youth Risk Behavior and Monitoring the Future Survey. Externalizing and internalizing symptoms were measured at ages 12, 14, and 16 using the Child Behavior Checklist. The number of substances used (ages 12, 14, 16, and 18) were created by summing the self-reported alcohol, tobacco, and marijuana use. Each type of maltreatment (birth to age 12) was assessed using the self-report. RESULTS: Autoregressive cross-lagged structural equation modeling explained the stability effects within each domain, as well as how different maltreatment types affect diverse developmental processes. Cross-lagged results showed the socialization effects of peers on substance use, whereas the peer selection effects on externalizing symptoms. Physical abuse was only associated with externalizing symptoms, while sexual abuse was associated with both externalizing and internalizing symptoms. Additionally, emotional abuse was associated with deviant peer affiliation and substance use. CONCLUSIONS: Identifying the underlying reciprocal processes offers a deeper understanding of peer relationships in the substance use and externalizing symptoms among at-risk of maltreatment sample.

Midlife body mass index, central adiposity and neuropsychological performance over 10 years in women living with and without HIV.

Background and objective: Observations of overweight and obesity in association with neuropsychological performance (NP) vary over the adult life course depending on baseline levels, biological sex, age, race, temporality of measurements, and other factors. Therefore, similar published analyses across cohorts are inconsistent. In our sample of women living with HIV (WLWH) and women without HIV (WWOH), we conducted comparable analyses as those published in men with and without HIV. We examined cross-sectional and longitudinal associations between body mass index (BMI) and waist circumference (WC) and NP. Methods: Four hundred thirty two 432 virologically-suppressed WLWH and 367 WWOH, ≥40 years in the Women's Interagency HIV Study (WIHS) with anthropometry and NP assessments every two years from 2009-2019 were included in the study. Demographically-adjusted T-scores were calculated for six NP domains: learning, memory, executive function, processing speed, attention and working memory, and motor function. Multivariable linear regression models stratified by HIV status were used to examine cross-sectional associations of BMI and WC by NP domain; repeated measures analyses assessed baseline BMI and WC in association with longitudinal change in NP. Covariates included sociodemographic, behavioral, and HIV-related characteristics. Results: At baseline among all women, the median age was 45 years, 65% were Non-Latinx Black women, and 45% were obese women. Obese WLWH (BMI≥30.0 kg/m2) had poorer executive function (ß=-2.27, 95%CI [-4.46, -0.07]) versus WLWH with healthy BMI (18.5-24.9 kg/m2). Longitudinally over ~8 years, obese versus overweight WWOH improved on memory (ß=2.19, 95%CI [0.13, 4.26]), however overweight versus healthy WWOH experienced declining memory (ß= -2.67, 95%CI [-5.40, -0.07]). Increasing WC was associated with declining executive, processing speed, and motor function (p's<0.05); an at-risk WC was associated with improved memory (ß=1.81, 95%CI [0.19, 3.44]) among WWOH. Among WLWH, increasing BMI was associated with improved learning (ß=0.07, 95%CI [0.00, 0.15]. Conclusion: Our cross-sectional and longitudinal analyses evaluating the associations of BMI and WC and NP were mixed compared to previous reports. This illustrates the importance of sociodemographic characteristics, baseline levels of exposures and outcomes, HIV status, temporality of measurements, and other factors when evaluating aging HIV epidemiology study results.

Differential expression of PSMC4, SKP1, and HSPA8 in Parkinson's disease: insights from a Mexican mestizo population.

Parkinson's disease (PD) is a complex neurodegenerative condition characterized by alpha-synuclein aggregation and dysfunctional protein degradation pathways. This study investigates the differential gene expression of pivotal components (UBE2K, PSMC4, SKP1, and HSPA8) within these pathways in a Mexican-Mestizo PD population compared to healthy controls. We enrolled 87 PD patients and 87 controls, assessing their gene expression levels via RT-qPCR. Our results reveal a significant downregulation of PSMC4, SKP1, and HSPA8 in the PD group (p = 0.033, p = 0.003, and p = 0.002, respectively). Logistic regression analyses establish a strong association between PD and reduced expression of PSMC4, SKP1, and HSPA8 (OR = 0.640, 95% CI = 0.415-0.987; OR = 0.000, 95% CI = 0.000-0.075; OR = 0.550, 95% CI = 0.368-0.823, respectively). Conversely, UBE2K exhibited no significant association or expression difference between the groups. Furthermore, we develop a gene expression model based on HSPA8, PSMC4, and SKP1, demonstrating robust discrimination between healthy controls and PD patients. Notably, the model's diagnostic efficacy is particularly pronounced in early-stage PD. In conclusion, our study provides compelling evidence linking decreased gene expression of PSMC4, SKP1, and HSPA8 to PD in the Mexican-Mestizo population. Additionally, our gene expression model exhibits promise as a diagnostic tool, particularly for early-stage PD diagnosis.

