ochratoxin a neurological symptoms

In addition, administration of radiolabeled OTA to rats indicated that effective metabolism of OTA was lacking in most tissues other than the intestines [12]. The https:// ensures that you are connecting to the The patient was encouraged to commence treatment with oral cholestyramine as soon as possible, but met with resistance from her transplant team and ultimately did not initiate therapy. Bethesda, MD 20894, Web Policies If elevated levels of urinary OTA are found, there are a number of safe treatments that should be considered to lower the body burden of this mycotoxin. In fact, there is evidence that some beneficial gastrointestinal flora can have positive effects on decreasing toxicity from OTA including specific strains of yeast [80]. Feeding experiments with ochratoxin A contaminated barley for bacon pigs. Her protein excretion in urine is followed regularly, and her mother reports an increased level of proteinuria upon moving to their most recent home. However, the evidence in humans is limited. Studies have shown that animals fed a diet of OTA plus cholestyramine had a significant shift of OTA from the plasma and urine to the stool, where it is presumably excreted bound to cholestyramine [74]. OTA causes The family sought care from the authors due to chronic symptoms and illnesses in all family members and history of exposure to water-damaged environments in past and current homes. JEM Spotlight: fungi, mycotoxins and microbial volatile organic compounds in mouldy interiors from water-damaged buildings. OTA was also shown to decrease testosterone secretion in testicular interstitial cells of gerbils [65]. OTA has been identified in studies of water-damaged buildings from air [41], dust [42], wallpaper [43], and agricultural dust and conidia [44]. Madsen A, Mortensen HP, Hald B. It is produced by several different fungi including Mycotoxins | FDA - U.S. Food and Drug Administration The site is secure. Environmental pollutants and the risk of neurological disorders Of concern, in 50 lactating mothers and their infants in Egypt, the presence of OTA was associated with significantly higher levels of urine microglobulin and microalbuminuria in the infants consistent with early renal injury [76]. Personal communication. Prevention measures and awareness are crucial. Current Review of Mycotoxin Biodegradation and Bioadsorption: Microorganisms, Mechanisms, and Main Important Applications. Urine mycotoxin testing was performed, and the patient was found to have significant elevations of ochratoxin A at 11.9ppb (limit of detection 2.0ppb). Received 2011 Oct 10; Accepted 2011 Nov 7. Recurrence of nephritic syndrome after transplantation in a mixed population of children and adults: course of glomerular lesions and value of the Columbia classification of histological variants of focal ad segmental glomerulosclerosis (FSGS). , In conclusion, ochratoxin A is a toxic substance that can cause damage to the nervous system and lead to neurodegenerative diseases. In addition, it can interfere with the metabolism of energy in brain cells, which can lead to cell death. Ochratoxin A reduced cell proliferation with sub G0/G1 cell cycle arrest by inhibiting CCND1, CCNE1, CDK4, and MYC expression. Early detection and treatment can improve outcomes. R01 CA153073/CA/NCI NIH HHS/United States, 5R01CA153073-2/CA/NCI NIH HHS/United States. The authors concluded that airborne dust and conidia can be sources of OTA and that peak exposures and absorptions from this route can be considerable, especially given the efficiency with which OTA is absorbed through the lung [44, 45]. - More research is needed to fully understand the link between OTA and neurodegenerative diseases, but reducing exposure to OTA-contaminated food may be a preventative measure. Ochratoxin A as a potential etiologic factor in endemic nephropathy: lessons from toxicity studies in rats. Mold toxins destroy myelin, axons, causes neurodegeneration, kills olfactory neurons, and damages our cell membranes and mitochondria. eCollection 2021. Prior to the dietary changes required by the onset of renal failure, the patient's diet was typical of the general population and did not include excessive consumption of foods known to contain OTA. To protect public health, many countries have established regulations on the maximum levels of ochratoxin A allowed in food and feed products. Huff JE. Biosynthesis of gold nanoparticles by Penicillium rubens and catalytic detoxification of ochratoxin A and organic dye pollutants. Gastroinestinal (Fecal) ToxEase GL or caps Chicory inulin. She