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At least 19 records

Epigenetic Regulation by Polycomb Complexes from Drosophila to Human and Its Relation to Communicable Disease Pathogenesis

Although all cells in the human body are made of the same DNA, these cells undergo differentiation and behave differently during development, through integration of external and internal stimuli via ‘specific mechanisms.’ Epigenetics is one such mechanism that comprises DNA/RNA, histone modifications, and non-coding RNAs that regulate transcription without changing the genetic code. The discovery of the first Polycomb mutant phenotype in Drosophila started the study of epigenetics more than 80 years ago. Since then, a considerable number of Polycomb Group (PcG) genes in Drosophila have been discovered to be preserved in mammals, including humans. PcG proteins exert their influence through gene repression by acting in complexes, modifying histones, and compacting the chromatin within the nucleus. In this article, we discuss how our knowledge of the PcG repression mechanism in Drosophila translates to human communicable disease research.

60 APPLIED LIFE SCIENCES↗

Communicable Disease Research

The COSMIC program FITLOS is used regularly by the Centers for Disease Control (CDC), for analyzing data from radioimmunoassays, which involve testing human body substances to provide information on how deficits or excesses of those substances affect a body's ability to ward off disease. A liquid scintillation counter's data is analyzed by the FITLOS program. FITLOS data, then aids in establishing reference methods for hospitals and other health laboratories in their radioimmunoassays. CDC's use of this program enabled them to avoid the cost of designing and developing a new program.

Source record↗

Differential contagiousness of respiratory disease across the United States

The initial contagiousness of a communicable disease within a given population is quantified by the basic reproduction number, $R_0$. This number depends on both pathogen and population properties. On the basis of compartmental models that reproduce Coronavirus Disease 2019 (COVID-19) surveillance data, we used Bayesian inference and the next-generation matrix approach to estimate region-specific $R_0$ values for 280 of 384 metropolitan statistical areas (MSAs) in the United States (US), which account for 95% of the US population living in urban areas and 82% of the total population. We focused on MSA populations after finding that these populations were more uniformly impacted by COVID-19 than state populations. Our maximum a posteriori (MAP) estimates for $R_0$ range from 1.9 to 7.7 and quantify the relative susceptibilities of regional populations to spread of respiratory diseases.

60 APPLIED LIFE SCIENCES↗

Recommended reporting items for epidemic forecasting and prediction research: The EPIFORGE 2020 guidelines

Background: The importance of infectious disease epidemic forecasting and prediction research is underscored by decades of communicable disease outbreaks, including COVID-19. Unlike other fields of medical research, such as clinical trials and systematic reviews, no reporting guidelines exist for reporting epidemic forecasting and prediction research despite their utility. We therefore developed the EPIFORGE checklist, a guideline for standardized reporting of epidemic forecasting research. Methods and findings: We developed this checklist using a best-practice process for development of reporting guidelines, involving a Delphi process and broad consultation with an international panel of infectious disease modelers and model end users. The objectives of these guidelines are to improve the consistency, reproducibility, comparability, and quality of epidemic forecasting reporting. The guidelines are not designed to advise scientists on how to perform epidemic forecasting and prediction research, but rather to serve as a standard for reporting critical methodological details of such studies. Conclusions: These guidelines have been submitted to the EQUATOR network, in addition to hosting by other dedicated webpages to facilitate feedback and journal endorsement.

60 APPLIED LIFE SCIENCES↗

Cross-cutting concepts to transform agricultural research

Agriculture is an important link to many issues that challenge society today, including adaptation to and mitigation of climate change, food security, and communicable and non-communicable diseases in animals and humans. Transformation of agriculture and food systems has become a priority for a range of federal agencies and global organizations. It is imperative that food and agricultural researchers effectively harness the global convergence of priorities to overcome research “silos” through deep and sustained systemic change. Herein, we identify intersections in federal and global initiatives encompassing climate adaptation and mitigation; human health and nutrition; animal health and welfare; food safety and security; and equity and inclusion. Many agencies and organizations share these priorities, but efforts to address them remain uncoordinated and opportunities for collaboration untapped. Based on the interconnectedness of the identified priority areas, we present a research framework to catalyze agricultural transformation, beginning with the research enterprise. We propose that transformation in agricultural research should incorporate (1) innovation, (2) integration, (3) implementation, and (4) evaluation. This framework provides approaches for food and agricultural research to contribute to sustainable, flexible, and coordinated transformation in the agricultural sector.

