The genetics of trichotillomania and excoriation disorder: A systematic review.

BACKGROUND: Trichotillomania (TTM) and excoriation disorder (ED) are impairing obsessive-compulsive related disorders that are common in the general population and for which there are no clear first-line medications, highlighting the need to better understand the underlying biology of these disorders to inform treatments. Given the importance of genetics in obsessive-compulsive disorder (OCD), evaluating genetic factors underlying TTM and ED may advance knowledge about the pathophysiology of these body-focused repetitive behaviors. AIM: In this systematic review, we summarize the available evidence on the genetics of TTM and ED and highlight gaps in the field warranting further research. METHOD: We systematically searched Embase, PsycInfo, PubMed, Medline, Scopus, and Web of Science for original studies in genetic epidemiology (family or twin studies) and molecular genetics (candidate gene and genome-wide) published up to June 2023. RESULTS: Of the 3536 records identified, 109 studies were included in this review. These studies indicated that genetic factors play an important role in the development of TTM and ED, some of which may be shared across the OCD spectrum, but there are no known high-confidence specific genetic risk factors for either TTM or ED. CONCLUSIONS: Our review underscores the need for additional genome-wide research conducted on the genetics of TTM and ED, for instance, genome-wide association and whole-genome/whole-exome DNA sequencing studies. Recent advances in genomics have led to the discovery of risk genes in several psychiatric disorders, including related conditions such as OCD, but to date, TTM and ED have remained understudied.

Per- and polyfluoroalkyl substances (PFAS) in construction and demolition debris (CDD): discerning sources and fate during waste management.

As regulatory frameworks for per- and polyfluoroalkyl substances (PFAS) evolve, the solid waste community seeks to manage PFAS risks effectively. Despite extensive research on PFAS in municipal solid waste (MSW) and wastewater sludge, there is limited information on a major global waste stream which seldom gleans regulatory oversight - construction and demolition debris (CDD). This study sampled a CDD processing facility to provide material-specific information on the PFAS profile within CDD. The bulk CDD accepted by this facility was separated into major categories, representatively sampled, then characterized for total available PFAS (∑92PFAS). As reprocessed CDD is ultimately recycled or landfilled, often unencapsulated or in unlined landfills, the PFAS leaching potential was also examined using two leaching procedures. Among the categories assessed for total PFAS, carpeting, carpet padding, and gypsum drywall showed elevated concentrations compared to other components, with most of the PFAS mass contributed by precursor species. However, materials with the highest total PFAS, such as carpeting, did not necessarily exhibit the highest leaching, and leachate was predominantly composed of terminal species rather than precursors. Extrapolating these findings with national CDD generation and management data inventories suggests that despite MSW having higher total available PFAS concentrations, the leachability of PFAS from landfilled CDD is comparable, raising legitimate concerns with CDD disposal practices, particularly in unlined CDD landfills.

Investigating the partitioning behavior of per- and polyfluoroalkyl substances (PFAS) during thermal landfill leachate evaporation.

Thermal landfill leachate evaporator systems can reduce the volume of leachate by up to 97%, while releasing water vapor and producing residuals (volume-reduced leachate and sludge) that are managed on-site. On-site thermal evaporators offer landfill operators leachate management autonomy without being subject to increasingly stringent wastewater treatment plant requirements. However, little is known about the partitioning of PFAS within these systems, nor the extent to which PFAS may be emitted into the environment via vapor. In this study, feed leachate, residual evaporated leachate, sludge, and condensed vapor were sampled at two active full-scale thermal landfill leachate evaporators and from a laboratory-scale leachate evaporation experiment. Samples were analyzed for 91 PFAS via ultra-high pressure liquid chromatography - tandem mass spectrometry (UHPLC-MS/MS). Similar trends were observed from Evaporator 1, Evaporator 2, and the laboratory-scale evaporator; ∑PFAS were concentrated in the residual evaporated leachate during evaporation by a factor of 5.3 to 20. All condensed vapors sampled (n = 5) contained PFAS, predominantly 5:3 fluorotelomer carboxylic acid (5:3FTCA), (full-scale vapors 729 - 4087 ng/L PFAS; lab-scale vapor 61.0 ng/L PFAS). For Evaporators 1 and 2, an estimated 9 - 24% and 10%, respectively, of the PFAS mass entering the evaporators in leachate was released with vapor during the days of sample collection. '.

