Reply to Ayoub-Charette et al. Lack of Biological Plausibility and Major Methodological Issues Cast Doubt on the Association between Aspartame and Autism. Comment on "Fowler et al. Daily Early-Life Exposures to Diet Soda and Aspartame Are Associated with Autism in Males: A Case-Control Study. Nutrients 2023, 15, 3772".

Thank you for the opportunity to respond to the concerns raised by Ayoub-Charette et al [...].

Biomedicines in Longevity and Aging the Quest to Resist Biological Decline.

Aging is considered part of the natural process of life, however in recent years medical literature has started to show that specific facets of aging are beginning to be understood and those factors may even be considered preventable with various measures. Aging is also considered the number one cause of poor quality of life, disease, disability, and death, so the importance of understanding the aging process and how to control certain aspects of it cannot be underestimated when age related suffering is factored in. The causes of aging are now becoming well understood, and in recent years many therapies have already become available to the public to attenuate specific corridors of aging. The heterogeneity of the aging process and the biological drivers involved is examined here in parallel with various compounds and therapies to combat biological decline. The benefits for governments in keeping their populations healthy and vibrant are vast, and at the same time offer a great incentive to invest into newly emerging technologies that may prevent the onset of preventable disease. Whilst this paper only discusses nine pathways to the aging process, many more exist.

An Exploratory Investigation of Organic Chemicals Detected in Baby Teeth: Differences in Children with and without Autism.

Autism spectrum disorder (ASD) is a behaviorally defined neurodevelopmental disorder characterized by deficits in language, communication, and social function with an estimated prevalence rate of between 1 in 30 and 44 U.S. births. Gene/environment (G × E) interactions are widely regarded as the most probable explanation for idiopathic ASD, especially because some genes are selectively targeted by various environmental xenobiotics. Because deciduous teeth are a likely biomarker of in utero exposure, the present study investigated if the quantity of chemicals found in deciduous teeth differs between children with and without ASD. Twenty-two deciduous teeth from children with ASD and 20 teeth from typically developed children were prepared and analyzed using THE Two-Dimensional Gas Chromatography Time-of-Flight Mass Spectrometer (GC × GC-TOF MS) with ChromaTOF version 23H2 software and Agilent 7890 gas chromatograph. The autism sample had significantly more chemicals in their teeth than the typical developing sample (99.4 vs. 80.7, respectively) (p < 0.0001). The majority of chemicals were identified as phthalates, plasticizers, pesticides, preservatives, or intermediary solvents used in the production of fragranced personal care or cleaning products or flavoring agents in foods. The known toxic analytes reported in this study are likely biomarkers of developmental exposure. Why there were greater concentrations of toxic chemicals in the teeth that came from children with ASD is unclear. A further understanding of the cavalcade of multiple biological system interactions (Interactome) could help with future efforts to reduce risks. Notwithstanding, the avoidance of pesticides, plastics, and scented personal care products may be warranted under the precautionary principle rule.

Assessing Chemical Intolerance in Parents Predicts the Risk of Autism and ADHD in Their Children.

BACKGROUND: We sought to replicate our 2015 findings linking chemical intolerance in parents with the risk of their children developing autism and/or ADHD. Drawing upon our 2021 discovery of a strong association between chemical intolerance and mast cells, we propose an explanation for this link. METHODS: In a population-based survey of U.S. adults, we used the internationally validated Quick Environmental Exposure and Sensitivity Inventory (QEESI) to assess symptom severity and chemical intolerance. Parents were asked how many of their biological children had been diagnosed with autism and/or ADHD. RESULTS: Parents with chemical intolerance scores in the top versus bottom tenth percentile had 5.7 times the risk of reporting a child with autism and 2.1 times for ADHD. CONCLUSIONS: High chemical intolerance scores among parents of children with autism, coupled with our 2021 discovery of mast cell activation as a plausible biomechanism for chemical intolerance, suggest that (1) the QEESI can identify individuals at increased risk, (2) environmental counseling may reduce personal exposures and risk, and (3) the global rise in autism and ADHD may be due to fossil-fuel-derived and biogenic toxicants epigenetically "turning on" or "turning off" critical mast cell genes that can be transmitted transgenerationally. It is important to note that this study was observational in nature; as such, further research is needed using controlled trials to confirm causality and explore the proposed mechanism.

