Abnormal Porphyrin Metabolism in Autism Spectrum Disorder and Therapeutic Implications.

Autism spectrum disorder (ASD) is a mosaic of neurodevelopmental conditions composed of early-onset social interaction and communication deficits, along with repetitive and/or restricted patterns of activities, behavior, and interests. ASD affects around 1% of children worldwide, with a male predominance. Energy, porphyrin, and neurotransmitter homeostasis are the key metabolic pathways affected by heavy metal exposure, potentially implicated in the pathogenesis of ASD. Exposure to heavy metals can lead to an altered porphyrin metabolism due to enzyme inhibition by heavy metals. Heavy metal exposure, inborn genetic susceptibility, and abnormal thiol and selenol metabolism may play a significant role in the urinary porphyrin profile anomalies observed in ASD. Altered porphyrin metabolism in ASD may also be associated with, vitamin B6 deficiency, hyperoxalemia, hyperhomocysteinemia, and hypomagnesemia. The present review considers the abnormal porphyrin metabolism in ASD in relation to the potential pathogenic mechanism and discusses the possible metabolic therapies such as vitamins, minerals, cofactors, and antioxidants that need to be explored in future research. Such targeted therapeutic therapies would bring about favorable outcomes such as improvements in core and co-occurring symptoms.

Association between low fluoride exposure and children's intelligence: a meta-analysis relevant to community water fluoridation.

OBJECTIVES: Previous meta-analyses have mainly focused on studies conducted in endemic fluorosis areas with relatively high fluoride concentrations. These are impoverished rural communities in China, India, and Iran, and the findings cannot be generalised to developed countries. Therefore, we investigated the association between fluoride concentrations relevant to community water fluoridation and children's cognition measured with IQ scores by synthesising effect sizes reported in observational studies. METHODS: A previous meta-analysis and the National Toxicology Program database that included a search of multiple databases and the authors' search of PubMed, Google Scholar, and Mendeley provided the data. Cross-sectional and cohort studies examining the association between fluoride and children's cognition and intelligence scores were selected. Two reviewers abstracted data using standard procedures. We performed three meta-analyses to synthesise the effects using the random effects models. RESULTS: Eight studies of standardized mean difference in IQ scores from non-endemic fluorosis areas found no statistically significant difference between recommended and lower levels of fluoride (standardized mean difference = 0.07; 95% confidence interval: -0.02, 0.17; I2 = 0%), and no significant fluctuation in IQ scores across the differences in fluoride concentrations by non-linear modeling with restricted cubic spline (P = 0.21). Meta-analyses of children's and maternal spot urinary fluoride associated pooled regression coefficients (Betachildren = 0.16; 95% confidence interval: -0.40, 0.73; P = 0.57; I2 = 0%, Betamaternal = -0.92; 95% CI: -3.29, 1.46; P = 0.45; I2 = 72%) were not statistically significant. Further regression analysis by standardizing absolute mean IQ scores from lower fluoride areas did not show a relationship between F concentration and IQ scores (Model Likelihood-ratio test: P-value = 0.34.) CONCLUSIONS: These meta-analyses show that fluoride exposure relevant to community water fluoridation is not associated with lower IQ scores in children. However, the reported association observed at higher fluoride levels in endemic areas requires further investigation.

A Horizon Scan to Support Chemical Pollution-Related Policymaking for Sustainable and Climate-Resilient Economies.

While chemicals are vital to modern society through materials, agriculture, textiles, new technology, medicines, and consumer goods, their use is not without risks. Unfortunately, our resources seem inadequate to address the breadth of chemical challenges to the environment and human health. Therefore, it is important we use our intelligence and knowledge wisely to prepare for what lies ahead. The present study used a Delphi-style approach to horizon-scan future chemical threats that need to be considered in the setting of chemicals and environmental policy, which involved a multidisciplinary, multisectoral, and multinational panel of 25 scientists and practitioners (mainly from the United Kingdom, Europe, and other industrialized nations) in a three-stage process. Fifteen issues were shortlisted (from a nominated list of 48), considered by the panel to hold global relevance. The issues span from the need for new chemical manufacturing (including transitioning to non-fossil-fuel feedstocks); challenges from novel materials, food imports, landfills, and tire wear; and opportunities from artificial intelligence, greater data transparency, and the weight-of-evidence approach. The 15 issues can be divided into three classes: new perspectives on historic but insufficiently appreciated chemicals/issues, new or relatively new products and their associated industries, and thinking through approaches we can use to meet these challenges. Chemicals are one threat among many that influence the environment and human health, and interlinkages with wider issues such as climate change and how we mitigate these were clear in this exercise. The horizon scan highlights the value of thinking broadly and consulting widely, considering systems approaches to ensure that interventions appreciate synergies and avoid harmful trade-offs in other areas. We recommend further collaboration between researchers, industry, regulators, and policymakers to perform horizon scanning to inform policymaking, to develop our ability to meet these challenges, and especially to extend the approach to consider also concerns from countries with developing economies. Environ Toxicol Chem 2023;42:1212-1228. © 2023 Crown copyright and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article is published with the permission of the Controller of HMSO and the King's Printer for Scotland.