60 APPLIED LIFE SCIENCES↗

Public health applications of remote sensing of the environment, an evaluation

The available techniques were examined in the field of remote sensing (including aerial photography, infrared detection, radar, etc.) and applications to a number of problems in the wide field of public health determined. The specific areas of public health examined included: air pollution, water pollution, communicable disease, and the combined problems of urban growth and the effect of disasters on human communities. The assessment of the possible applications of remote sensing to these problems was made primarily by examination of the available literature in each field, and by interviews with health authorities, physicists, biologists, and other interested workers. Three types of programs employing remote sensors were outlined in the air pollution field: (1) proving ability of sensors to monitor pollutants at three levels of interest - point source, ambient levels in cities, and global patterns; (2) detection of effects of pollutants on the environment at local and global levels; and (3) routine monitoring.

Source record↗

Medical support and technology for long-duration space missions

The current philosophy and development directions being taken towards realization of medical systems for use on board space stations are discussed. Data was gained on the performance of physical examinations, venipuncture and blood flow, blood smear and staining, white blood cell differential count, throat culture swab and colony count, and microscopy techniques during a 28-day period of the Skylab mission. It is expected that the advent of Shuttle flights will rapidly increase the number of persons in space, create a demand for in-space rather than on-earth medical procedures, and necessitate treatments for disorders without the provision for an early return to earth. Attention is being given to pressurized environment and extravehicular conditions of treatment, the possibilities of the use of the OTV for moving injured or ill crewmembers to other space stations, and to isolation of persons with communicable diseases from station crews.

Furukawa, S.↗

Microbial growth and physiology in space - A review

An overview of microbial behavior in closed environments is given with attention to data related to simulated microgravity and actual space flight. Microbes are described in terms of antibiotic sensitivity, subcellular structure, and physiology, and the combined effects are considered of weightlessness and cosmic radiation on human immunity to such microorganisms. Space flight results report such effects as increased phage induction, accelerated microbial growth rates, and the increased risk of disease communication and microbial exchange aboard confining spacecraft. Ultrastructural changes are also noted in the nuclei, cell membranes, and cytoplasmic streaming, and it appears that antibiotic sensitivity is reduced under both actual and simulated conditions of spaceflight.

Cioletti, Louis A.↗

Johnson Space Center Flight Medicine Clinic Experience

Being a member of the Flight Medicine Clinic (FMC) Staff is a great experience. I joined the FMC staff 2 years ago when I became part of the Kelsey-Seybold team. The FMC staff consists of Flight Surgeons, Family Clinic Physician, Nursing staff, Wellness Coordinator and Support staff. We serve as the Primary Care Physicians for the astronauts and their families and provide annual physicals for the retired astronauts. We have approximately 800 patients in the FMC. As the Family Clinic Physician, I care for the astronaut spouses and children and provide annual physicals for the retired astronauts. Since we have a small patient population, we have the opportunity to spend increased personal time with our patients, which I enjoy. We have a pretty healthy patient population, who are very interested in their overall health and preventive care. In preparation for a shuttle launch, our nursing staff assists the flight surgeons with the astronaut physical exams, which occur 10 days prior to launch and again 3 days after their return. We also provide Primary Contact physicals for the families and guests, who will be in close contact with shuttle crew members. During these physicals, we provide education, emphasizing the importance of preventing the spread of communicable diseases to shuttle crew members. Being a part of the Space Medicine Program is an honor. To know that you contribute in some way to our nation s Space Program is very special. (This article was prepared by Dr. Trela Landry, M.D. for inclusion in a Kelsey-Seybold newsletter on 25 OCT 2006.)