Characteristics of Work and Employment Related to Leisure-Time Physical Activity: Results of the National Health Survey, Brazil, 2013.

Leisure-time physical activity (LTPA) is a crucial behavior to reduce the global burden of disease. The objective of this study was to understand the relationship between LTPA, employment status, and physical workload (PWL). This study analyzed data from 38 449 individuals interviewed in the National Health Survey (NHS), representative of the Brazilian population. This paper examines LTPA in the last 30 days and whether participants achieved the recommended physical activity (≥150 min week-1) according to employment status and PWL utilizing Poisson regression models. One third and » of the participants reported LTPA in the last 30 days and achieved the recommended LTPA, respectively. Intense PWL was reported by 28.7% [95% confidence interval (CI): 27.8-29.6%] of participants; 32.2% among men (95% CI: 31.0-33.5%); 24.3% among women (95% CI: 23.1-25.5%). Precarious employment was associated with a lower prevalence of physical activity among men [adjusted prevalence ratio (PRa) = 0.92; P = 0.016], but not among women (PRa = 1.11; P = 0.039). Employment policies and protection of the work environment are relevant aspects to stimulate physical activity, and may vary by gender.

Intraarticular injection of heparin-binding insulin-like growth factor 1 sustains delivery of insulin-like growth factor 1 to cartilage through binding to chondroitin sulfate.

OBJECTIVE: Insulin-like growth factor 1 (IGF-1) stimulates cartilage repair but is not a practical therapy due to its short half-life. We have previously modified IGF-1 by adding a heparin-binding domain and have shown that this fusion protein (HB-IGF-1) stimulates sustained proteoglycan synthesis in cartilage. This study was undertaken to examine the mechanism by which HB-IGF-1 is retained in cartilage and to test whether HB-IGF-1 provides sustained growth factor delivery to cartilage in vivo and to human cartilage explants. METHODS: Retention of HB-IGF-1 and IGF-1 was analyzed by Western blotting. The necessity of heparan sulfate (HS) or chondroitin sulfate (CS) glycosaminoglycans (GAGs) for binding was tested using enzymatic removal and cells with genetic deficiency of HS. Binding affinities of HB-IGF-1 and IGF-1 proteins for isolated GAGs were examined by surface plasmon resonance and enzyme-linked immunosorbent assay. RESULTS: In cartilage explants, chondroitinase treatment decreased binding of HB-IGF-1, whereas heparitinase had no effect. Furthermore, HS was not necessary for HB-IGF-1 retention on cell monolayers. Binding assays showed that HB-IGF-1 bound both CS and HS, whereas IGF-1 did not bind either. After intraarticular injection in rat knees, HB-IGF-1 was retained in articular and meniscal cartilage, but not in tendon, consistent with enhanced delivery to CS-rich cartilage. Finally, HB-IGF-1 was retained in human cartilage explants but IGF-1 was not. CONCLUSION: Our findings indicate that after intraarticular injection in rats, HB-IGF-1 is specifically retained in cartilage through its high abundance of CS. Modification of growth factors with heparin-binding domains may be a new strategy for sustained and specific local delivery to cartilage.

α-syn and SNP rs356219 as a potential biomarker in blood for Parkinson's disease in Mexican Mestizos.