The Rationale for Vitamin, Mineral, and Cofactor Treatment in the Precision Medical Care of Autism Spectrum Disorder.

Children with autism spectrum disorder may exhibit nutritional deficiencies due to reduced intake, genetic variants, autoantibodies interfering with vitamin transport, and the accumulation of toxic compounds that consume vitamins. Importantly, vitamins and metal ions are essential for several metabolic pathways and for neurotransmitter functioning. The therapeutic benefits of supplementing vitamins, minerals (Zinc, Magnesium, Molybdenum, and Selenium), and other cofactors (coenzyme Q10, alpha-lipoic acid, and tetrahydrobiopterin) are mediated through their cofactor as well as non-cofactor functions. Interestingly, some vitamins can be safely administered at levels far above the dose typically used to correct the deficiency and exert effects beyond their functional role as enzyme cofactors. Moreover, the interrelationships between these nutrients can be leveraged to obtain synergistic effects using combinations. The present review discusses the current evidence for using vitamins, minerals, and cofactors in autism spectrum disorder, the rationale behind their use, and the prospects for future use.

Sustaining capacity building and practical skills training during the COVID-19 pandemic: Lessons from India.

Background: The scale and duration of the COVID-19 pandemic posed a threat to provide the required support needed by emergency medicine (EM) trainees in India participating in the masters in EM program, a global partnership between the Ronald Reagan Institute for Emergency Medicine at the George Washington University and 14 institutions in India. While some of this support has been filled by remote education through thrice-weekly online video conferencing and webinars, the gap in procedural teaching posed a different challenge. Methods: We developed a two-part innovation to teach suture skills, a required procedure for EM trainees. The innovation consisted of a hands-on procedure lab with the opportunity for live feedback followed by an independent competitive skill demonstration. Trainees were notified in advance of materials needed for the procedure lab to encourage attendance and participation. Results: A total of 160 trainees attended the virtual suture skills lab; 74 trainees (46% of attendees) submitted feedback back of whom 94% were able to practice skills in real time. Written feedback was overwhelmingly positive and included requests to implement this method for other procedural skills. Twenty-one residents participated in the Innovative Suture Challenge, with the top three submissions receiving accolades in the following grand rounds-style session. Conclusions: The combination of virtual teaching with the opportunity for real-time feedback and an integrated project to independently showcase skills learned is a way to continue procedural skills teaching in a remote environment. The aim of this innovation was to test the feasibility, acceptability, and level of engagement of conducting virtual, live supervised suturing remotely across multiple geographical locations. Our next step would be to gather pre and post data to measure the impact. Additionally, we believe this provides a proof-of-concept model to further explore sustainable, cost-effective, and scalable models for remote procedure-based teaching.

Establishing a Standardized Facial Cosmetic Preinjection Safety Tool: The ACIST.

In the past 20 years, the American population has seen an increased demand for nonsurgical minimally invasive facial rejuvenation solutions for the aging process. This widespread and increased demand for cosmetic injections brings a greater propensity for complications and adverse events. Choosing suitable patients for dermal filler is essential, as is concrete knowledge of the factors related to adverse events; however, there was no standardized tool to facilitate this process. The Joint Commission's Universal Safety checklist tools have been integrated into hospital surgical operating rooms and ambulatory outpatient settings across America and internationally and have successfully reduced errors in patient safety and outcomes. This article establishes the importance of integrating the Assessment Cosmetic Injection Safety Tool (ACIST), a standardized preinjection safety tool, into the cosmetic practice to decrease the incidence of adverse events associated with dermal filler and to achieve optimal patient satisfaction and outcomes. The ACIST was designed from the scientific literature, piloted at an urban cosmetic practice in the southern United States, finalized on the basis of feedback from participating staff members at the pilot study center, and disseminated to cosmetic nurse injectors.