Landry, Trela↗

Influence of the broadly neutralizing antibody VRC01 on HIV breakthrough virus populations in antibody-mediated prevention trials

In the antibody mediated prevention (AMP) trials, the broadly neutralizing antibody (bNAb) VRC01 demonstrated protective efficacy against susceptible HIV strains. To understand how VRC01 shaped breakthrough infections, deep sequencing was performed on 172 participants (>100,000 gag-Δpol and rev-env-Δnef sequences), at diagnosis and over time, in the placebo and treatment arms of the African (HVTN703/HPTN081; NCT02568215) and Americas/Europe (HVTN704/HPTN085; NCT02716675) cohorts. A high frequency of multilineage infections was detected (38%), including co-infection with both VRC01 sensitive and resistant viruses. This high frequency is largely accounted for by low-abundance lineages. Although VRC01 does not significantly affect the genetic transmission bottleneck compared to placebo, higher VRC01 doses trend towards greater VRC01 neutralization differences among co-infecting lineages. Two-thirds of multilineage infections showed evidence of recombination at the diagnostic timepoint. In the treatment group there is evidence of recombinant viruses preferentially inheriting resistance-associated mutations. This study provides critical insights into viral genetic and antigenic diversity that needs to be targeted to achieve protection, and highlights the role of recombination in facilitating escape.

59 BASIC BIOLOGICAL SCIENCES↗

Estimating coccidioidomycosis endemicity while accounting for imperfect detection using spatio - temporal occupancy modeling

Coccidioidomycosis, or Valley fever, is an infectious disease caused by inhaling Coccidioides fungal spores. Incidence has risen in recent years, and it is believed the endemic region for Coccidioides is expanding in response to climate change. While Valley fever case data can help us understand trends in disease risk, using case data as a proxy for Coccidioides endemicity is not ideal because case data suffers from imperfect detection, including false positives (e.g., travel-related cases reported outside of endemic area) and false negatives (e.g., misdiagnosis or underreporting). Here we proposed a Bayesian, spatio-temporal occupancy model to relate monthly, county-level presence/absence data on Valley fever cases to latent endemicity of Coccidioides, accounting for imperfect detection. We used our model to estimate endemicity in the western United States. We estimated high probability of endemicity in southern California, Arizona, and New Mexico, but also in regions without mandated reporting, including western Texas, eastern Colorado, and southeastern Washington. We also quantified spatio-temporal variability in detectability of Valley fever, given an area is endemic to Coccidioides. We estimated an inverse relationship between lagged 3- and 9-month precipitation and case detection, and a positive association with agriculture. This work can help inform public health surveillance needs and identify areas that would benefit from mandatory case reporting.

60 APPLIED LIFE SCIENCES↗

Microbial contamination of spacecraft

Spacecraft and space habitats supporting human exploration contain a diverse population of microorganisms. Microorganisms may threaten human habitation in many ways that directly or indirectly impact the health, safety, or performance of astronauts. The ability to produce and maintain spacecraft and space stations with environments suitable for human habitation has been established over 40 years of human space flight. An extensive database of environmental microbiological parameters has been provided for short-term (< 20 days) space flight by more than 100 missions aboard the Space Shuttle. The NASA Mir Program provided similar data for long-duration missions. Interestingly, the major bacterial and fungal species found in the Space Shuttle are similar to those encountered in the nearly 15-year-old Mir. Lessons learned from both the US and Russian space programs have been incorporated into the habitability plan for the International Space Station. The focus is on preventive measures developed for spacecraft, cargo, and crews. On-orbit regular housekeeping practices complete with visual inspections are essential, along with microbiological monitoring. Risks associated with extended stays on the Moon or a Mars exploration mission will be much greater than previous experiences because of additional unknown variables. The current knowledge base is insufficient for exploration missions, and research is essential to understand the effects of space flight on biological functions and population dynamics of microorganisms in spacecraft. Equally important is a better understanding of the immune response and of human-microorganism-environment interactions during long-term space habitation.

