Conservation of Endangered Cordyceps sinensis Through Artificial Cultivation Strategies of C. militaris, an Alternate.

Cordyceps, an entomopathogenic fungus belonging to the Ascomycota phylum, is a familiar remedial mushroom that is extensively used in the traditional medicinal system, especially in South Asian nations. The significance of this genus' members in a range of therapeutic and biotechnological applications has long been acknowledged. The exceedingly valuable fungus Ophiocordyceps sinensis (Cordyceps sinensis) is found in the alpine meadows of Bhutan, Nepal, Tibet, and India, where it is severely harvested. Driven by market demand and ecological concerns, the study highlights challenges in natural C. sinensis collection and emphasizes the shift towards sustainable artificial cultivation methods. This in-depth review navigates Cordyceps cultivation strategies, focusing on C. sinensis and the viable alternative, C. militaris. The escalating demand for Cordyceps fruiting bodies and bioactive compounds prompts a shift toward sustainable artificial cultivation. While solid-state fermentation on brown rice remains a traditional method, liquid culture, especially submerged and surface/static techniques, emerges as a key industrial approach, offering shorter cultivation periods and enhanced cordycepin production. The review accentuates the adaptability and scalability of liquid culture, providing valuable insights for large-scale Cordyceps production. The future prospects of Cordyceps cultivation require a holistic approach, combining scientific understanding, technological innovation, and sustainable practices to meet the demand for bioactive metabolites while ensuring the conservation of natural Cordyceps populations.

Functional characterization of Malabar grouper (Epinephelus malabaricus) interferon regulatory factor 9 involved in antiviral response.

IRF9 is a crucial component in the JAK-STAT pathway. IRF9 interacts with STAT1 and STAT2 to form IFN-I-stimulated gene factor 3 (ISGF3) in response to type I IFN stimulation, which promotes ISG transcription. However, the mechanism by which IFN signaling regulates Malabar grouper (Epinephelus malabaricus) IRF9 is still elusive. Here, we explored the nd tissue-specific mRNA distribution of the MgIRF9 gene, as well as its antiviral function in E. malabaricus. MgIRF9 encodes a protein of 438 amino acids with an open reading frame of 1317 base pairs. MgIRF9 mRNA was detected in all tissues of a healthy M. grouper, with the highest concentrations in the muscle, gills, and brain. It was significantly up-regulated by nervous necrosis virus infection and poly (I:C) stimulation. The gel mobility shift test demonstrated a high-affinity association between MgIRF9 and the promoter of zfIFN in vitro. In GK cells, grouper recombinant IFN-treated samples showed a significant response in ISGs and exhibited antiviral function. Subsequently, overexpression of MgIRF9 resulted in a considerable increase in IFN and ISGs mRNA expression (ADAR1, ADAR1-Like, and ADAR2). Co-immunoprecipitation studies demonstrated that MgIRF9 and STAT2 can interact in vivo. According to the findings, M. grouper IRF9 may play a role in how IFN signaling induces ISG gene expression in grouper species.

Phytofabricated bimetallic synthesis of silver-copper nanoparticles using Aerva lanata extract to evaluate their potential cytotoxic and antimicrobial activities.

In this study, we demonstrate the green synthesis of bimetallic silver-copper nanoparticles (Ag-Cu NPs) using Aerva lanata plant extract. These NPs possess diverse biological properties, including in vitro antioxidant, antibiofilm, and cytotoxic activities. The synthesis involves the reduction of silver nitrate and copper oxide salts mediated by the plant extract, resulting in the formation of crystalline Ag-Cu NPs with a face-centered cubic structure. Characterization techniques confirm the presence of functional groups from the plant extract, acting as stabilizing and reducing agents. The synthesized NPs exhibit uniform-sized spherical morphology ranging from 7 to 12 nm. They demonstrate significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa, inhibiting extracellular polysaccharide secretion in a dose-dependent manner. The Ag-Cu NPs also exhibit potent cytotoxic activity against cancerous HeLa cell lines, with an inhibitory concentration (IC50) of 17.63 µg mL-1. Additionally, they demonstrate strong antioxidant potential, including reducing capability and H2O2 radical scavenging activity, particularly at high concentrations (240 µg mL-1). Overall, these results emphasize the potential of A. lanata plant metabolite-driven NPs as effective agents against infectious diseases and cancer.