did, however, follow the recommendation to move from her home to which she has not yet returned and has avoided further exposure to items exposed to the mold contaminated home. Prevention is key, as there is no specific cure for Ochratoxin A toxicity. Study of ochratoxin A as an environmental risk that causes renal injury in breast-fed Egyptian infants. Adult hippocampal neural stem/progenitor cells in vitro are vulnerable to the mycotoxin ochratoxin-A. Nephrotoxicity is probably due to ochratoxin A-induced suppression of the collagen regulator mir-29b that results in an increase of translated collagen, fibrotic alteration, and nephropathy. Belmadani A, Steyn PS, Tramu G, Betbeder AM, Baudrimont I, Creppy EE. Ochratoxin A protective effect of melatonin and licorice plant extract was demonstrated in rats exposed to OTA for 28 days and alleviated most of the biochemical abnormalities associated with the exposure [36]. Zepnik H, Pahler A, Schauer U, Dekant W. Ochratoxin A induced tumour formation: is there a role of reactive ochratoxin A metabolites? 2015 Mar 23;10(3):e0119912. Syntheses of. Neurological Symptoms from Ochratoxin A - Symptom Finder Antioxidants, including glutathione, are also likely to be helpful for their antioxidant and detoxification effects [23]. Gautier JC, Richoz J, Welti DH, et al. The couple who were exposed to this granary experienced respiratory distress, retrosternal burning, epigastric tension, and asthenia. Two patients histories of FSGS associated with OTA exposure encountered by the authors are presented. Stemmer K, Ellinger-Ziegelbauer H, Ahr HJ, Dietrich DR. Molecular characterization of preneoplastic lesions provides insight on the development of renal tumors. pp. Metabolites. If a product exceeds the limit, it cannot be sold or consumed. 12. It is not uncommon for people to experience a litany of cognitive symptoms, including, but not limited to, brain fog, confusion, inattention, disorientation, and difficulties with memory, problem solving, following conversation, reaction time, and learning. Focal segmental glomeruloscerosis. Int J Clin Exp Pathol. , The effects of ochratoxin A on the nervous system are dose-dependent, meaning that higher levels of exposure can cause more severe damage. Studies have shown that OTA can lead to significant oxidative damage to multiple brain regions and is highly X. Zhang, C. Boesch-Saadatmandi, Y. Lou, S. Wolffram, P. Huebbe, and G. Rimbach, Ochratoxin A induces apoptosis in neuronal cells, Genes and Nutrition, vol. 4, pp. 4148, 2009. 8600 Rockville Pike Attempts to control the disease with long-term high-dose steroids were unsuccessful, and the disease progressed to the point where she was placed on peritoneal dialysis and the search for a donor kidney commenced. 2011 Nov;63(7-8):613-8. doi: 10.1016/j.etp.2010.05.001. Selection of studies for inclusion in systematic review of adverse health effects associated with ochratoxin A (OTA) exposure as measured by urinary OTA. Before Dietary exposure to OTA has been extensively documented in the literature and worldwide remains a significant source of OTA exposure in humans [1, 4]. WebWe know that ochratoxin A can cause kidney damage in animals. Ochratoxin A - Lab Results explained | HealthMatters.io Thrasher J. Grbay A, Girgin G, Sabuncuolu SA, et al. Cuciureanu M, Tuchilu C, Vartolomei A, Tamba BI, Filip L. Toxins (Basel). Upon diagnosis she was placed on a 6-week course of high-dose prednisone and has since used tacrolimus and enalapril as well as galactose. It is also a frequent contaminant of water-damaged houses and of heating ducts. - OTA has been classified as a possible human carcinogen and is also associated with kidney disease. official website and that any information you provide is encrypted Pei X, Zhang W, Jiang H, Liu D, Liu X, Li L, Li C, Xiao X, Tang S, Li D. Oxid Med Cell Longev. PMC We have reviewed two cases of FSGS associated with significant elevations in urinary OTA excretion following inhalational exposure in water-damaged buildings. Collectively, ochratoxin A exerts neurotoxicity through anti-proliferation and mitochondria-dependent apoptosis in human astrocytes. Microbiologicals for deactivating mycotoxins. Federal government websites often end in .gov or .mil. Breitholtz-Emanuelsson A, Fuchs R, Hult K, Appelgren LE. Castegnaro M, Mohr U, Pfuhl-Leszkowicz A, et al. Risk assessment of the mycotoxin ochratoxin A. Benford D, Boyle C, Dekant W, et al. Exposure to ochratoxin A has been linked to Parkinsons and Alzheimers disease, as well as other neurological disorders. Ochratoxin The toxin can cross the blood-brain barrier, making it particularly concerning for neurological health. It induced apoptosis of NHA-SV40LT cells through mitochondrial membrane potential (MMP) loss and up-regulation of BAX and TP53. Undoubtedly, like most human illnesses, it will involve a complex interaction of environmental exposures with underlying genetics. This clearly makes inhalational exposure to OTA a very significant risk. The https:// ensures that you are connecting to the - The toxin can also lead to cognitive impairment, including memory and learning deficits. 