Key actions for a sustainable chemicals policy.

Chemicals policies have spawned a wide range of regulations aimed at limiting damage to the environment and human health. Most instruments are reactive and fragmented. We propose a simple underpinning philosophy, "Do no harm", to ensure a more sustainable, safe "chemical environment" for the future.

Establishing a Standardized Facial Cosmetic Preinjection Safety Tool: The ACIST.

In the past 20 years, the American population has seen an increased demand for nonsurgical minimally invasive facial rejuvenation solutions for the aging process. This widespread and increased demand for cosmetic injections brings a greater propensity for complications and adverse events. Choosing suitable patients for dermal filler is essential, as is concrete knowledge of the factors related to adverse events; however, there was no standardized tool to facilitate this process. The Joint Commission's Universal Safety checklist tools have been integrated into hospital surgical operating rooms and ambulatory outpatient settings across America and internationally and have successfully reduced errors in patient safety and outcomes. This article establishes the importance of integrating the Assessment Cosmetic Injection Safety Tool (ACIST), a standardized preinjection safety tool, into the cosmetic practice to decrease the incidence of adverse events associated with dermal filler and to achieve optimal patient satisfaction and outcomes. The ACIST was designed from the scientific literature, piloted at an urban cosmetic practice in the southern United States, finalized on the basis of feedback from participating staff members at the pilot study center, and disseminated to cosmetic nurse injectors.

The Interprofessional Role in Dental Caries Management: Ways Medical Providers Can Support Oral Health (Perspectives from a Physician).

Medical providers are important allies in the prevention of dental caries. Through raising the issue by asking about risks and strengths, offering anticipatory guidance and counseling, encouraging and following up on referrals, and applying preventive fluoride, medical providers can have a direct, positive impact on oral health. Further, improving communication with referrals, bidirectionally, benefits patient care as well as provider satisfaction. By collaborating on advocacy efforts, medical and dental providers can broaden their impact while building relationships, with the end goal of improved health for patients throughout their lifetime. Reintegrating the mouth into the body and oral health into systemic health has benefits for patients and providers alike, and can and should be accomplished in the medical home.

Using Motivational Interviewing to Address Tobacco Cessation: Two Standardized Patient Cases for Pediatric Residents.

Introduction: Motivational interviewing (MI) is a well-established evidence-based method of working with patients to promote health behavior change. Standardized patient (SP) simulation allows trainees to practice and receive feedback on clinical and communication skills and may be useful in applying MI techniques to address tobacco use and exposure. Methods: We developed two SP cases for pediatric residents to practice addressing tobacco use with parents of their patients. Results: Thirty-six residents participated, 26 of whom had prior MI training. Resident postencounter self-reflection identified MI-specific skills, including eliciting the SP's view on positive/negative aspects of smoking, identifying stressors/triggers associated with smoking, eliciting reasons for smoking, asking about motivation/willingness to quit, eliciting benefits of quitting smoking, letting the SP do the talking, and guiding the SP in making a quit plan. On paired-samples t tests, resident self-evaluation checklist scores averaged 6.79 out of 8.00 (SD = 1.018, SEM = 0.165), compared with SP checklist scores, which averaged 7.08 out of 8.00 (SD = 1.217, SEM = 0.197). Discussion: These two SP cases were useful in many ways, allowing residents with prior MI training the opportunity for practice/feedback on skills learned and introducing residents with no prior MI training to MI concepts through experience/feedback. Residents consistently identified using MI concepts on postencounter self-reflection; resident self-evaluation and SP evaluation of residents showed agreement. These sessions could be utilized within a communication/MI curriculum or as stand-alone sessions to introduce MI concepts/techniques for addressing tobacco cessation in the pediatric setting.

Preventing Oral Disease: Alternative Providers and Places to Address This Commonplace Condition.

Oral health disease in young children has not decreased, despite adequate modalities for treatment and prevention. Because many children may not see a dentist before oral disease has begun, disease progression can be expected, affecting short-term and long-term oral health. However, most children are seen by other health professionals frequently in their youngest years, providing a unique opportunity to help weave a safety net of oral health care until they are established in a dental home. This article details ways primary care providers can promote oral health, including ways to integrate ancillary dental professionals into the primary care home.