INFLAMMATION's cognitive impact revealed by a novel "Line of Identity" approach.

IMPORTANCE: Dementia is an "overdetermined" syndrome. Few individuals are demented by any single biomarker, while several may independently explain small fractions of dementia severity. It may be advantageous to identify individuals afflicted by a specific biomarker to guide individualized treatment. OBJECTIVE: We aim to validate a psychometric classifier to identify persons adversely impacted by inflammation and replicate it in a second cohort. DESIGN: Secondary analyses of data collected by the Texas Alzheimer's Research and Care Consortium (TARCC) (N = 3497) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 1737). SETTING: Two large, well-characterized multi-center convenience samples. PARTICIPANTS: Volunteers with normal cognition (NC), Mild Cognitive Impairment (MCI) or clinical "Alzheimer's Disease (AD)". EXPOSURE: Participants were assigned to "Afflicted" or "Resilient" classes on the basis of a psychometric classifier derived by confirmatory factor analysis. MAIN OUTCOME(S) AND MEASURE(S): The groups were contrasted on multiple assessments and biomarkers. The groups were also contrasted regarding 4-year prospective conversions to "AD" from non-demented baseline diagnoses (controls and MCI). The Afflicted groups were predicted to have adverse levels of inflammation-related blood-based biomarkers, greater dementia severity and greater risk of prospective conversion. RESULTS: In ADNI /plasma, 47.1% of subjects were assigned to the Afflicted class. 44.6% of TARCC's subjects were afflicted, 49.5% of non-Hispanic Whites (NHW) and 37.2% of Mexican Americans (MA). There was greater dementia severity in the Afflicted class [by ANOVA: ADNI /F(1) = 686.99, p <0.001; TARCC /F(1) = 1544.01, p <0.001]. "INFLAMMATION" factor composite scores were significantly higher (adverse) in Afflicted subjects [by ANOVA in ADNI /plasma F(1) = 1642.64, p <0.001 and in TARCC /serum F(1) = 3059.96, p <0.001]. Afflicted cases were more likely to convert to AD in the next four years [by Cox's F, ADNI /plasma: F (252, 268) = 3.74 p < 0.001; TARCC /serum: F (160, 134) = 3.03, p < 0.001 (in TARCC's entire sample), F (110, 90) = 4.92, p <0.001 in NHW, and F(50, 44) = 2.13, p = 0.006 in MA]. The proportions converting were similar among afflicted NHW in both cohorts /biofluids but MA exhibited a lower risk (7% in TARCC /serum at 48 months). CONCLUSIONS AND RELEVANCE: Our inflammation-specific psychometric classifier selects individuals with pre-specified biomarker profiles and predicts conversion to "AD" across cohorts, biofluids, and ethnicities. This algorithm might be applied to any dementia-related biomarker making the psychometric estimation of individual biomarker effects feasible without biomarker assessment. Our approach also distinguishes individuals resilient to individual biomarker effects allowing for more accurate prediction and precision intervention.

Statin use moderates APOE's and CRP's associations with dementia and is associated with lesser dementia severity in ε4 carriers.