Prevalence of Cardiovascular Diseases in South Asians: Scrutinizing Traditional Risk Factors and Newly Recognized Risk Factors Sarcopenia and Osteopenia/Osteoporosis.

One of the primary reasons for complications and death worldwide are cardiovascular diseases (CVDs), with a death toll of approximately 18 million per year. CVDs include cardiomyopathy, hypertension, ischemic heart disease, coronary heart disease, myocardial infarction, heart attack, hearth failure, etc. Over 80% of the CVD mortality is recorded from lower and middle-income countries. Records from the past decade have highlighted the increase of CVDs among the South Asian populations, and the prime purpose of the review is to jot down the reasons for the steep spike in CVDs. Studies analyzing the causative factors for the increase of CVDs in South Asians are still to be verified. Apart from known predisposing and lifestyle factors, other emerging risk factors associated with CVDs, namely the musculoskeletal diseases sarcopenia and osteopenia, should be tracked to tackle research gaps in upcoming analyses. This requires loads of scientific efforts. With proper monitoring, the raising alarm that the CVD burden generates can be reduced. This review discusses the already established signs and recognizes important clues to the emerging etiology of CVDs in the Asian population and prevention measures to keep it at bay.

Review on impacts of micro- and nano-plastic on aquatic ecosystems and mitigation strategies.

The rapid proliferation of microplastics (MPs) and nanoplastics (NPs) in our environment presents a formidable hazard to both biotic and abiotic components. These pollutants originate from various sources, including commercial production and the breakdown of larger plastic particles. Widespread contamination of the human body, agroecosystems, and animals occurs through ingestion, entry into the food chain, and inhalation. Consequently, the imperative to devise innovative methods for MPs and NPs remediation has become increasingly apparent. This review explores the current landscape of strategies proposed to mitigate the escalating threats associated with plastic waste. Among the array of methods in use, microbial remediation emerges as a promising avenue for the decomposition and reclamation of MPs and NPs. In response to the growing concern, numerous nations have already implemented or are in the process of adopting regulations to curtail MPs and NPs in aquatic habitats. This paper aims to address this gap by delving into the environmental fate, behaviour, transport, ecotoxicity, and management of MPs and NPs particles within the context of nanoscience, microbial ecology, and remediation technologies. Key findings of this review encompass the intricate interdependencies between MPs and NPs and their ecosystems. The ecological impact, from fate to ecotoxicity, is scrutinized in light of the burgeoning environmental imperative. As a result, this review not only provides an encompassing understanding of the ecological ramifications of MPs and NPs but also highlights the pressing need for further research, innovation, and informed interventions.

One-Pot Synthesis of Silver Nanoparticles from Garcinia gummi-gutta: Characterisation, Antimicrobial, Antioxidant, Anti-Cancerous and Photocatalytic Applications.

BACKGROUND: Methods like the bio-synthesis of silver nanoparticles (Ag NPs) using plant extracts have become promising due to their eco-friendly approach. The study aimed to examine the utilization of Garcinia gummi-gutta fruit phytochemicals as agents in the biosynthesis of Ag NPs, evaluation of the antimicrobial, antioxidant, and anti-cancerous properties, as well as the photocatalytic ability of bio-synthesized Ag NPs against Crystal Violet (CV), a triphenylmethane dye. METHODS: The characterization of the physical properties of the Ag NPs synthesized via the green route was done using UV-Vis spectrophotometry (UV-Vis), X-ray Diffraction (XRD), Fourier Transform Infrared Spectrophotometry (FTIR), Scanning Electron Microscopy (SEM), Zeta potential analysis, and Transmission Electron Microscopy (TEM). The dye degradation efficiency of CV was determined using synthesized Ag NPs under UV light by analyzing the absorption maximum at 579 nm. The antimicrobial efficacy of Ag NPs against E. coli, S. aureus, Candida tropicalis, and Candida albicans was examined using the broth dilution method. The antioxidant and anti-cancer properties of the synthesized Ag NPs were assessed using the DPPH and MTT assays. RESULTS: The UV analysis revealed that the peak of synthesized Ag NPs was 442 nm. Data from FTIR, XRD, Zeta potential, SEM, and TEM analysis confirmed the formation of nanoparticles. The SEM and TEM analysis identified the presence of spherical nanoparticles with an average size of 29.12 nm and 24.18 nm, respectively. Maximum dye degradation efficiency of CV was observed at 90.08% after 320 min without any silver leaching, confirming the photocatalytic activity of Ag NPs. The bio-efficiency of the treatment was assessed using the Allium cepa root growth inhibition test, toxicity analysis on Vigna radiata, and Brine shrimp lethality assay. CONCLUSIONS: The findings revealed the environmentally friendly nature of green Ag NPs over physical/chemically synthesized Ag NPs. The synthesized Ag NPs can effectively be used in biomedical and photocatalytic applications.