Honest advocacy for nature: presenting a persuasive narrative for conservation.

Conservation scientists are increasingly recognising the value of communicating policy-relevant knowledge to policy-makers. Whilst considerable progress has been made in offering practical advice for scientists seeking to engage more closely with decision-makers, researchers have provided few tangible examples to learn from. This paper uses an English case study, but draws out important high-level messages relevant to conservation scientists worldwide. The case study looks at how the Lawton Review presented knowledge persuasively about the suitability of England's ecological network to deal with future pressures. Through skilful framing of rigorous scientific knowledge it was able to make a significant impact on government policy. Impact was achieved through: (1) selecting politically salient frames through which to communicate; (2) using clear, accessible language, and; (3) conducting rigorous science using an authoritative team of experts. Although its publication coincided with a favourable policy window, the Lawton Review seized on this opportunity to communicate a rigorously argued, persuasive and practical conservation message; in other words, it performed 'honest advocacy'. Thus, whilst it remains important to conduct scientific research with technical rigour, conservation scientists could also benefit from identifying salient frames for conservation and communicating clearly.

Oral and Dental Aspects of Child Abuse and Neglect.

In all 50 states, health care providers (including dentists) are mandated to report suspected cases of abuse and neglect to social service or law enforcement agencies. The purpose of this report is to review the oral and dental aspects of physical and sexual abuse and dental neglect in children and the role of pediatric care providers and dental providers in evaluating such conditions. This report addresses the evaluation of bite marks as well as perioral and intraoral injuries, infections, and diseases that may raise suspicion for child abuse or neglect. Oral health issues can also be associated with bullying and are commonly seen in human trafficking victims. Some medical providers may receive less education pertaining to oral health and dental injury and disease and may not detect the mouth and gum findings that are related to abuse or neglect as readily as they detect those involving other areas of the body. Therefore, pediatric care providers and dental providers are encouraged to collaborate to increase the prevention, detection, and treatment of these conditions in children.

Oral and Dental Aspects of Child Abuse and Neglect.

In all 50 states, health care providers (including dentists) are mandated to report suspected cases of abuse and neglect to social service or law enforcement agencies. The purpose of this report is to review the oral and dental aspects of physical and sexual abuse and dental neglect in children and the role of pediatric care providers and dental providers in evaluating such conditions. This report addresses the evaluation of bite marks as well as perioral and intraoral injuries, infections, and diseases that may raise suspicion for child abuse or neglect. Oral health issues can also be associated with bullying and are commonly seen in human trafficking victims. Some medical providers may receive less education pertaining to oral health and dental injury and disease and may not detect the mouth and gum findings that are related to abuse or neglect as readily as they detect those involving other areas of the body. Therefore, pediatric care providers and dental providers are encouraged to collaborate to increase the prevention, detection, and treatment of these conditions in children.

Increased public reimbursement for prophylactic visits with dentists associated with increased receipt of preventive dental services in children.

OBJECTIVE: To determine whether higher reimbursement for children's preventive dentistry correlates with greater utilization of preventive dental care. METHODS: A cross-sectional analysis of National Survey of Children's Health 2011/2012 was conducted, combined with state Medicaid reimbursement rates for preventive dentistry. Analyses included prevalence, unadjusted odds ratios, and multivariable logistic regression for receipt of preventive dental services. RESULTS: Of all surveyed American children 1-17 years, almost 20 percent had not received preventive dental care in prior year; this percentage is even higher in those with public insurance. Each $10 increase in state reimbursement was associated with a 17 percent decrease in odds of children not receiving preventive services. CONCLUSIONS: Higher state reimbursement for preventive services may increase children's receipt of preventive dental care.

A Rural Hospital's Journey to Becoming a Certified Acute Stroke-Ready Hospital.

PROBLEM: For many stroke patients, rural emergency departments are the first point of medical care to stop brain cell death. We identified a need to meet standards to improve outcomes for stroke care. METHODS: An interdisciplinary Stroke Continuous Process Improvement Committee was formed. We conducted a gap analysis to address current stroke care processes. Chart audits were performed, and strategies to meet the requirements for recognition as an Acute Stroke Ready Hospital (ASRH) were implemented. The ASRH guidelines guided our certification journey. RESULTS: ASRH certification was achieved. In addition, stroke care outcomes such as door-to-computed tomography results, door-to-international normalized ratio results, door teleneurology consultation, and door-to-needle time have improved. IMPLICATIONS FOR PRACTICE: Achieving certification makes a strong statement to the community about a hospital's efforts to provide the highest quality in stroke care services. Becoming a certified ASRH promotes quality of patient care by reducing variation in clinical processes.