Mir Project↗

Education, outreach and the future of remote sensing in human health

The human health community has been slow to adopt remote sensing technology for research, surveillance, or control activities. This chapter presents a brief history of the National Aeronautics and Space Administration's experiences in the use of remotely sensed data for health applications, and explores some of the obstacles, both real and perceived, that have slowed the transfer of this technology to the health community. These obstacles include the lack of awareness, which must be overcome through outreach and proper training in remote sensing, and inadequate spatial, spectral and temporal data resolutions, which are being addressed as new sensor systems are launched and currently overlooked (and underutilized) sensors are newly discovered by the health community. A basic training outline is presented, along with general considerations for selecting training candidates. The chapter concludes with a brief discussion of some current and future sensors that show promise for health applications.

Review, Tutorial↗

Extending unbiased stereology of brain ultrastructure to three-dimensional volumes

OBJECTIVE: Analysis of brain ultrastructure is needed to reveal how neurons communicate with one another via synapses and how disease processes alter this communication. In the past, such analyses have usually been based on single or paired sections obtained by electron microscopy. Reconstruction from multiple serial sections provides a much needed, richer representation of the three-dimensional organization of the brain. This paper introduces a new reconstruction system and new methods for analyzing in three dimensions the location and ultrastructure of neuronal components, such as synapses, which are distributed non-randomly throughout the brain. DESIGN AND MEASUREMENTS: Volumes are reconstructed by defining transformations that align the entire area of adjacent sections. Whole-field alignment requires rotation, translation, skew, scaling, and second-order nonlinear deformations. Such transformations are implemented by a linear combination of bivariate polynomials. Computer software for generating transformations based on user input is described. Stereological techniques for assessing structural distributions in reconstructed volumes are the unbiased bricking, disector, unbiased ratio, and per-length counting techniques. A new general method, the fractional counter, is also described. This unbiased technique relies on the counting of fractions of objects contained in a test volume. A volume of brain tissue from stratum radiatum of hippocampal area CA1 is reconstructed and analyzed for synaptic density to demonstrate and compare the techniques. RESULTS AND CONCLUSIONS: Reconstruction makes practicable volume-oriented analysis of ultrastructure using such techniques as the unbiased bricking and fractional counter methods. These analysis methods are less sensitive to the section-to-section variations in counts and section thickness, factors that contribute to the inaccuracy of other stereological methods. In addition, volume reconstruction facilitates visualization and modeling of structures and analysis of three-dimensional relationships such as synaptic connectivity.

NASA Discipline Neuroscience↗

Remote sensing and human health: new sensors and new opportunities

Since the launch of Landsat-1 28 years ago, remotely sensed data have been used to map features on the earth's surface. An increasing number of health studies have used remotely sensed data for monitoring, surveillance, or risk mapping, particularly of vector-borne diseases. Nearly all studies used data from Landsat, the French Systeme Pour l'Observation de la Terre, and the National Oceanic and Atmospheric Administration's Advanced Very High Resolution Radiometer. New sensor systems are in orbit, or soon to be launched, whose data may prove useful for characterizing and monitoring the spatial and temporal patterns of infectious diseases. Increased computing power and spatial modeling capabilities of geographic information systems could extend the use of remote sensing beyond the research community into operational disease surveillance and control. This article illustrates how remotely sensed data have been used in health applications and assesses earth-observing satellites that could detect and map environmental variables related to the distribution of vector-borne and other diseases.