Assessing the suitability of leachability-based screening levels for per- and polyfluoroalkyl substances (PFAS) risk assessment.

In recent years, soil screening levels have been adopted by regulatory agencies for certain per- and polyfluoroalkyl substances (PFAS) to assess the risk of groundwater contamination through leaching. These soil screening levels, determined using an established equilibrium-based partitioning equation, have high variability among regulatory groups largely attributed to the diverse reported partitioning coefficients in the literature. This variability between reported partitioning coefficients, and subsequently soil screening levels, is due to the complex leaching behavior of PFAS not being predicted well by the standard equilibrium-based model. This has led one regulatory group to require batch leaching to assess risk rather than setting default soil screening levels based on partitioning equations. In this work, we conducted leaching experiments on five field-sampled soils impacted by aqueous film-forming foams (AFFF), following Leaching Environmental Assessment Framework (LEAF) Method 1316 and compared the results to expected leaching utilizing an equilibrium-based partitioning equation commonly employed by regulatory agencies to establish soil screening levels. Our analysis found among the six PFAS detected in the soils, which have regulatory leaching thresholds established, the partitioning values assumed by the U.S. EPA exhibited the highest accuracy in predicting leachate concentrations. These partitioning values predicted actual leaching within a ± 20 % margin of error for approximately 50 % of sample points, highlighting limitations in relying solely on equilibrium-based partitioning values as predictors of leaching behavior. This discrepancy between predicted and actual leaching has implications for site managers and regulatory entities overseeing PFAS-contaminated sites, suggesting that soil screening level determinations for PFAS might need to be revised to account for the unique transport characteristics of PFAS.

Improvement of sensory deficits in fragile X mice by increasing cortical interneuron activity after the critical period.

Changes in the function of inhibitory interneurons (INs) during cortical development could contribute to the pathophysiology of neurodevelopmental disorders. Using all-optical in vivo approaches, we find that parvalbumin (PV) INs and their immature precursors are hypoactive and transiently decoupled from excitatory neurons in postnatal mouse somatosensory cortex (S1) of Fmr1 KO mice, a model of fragile X syndrome (FXS). This leads to a loss of parvalbumin INs (PV-INs) in both mice and humans with FXS. Increasing the activity of future PV-INs in neonatal Fmr1 KO mice restores PV-IN density and ameliorates transcriptional dysregulation in S1, but not circuit dysfunction. Critically, administering an allosteric modulator of Kv3.1 channels after the S1 critical period does rescue circuit dynamics and tactile defensiveness. Symptoms in FXS and related disorders could be mitigated by targeting PV-INs.

Emerging polycyclic aromatic hydrocarbon (PAH) and trace metal leachability from reclaimed asphalt pavement (RAP).

The environmental risks associated with the storage, reuse, and disposal of unencapsulated reclaimed asphalt pavement (RAP) has been previously examined, but because of a lack of standardized column testing protocols and recent interest on emerging constituents with higher toxicity, questions surrounding leaching risks from RAP continue. To address these concerns, RAP from six, discrete stockpiles in Florida was collected and leach tested following the most up-to-date, standard column leaching protocol - United States Environmental Protection Agency (US EPA) Leaching Environmental Assessment Framework (LEAF) Method 1314. Sixteen EPA priority polycyclic aromatic hydrocarbons (PAHs), 23 emerging PAHs, identified through relevance in literature, and heavy metals were investigated. Column testing showed minimal leaching of PAHs; only eight compounds, three priority PAHs and five emerging PAHs, were released at quantifiable concentrations, and where applicable, were below US EPA Regional Screening Levels (RSL). Though emerging PAHs were identified more frequently, in most cases, priority compounds dominated contributions to overall PAH concentration and benzo(a)pyrene (BaP) equivalent toxicity. Except for arsenic, molybdenum, and vanadium in two samples, metals were found below limits of detection (LOD) or below risk thresholds. Arsenic and molybdenum concentrations diminished over time with increased exposure to liquid, but elevated vanadium concentrations persisted in one sample. Further batch testing linked vanadium to the aggregate component of the sample, unlikely to be encountered in typical RAP sources. As demonstrated by generally low constituent mobility observed during testing, the leaching risks associated with the beneficial reuse of RAP are limited, and under typical reuse conditions, factors of dilution and attenuation would likely reduce leached concentrations below relevant risk-based thresholds at a point of compliance. When considering emerging PAHs with higher toxicities, analyses indicated minimal impact to overall leachate toxicity, further suggesting that with proper management, this heavily recycled waste stream is unlikely to pose leaching risk.

