Age-Stratified Profiles of Serum IL-6, IL-10, and TNF-α Cytokines Among Kenyan Children with Schistosoma haematobium, Plasmodium falciparum, and Other Chronic Parasitic Co-Infections.

In a study of children having polyparasitic infections in a Schistosoma haematobium-endemic area, we examined the hypothesis that S. haematobium-positive children, compared with S. haematobium-negative children (anti-soluble worm antigen preparation [SWAP] negative and egg negative) have increased systemic production of pro-inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α) and decreased down-regulatory IL-10. A total of 804 children, 2-19 years of age, were surveyed between July and December 2009 and tested for S. haematobium, Plasmodium falciparum, filariasis, and soil-transmitted helminth infections. Plasma levels of IL-6, TNF-α, and IL-10 were compared for S. haematobium-positive and S. haematobium-negative children, adjusting for malaria, filaria, and hookworm co-infections, and for nutritional status, age group, sex, and geographic location. IL-10 was significantly elevated among children infected with S. haematobium, showing bimodal peaks in 7-8 and 13-14 years age groups. IL-10 was also higher among children who were acutely malnourished, whereas IL-10 levels were lower in the presence of S. haematobium-filaria co-infection. After adjustment for co-factors, IL-6 was significantly elevated among children of 5-6 years and among those with P. falciparum infection. Lower levels of IL-6 were found in malaria-hookworm co-infection. High levels of TNF-α were found in children aged 11-12 years regardless of infection status. In addition, village of residence was a strong predictor of IL-6 and IL-10 plasma levels. In adolescent children infected with S. haematobium, there is an associated elevation in circulating IL-10 that may reduce the risk of later morbidity. Although we did not find a direct link between S. haematobium infection and circulating pro-inflammatory IL-6 and TNF-α levels, future T-cell stimulation studies may provide more conclusive linkages between infection and cytokine responses in settings that are endemic for multiple parasites and multiple co-infections

Expedited evaluation of hereditary hematopoietic malignancies in the setting of stem cell transplantation

Not available

Drug Discovery for Schistosomiasis: Hit and Lead Compounds Identified in a Library of Known Drugs by Medium-Throughput Phenotypic Screening

The flatworm disease schistosomiasis infects over 200 million people with just one drug (praziquantel) available—a concern should drug resistance develop. Present drug discovery approaches for schistosomiasis are slow and not conducive to automation in a high-throughput format. Therefore, we designed a three-component screen workflow that positions the larval (schistosomulum) stage of S. mansoni at its apex followed by screens of adults in culture and, finally, efficacy tests in infected mice. Schistosomula are small enough and available in sufficient numbers to interface with automated liquid handling systems and prosecute thousands of compounds in short time frames. We inaugurated the workflow with a 2,160 compound library that includes known drugs in order to cost effectively ‘re-position’ drugs as new therapies for schistosomiasis and/or identify compounds that could be modified to that end. We identify a variety of ‘hit’ compounds (antibiotics, psychoactives, antiparasitics, etc.) that produce behavioral responses (phenotypes) in schistosomula and adults. Tests in infected mice of the most promising hits identified a number of ‘leads,’ one of which compares reasonably well with praziquantel in killing worms, decreasing egg production by the parasite, and ameliorating disease pathology. Efforts continue to more fully automate the workflow. All screen data are posted online as a drug discovery resource

Enhanced Growth and Osteogenic Differentiation of Human Osteoblast-Like Cells on Boron-Doped Nanocrystalline Diamond Thin Films

Intrinsic nanocrystalline diamond (NCD) films have been proven to be promising substrates for the adhesion, growth and osteogenic differentiation of bone-derived cells. To understand the role of various degrees of doping (semiconducting to metallic-like), the NCD films were deposited on silicon substrates by a microwave plasma-enhanced CVD process and their boron doping was achieved by adding trimethylboron to the CH4:H2 gas mixture, the B∶C ratio was 133, 1000 and 6700 ppm. The room temperature electrical resistivity of the films decreased from >10 MΩ (undoped films) to 55 kΩ, 0.6 kΩ, and 0.3 kΩ (doped films with 133, 1000 and 6700 ppm of B, respectively). The increase in the number of human osteoblast-like MG 63 cells in 7-day-old cultures on NCD films was most apparent on the NCD films doped with 133 and 1000 ppm of B (153,000±14,000 and 152,000±10,000 cells/cm2, respectively, compared to 113,000±10,000 cells/cm2 on undoped NCD films). As measured by ELISA per mg of total protein, the cells on NCD with 133 and 1000 ppm of B also contained the highest concentrations of collagen I and alkaline phosphatase, respectively. On the NCD films with 6700 ppm of B, the cells contained the highest concentration of focal adhesion protein vinculin, and the highest amount of collagen I was adsorbed. The concentration of osteocalcin also increased with increasing level of B doping. The cell viability on all tested NCD films was almost 100%. Measurements of the concentration of ICAM-1, i.e. an immunoglobuline adhesion molecule binding inflammatory cells, suggested that the cells on the NCD films did not undergo significant immune activation. Thus, the potential of NCD films for bone tissue regeneration can be further enhanced and tailored by B doping and that B doping up to metallic-like levels is not detrimental for cells

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Quantitative estimates of glacial refugia for chimpanzees (Pan troglodytes) since the Last Interglacial (120,000 BP).