2021 Sep 28;2021:9967334. doi: 10.1155/2021/9967334. Ochratoxin A. Ochratoxin A (OTA) is a fungal metabolite produced by Aspergillus ochraceus and Penicillium verrucosum. In: Proceedings of the 4th Mid-Atlantic Nutrition Conference; March 2006; Timonium, Maryland. Hooper DG, Bolton VE, Guilford FT, Straus DC. WebPMID: 17195275 DOI: 10.1002/mnfr.200600137 Abstract Ochratoxin A (OTA) is a ubiquitous mycotoxin produced by fungi of improperly stored food products. OTA is commonly found in contaminated food, such as grains, coffee, and wine. Exposure level to OTA. Pfohl-Leszkowicz A, Tozlovanu M, Manderville R, Peraica M, Castegnaro M, Stefanovic V. New molecular and field evidences for the implication of mycotoxins but not aristolochic acid in human nephropathy and urinary tract tumor. Hallen IP, Breitholtz-Emanuelsson A, Hult K, Olsen M, Oskarsson A. Placental and lactational transfer of ochratoxin A in rats. Additionally, consideration should be given to the testing of breast milk for OTA and other mycotoxins in mothers exposed to water-damaged environments as the data is strong that OTA can be excreted in breast milk and that the consequences of this exposure can be significant especially given the increased susceptibility of the neonate to toxins. HHS Vulnerability Disclosure, Help You Have Been Diagnosed With Mycotoxin Illness, Now What? It can also affect behavior and cognitive function. Patients who have developed symptoms as a result of exposure to mold and mycotoxins can present similarly with several classic neurologic disorders including pain What is Invasive Aspergillosis? Studies of sweat have shown the presence of OTA in sweat on at least one occasion [47] supporting treatments such as sauna to increase excretion of OTA. Epilepsy and seizures. Chakor K, Creppy EE, Dirheimer G. In vivo studies on the relationship between hepatic metabolism and toxicity of ochratoxin A. Malekinejad H, Farshid A, Mirzakhani N. Liquorice plant extract reduces ochratoxin A-induced nephrotoxicity in rats. Regular testing of food and feed for Ochratoxin A is crucial to prevent its harmful effects on human health. Format of figure: Liu et al., 2012. Ferrufino-Guardia EV, Tangni EK, Larondelle Y, Ponchaut S. Transfer of ochratoxin A during lactation: exposure of suckling via the milli of rabbit does fed a naturally-contaminated feed. Apoptosis; Astrocyte; Ochratoxin A; Proliferation; Toxicity. Copyright 2019 Elsevier B.V. All rights reserved. Cases are considered primary with no cause identified or secondary due to infections (HIV, Hep B, Parvovirus), toxins (heroin, pamidronate, analgesics), familial, or nephron loss from chronic pyelonephritis, obesity, diabetes, sickle cell disease, or anatomic abnormalities and malignancies [71]. An official website of the United States government. What Is Mold Toxicity? Uncovering This Hidden Health Threat In the blood, OTA binds to albumin and the bound fraction constitutes a mobile reserve of OTA [6]. OTA is a proven carcinogen in animals and is classified as a class 2B, possible human carcinogen by the International Agency for Research on Cancer [4]. In another study evaluating the neurotoxicity of ochratoxin A, primary neurons and neuronal cells were incubated with increasing concentrations of OTA [66]. Mycotoxins' Prevalence in Food Industry By-Products: A Systematic Review. - OTA can cross the blood-brain barrier and accumulate in the brain. Kuiper-Goodman T, Scott PM. The diagnosis of FSGS followed several kidney biopsies after it was initially undetected. The main nephrotoxic effect is in the postproximal nephron and proximal tubule which have been reported as a self-enhancing effect [53, 54]. Pour a 3 percent concentration hydrogen peroxide into a spray bottle, and spray the moldy areas until they are saturated. In addition, in cases where the disease has progressed to the state where kidney transplantation is indicated, knowing if the existing kidneys have a significant concentration of OTA might affect the decision about whether to leave the diseased kidneys in place at the time of transplantation. 