Up in the air: Polyfluoroalkyl phosphate esters (PAPs) in airborne dust captured by air conditioning (AC) filters.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitously present in our indoor living environments. Dust is thought to accumulate PFAS released indoors and serve as an exposure pathway for humans. Here, we investigated whether spent air conditioning (AC) filters can be exploited as opportunistic samplers of airborne dust for assessing PFAS burden in indoor environments. Used AC filters from campus facilities (n = 19) and homes (n = 11) were analyzed for 92 PFAS via targeted ultra-high pressure liquid chromatography - tandem mass spectrometry (UHPLC-MS/MS). While 27 PFAS were measured (in at least one filter), the predominant species were polyfluorinated dialkylated phosphate esters (diPAPs), with the sum of 6:2-, 8:2-, and 6:2/8:2diPAPs accounting for approximately 95 and 98 percent of ∑27PFAS in campus and household filters, respectively. Exploratory screening of a subset of the filters revealed the presence of additional species of mono-, di-, and tri-PAPs. Considering the constant human exposure to dust indoors and the potential of PAPs to degrade into terminal species with well-established toxicological risks, assessing dust for these precursor PFAS warrants further investigation with respect to both human health and PFAS loading to landfills from this under studied waste stream.

Characteristics of trichotillomania and excoriation disorder across the lifespan.

Trichotillomania (hair-pulling disorder) and excoriation (skin-picking) disorder are body-focused repetitive behaviors, which often first present in adolescence and cause distress and impairment into adulthood. Few studies have examined the clinical characteristics of the co-occurrence of these conditions across the lifespan. We examined cross-sectional survey responses collected from April 2018-February 2020 to evaluate the relationship between trichotillomania, excoriation disorder, and their co-occurrence. Responses from individuals with trichotillomania (n = 50), excoriation disorder (n = 52), and both conditions (n = 50) ages 4-67 years old were compared for co-occurring conditions and current symptoms. Self-report measures of hair-pulling and skin-picking severity and subtypes were assessed. Gender, race, and co-occurring conditions were generally similarly distributed across the three groups with high rates of self-reported anxiety (63-82%), depression (34-50%), obsessive-compulsive disorder (16-29%), and attention-deficit/hyperactivity disorder (12-32%). Among individuals with both trichotillomania and excoriation disorder, significant positive correlations were observed between hair-pulling and skin-picking severity scores as well as hair-pulling and skin-picking subtypes. Hair-pulling and skin-picking severity peaked at the transition from adolescence to adulthood and hair-pulling/skin-picking styles appeared to shift across the lifespan. Our results support several similarities between trichotillomania and excoriation disorder, providing new insight into the clinical characteristics of these conditions.

Trimethylguanosine synthase 1 is a novel regulator of pancreatic beta-cell mass and function.

Type 2 diabetes is a metabolic disorder associated with abnormal glucose homeostasis and is characterized by intrinsic defects in ß-cell function and mass. Trimethylguanosine synthase 1 (TGS1) is an evolutionarily conserved enzyme that methylates small nuclear and nucleolar RNAs and that is involved in pre-mRNA splicing, transcription, and ribosome production. However, the role of TGS1 in ß-cells and glucose homeostasis had not been explored. Here, we show that TGS1 is upregulated by insulin and upregulated in islets of Langerhans from mice exposed to a high-fat diet and in human ß-cells from type 2 diabetes donors. Using mice with conditional (ßTGS1KO) and inducible (MIP-CreERT-TGS1KO) TGS1 deletion, we determined that TGS1 regulates ß-cell mass and function. Using unbiased approaches, we identified a link between TGS1 and endoplasmic reticulum stress and cell cycle arrest, as well as and how TGS1 regulates ß-cell apoptosis. We also found that deletion of TGS1 results in an increase in the unfolded protein response by increasing XBP-1, ATF-4, and the phosphorylation of eIF2α, in addition to promoting several changes in cell cycle inhibitors and activators such as p27 and Cyclin D2. This study establishes TGS1 as a key player regulating ß-cell mass and function. We propose that these observations can be used as a stepping-stone for the design of novel strategies focused on TGS1 as a therapeutic target for the treatment of diabetes.