Nutrition paves the way to environmental toxicants and influences fetal development during pregnancy.

Nutrition plays a major role in the healthy pregnancy and development of the fetus. In addition, nutrition can expose humans to a wide range of potentially hazardous environmental constituents, such as organic pollutants and heavy metals from marine or agricultural food products while processing, producing, and packaging. Humans constantly face these constituents through air, water, soil, food, and domestic products. During pregnancy, the rate of cellular division and differentiation is higher; exposure to any of these environmental toxicants can lead to developmental defects as they cross the placental barrier and, in some cases, can harm the successive generation too, as some contaminants can act on the reproductive cells of the fetus (Diethylstilbestrol). Pregnant women are considered a vulnerable population to food contaminant exposure and require a proper dietary chart and conscious food choices. Food is a source of both essential nutrients and environmental toxicants. Here, we have researched the possible toxicants of the food industry and their influence on the fetus's in-utero development, along with the importance of dietary interventions and the need to balance a healthy diet to overcome the harms. The cumulative exposure to environmental toxicants can influence the mother's prenatal environment and affect the fetus's development.

Understanding the Role of Antimicrobial Peptides in Neutrophil Extracellular Traps Promoting Autoimmune Disorders.

AMPs are small oligopeptides acting as integral elements of the innate immune system and are of tremendous potential in the medical field owing to their antimicrobial and immunomodulatory activities. They offer a multitude of immunomodulatory properties such as immune cell differentiation, inflammatory responses, cytokine production, and chemoattraction. Aberrancy in neutrophil or epithelial cell-producing AMPs leads to inflammation culminating in various autoimmune responses. In this review, we have tried to explore the role of prominent mammalian AMPs-defensins and cathelicidins, as immune regulators with special emphasis on their role in neutrophil extracellular traps which promotes autoimmune disorders. When complexed with self-DNA or self-RNA, AMPs act as autoantigens which activate plasmacytoid dendritic cells and myeloid dendritic cells leading to the production of interferons and cytokines. These trigger a series of self-directed inflammatory reactions, leading to the emergence of diverse autoimmune disorders. Since AMPs show both anti- and pro-inflammatory abilities in different ADs, there is a dire need for a complete understanding of their role before developing AMP-based therapy for autoimmune disorders.

Out of Box Thinking to Tangible Science: A Benchmark History of 3D Bio-Printing in Regenerative Medicine and Tissues Engineering.

Advancements and developments in the 3D bioprinting have been promising and have met the needs of organ transplantation. Current improvements in tissue engineering constructs have enhanced their applications in regenerative medicines and other medical fields. The synergistic effects of 3D bioprinting have brought technologies such as tissue engineering, microfluidics, integrated tissue organ printing, in vivo bioprinted tissue implants, artificial intelligence and machine learning approaches together. These have greatly impacted interventions in medical fields, such as medical implants, multi-organ-on-chip models, prosthetics, drug testing tissue constructs and much more. This technological leap has offered promising personalized solutions for patients with chronic diseases, and neurodegenerative disorders, and who have been in severe accidents. This review discussed the various standing printing methods, such as inkjet, extrusion, laser-assisted, digital light processing, and stereolithographic 3D bioprinter models, adopted for tissue constructs. Additionally, the properties of natural, synthetic, cell-laden, dECM-based, short peptides, nanocomposite and bioactive bioinks are briefly discussed. Sequels of several tissue-laden constructs such as skin, bone and cartilage, liver, kidney, smooth muscles, cardiac and neural tissues are briefly analyzed. Challenges, future perspectives and the impact of microfluidics in resolving the limitations in the field, along with 3D bioprinting, are discussed. Certainly, a technology gap still exists in the scaling up, industrialization and commercialization of this technology for the benefit of stakeholders.