8600 Rockville Pike A study of rats exposed to OTA preconception, during gestation and during lactation showed that the exposed offspring had three to four times higher levels of OTA than the controls. Symptoms will vary from person to person depending in their individual health status but common symptoms include: IBS; FSGS accounts for approximately one sixth of the cases of nephrotic syndrome in children and is a common cause of kidney failure in adults. - Exposure to OTA can lead to oxidative stress and inflammation in the brain. Interestingly, aspartame has been found to decrease toxicity of OTA through a phenylalanine-mediated mechanism [38]; however, there may be some concerns about other potential toxicities associated with aspartame. government site. Since testing for mycotoxins in urine and other tissues is now readily available [40], it is appropriate to obtain this testing on urine and renal biopsy tissue to help elucidate whether this is a potential contributor to illness. Toxins (Basel). Unfortunately, in the case of exposures to mycotoxins including ochratoxin, it is imperative to address issues of cross contamination of items exposed to water-damaged/mold contaminated environment. Hassan AM, Sheashaa HA, Fattah MFA, Ibrahim AZ, Gaber OA, Sobh MA. Specific mycotoxins affect various organs and/or tissues, such as the liver, kidneys, brain, mucous membrane of the gastrointestinal, respiratory tract, reproductive and urogenital system, and skin (Devegowda and Murthy, 2005). Administration of piperonyl butoxide was also shown to significantly decrease the LD50 of OTA [35] thus increasing toxicity. Stay informed and spread the word to protect yourself and others. Testing indicated the patient did not have a genetic cause for FSGS. - There are regulations in place worldwide to limit OTA levels in food and feed. At the time of presentation to this office, the patient was also reporting symptoms of night sweats, heat intolerance, frequent episodes of otitis media and conjunctivitis, dizziness, hair loss, fungal skin rashes, episodes of excessive thirst, and the recent onset of reversing letters when she writes. Web Neurological symptoms can be caused by a variety of factors, including exposure to toxins. Summary. In a subsequent study using high-performance liquid chromatography to quantify airborne mycotoxins in a poultry house in Dalian, China, OTA along with aflatoxin and zearalenone was detected [41]. Aspergillus fumigatus is responsible for a life-threatening systemic disease called invasive aspergillosis (IA) in immunocompromised individuals where mold actually grows inside the lungs but can invade other areas as well. Furthermore, ochratoxin A regulated the phosphorylation of AKT, ERK1/2, and JNK signal molecules of human astrocytes. Ochratoxin A and human health risk: a review of the She moved into the home 12 years prior to presentation and believes the water damage to have been long standing, predating her move. Intestinal microflora also appear to contribute significantly to the metabolism of OTA via hydrolyzation to the less toxic ochratoxin alpha in rats [10]. Implement good agricultural practices to reduce fungal contamination. Comp Biochem Physiol C Toxicol Pharmacol. An official website of the United States government. Thus, a thorough approach is needed to address contamination of items exposed to water-damaged environments to avoid continued exposure to mycotoxins including ochratoxin through these items even if the building is no longer a source of exposure. Ethnic differences are seen in the prevalence of the disease with blacks affected seven times more often as whites with a worse prognosis once the disease is acquired [72]. Pfohl-Leszkowicz A, Pinelli E, Bartsch H, Mohr U, Castegnaro M. Sex- and strain-specific expression of cytochrome P450s in ochratoxin A- induced genotoxicity and carcinogenicity in rats. Oxidative stress is another component of OTA toxicity [21]. OTA causes nephrotoxicity and renal tumors in a variety of animal species; however, human health effects are less well-characterized. Lopes P, Sobral MMC, Lopes GR, Martins ZE, Passos CP, Petronilho S, Ferreira IMPLVO. This paper reviews Ochratoxin A and its relationship to human health and kidney disease with a focus on a possible association with focal segmental glomerulosclerosis (FSGS) in humans. OTA is excreted in both the stool and urine. Toxicol Lett. Other authors have previously Results of a recent biomonitoring study in Chile confirmed the presence of OTA in breast milk at levels such that the tolerable daily intake could be exceeded [75]. Moreover, a study in rabbits showed an effective