INTRODUCTION: We tested the effect of statins on C-reactive protein (CRP) and apolipoprotein E (APOE)'s associations with dementia severity. METHODS: A total of 1725 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI) were assigned from 12-month follow-up data into the following groups: (1) ε4 (-)/statin (-), (2) ε4 (-)/statin (+), (3) ε4 (+)/statin (-), and (4) ε4 (+)/statin (+). Dementia severity was assessed by a δ homolog: "dHABS." A mediation model was stratified on statin use and moderation effects tested by a chi-square difference. RESULTS: Plasma CRP level decreased with ε4 allelic dose. Statins had no effect on the dHABS d-score in non-carriers but were associated with better scores in carriers. Treated carriers did not have more severe dementia than non-carriers. Statin use moderated the mutual adjusted effects of APOE and CRP. CRP was not a mediator of APOE's effect. DISCUSSION: Statins may provide a protective effect on the dementia severity of ε4 carriers. HIGHLIGHTS: δ is a dementia-specific phenotype related to general intelligence "g" and is assessed via a "d-score." Apolipoprotein E (APOE) and plasma C-reactive protein (CRP) are independently associated with δ. Plasma CRP decreases with ε4 allelic dose. Statins were associated with better (less demented) d-scores in ε4 carriers but had no effect in non-ε4 carriers. Treated ε4 carriers did not have more severe dementia than non-carriers. Statin use moderated the effects of APOE and CRP on δ. CRP was not a mediator of APOE's effect on δ.

Chemical Intolerance and Mast Cell Activation: A Suspicious Synchronicity.

Background: Chemical Intolerance (CI) is characterized by intolerances for chemicals, foods, and drugs with multi-system symptoms. As yet, the biomechanism remains unclear. One study reported converging lines of evidence supporting a substantive association between mast cell activation syndrome (MCAS) and CI. The purpose of this study is to (1) confirm a previous report demonstrating that 60% of MCAS patients report CI and (2) examine the parallels between symptoms and intolerances in CI and MCAS. Methods: Five hundred forty-four MCAS patients were assigned a clinical MCAS score using a validated assessment instrument and were assessed for CI using the validated Quick Environmental Exposure Sensitivity Index. Results: Our outcomes confirm the previously published study where the majority of MCAS patients also have CI. There was a clear overlap between various ICD-10 diagnostic categories and CI symptoms, providing further support for a potential shared mechanism. Conclusions: Exposures to pesticides, volatile organic compounds, combustion products, and mold have previously been reported as initiators of CI. However, until recently, little was known about the biological mechanism involved that could explain the multisystem symptoms associated with CI. This paper addresses a newly identified biomechanism for disease, which may underlie a host of "medically unexplained symptoms" triggered by xenobiotics.

The effects of CNS atrophy and ICVD on tests of executive function and functional status are mediated by intelligence.

Background: Impairments in executive function (EF) are often attributed to ischemic cerebrovascular disease (ICVD) and frontal circuit pathology. However, EF can be distinguished from general intelligence and the latter is likely to manifest in "executive" measures. We aimed to distinguish the effects of imaging biomarkers on these constructs. Methods: We tested neuroimaging biomarkers as independent predictors of observed 12 month-prospective cognitive performance by a Multiple Indicators Multiple Causes (MIMIC) model in the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N ≅ 1750). Results: ICVD was associated with ''Organization" (ORG) and "Planning" (PLAN) domain scores from the test of Every Day Cognition. Left anterior cingulate (LAC) atrophy was independently associated with Trail-Making part B and Animal Naming. The MIMIC model had excellent fit and tests additional latent variables i.e., EF and dEF (a latent δ homolog derived from Spearman's general intelligence factor, g). Only dEF was associated with instrumental activities of daily living (IADL). ICVD and LAC were both associated with observed executive measures through dEF. ICVD was independently associated with those same measures through EF. Conclusions: Observed EF is independently determined by multiple factors. The effects of EF-associated MRI biomarkers can be related to disability and dementia only via their effects on g. Because g /δ are unlikely to be located within the frontal lobes, the dementia-specific variance in executive measures may have little to do with either frontal structure or function. Conversely, domain-specific variance in EF may have little to do with either IADL-impairment or dementia.

Daily Early-Life Exposures to Diet Soda and Aspartame Are Associated with Autism in Males: A Case-Control Study.