Green Synthesis of Bioinspired Nanoparticles Mediated from Plant Extracts of Asteraceae Family for Potential Biological Applications.

The Asteraceae family is one of the largest families in the plant kingdom with many of them extensively used for significant traditional and medicinal values. Being a rich source of various phytochemicals, they have found numerous applications in various biological fields and have been extensively used for therapeutic purposes. Owing to its potential phytochemicals present and biological activity, these plants have found their way into pharmaceutical industry as well as in various aspects of nanotechnology such as green synthesis of metal oxide nanoparticles. The nanoparticles developed from the plants of Asteraceae family are highly stable, less expensive, non-toxic, and eco-friendly. Synthesized Asteraceae-mediated nanoparticles have extensive applications in antibacterial, antifungal, antioxidant, anticancer, antidiabetic, and photocatalytic degradation activities. This current review provides an opportunity to understand the recent trend to design and develop strategies for advanced nanoparticles through green synthesis. Here, the review discussed about the plant parts, extraction methods, synthesis, solvents utilized, phytochemicals involved optimization conditions, characterization techniques, and toxicity of nanoparticles using species of Asteraceae and their potential applications for human welfare. Constraints and future prospects for green synthesis of nanoparticles from members of the Asteraceae family are summarized.

DNA Damage on Buccal Epithelial Cells, Personal Working in the Rubber Industry Occupationally Exposed to Carbon Disulfide (CS2).

INTRODUCTION: The most significant industrial utilization of carbon disulfide (CS2) has been in the manufacture of cellulose rayon, cellophane, and rubber industry. CS2 prompts expanded recurrence of chromosomal variations in laborers occupationally exposed to CS2. MATERIALS AND METHODS: In the current study, the DNA analysis was carried out from exfoliated buccal epithelial cells from rubber industry workers exposed to CS2 and an equal number of healthy control subjects. Both the control and experimental subjects were categorized by their smoking habits such as smokers (S) and non-smokers (NS). Furthermore, experimental subjects were further separated based on their exposure period. Students t-test statistical tools were used to analyze the final results. RESULTS: The present analysis identified a high frequency of DNA damage in rubber industry workers (16.55±0.43) than control subjects (9.8±0.21). Also, maximum number of DNA damage detected in smoking experimental group (18.27±0.02) than non-smoking experimental (15.02±0.01) and smoking control groups (10.25±0.04 ). CONCLUSION: Smoking habits synergistically increased the DNA damage in the rubber industry workers exposed to CS2.

The crux of bioactive metabolites in endophytic and thermophilic fungi and their proximal prospects in biotechnological and industrial domains.

Fungi are ubiquitous in distribution and are found in grasses to hot springs. Their mode of nutrition provides sustenance for living and propagation. Ironically, varied fungal species have developed customized strategies for protection and survival by producing diverse secondary metabolites. The review aimed to project the contrasting potential features of the endophytic and thermophilic fungi groups. The metabolites and the enzymes of endophytic and thermophilic fungi served as the backbone to thrive and adapt within-host and in extreme conditions like higher pH, heat, and salinity, respectively. Identification, knowledge of their biochemistry and pathway, exploration, production, and utilization of these bioactive molecules in various commercial, industrial, and pharmaceutical domains were briefly discussed. The uniqueness of endophytes includes stress management and improved biomass production of the host, green fuel production, omnipresence, selected triple-symbiosis with the virus, synthesis of polyketides, and other active metabolites are widely used in biomedical applications and agriculture management. This review attempted to limelight the specific applications of thermophilic fungal metabolites and the roles of thermo-stable enzymes in bioprospecting. Moreover, probing the metabolites of thermophiles rendered novel antibiotic compounds, which were proven effective against multi-drug resistant bacteria and harboured the potential to curtail infectious diseases.

Cytokine see-saw across pregnancy, its related complexities and consequences.