transport of OTA from blood to milk and subsequently to the offspring with plasma and kidney concentrations much higher in offspring than adults, possibly due to slower detoxification in the offspring [61]. Gekle M, Oberleithner H, Silbernagl S. Ochratoxin A impairs postproximal nephron function in vivo and blocks plasma membrane anion conductance in Madin-Darby canine kidney cells in vitro. Supportive therapies such as physical therapy and counseling can help manage symptoms. However, inhalation exposure in water-damaged buildings with amplified indoor growth of ochratoxin producing species of mold remains a significant risk. - The European Union has set maximum limits for OTA in various food products. Int Microbiol. In: Castegnaro M, Plestina R, Dirheimer G, Chernozemsky IN, Bartsch H, editors. 132143. Identifying Noise Symptoms of Bad Shock Absorbers. She was born by NSVD at 39 weeks gestation. Genuis. Astrocytes are the major glial cell type in the central nervous system (CNS), and the distal part of the astrocyte forms the blood-brain barrier with nearby blood vessels. The .gov means its official. The site is secure. Ochratoxin A and its Potential Role in Neurodegenerative Diseases, 7. Before As such, it is important to be aware of the potential risks associated with consuming these products and to take steps to minimize exposure. Additionally, she has a history of significant dental disease including requiring a root canal at the age of 4. Ochratoxin A Zearalenone T-2 Toxin (trichothecene) AFB-1 DON. June 2011. Striking similarities have been noted between OTA-induced porcine nephropathy in pigs and BEN in humans [21]. 5. This was associated with an increased excretion of OTA in feces which was felt to reduce the potential nephrotoxicity of OTA. Mold, mycotoxin and what it means for your brain health. As we learn more about genomic studies, including the evaluation of cytochrome p450 and glutathione (GSTP and GSTM) pathways, it may be possible to identify those who may be most vulnerable to illness after exposure to ochratoxin and other toxic agents and having this information could be invaluable in directing appropriate therapies and medication use in the future. There is some evidence that sauna shifts the excretion of ochratoxin to sweat; however, use of sauna needs to be very carefully monitored, especially on initiation. PMC As has been discussed, a toxin as potent as OTA that is known to be found in the highest concentrations in kidney tissue could certainly play a role in the onset and progression of the disease. Exposure to Ochratoxin A can cause various neurological symptoms, including: These symptoms can be mild or severe, depending on the level and duration of exposure. - Ochratoxin A exposure can cause various neurological symptoms such as tremors, seizures, and ataxia. She was breastfed for 14 months. Lab tests can confirm the presence of Ochratoxin A in blood or urine. PLoS One. Micco C, Ambruzzi A, Miraglia M, et al. HHS Vulnerability Disclosure, Help Additionally, she has experienced rejection of the transplanted kidney requiring a course of solumedrol and long-term use of immunosuppressant agents. Bauer J, Gareis M. Ochratoxin A in the food chain. An official website of the United States government. Feeding experiments with ochratoxin A contaminated barley for bacon pigs. Mechanisms of Mycotoxin-Induced Neurotoxicity through Long-term exposure to Ochratoxin A may increase the risk of developing neurodegenerative diseases such as Parkinsons and Alzheimers. Also, other family members tested positive for OTA in urine and nasal secretion samples, while the pet dog was positive for OTA in its urine and an ear mass [33]. Vitamins A, C, E and selenium are other potentially beneficial antioxidants that may be protective in their role as superoxide anion scavengers [22, 75]. OTA was detected in 6 out of 14 samples with concentrations ranging from 0.2 to 70g/kg (ppb) [44]. and transmitted securely. Federal government websites often end in .gov or .mil. In addition, ochratoxin A increased cytosolic and mitochondrial calcium levels, resulting in an increase in MMP2 and PLAUR mRNA expression in NHA-SV40LT cells. Ochratoxin A and aflatoxins in breast milk samples from Sierra Leone. Toxicity from ochratoxin is considered serious enough that it is among approximately 20 mycotoxins monitored in food. The https:// ensures that you are connecting to the A Review of the Mechanism of Injury and Treatment Approaches - OTA has been linked to neurotoxicity and neurodegenerative diseases. sharing sensitive information, make sure youre on a federal The affinity for