Introduction:
Genomic & Epigenomic Alterations to the
Key Molecular Signaling Pathways Impaired by Exposure
Exposure to permethrin and DEET induces widespread oxidative stress and cellular injury, triggering toxin-specific differentially methylated regions (DMRs) and stable, heritable shifts in DNA methylation patterns. These changes disrupt transcriptional regulation across immune, neurological, endocrine, gastrointestinal, and reproductive pathways—initiating a cascade of multisystem failure. These effects are not isolated to the exposed individual but are shown to be transgenerational, with epimutations observed in germline cells and inherited disease phenotypes confirmed across animal models.
Neurological Damage and Cognitive Decline
• Nurr1 Dysregulation: Suppressed neurogenesis, sustained neuroinflammation, and loss of neuroplasticity contributes to increased risk of Parkinson’s, Alzheimer’s, ALS, and cognitive decline.
• Benzodiazepine Receptor Pathway Disruption: Alters GABAergic signaling, causing agitation, sleep dysfunction (including REM Sleep Behavior Disorder), depression, and anxiety.
• Endocannabinoid System (ECS) Dysfunction: Results in impaired neuroprotection, chronic pain syndromes, mood instability, and autonomic dysregulation.
• Mitochondrial Biogenesis Failure (PGC1-α Dysfunction): Triggers energy deficits in neural tissue, neurodegeneration, and worsening of fatigue-related conditions such as ME/CFS. Chronic Inflammation and Autoimmune Activation
• NF-κB Pathway Activation: Persistent pro-inflammatory signaling drives autoimmunity, endothelial damage, and oncogenesis.
• LPS Biosynthesis Overactivation: Elevates gut-derived endotoxemia, fueling systemic inflammation, dysbiosis, and increased IBD risk.
• Nrf2 Pathway Suppression: Compromises antioxidant defenses, accelerates cellular aging, and impairs detoxification of environmental insults. Gastrointestinal and Metabolic Dysfunction
• COX-2 Overexpression: Elevates prostaglandin synthesis, promoting mucosal inflammation, ulcer formation, GI bleeding, and cancerous polyp progression.
• Butyrate Production Pathway Disruption: Reduces microbial short-chain fatty acid synthesis, weakening the colonic barrier and increasing permeability (“leaky gut”), sepsis risk, and IBD.
• Sulfide & Oxalate Metabolism Impairment: Increases epithelial toxicity, oxidative burden, and risk of nephrolithiasis, diverticulitis, and metabolic syndrome.
• Uric Acid Pathway Dysfunction: Leads to hyperuricemia, insulin resistance, and chronic renal stress. Cardiovascular and Endothelial Dysfunction
• eNOS (Endothelial Nitric Oxide Synthase) Impairment: Disrupts vasodilation and microvascular integrity, causing hypertension, hypoxia, and ischemia in vulnerable tissues.
• TMA/TMAO Pathway Dysregulation: Elevates atherosclerotic risk and endothelial inflammation, compounding small-vessel disease and HFpEF risk. Hormonal, Reproductive, and Oncogenic Dysregulation
• ERKO (Estrogen Receptor Knockout) Signaling Failure: Alters hormone metabolism and receptor sensitivity, leading to infertility, azoospermia, gynecomastia, early-onset testicular cancer, breast and ovarian cancers, and reproductive tissue degeneration.
• Wnt Pathway Dysregulation: Impairs cell cycle control, tissue regeneration, and oncogenic suppression, increasing risks across reproductive and gastrointestinal tissues. Immunological Breakdown and Pathogen Susceptibility
• Biofilm Formation and Chemotaxis Impairment: Hinders microbial defense mechanisms, increasing risk of chronic UTI, prostatitis, bronchitis, sinusitis, and skin infections.
• Virulence Pathway Alterations: Enable colonization by opportunistic bacteria and fungi, prolonging inflammation and resistance to standard treatment.
Case Application: Survivor-Specific Pathway Disruption and alteration of genomic expression.
BioSymphony, through collaboration with CLIA and CAP Certified Labs out of Peachtree Georgia, Alabama, and Chicago- has mapped the following molecular disruptions in this survivor’s clinical and omic data showing the alarming, direct causation and aggravation of this growing cascade of disease documented in his EMR.
1. Nurr1
2. NF-κB
3. Nrf2
4. Wnt
5. COX-2
6. eNOS
7. ERKO
8. Benzodiazepine Receptor
9. UPP (Ubiquitin-Proteasome Pathway)
10. ECS (Endocannabinoid System)
11. Butyrate Production Pathway
12. LPS Biosynthesis
13. Sulfide Gas Pathway
14. Oxalate Metabolism
15. Uric Acid Metabolism
16. TMA/TMAO Pathway
17. Mitochondrial Biogenesis (PGC1-α and NAD⁺ precursors)
18. Biofilm Formation
19. Chemotaxis
20. Virulence Gene Expression
These disruptions are supported by clinical history (ulcerative colitis, hypogonadism, toxic polyneuropathy, azoospermia, testicular cancer, recurrent myocardial infarction), imaging, biomarker testing, and genetic sequencing. The cumulative effect is a systems-level breakdown rooted in epigenetic reprogramming and mitochondrial exhaustion.