During pregnancy, a woman's immune system adapts to the changing hormonal concentrations, causing immunologic transition. These immunologic changes are required for a full-term pregnancy, preserving the fetus' innate and adaptive immunity. Preterm labor, miscarriage, gestational diabetes mellitus, and pre-eclampsia are all caused by abnormal cytokine expression during pregnancy and childbirth. A disruption in the cytokine balance can lead to autoimmune diseases or microbiologic infections, or to autoimmune illness remission during pregnancy with postpartum recurrence. The cytokine treatments are essential and damaging to the developing fetus. The current review summarizes the known research on cytokine changes during pregnancy and their possible consequences for pregnant women. Studies suggest that customizing medication for each woman and her progesterone levels should be based on the cytokine profile of each pregnant woman. Immune cells and chemicals play an important function in development of the placenta and embryo. During pregnancy, T cells divide and move, and a careful balance between proinflammatory and anti-inflammatory cytokines is necessary. The present review focuses on the mother's endurance in generating fetal cells and the immunologic mechanism involved.

Genotoxic repercussion of high-intensity radiation (x-rays) on hospital radiographers.

Recent technological advances in the medical field have increased the plausibility of exposing humans to high-intensity wavelength radiations like x-rays and gamma rays while diagnosing or treating specific medical maladies. These radiations induce nucleotide changes and chromosomal alterations in the exposed population, intentionally or accidentally. A radiological investigation is regularly used in identifying the disease, especially by the technicians working in intensive care units. The current study observes the genetic damages like chromosomal abnormalities (CA) in clinicians who are occupationally exposed to high-intensity radiations (x-rays) at their workplaces using universal cytogenetic tools like micronucleus assay (MN), sister chromatid exchange and comet assay. The study was conducted between 100 exposed practitioners from the abdominal scanning, chest scanning, cranial and orthopedic or bone scanning department and age-matched healthy controls. We observed a slightly higher rate of MN and CA (p < .05) in orthopedic and chest department practitioners than in other departments concerning increasing age and duration of exposure at work. Our results emphasize taking extra precautionary measures in clinical and hospital radiation laboratories to protect the practitioners.

The Puzzle of Hereditary Spastic Paraplegia: From Epidemiology to Treatment.

Inherited neurodegenerative pathology characterized by lower muscle tone and increasing spasticity in the lower limbs is termed hereditary spastic paraplegia (HSP). HSP is associated with changes in about 80 genes and their products involved in various biochemical pathways, such as lipid droplet formation, endoplasmic reticulum shaping, axon transport, endosome trafficking, and mitochondrial function. With the inheritance patterns of autosomal dominant, autosomal recessive, X-linked recessive, and mitochondrial inheritance, HSP is prevalent around the globe at a rate of 1-5 cases in every 100,000 individuals. Recent technology and medical interventions somewhat aid in recognizing and managing the malaise. However, HSP still lacks an appropriate and adequate therapeutic approach. Current therapies are based on the clinical manifestations observed in the patients, for example, smoothing the relaxant spastic muscle and physiotherapies. The limited clinical trial studies contribute to the absence of specific pharmaceuticals for HSPs. Our current work briefly explains the causative genes, epidemiology, underlying mechanism, and the management approach undertaken to date. We have also mentioned the latest approved drugs to summarise the available knowledge on therapeutic strategies for HSP.

Ochratoxin A as an alarming health threat for livestock and human: A review on molecular interactions, mechanism of toxicity, detection, detoxification, and dietary prophylaxis.

Ochratoxin A (OTA) is a toxic metabolite produced by Aspergillus and Penicillium fungi commonly found in raw plant sources and other feeds. This review comprises an extensive evaluation of the origin and proprieties of OTA, toxicokinetics, biotransformation, and toxicodynamics of ochratoxins. In in vitro and in vivo studies, the compatibility of OTA with oxidative stress is observed through the production of free radicals, resulting in genotoxicity and carcinogenicity. The OTA leads to nephrotoxicity as the chief target organ is the kidney. Other OTA excretion and absorption rates are observed, and the routes of elimination include faeces, urine, and breast milk. The alternations in the Phe moiety of OTA are the precursor for the amino acid alternation, bringing about Phe-hydroxylase and Phe-tRNA synthase, resulting in the complete dysfunction of cellular metabolism. Biodetoxification using specific microorganisms decreased the DNA damage, lipid peroxidation, and cytotoxicity. This review addressed the ability of antioxidants and the dietary components as prophylactic measures to encounter toxicity and demonstrated their capability to counteract the chronic exposure through supplementation as feed additives.

Carcinogens in Food: Evaluating the Presence of Cadmium, Lead, in Poultry Meat in South India.