Clinical criteria diagnose Parkinson's disease (PD), therefore, it is crucial to find biological elements that could support diagnosis or even act as prognostic tools of PD. The SNCA gene codifies a protein called α - synuclein; several studies associate genetic and biochemical factors of SNCA with PD, including transcript and plasmatic protein levels, however, contradictory evidence indicates inconclusive results. We aim to compare SNCA mRNA expression, plasmatic α-syn protein and rs356219 SNP between PD cases and a control group, and to identify a potential biomarker in Mexican mestizos', focusing on these three components determined in blood. We included 88 PD patients and 88 age-matched controls. We observed higher α-syn protein and decreased SNCA mRNA levels in PD subjects, compared to control group (p = 0.044 and p < 0.001, respectively). A statistically significant difference was found in allelic and genotypic frequencies of SNP rs356219 between PD patients and normal subjects (p = 0.006 and p = 0.023, respectively). Logistic regression analysis determined as optimal predictors of PD the GG genotype of SNP rs356219 (OR 2.49; p = 0.006) in a recessive model and α-syn protein (OR 1.057; p = 0.033). Furthermore, the G allele of SNP rs356219 was associated with higher plasmatic α-syn and mRNA levels in PD subjects. The receiver operating curves (ROC) distinguished PD from healthy controls with good sensitivity and specificity considering the plasmatic α-syn protein (AUC = 0.693, Sensitivity = 66.7 %, Specificity = 63.9 %) or a predictive probability of plasmatic α-syn protein and SNP rs356219 in a single model (AUC = 0.692, Sensitivity = 62.3 %, Specificity = 62.5 %). The performance of this classifier model in PD at early stage (n = 31) increase the discriminant power in both, plasmatic α-syn protein (AUC = 0.779, Sensitivity = 72.7 %, Specificity = 73.9 %) and predictive probability (AUC = 0.707, Sensitivity = 63.6 %, Specificity = 62.5 %). We propose that α-syn protein and SNP rs356219 together may work as a good signature of PD, and they can be suggested as a non-invasive biomarker of PD risk.

Characterization of TIMP-3 in human articular talar cartilage.

Tissue inhibitor of matrix metalloproteinase 3 (TIMP-3) is an inhibitor of matrix degradation; however, little else is known about the role(s) of this protein in articular cartilage. In this study we compared levels of TIMP-3 in human knee and ankle cartilages and in normal and degraded cartilages. In addition, our studies focused on the compartmentalization of TIMP-3 in human adult articular cartilage matrix, identification of its potential binding partners, and determining the effects of cytokines on its matrix compartment deposition. We extracted TIMP-3 from cartilage and found that while TIMP-3 was localized throughout the matrix, it was predominately associated with the chondrocyte. We also found that more TIMP-3 was extracted from normal compared to degraded cartilage and more in ankle than knee cartilage suggesting the potential of this inhibitor as a protective agent. Our data suggest that TIMP-3 interacts with heparan sulfate and heparan sulfate proteoglycans and to a lesser extent with heparin and chondroitin sulfate. Stimulation with Interleukin-1ß and osteogenic protein-1 decreased while tumor necrosis factor alpha and transforming growth factor beta increased TIMP-3 protein levels; however, TIMP-3 mRNA was not significantly affected by any of these treatments. These characteristics indicate the chondroprotective nature of TIMP-3 and its potential as a therapeutic agent for osteoarthritis.

CYP and GST polymorphisms and survival in advanced non-small cell lung cancer patients.

UNLABELLED: Several polymorphisms in cytochrome P-450s (CYP)s and Glutathione S-transferases (GST)s have been reported to be associated with survival rates of patients with non-small cell lung cancer (NSCLC) but the studies in this regard are scarce and the results are contradictory. In this study, CYP1A1 (Ile462Val), CYP1B1(Asn453Ser), GST M1, GSTP1 exon 5 (Ile105Val) and exon 6(Ala114Val) and GSTT1 polymorphisms were determined in 138 patients with advanced NSCLC to evaluate their role in survival. Of the studied CYP and GST polymorphisms only GSTP1 exon 6 variant significantly altered (improved) the survival compared to wild type (p=0.036) with median survival of 22.2 months and 16.1 months, respectively. Multivariate analysis also revealed a significant reduction of adjusted hazard ratio of death associated only with the GSTP1 exon 6 variant genotype of 0.45 (95% confidence interval (95% CI), 0.23-0.89, p=0.022). These results show that the GSTP1 exon 6 variant genotype is associated with improved survival in the patients with advanced NSCLC. KEYWORDS: Cytochrome P-450, glutathione S-transferase, non small cell lung cancer, polymorphism, survival.

ProTECT-Prediction of T-Cell Epitopes for Cancer Therapy.

Somatic mutations in cancers affecting protein coding genes can give rise to potentially therapeutic neoepitopes. These neoepitopes can guide Adoptive Cell Therapies and Peptide- and RNA-based Neoepitope Vaccines to selectively target tumor cells using autologous patient cytotoxic T-cells. Currently, researchers have to independently align their data, call somatic mutations and haplotype the patient's HLA to use existing neoepitope prediction tools. We present ProTECT, a fully automated, reproducible, scalable, and efficient end-to-end analysis pipeline to identify and rank therapeutically relevant tumor neoepitopes in terms of potential immunogenicity starting directly from raw patient sequencing data, or from pre-processed data. The ProTECT pipeline encompasses alignment, HLA haplotyping, mutation calling (single nucleotide variants, short insertions and deletions, and gene fusions), peptide:MHC binding prediction, and ranking of final candidates. We demonstrate the scalability, efficiency, and utility of ProTECT on 326 samples from the TCGA Prostate Adenocarcinoma cohort, identifying recurrent potential neoepitopes from TMPRSS2-ERG fusions, and from SNVs in SPOP. We also compare ProTECT with results from published tools. ProTECT can be run on a standalone computer, a local cluster, or on a compute cloud using a Mesos backend. ProTECT is highly scalable and can process TCGA data in under 30 min per sample (on average) when run in large batches. ProTECT is freely available at https://www.github.com/BD2KGenomics/protect.

