Publications by authors named "William D Graf"

Accurate determination of death is a necessary responsibility of the medical profession. Brain death, or death by neurological criteria (DNC), can be legally declared after the determination of permanent loss of clinical brain function, including the capacity for consciousness, brainstem reflexes, and the ability to breathe spontaneously. Despite longstanding debates over the exact definition of brain death or DNC and how it is determined, most middle- and high-income countries have compatible medical protocols and legal policies for brain death or DNC.

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The aim of this review was to discuss bioethics in prenatal diagnosis and health care after recent legislative and judicial changes affecting reproductive rights, such as the repeal of 'Roe v. Wade' in the United States. We recognize that abortion involves particular moralities that are not universal or shared by all cultures, groups, and individuals.

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High drug prices have created substantial challenges for patients, physicians, health systems, and payers. High drug prices can affect patient care in many ways, including limiting access to treatment, increasing the burden of administrative tasks, and contributing to physician burnout. Exorbitant drug pricing poses direct challenges for distributive justice, which is concerned with fairly distributing benefits and burdens across society.

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PAX5 is a transcription factor associated with abnormal posterior midbrain and cerebellum development in mice. PAX5 is highly loss-of-function intolerant and missense constrained, and has been identified as a candidate gene for autism spectrum disorder (ASD). We describe 16 individuals from 12 families who carry deletions involving PAX5 and surrounding genes, de novo frameshift variants that are likely to trigger nonsense-mediated mRNA decay, a rare stop-gain variant, or missense variants that affect conserved amino acid residues.

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Article Synopsis
  • Semaphorins and plexins, important for brain development, include the PLXNA3 gene, which affects brain signaling and is linked to conditions like autism and intellectual disabilities in boys with specific genetic variants.
  • This study examined 14 boys with these hemizygous PLXNA3 variants, finding a range of issues such as autism, motor difficulties, and seizures, highlighting a connection between the gene variations and the severity of neurodevelopmental disorders.
  • The findings suggest a potential new X-linked intellectual disability syndrome tied to PLXNA3 variants and emphasize the need for more research on their impact in humans.
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  • ALG13 is crucial for synthesizing a specific molecule necessary for glycosylation, and mutations in this gene cause a rare form of epilepsy called EIEE36, also classified as ALG13-CDG.
  • Despite being a glycosylation disorder, cases of ALG13-CDG do not exhibit the expected glycosylation defects typically found in other disorders.
  • A study identified 29 new cases affected by ALG13 mutations, revealing a high prevalence of West syndrome, with patients responding well to certain treatments like adrenocorticotropic hormone and a ketogenic diet for managing epilepsy.
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Classic autism has gradually evolved into the concept of a larger "spectrum disorder." The rising prevalence of autism and autism spectrum disorder (autism/ASD) diagnoses can be largely attributed to broader diagnostic criteria, adoption of dimensional assessment strategies, increased awareness, linking of services to diagnosis, and the inclusion of milder neurodevelopmental differences bordering on normality. The spectrum disorder diagnosis raises numerous bioethical issues for individuals and society.

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The prevalence of attention deficit hyperactivity disorder (ADHD) diagnoses is rising. ADHD is closely linked to its treatment with medications such as methylphenidate and amphetamines, which have popular appeal as neuroenhancement drugs by persons without a neurological disorder. The three main reasons for the increase in ADHD medication demand, production, and consumption are a) the inclusion of milder ADHD diagnoses; b) the vast marketing of ADHD medications by the pharmaceutical industry; and c) the illegal diversion of controlled ADHD medication to consumers seeking stimulants as neuroenhancements.

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Neurodevelopmental disorders result from an inordinate number of genetic and environmental causes during the embryological and fetal periods of life. In the clinical setting, deciphering precise etiological diagnoses is often difficult. Newer screening technologies allow a gradual shift from traditional nature-versus-nurture debates toward the focused analysis of gene-by-environment interactions (G X E).

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