OBJECTIVE: Local chickens were spontaneously sampled and slaughtered in the central markets of Coimbatore, Erode, and Namakkal districts, South India. MATERIALS AND METHODS: Wet digestion was used to extract lead (Pb), cadmium (Cd), and zinc (Zn) in their blood and selected different organs (intestine, breast, liver, and gizzard), and their concentrations were measured using an atomic absorption spectrophotometer. RESULTS: Apart from the blood of chickens from Coimbatore and Namakkal, where Pb was not found, the concentrations of Pb in the blood and organs of chickens from the three towns ranged from 1.8 to 8.33 mg/kg, exceeding the maximum tolerance thresholds (0.1 mg/kg) in internal organs of poultry birds. Except for the intestine of chickens from the three areas, Cd was only found in the heart, blood, and gizzard of Erode chickens, as well as the liver and gizzard of Namakkal chickens, in concentrations ranging from 0.13 to 0.58. According to threshold level, the upper limit met the maximum limits (0.5 mg/kg). Zn was found in all sections of chickens from the three selected districts, with concentrations ranging from 4.96 to 174.17 mg/kg. CONCLUSION: Its concentrations were within the permissible limits (10-50 mg/kg) in some areas of certain chickens, but it surpassed the permissible limit in the liver of chicken from Coimbatore. Any organs and blood from local chickens sold in Coimbatore, Erode, and Namakkal areas can be hazardous to one's health.

Cytogenetic Consequences of Food Industry Workers Occupationally Exposed to Cooking Oil Fumes (COFs).

BACKGROUND: Cooking oil fumes (COFs) with smoking habits is a substantial risk that aggravates genetic modifications. The current study was to estimate the biological markers of genetic toxicity counting Micronucleus changes (MN), Chromosome Aberrations (CA) and DNA modifications among COFs exposures and control subjects inherent from South India. MATERIALS AND METHODS: Present analysis comprised 212 COFs with tobacco users and equivalent number of control subjects. RESULTS: High frequency of CA (Chromatid type: and chromosome type) were identified in group II experimental subjects also high amount of MN and DNA damage frequency were significantly (p < 0.05) in both subjects (experimental smokers and non-smokers). Present analysis was observed absence of consciousness among the COFs exposures about the destructive level of health effects of tobacco habits in working environment. CONCLUSION: COFs exposed workers with tobacco induce the significant alteration in chromosomal level. Furthermore, a high level of rate of genetic diseases (spontaneous abortion) were identified in the experimental subjects. This finding will be helpful for preventive measures of COFs exposed workers and supportive for further molecular analysis.

Cytogenetic endpoints and Xenobiotic gene polymorphism in lymphocytes of hospital workers chronically exposed to ionizing radiation in Cardiology, Radiology and Orthopedic Laboratories.

Ionizing radiation (IR) is known as a classical mutagen capable of inducing various kinds of stable and unstable chromosomal aberrations (CA) including the possibility of increasing the incidence of DNA damage. This study aims to assess occupationally induced CA in workers chronically exposed to low doses of IR in Radiology (RL), Cardiology (CL) and Orthopedic (OL) Laboratories in hospitals of Tamil Nadu. We performed the analysis of CA by trypsin G-banding, micronucleus (MN) assay, Comet assay and Xenobiotic-metabolizing gene polymorphisms (GSTM1, GSTT1 and GSTP1) in 56 exposed and 56 control subjects who were matched for gender and age (± 2 years). Higher degree of CA and MN frequencies were observed in exposed groups, especially in CL subjects compared to other exposed groups and controls (p<0.05). Higher frequency of DNA tail length and tail moment was observed in the CL exposed subjects compared to the RL and OL subjects. The frequencies of GSTM1 and GSTT1 null genotypes were 39.3 percent and 14.3 percent, respectively. No significant difference in allele frequencies between exposed subjects and controls were observed (p=0.0128). Using multiple linear regression analysis, statistical significance was determined for work duration and age for the CL, RL and OL workers and the examination of the possible impact by confounding factors showed few significant influences on the radiation exposure, as a specific biomarker. However, the findings from the present study suggest that, awareness should be created among the personnel exposed to radiations in hospital laboratories, highlighting the necessity of applying radiation protection principles against medical radiation exposure.