Since its introduction, aspartame-the leading sweetener in U.S. diet sodas (DS)-has been reported to cause neurological problems in some users. In prospective studies, the offspring of mothers who consumed diet sodas/beverages (DSB) daily during pregnancy experienced increased health problems. We hypothesized that gestational/early-life exposure to ≥1 DS/day (DSearly) or equivalent aspartame (ASPearly: ≥177 mg/day) increases autism risk. The case-control Autism Tooth Fairy Study obtained retrospective dietary recalls for DSB and aspartame consumption during pregnancy/breastfeeding from the mothers of 235 offspring with autism spectrum disorder (ASD: cases) and 121 neurotypically developing offspring (controls). The exposure odds ratios (ORs) for DSearly and ASPearly were computed for autism, ASD, and the non-regressive conditions of each. Among males, the DSearly odds were tripled for autism (OR = 3.1; 95% CI: 1.02, 9.7) and non-regressive autism (OR = 3.5; 95% CI: 1.1, 11.1); the ASPearly odds were even higher: OR = 3.4 (95% CI: 1.1, 10.4) and 3.7 (95% CI: 1.2, 11.8), respectively (p < 0.05 for each). The ORs for non-regressive ASD in males were almost tripled but were not statistically significant: DSearly OR = 2.7 (95% CI: 0.9, 8.4); ASPearly OR = 2.9 (95% CI: 0.9, 8.8). No statistically significant associations were found in females. Our findings contribute to the growing literature raising concerns about potential offspring harm from maternal DSB/aspartame intake in pregnancy.

Deciduous tooth biomarkers reveal atypical fetal inflammatory regulation in autism spectrum disorder.

Atypical regulation of inflammation has been proposed in the etiology of autism spectrum disorder (ASD); however, measuring the temporal profile of fetal inflammation associated with future ASD diagnosis has not been possible. Here, we present a method to generate approximately daily profiles of prenatal and early childhood inflammation as measured by developmentally archived C-reactive protein (CRP) in incremental layers of deciduous tooth dentin. In our discovery population, a group of Swedish twins, we found heightened inflammation in the third trimester in children with future ASD diagnosis relative to controls (n = 66; 14 ASD cases; critical window: -90 to -50 days before birth). In our replication study, in the US, we observed a similar increase in CRP in ASD cases during the third trimester (n = 47; 23 ASD cases; -128 to -21 days before birth). Our results indicate that the third trimester is a critical period of atypical fetal inflammatory regulation in ASD.

Multiple Adipokines Predict Dementia Severity as Measured by δ: Replication Across Biofluids and Cohorts.

BACKGROUND: We have explored dementia's blood-based protein biomarkers in the Texas Alzheimer's Research and Care Consortium (TARCC) study. Among them are adipokines, i.e., proteins secreted by adipose tissue some of which have been associated with cognitive impairment. OBJECTIVE: To associate adipokines with dementia severity and replicate their association across cohorts and biofluids (serum /plasma). METHODS: We used eight rationally chosen blood-based protein biomarkers as indicators of a latent variable, i.e., "Adipokines". We then associated that construct with dementia severity as measured by the latent dementia-specific phenotype "δ" in structural equation models (SEM). Significant factor loadings and Adipokines' association with δ were replicated across biofluids in the Alzheimer's Disease Neuroimaging Initiative (ADNI). RESULTS: Eight adipokine proteins loaded significantly on the Adipokines construct. Adipokines measured in plasma (ADNI) or serum (TARCC) explained 24 and 70% of δ's variance, respectively. An Adipokine composite score, derived from the latent variables, rose significantly across clinical diagnoses and achieved high areas under the receiver operating characteristic curve (ROC/AUC) for discrimination of Alzheimer's disease from normal controls (NC) or cases of mild cognitive impairment (MCI) and between NC and MCI. CONCLUSION: These results again suggest that SEM can be used to create latent biomarker classifiers that replicate across samples and biofluids, and that a substantial fraction of dementia's variance is attributable to peripheral blood-based protein levels via the patterns codified in those latent constructs.

Determination of safe levels of persistent organic pollutants in toxicology and epidemiology.