Paleoclimate reconstructions have enhanced our understanding of how past climates have shaped present-day biodiversity. We hypothesize that the geographic extent of Pleistocene forest refugia and suitable habitat fluctuated significantly in time during the late Quaternary for chimpanzees (Pan troglodytes). Using bioclimatic variables representing monthly temperature and precipitation estimates, past human population density data, and an extensive database of georeferenced presence points, we built a model of changing habitat suitability for chimpanzees at fine spatio-temporal scales dating back to the Last Interglacial (120,000 BP). Our models cover a spatial resolution of 0.0467° (approximately 5.19 km2 grid cells) and a temporal resolution of between 1000 and 4000 years. Using our model, we mapped habitat stability over time using three approaches, comparing our modeled stability estimates to existing knowledge of Afrotropical refugia, as well as contemporary patterns of major keystone tropical food resources used by chimpanzees, figs (Moraceae), and palms (Arecacae). Results show habitat stability congruent with known glacial refugia across Africa, suggesting their extents may have been underestimated for chimpanzees, with potentially up to approximately 60,000 km2 of previously unrecognized glacial refugia. The refugia we highlight coincide with higher species richness for figs and palms. Our results provide spatio-temporally explicit insights into the role of refugia across the chimpanzee range, forming the empirical foundation for developing and testing hypotheses about behavioral, ecological, and genetic diversity with additional data. This methodology can be applied to other species and geographic areas when sufficient data are available

Examining the Pathoplastic Moderating Role of Education on the Association between Depressive Mood and Self-Rated Health among Cancer Survivors: A Population-Based Study

Objective: Self-rated health (SRH) is a salient patient outcome for cancer survivors, and depressive mood and education are known determinants of cancer survivors’ SRH. Moving beyond the well-established direct association between depressive mood, education, and SRH among cancer survivors, this epidemiological study investigated the pathoplastic role of education on depressive mood in relation to SRH among a nationally representative sample of cancer survivors in the United States. Methods: The 2019 National Health Interview Survey was analyzed using data from adult participants (≥18 years old) who self-reported as cancer survivors (n = 3844). Ordered logistic regression was used to evaluate the direct impact of depressive mood and education in relation to SRH. In addition, the pathoplastic moderating effect was evaluated using ordered logistic regression with an interaction term of depressive mood and education in the regression model. All analyses adjusted for complex sample weights so that findings are nationally representative. Results: After adjusting for all covariates, U.S. cancer survivors’ depressive mood was significantly associated with lower SRH, and U.S. cancer survivors’ higher education was significantly associated with higher SRH. As a pathoplastic moderator, cancer survivors’ education significantly moderated the association between depressive mood and SRH. The negative association between depressive mood and SRH was significantly greater among those with higher education. Conclusion: Moving beyond the direct association between depressive mood, education, and SRH, education served as a pathoplastic moderator in relation to depressive mood and SRH. Psycho-oncology providers need to be mindful of the “protective-risk” effect of education in relation to cancer survivors’ depressive mood and SRH

Treating Mental Health and Quality of Life in Older Cancer Patients with Cognitive Behavioral Therapy: A Systematic Review and Meta-Analysis

Background: Cognitive behavioral therapy (CBT) has been successfully utilized in improving mental health (MH) and quality of life (QoL) in the general population, regardless of age. Cancer, which is most frequently diagnosed in older adults, is a debilitating illness that has a detrimental and long-lasting effect on patients’ MH and QoL. While numerous studies have demonstrated CBT’s efficacy, little evidence exists for its role in older cancer patients. This study, using MH and QoL metrics, evaluates the effectiveness of CBT for older adult cancer patients. Methods: Focusing on MH and QoL and an average age of over 60 years old, a final analysis was performed on 17 clinical trials with a total of 124 effect sizes, including 3073 participants receiving CBT. “Metaphor” and “Robumeta” packages in R Statistical Software (version 4.2.2) were used for analysis, which included robust variance estimation (RVE) in intercept-only meta-regression, and univariate meta-regression for moderator analysis. Results: With 17 clinical trials and 124 effect sizes, our results show that CBT moderately improves MH and QoL in cancer patients d = 0.19, 95% CI 0.0166–0.364, p < 0.0399. The delivery format was shown to be a strong moderator of CBT effectiveness with interpersonal technological interventions combined with pre-programmed segments having a very strong treatment effect size (d = 1.7307, 95% CI 1.5244–1.937, p < 0.001). Conclusions: The use of CBT in older adult cancer patients statistically improves MH and QoL, with delivery format and stages of treatment having important roles. Tech-only interpersonal interventions combined with pre-programmed CBT provide an avenue for targeting older adult cancer patients

Evaluating the Feasibility and Acceptability of an Artificial-Intelligence-Enabled and Speech-Based Distress Screening Mobile App for Adolescents and Young Adults Diagnosed with Cancer: A Study Protocol

Adolescents and young adults (AYAs) diagnosed with cancer are an age-defined population, with studies reporting up to 45% of the population experiencing psychological distress. Although it is essential to screen and monitor for psychological distress throughout AYAs&rsquo; cancer journeys, many cancer centers fail to effectively implement distress screening protocols largely due to busy clinical workflow and survey fatigue. Recent advances in mobile technology and speech science have enabled flexible and engaging methods to monitor psychological distress. However, patient-centered research focusing on these methods&rsquo; feasibility and acceptability remains lacking. Therefore, in this project, we aim to evaluate the feasibility and acceptability of an artificial intelligence (AI)-enabled and speech-based mobile application to monitor psychological distress among AYAs diagnosed with cancer. We use a single-arm prospective cohort design with a stratified sampling strategy. We aim to recruit 60 AYAs diagnosed with cancer and to monitor their psychological distress using an AI-enabled speech-based distress monitoring tool over a 6 month period. The primary feasibility endpoint of this study is defined by the number of participants completing four out of six monthly distress assessments, and the acceptability endpoint is defined both quantitatively using the acceptability of intervention measure and qualitatively using semi-structured interviews