Considering evidence: The approach taken by the Hazardous Substances Advisory Committee in the UK.

The Hazardous Substances Advisory Committee (HSAC) provides expert advice to UK officials, Ministers and other relevant bodies on the protection of the environment, and human health via the environment, from potentially hazardous substances and articles. Hazardous substances are often the subject of controversy, on which individuals, and different groups in society, hold divergent views. This paper details the approach taken by HSAC when considering the evidence to provide advice on hazardous substances. Firstly HSAC reviews the range of evidence and determines its quality considering: transparency of aims, the methodology and results, completeness, independent review and accessibility. HSAC does not follow one explicit methodology as the wide range of hazardous substances we consider means they need to be addressed on a case by case basis. Most notably HSAC considers the evidence in the wider context, being aware of factors that influence individuals in their decision making when receiving a HSAC opinion e.g. trust in the source of the evidence, defensibility, conformity to a 'world view' and framing. HSACs also reflect on its own perspectives with the aim of addressing bias by the diversity of its membership. The Committee's intention, in adopting this rounded approach, is to reach opinions that are robust, relevant and defensible.

Multidisciplinary team review of best practices for collection and handling of blood cultures to determine effective interventions for increasing the yield of true-positive bacteremias, reducing contamination, and eliminating false-positive central line-associated bloodstream infections.

BACKGROUND: A literature search was conducted using keywords for articles published in English from January 1990 to March 2015. Using criteria related to blood culture collection and handling, the search yielded 101 articles. References used also included Microbiology Laboratory standards, guidelines, and textbook information. RESULTS: The literature identified diverse and complex issues surrounding blood culture practices, including the impact of false-positive results, laboratory definition of contamination, effect on central line-associated bloodstream infection (CLABSI) reporting, indications for collecting blood cultures, drawing from venipuncture sites versus intravascular catheters, selection of antiseptics, use of needleless connectors, inoculation of blood culture bottles, and optimizing program management in emergency departments, education, and implementation of bundled practice initiatives. CONCLUSION: Hospitals should optimize best practice in the collection, handling, and management of blood culture specimens, an often overlooked but essential component in providing optimal care of patients in all settings and populations, reducing financial burdens, and increasing the accuracy of reportable CLABSI. Although universal concepts exist in blood culture practices, some issues require further research to determine benefit. Institutions undertaking a review of their blood culture programs are encouraged to use a checklist that addresses elements that encompass the research contained in this review.

Maternal differences and birth outcome disparities: Diversity within a high risk prenatal clinic.

BACKGROUND: We examined the influence of race/ethnicity on appointment attendance, maternal psychiatric and medical diagnoses, and birth outcomes within a diverse, low income, high risk pregnant population to determine whether birth outcome disparities would be lessened in a sample with high biopsychosocial risk across all groups. METHODS: Data were retrospectively obtained on all women scheduled for appointments in the San Francisco Genera Hospital (SFGH) High-Risk Obstetrics (HROB) clinic during a three-month period. General linear model and logistic regression procedures were used to examine the associations of race/ethnicity with maternal characteristics, clinic attendance, and birth outcomes. RESULTS: Our sample included 202 maternal-infant pairs (Hispanic 57%, Black 16%, Asian 15%, White 12%). Racial/ethnic differences were seen in language (p < .001), gravidity (p < .001), parity (p = .005), appointment attendance (p < .001), diabetes (p = .005), psychiatric diagnosis (p = .02), illicit drug use (p < .001), smoking (p < .001). These maternal characteristics, including rate of attendance at specialized prenatal appointments, did not predict birth outcomes with the exception of an association between diabetes and earlier gestational age (p = .03). In contrast, Black maternal race/ethnicity was associated with earlier gestational age at birth (p = .004) and lower birth weight (p < .001) compared to Whites. CONCLUSIONS: Within a diverse maternal population of high biopsychosocial risk, racial/ethnic disparities in birth outcomes persist. These disparities have implications for infant health trajectory throughout the lifecourse and for intervention implementation in high risk groups.