We reviewed published manuscripts from toxicology and epidemiology reporting harmful health effects and doses of persistent organic pollutants (POPs), published between 2000 and 2021. We found 42 in vitro, 32 in vivo, and 74 epidemiological studies and abstracted the dose associated with harm in a common Molar unit. We hypothesized that the dose associated with harm would vary between animal and human studies. To test this hypothesis, for each of several POPs, we assessed the significance of variation in the dose associated with a harmful effect [categorized as non-thyroid endocrine (NTE), developmental neurotoxicity (DNT), and Thyroid] with study type (in vitro, in vivo, and Epidemiology) using a linear model after adjustment for basis (lipid weight, wet weight). We created a Calculated Safety Factor (CSF) defined as the toxicology dose divided by epidemiology dose needed to exhibit significant harm. Significant differences were found between study types ranging from <1 to 5.0 orders of magnitude in the dose associated with harm. Our CSFs in lipid weight varied from 12.4 (95% confidence interval (CI) 3.3, 47) for NTE effects in Epidemiology relative to in vivo studies to 6,244 (95% CI 2510, 15530) for DNT effects in Epidemiology relative to in vitro in wet weight representing 12.4 to 6.2 thousand-fold more sensitivity in people relative to animals, and mechanistic models, respectively. In lipid weight, all CSF 95% CI lower bounds across effect categories were less than 6.5. CIs for CSFs ranged from less than one to four orders of magnitude for in vivo, and two to five orders of magnitude for in vitro vs. Epidemiology. A global CSF for all Epidemiology vs. all Toxicology was 104.6 (95% CI 72 to 152), significant at p<0.001.

Air Pollution and Maximum Temperature Are Associated with Neurodevelopmental Regressive Events in Autism Spectrum Disorder.

Neurodevelopmental regression (NDR) is an enigmatic event associated with autism spectrum disorder (ASD) during which a child loses previously acquired skills and develops ASD symptoms. In some, a trigger which precedes the NDR event, such as a fever, can be identified, but in many cases no trigger is obvious. We hypothesize that air pollution (PM2.5) may trigger NDR, especially in those children without an identified trigger. Average daily PM2.5, ozone, precipitation and maximum temperature (Tmax) were derived from Environmental Protection Agency models and National Oceanic and Atmospheric Administration monitors based on zip-code information from 83 ASD participants during the six-weeks following the onset month of an NDR event and a reference period defined as one year before and one year after the event. Seasonally adjusted logistic regression (LR) and linear mixed models (LMM) compared cases (with a history of NDR) and matched controls (without a history of NDR). LR models found that the risk of NDR was related to higher PM2.5 during 3 to 6 weeks of the NDR event period, particularly in those without a trigger. Overall, both models converged on NDR being related to a higher PM2.5 and lower Tmax both during the NDR event period as well as the reference period, particularly in those without a known trigger. This temporal pattern suggests that environmental triggers, particularly PM2.5, could be related to NDR, especially in those without an identifiable trigger. Further studies to determine the underlying biological mechanism of this observation could help better understand NDR and provide opportunities to prevent NDR.

Covid 19 vaccines and the misinterpretation of perceived side effects clarity on the safety of vaccines.

In the era of Covid 19 and mass vaccination programs, the anti-vaccination movement across the world is currently at an all-time high. Much of this anti-vaccination sentiment could be attributed to the alleged side effects that are perpetuated across social media from anti-vaccination groups. Fear mongering and misinformation being peddled by people with no scientific training to terrorise people into staying unvaccinated is not just causing people to remain susceptible to viral outbreaks, but could also be causing more side effects seen in the vaccination process. This brief review will offer data that may demonstrate that misinformation perpetuated by the anti-vaccination movement may be causing more deaths and side effects from any vaccine. A mini review of published literature has been conducted and found that mental stress clearly causes vasoconstriction and arterial constriction of the blood vessels. Therefore, if subjects are panicked, concerned, stressed or scared of the vaccination, their arteries will constrict and become smaller in and around the time of receiving the vaccine. This biological mechanism (the constriction of veins, arteries and vessels under mental stress) is the most likely cause for where there has been blood clots, strokes, heart attacks, dizziness, fainting, blurred vision, loss of smell and taste that may have been experienced shortly after vaccine administration. The extreme mental stress of the patient could most likely be attributed to the fear mongering and scare tactics used by various anti-vaccination groups. This paper does not aim to rule in or out every side effect seen, but it is highly likely that many apparent side effects seen shortly after a subject has received a vaccine could be the result of restricted or congested blood flow from blood vessel or arterial constriction caused by emotional distress or placebo based on fear around vaccines.