the hippocampus In vitro and in vivo research has demonstrated cerebellar [66, 67], hippocampal [68], and other adverse neurological effects due to OTA [6669]. Ochratoxin A (OTA) is a mycotoxin produced by several fungal species including Aspergillus ochraceus, A. carbonarius, A. niger, and Penicillium verrucosum. Skaug MA, Eduard W, Strmer FC. The authors do wish to give a special thanks to Tony Marcel, M.D., Ph.D., for his thoughtful review and invaluable input. WebModerate deficiency can cause hemolytic anemia, elevated acidity metabolic acidosis. In light of the detection of OTA in individuals with chronic fungal sinusitis [33], testing of nasal secretions for OTA and other mycotoxins should also be considered. Treatment involves removing the source of exposure and managing symptoms. - Prevention of OTA exposure through proper food storage and processing is crucial in reducing the risk of neurological symptoms. 2016 Jul 4;8(7):191. doi: 10.3390/toxins8070191. Symptoms government site. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). There are also complex relationships between Aspergillus, T regulatory lymphocytes and candidiasis [71], which can be clinically relevant in humans. Clay and zeolite have been studied for their efficacy of mycotoxin binding in animals [78, 79] and likely have a use in human illness caused by mycotoxins including OTA. Liver necrosis and enteritis were also observed. Larger cohort or case-control studies are needed in the future to better establish potential OTA-related human health effects, and further duplicate-diet studies are needed to validate biomarkers of OTA exposure in humans. Presence of ochratoxin A in Tunisian blood nephropathy patients. Neurological exams and imaging tests may be necessary. Organ System for Detox. Ochratoxin A Regulations and Safety Measures for Protecting Public Health. 5 neurological disorders: Symptoms explained Bethesda, MD 20894, Web Policies 5 different neurological disorders and their symptoms. Various substances have been found to either increase or decrease the toxicity of OTA. Ochratoxin A can also disrupt the blood-brain barrier, which normally protects the brain from harmful substances. Here are some strategies: Early detection and treatment of ochratoxin A exposure can prevent neurological symptoms. Based on these data, the authors speculated that OTA may contribute to the development of neurodegenerative diseases such as Alzheimer's and Parkinson's in which apoptotic processes are centrally involved [66]. II. The .gov means its official. - Ochratoxin A (OTA) is a mycotoxin produced by fungi commonly found in food. In addition, animals exposed to OTA contain OTA in the testes and OTA causes adducts in testicular DNA [56]. One Egyptian study showed a significantly higher risk of nephritic syndrome in those with very high urinary OTA levels compared with relatively unexposed individuals; however, other potential risk factors were not controlled for in the study. FSGS is a potentially devastating kidney disease that occurs most frequently in children and young adults but can occur at any age. The Ultimate Guide To Food Chem Toxicol. In: Castegnaro M, Plestina R, Dirheimer G, Chemozemsky IN, Bartsch H, editors. After initial exposure from any source, the urinary and fecal excretory routes of OTA are both important with the relative contribution of each dependent upon factors such as route of administration and dose [5]. Neurological symptoms can be caused by a variety of factors, including exposure to toxins. - Diagnosis of OTA-induced neurological symptoms can be challenging due to the lack of specific biomarkers. . NCI CPTC Antibody Characterization Program. 1995 Dec;82-83:869-77. doi: 10.1016/0378-4274(95)03601-6. Limited information is available on the metabolic disposition of OTA in humans, although it has been suggested that it has a long serum half-life due to strong binding to human serum macromolecules [7, 14]. A recent study in Sri Lanka measuring mycotoxin levels in the urine of patients with kidney disease demonstrated the presence of ochratoxin in 93.5 percent of patients tested although ochratoxin was also found in individuals without kidney disease [55]. Her physical exam was remarkable for nasal mucosal swelling with clear discharge and erythematous right tympanic membrane consistent otitis media, slightly enlarged bilateral submandibular lymph nodes, and moderate sway when balancing on toes with eyes open and an inability to balance on toes with eyes closed. Mold and Mycotoxin Illness/CIRS | Holistic Child Psychiatry

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