Satellite Communications↗

Editorial: Nanotechnology for natural products

Humans around the globe have lived through an unprecedented time. The emergence and rapid spread of coronavirus disease 2019 (COVID-19) have resulted in the loss of millions of lives, and this number is still climbing every day and hour. As a consequence, there have been drastic changes over the past two years in how we live, communicate, and work, some of which may have changed forever: remote conferencing has become a new norm for businesses, schools, and academia; work-from-home and hybrid working is now more than just acceptable in many industries; most importantly, COVID-19 has raised global awareness of infectious diseases and pandemic responses to an exceptional level. Certainly, COVID-19 is not the only disease that is causing human suffering at this moment. Other highly contagious and lethal viruses, such as the human immunodeficiency virus (HIV), Ebola, and the recent addition to the list, Monkeypox, pose extraordinary challenges to modern civilizations. On the other hand, non-communicable diseases, such as heart disease, stroke, and cancer, are still claiming the majority of deaths on a global level (World Health Organization, 2020). Before the availability of synthetic drugs, civilizations worldwide relied on natural products extracted from the environment and various organisms for healthcare. Natural products and their derivatives continue to be critical components in the drug library available today. Indeed, almost a quarter of the new drugs approved by the US Food and Drug Administration (FDA) since 1981 are natural products, botanical mixtures, or their derivatives (Newman and Cragg, 2020). Recent developments in analytical characterization, genome mining, and engineering have further increased interest in drug discovery from the pool of natural products (Atanasov et al., 2021). This Research Topic celebrates a collection of studies at the intersection of natural product research and nanotechnological advances. As a successor and extension of the Research Topic in “Nanotechnology in Traditional Medicines and Natural Products” published last year (Zhang et al., 2021), the present collection focused more on recent developments in employing the synthesis and characterization of nanostructures for the delivery of functional natural products. Specifically, the use of carrier nanostructures to conjugate or encapsulate therapeutically active natural products with carrier nanostructures could enable their robust, targeted delivery tailored to either tackle a specific disease or unlock a drug administration pathway. Over the last decade, nanostructures such as liposomes (Pattni et al., 2015) and lipid nanoparticles (Hou et al., 2021) have been developed as versatile platforms for the inclusion and delivery of a wide range of therapeutical compounds; a significant advance in this aspect is the stabilization of mRNA strands for COVID-19 vaccination recently produced by Pfizer/BioNTech and Moderna (Tenchov et al., 2021). Such engineered nanomaterials are now widely used in the development of new drugs, while regulatory forces, such as the US FDA, remain cautious with the evaluation of each product on a case-by-case basis (Wang and Grainger, 2022). In this collection, Zeng et al. provided a timely review of natural products conjugated to and contained within nanomaterials for the ongoing COVID-19 pandemic. Natural products that are potentially useful in the mitigation of this disease, such as chloroquine and curcumin, supported in nanocarrier systems, have been discussed in detail. More broadly, Cheng et al. comprehensively reviewed the use of liposomes as a nanocarrier for natural products. This article provides a summary of natural product compounds and extracts used to form liposomal structures. Readers can further enjoy the practical aspects of these engineered drugs for the treatment of specific diseases as well as insights into future directions in this field.

peptides↗

The Connected We St@nd programme: A feasibility pilot study of an online self‐management intervention for adults on in‐centre haemodialysis and family caregivers

Abstract Objective The ‘Connected We St@nd’ is an online self‐management intervention programme for people receiving in‐centre haemodialysis and family caregivers that combines an educational and psychosocial support component. This study aimed to evaluate its feasibility and acceptability before proceeding to a large‐scale trial. Design This was a pre‐post single‐arm feasibility pilot study conducted with adults undergoing in‐centre haemodialysis and family caregivers. Methods Feasibility was based on eligibility, consent, retention, completion and intervention adherence rates, while acceptability was assessed in post‐intervention focus group interviews. Results Twenty‐six people (16 adults on haemodialysis and 10 family caregivers) recruited through social networks completed the intervention. Consent, retention and completion rates were excellent (>90%) and eligibility (77.5%) and intervention adherence were satisfactory (69% for the psychosocial support sessions). Qualitative findings revealed that participants shared positive feelings regarding their participation in the programme. The valuable interactions with group peers and health psychologists during the support sessions, the perception of the adequacy and coherence of the programme's contents and materials and the participants' confidence in using the platform developed to deliver the intervention were some of the aspects highlighted as facilitators of intervention acceptability. Additionally, people on haemodialysis and caregivers reported that participation in the programme brought several educational and emotional benefits (e.g., additional disease‐related knowledge, improved communication and coping skills, greater confidence in managing dialysis complications or caregiving demands) that helped increase their self‐management skills and psychosocial adjustment to the demands of kidney failure and renal therapies. Conclusions The results suggested that the ‘Connected We St@nd’ programme is likely to be feasible and acceptable for adults on haemodialysis and family caregivers, thus representing a promising resource for the future of interdisciplinary renal rehabilitation. Suggestions were made to fine‐tune the intervention design to proceed with a large‐scale trial.

Sousa, Helena↗