Community Health Workers as Trust Builders and Healers: A Cohort Study in Primary Care.

PURPOSE: Improving patients' self-care for chronic disease is often elusive in the context of social deprivation. We evaluated whether a practice-integrated community health worker (CHW) intervention could encourage effective long-term self-management of type 2 diabetes mellitus (T2DM). METHODS: This cohort study, in a safety-net primary care practice, enrolled patients with uncontrolled T2DM and psychosocial risk factors. Patients were identified through a practice diabetes registry or by clinicians' referrals. The CHWs engaged patients in trust building and sensemaking to understand their social context, identify goals, navigate health care, and connect to community resources. Primary outcome was progress through 3 prospectively defined stages of self-care: outreach (meeting face-to-face); stabilization (collaborating to address patients' life circumstances); and self-care generativity (achieving self-care competencies). Secondary outcomes were change in hemoglobin A1c (HbA1c) and need for urgent care, emergency department, or hospital visits. RESULTS: Of 986 participating patients, 27% remained in outreach, 41% progressed to stabilization, and 33% achieved self-care generativity. Repeated measures ANOVA demonstrates an overall decline in HbA1c, without group differences, through the 4th HbA1c measurement (mean follow-up 703 days). Beginning at the 5th HbA1c measurement (mean 859 days), the self-care generativity group achieved greater declines in HbA1c, which widened through the 10th measurement (mean 1,365 days) to an average of 8.5% compared with an average of 8.8% in the outreach group and 9.0% in the stabilization group (P = .003). Rates of emergency department and hospital visits were lower in the self-care generativity group. CONCLUSIONS: Practice-linked CHWs can sustainably engage vulnerable patients, helping them advance self-management goals in the context of formidable social disadvantage.

Aging clocks & mortality timers, methylation, glycomic, telomeric and more. A window to measuring biological age.

As humans age multiple forms of biological decay ensue, and many aspects of human biology can be measured to determine how far biological machinery has drifted from homeostasis. Research has led to aging clocks being developed that claim to predict biological age as opposed to chronological age. Aging could be regarded as a measured loss of homeostatic biological equilibrium that augments biological decay in fully developed tissues. Measuring aspects of how far various elements of biology have drifted from a youthful state may allow us to make determinations on a subject's health but also make informed predictions on their biological age. As we see across human physiology, many facets that maintain human health taper off such as nicotinamide adenine dinucleotide, glutathione, catalase, super oxide dismutase, and more. Extracellular vesicle density also tapers off during age combined with epigenetic drift, telomere attrition, and stem cell exhaustion, whilst genomic instability and biological insults from environment and lifestyle factors increase. Measuring these types of biomarkers with aging clocks may allow subjects to understand their own health more accurately and enable subjects to better focus on their efforts in the pursuit of longevity and, in addition, allow healthcare practitioners to deliver better health advice.

The intervention on aging system: A classification model, the requirement for five novel categories.

Aging is widely considered an immovable fact of life. Cultural conditioning has ensured that therapeutics for extreme human lifespans are considered out of reach technologies. However, longevity therapies such as stem cell replacement, fasting, gene therapies, fasting mimetics such as metformin and rapamycin, regulation and tissue reprogramming with OSK transcription factors, blood dilution, metabolic pathway engineering, reversal of epigenetic drift, heterochronic parabiosis, coenzyme replacement technologies (nicotinamide adenine dinucleotide) and a plethora of other established sciences are showing great potential at slowing down the rate at which tissues enter dysfunction. Recent discoveries have shed light on major mysteries of the aging process. Longevity-based discoveries are not only landing quickly, but therapies to prevent or reverse those drivers of aging are also being devised regularly and this is opening up an entirely new industry, the longevity industry. This presents the requirement for a new classification system where subjects can be divided into specific groups based on their potential for mortality. This system also enables the public to target which class of this classification system they wish to be on. Moving the population on the classification system to become more disease resistant holds great benefit for society and governments as a whole.