Presumptive Conditions (ongoing - open claims for most) affecting non-deployed ACU prototype survivor:
The Musculoskeletal System
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Muscle twitching and cramping
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Bilateral flank pain
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Bilateral lower back pain
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Bone pain
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Joint pain
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Arthritis in left shoulder
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Ankylosing spondylitis of the hips
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Myofascial Pain Syndrome
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Post-exertional malaise (PEM)
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Mitochondrial dysfunction
The Organs of Special Sense (Vision, Auditory)
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Light sensitivity
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Photophobia
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Tinnitus
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Lazy eye – Right
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Rapid eye movement (REM)
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Blurred vision or ocular migraines
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Hearing sensitivity or mild loss (toxicant-linked)
Infectious Diseases, Immune Disorders, and Nutritional Deficiencies
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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (M.E./CFS)
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Fibromyalgia
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Inflammatory disorders
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Weakened immune system
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Vitamin B deficiency (entire complex)
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Vitamin D deficiency
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Magnesium deficiency
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Leaky gut / Increased intestinal permeability
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Histamine Intolerance / Mast Cell Activation Syndrome (MCAS)
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Mitochondrial dysfunction
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Impaired wound healing.
The Respiratory System
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Recurring allergic rhinitis
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Recurring sinusitis
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Recurring upper respiratory infections
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Recurring bronchitis
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Recurring pneumonia
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Patchy-air lung disease
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Left perifissural nodule, intrapulmonary lymph node (2 mm)
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Pulmonary nodule (2.3 cm in upper right lobe)
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Mild obstructive sleep apnea
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Mitochondrial dysfunction
The Cardiovascular System
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Tachycardia
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Bradycardia
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Palpitations
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Assumed HFpEF (heart failure with preserved ejection fraction)
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Myocardial infarction of unknown etiology (x4)
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Left partial bundle branch block
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Left full bundle branch block
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Right partial bundle branch block
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Right full bundle branch block
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Stroke-like episodes with hospital/ER admissions
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Hypertension
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Hypotension
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Positional hypotension
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Near Syncope
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Postural Orthostatic Tachycardia Syndrome (POTS) symptoms
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Exercise intolerance
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Mitochondrial dysfunction
The Digestive System
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Ulcerative colitis (UC; cancer in situ)
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Ulcerative proctitis
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Diverticulitis
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Inflammatory bowel disease - mixed
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Recurring pancreatitis
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GERD (gastroesophageal reflux disease)
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Duodenal ulcers
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Cushing’s ulcer
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Melena (blood in stool)
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Hematochezia (blood in stool)
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Abdominal pain
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Bilateral flank pain
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Bloating
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Delayed gastric emptying
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Nausea
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Hypersalivation
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Lack of natural hunger cues
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Difficulty preventing weight gain and obesity
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Difficulty losing weight and maintaining weight
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History of H. pylori infection (post-toxic exposure, TBI)
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Mitochondrial dysfunction
The Genitourinary System
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Hematospermia (blood in semen)
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Hematuria (blood in urine)
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Recurring urinary tract infections
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Recurring prostatitis
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Azoospermia (infertility)
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Hypogonadism
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Low testosterone
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Elevated sex hormone-binding globulin (SHBG)
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Erectile dysfunction
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Testicular cancer (in remission)
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Cross-system hormonal disruptions grouped under Endocrine
The Hematologic and Lymphatic Systems
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Renal cysts
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2.25 x 2.3 cm low-density lesion (Right kidney)
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0.6 x 0.5 cm low-density lesion (Left kidney)
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GI bleeding
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Urinary tract bleeding
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Metastatic cancer in abdominal lymph nodes
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Lymphadenopathy (transient or persistent swollen lymph nodes)
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Blood cell irregularities
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Mitochondrial dysfunction
The Skin / Integumentary System
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Allergic dermatitis (permethrin-induced)
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Susceptibility to fungal and bacterial skin infections
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Impaired wound healing
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Scarring from chronic exposure reactions
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Hypopigmentation / hyperpigmentation
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Mitochondrial dysfunction
The Endocrine System
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Diabetes mellitus
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Hypoglycemia
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Metabolic syndrome
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Difficulty thermoregulating
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Episodes of hyponatremia
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Adrenal dysfunction (suspected)
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Cortisol dysregulation (suspected or tested)
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Chronic fatigue
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Chronic pain
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Mitochondrial dysfunction
Neurological Conditions and Convulsive Disorders
Central Nervous System Injury: (Systemic Toxic Burden followed by TBI)
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Frontal lobe damage
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Right temporal lobe damage
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Right parietal lobe damage
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Occipital lobe damage
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Hippocampal damage
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Pituitary injury
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Frontal cortex injury
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Cerebellar dysfunction
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Damage to blood-brain barrier
Peripheral and Autonomic Nervous Systems:
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Toxic polyneuropathies
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Peripheral nerve dysfunction
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Autonomic dysregulation
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Hypotension
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Syncope
Neurocognitive Deficits:
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Chronic brain fog
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Short-term memory issues
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Difficulty learning new skills
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Poor information retention
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ADHD (post-toxin exposure compound by TBI that followed)
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Balance issues, drop foot, altered gait
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Fine motor skill dysfunction
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Motor planning impairment
Neurobehavioral and Sleep:
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Chronic fatigue
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Chronic pain
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Chronic inflammation
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Concussion syndrome
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Migraines
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Vertigo
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Dream enactment behavior
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REM sleep behavior disorder
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Dizzy spells
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Mild obstructive sleep apnea
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Toxicant + TBI-induced tinnitus
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Sensory hypersensitivities (light, sound, smell)
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Mitochondrial dysfunction
Mental Health
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PTSD (toxicant exposure followed by personal assault + TBI)
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Depression
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Anxiety
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ADHD (post toxicant exposure compounded by TBI)
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REM sleep behavior disorder
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Neurocognitive deficits (nested above)
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Difficulty in social settings, workplace, and home
Dental and Oral Health
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Bruxism
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Pitting enamel
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Thin enamel
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Hypersalivation
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Tooth loss (x3)
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Tooth implants with bone grafting (x2)