COVID-19 symptoms and SARS-CoV-2 infection among people living with HIV in the US: the MACS/WIHS combined cohort study.

BACKGROUND: SARS-CoV-2 infection among People Living With HIV (PLWH) is not well-described. OBJECTIVE: To study COVID-19 symptoms and SARS-CoV-2 PCR-based swab testing among participants of the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS). METHODS: A telephone survey was collected April-June 30, 2020. Symptom and testing prevalence were explored. Multivariable logistic regression was used to examine the factors associated with SARS-CoV-2 positivity. RESULTS: The survey was completed by 3411 participants, including 2078 (61%) PLWH and 1333 HIV-seronegative (SN) participants from across the US. Thirteen percent (n = 441) were tested for SARS-CoV-2 infection (13.4% of PLWH vs 12.2% of SN). Among those tested, positivity was higher in PLWH than SN (11.2% vs 6.1%, p = 0.08). Reasons for not being tested included testing not being available (30% of participants) and not knowing where to get tested (16% of participants). Most symptoms reported since January 2020 were similar in PLWH and SN, including headache (23% vs. 24%), myalgias (19% vs 18%), shortness of breath (14% vs 13%), chills (12% vs 10%), fever (6% vs 6%) and loss of taste or smell (6% vs 7%). Among PLWH who tested positive for SARS-CoV-2 DNA, the most common symptoms were headache (71%), myalgia (68%), cough (68%) and chills (65%). In multivariable analysis among those tested, the odds of SARS-CoV-2 positivity were higher among PLWH than SN (aOR = 2.22 95%CI = 01.01-4.85, p = 0.046) and among those living with others versus living alone (aOR = 2.95 95%CI = 1.18-7.40). CONCLUSION: Prevalence and type of COVID-19 symptoms were similar in PLWH and SN. SARS-CoV-2 infection may be elevated among PLWH.

Chemotaxis disruption in Pratylenchus scribneri by tall fescue root extracts and alkaloids.

Tall fescue (Festuca arundinacea) forms a symbiotic relationship with the clavicipitalean fungal endophyte Neotyphodium coenophialum. Endophyte-infected grass is tolerant to nematode, but the factors responsible are unknown. One objective of this work was to determine if root extracts of tall fescue effected chemoreceptor activity of Pratylenchus scribneri by using an in vitro chemoreception bioassay. Another objective was to determine if specific ergot alkaloids (ergovaline, ergotamine, a-ergocryptine, ergonovine), and loline alkaloids, all produced by the fungal endophyte, altered chemotaxis with this bioassay. Methanolic extract from roots altered chemotaxis activities in this nematode but only from roots of plants cultured 45 > or = d, which repelled nematodes. Extracts prepared from noninfected grasses were attractants. This assay indicated that the alkaloids were either repellents or attractants. N-formylloline was an attractant at concentrations of 20 microg/ml and lower, while at higher concentrations it was a repellent. Ergovaline, the major ergot alkaloid produced by the endophyte, was repellent at both high and low concentrations and caused complete death of the nematodes.

Expression of CYP and GST in human normal and colon tumor tissues.

We investigated the immunohistochemical staining characteristics of cytochrome P450 1A1 (CYP1A1), CYPB1, CYP2E1, and glutathione S-transferase P1 (GSTP1), GSTT1, GSTO1, GSTK1 in colon tumor and surrounding normal colon tissues. Tissues were obtained from 47 patients with colon adenocarcinoma and the staining intensity of tumor and control tissues was compared. CYP1A1, CYP1B1, CYP2E1, GSTP1, GSTT1, GSTO1 and GSTK1 expressions in colon cancer cells were significantly greater than those in normal colon epithelial cells. No significant relation was found between the isoenzyme expressions and age, gender, smoking status, tumor grade and tumor stage. The higher expressions of CYP1A1, CYP1B1, CYP2E1, GSTP1, GSTO1, GSTT1 and GSTK1 in tumor than in normal colon tissues may be important for colon cancer progression and development.