Does improving indoor air quality lessen symptoms associated with chemical intolerance?

AIM: To determine whether environmental house calls that improved indoor air quality (IAQ) is effective in reducing symptoms of chemical intolerance (CI). BACKGROUND: Prevalence of CI is increasing worldwide. Those affected typically report symptoms such as headaches, fatigue, 'brain fog', and gastrointestinal problems - common primary care complaints. Substantial evidence suggests that improving IAQ may be helpful in reducing symptoms associated with CI. METHODS: Primary care clinic patients were invited to participate in a series of structured environmental house calls (EHCs). To qualify, participants were assessed for CI with the Quick Environmental Exposure and Sensitivity Inventory. Those with CI volunteered to allow the EHC team to visit their homes to collect air samples for volatile organic compounds (VOCs). Initial and post-intervention IAQ sampling was analyzed by an independent lab to determine VOC levels (ng/L). The team discussed indoor air exposures, their health effects, and provided guidance for reducing exposures. FINDINGS: Homes where recommendations were followed showed the greatest improvements in IAQ. The improvements were based upon decreased airborne VOCs associated with reduced use of cleaning chemicals, personal care products, and fragrances, and reduction in the index patients' symptoms. Symptom improvement generally was not reported among those whose homes showed no VOC improvement. CONCLUSION: Improvements in both IAQ and patients' symptoms occur when families implement an action plan developed and shared with them by a trained EHC team. Indoor air problems simply are not part of most doctors' differential diagnoses, despite relatively high prevalence rates of CI in primary care clinics. Our three-question screening questionnaire - the BREESI - can help physicians identify which patients should complete the QEESI. After identifying patients with CI, the practitioner can help by counseling them regarding their home exposures to VOCs. The future of clinical medicine could include environmental house calls as standard of practice for susceptible patients.

Trimethylamine N-oxide (TMAO): a new attractive target to decrease cardiovascular risk.

Cardiovascular disease (CVD) is one of the greatest disease burdens and takes the lives of many each year. There are many risk factors both modifiable and non-modifiable which contribute to the onset and progression of the disease. Trimethylamine N-oxide (TMAO) in recent years has been found to have a correlation with CVD onset. Those with increased levels of the metabolite have a markedly increased risk of future development of cardiometabolic disorders.This literature review aimed to critique past studies undertaken to find a consensus of the significance of the interrelationship between TMAO and cardiovascular risk. A definite link between TMAO levels and a CVD outcome was found. The majority of the literature stated the relationship with evidence; however, there is still some uncertainty as to why and how the correlation occurs. Further study needs to be done to further dissect and understand the relationship between TMAO and CVD risk.

Three Tiers to biological escape velocity: The quest to outwit aging.

As longevity companies emerge with new products and the fields of anti-aging research develop new cutting-edge therapies, three distinct classes of longevity methodologies emerge. This discussion finds that there are three clear classes (Tiers) of longevity systems that are currently under development, and all three will be paramount to achieve biological escape velocity (where tissues can be repaired faster than aging can damage them). These classes are referred to as Tier 1, Tier 2, and Tier 3 treatments and are described in detail below. These three Tiers are required for easy identification for pharmaceutical companies and research companies to determine the type of therapy they may choose to deliver being noninvasive, invasive, time consuming, or simple end user products. Specific targets and goals need to be defined clearly from an early perspective in the development of these technologies for future precision medicines. This allows consumers of future anti-aging technologies to consider which Tier a particular therapy may be, delivering a more informed choice.