Optimized Patient Outcomes With the Novel Modality of Corrective Chemical Peel and Neurotoxin on Same-Day Treatment.

BACKGROUND: This study was conducted to improve standards of care in the cosmetic treatment of sun damage, fine lines, and wrinkles. Chemical Peels and Neurotoxins have been traditionally used cosmetically as monotherapies. This study aimed to confirm that the same-day combination created no additional side effects while also improving outcomes. METHODS: The multi-generational study enrolled 30 patients with Fitzpatrick I-VI representation. The Roberts Skin Type Classification System was used to establish baseline patient information. Patients were treated with a VI Peel®, followed by Botox®. Objectively, photographic matching, Wrinkle Severity Scale, Uniformity of Pigment Scale, and Skin Tone Scales were used to evaluate skin improvement. Patient questionnaires were issued to assess satisfaction. RESULTS: Safety of the same-day combination was established with no adverse events reported. Improvements on the Wrinkle Severity Scale showed an average rating dropping from 1.46 to 0.59 representing a 60% improvement. Improvements on the Uniformity of Pigment Scale showed an average rating dropping from 2.27 to 0.92 representing a 59% improvement. Improvements on the Skin Tone Scale showed an average rating dropping from 2.35 to 0.71 representing a 70% improvement. Questionnaires correlated with objective findings with high satisfaction.  Conclusion: This study confirmed the safety of the same-day combination. The efficacy of VI Peel & Botox same-day treatment was clinically proven by the improvements to Wrinkle Severity, Uniformity of Pigment, and Skin Tone via photographic matching. While perception studies indicated strong patient satisfaction with the combination. J Drugs Dermatol. 2024;23(1):1349-1354.   doi:10.36849/JDD.7194R1.

Continuity of trajectories of autism symptom severity from infancy to childhood.

BACKGROUND: Behavioral symptom trajectories are informative of the development of young children at increased likelihood for autism spectrum disorder (ASD). METHODS: Developmental trajectories of early signs were examined in a cohort of siblings of children diagnosed with ASD (n = 502) from 6 to 18 months using the Autism Observation Scale for Infants (AOSI), and from 18 months to 5-7 years using the Autism Diagnostic Observation Schedule (ADOS). Diagnostic outcomes for ASD at age 3 confirmed diagnosis for 137 children. We further analyzed the conditional probability of a switch from a trajectory measured with the AOSI to a trajectory measured with the ADOS as well as predictors from age 6 months. RESULTS: We derived three early trajectories of behavioral signs ("Low," "Intermediate," and "Increasing") from 6 to 18 months using the AOSI. We then derived three similar, distinct trajectories for the evolution of symptom severity between 18 and 60-84 months of age (Low, Intermediate, Increasing) using the ADOS. Globally, the Low trajectory included children showing fewer ASD signs or symptoms and the Increasing trajectory included children showing more severe symptoms. We also found that most children in the Low AOSI trajectory stayed in the corresponding ADOS trajectory, whereas children in an Increasing AOSI trajectory tended to transition to an Intermediate or Increasing ADOS trajectory. Developmental measures taken at 6 months (early signs of ASD, Fine Motor, and Visual Reception skills) were predictive of trajectory membership. CONCLUSIONS: Results confirm substantial heterogeneity in the early emergence of ASD signs in children at increased likelihood for ASD. Moreover, we showed that the way those early behavioral signs emerge in infants is predictive of later symptomatology. Results yield clear clinical implications, supporting the need to repeatedly assess infants at increased likelihood for ASD as this can be highly indicative of their later development and behavior.

Precursors of self-regulation in infants at elevated likelihood for autism spectrum disorder.

Research concerning temperament in children and adults with autism spectrum disorder (ASD) has suggested a consistent profile of low positive affect, high negative affect, and low regulation (Visser et al., 2016). One area receiving less attention is individual differences among children diagnosed with ASD. The primary objective of this study was to use a person-centered approach to explore heterogeneity of early temperament precursors of regulation in a large sample of infants with elevated familial likelihood of ASD. Early precursors of regulation included temperament assessed at 6, 12, and 24 months whereas outcome measures were diagnosis of ASD, cognitive ability and adaptive behavior at 36 months. Participants included 176 low-likelihood and 473 elevated-likelihood infants, 129 of whom were diagnosed with ASD at 3 years. Results supported a three-profile solution: a well-regulated profile (high positive affect and high attentional focus and shifting), a low attention focus profile (higher attentional shifting compared to attentional focus), and a low attention shifting profile (higher attentional focus compared to attentional shifting). A higher proportion of children diagnosed with ASD were classified into the low attention shifting profile. Furthermore, children with the well-regulated profile were differentiated from the other profiles by a pattern of higher social competence and lower dysregulation whereas children with the low attention focus profile were distinguished from the other profiles by higher cognitive ability at 3 years. The findings indicate that the combination of early positive affect with attention measures may provide an enhanced tool for prediction of self-regulation and later outcomes.

1,550 nm Erbium-Doped and 1,927 nm Thulium Nonablative Fractional Laser System: Best Practices and Treatment Setting Recommendations.

BACKGROUND: The Fraxel Dual laser system (Solta Medical, Inc., Bothell, WA) contains a 1,550 and 1,927 nm wavelength single handpiece with different indications for each wavelength. OBJECTIVE: To discuss treatment setting recommendations and best practices for select on-label and investigational applications of the 1,550 and 1,927 nm dual laser system. MATERIALS AND METHODS: Eight board-certified dermatologists with 10 or more years of experience with the 1,550 and 1,927 nm laser system completed an online survey about their clinical experience with the system and then participated in a roundtable to share clinical perspectives and best practices for using the laser system. RESULTS: For all Fitzpatrick skin types, treatment recommendations were described for selected approved indications for the 1,550 and 1,927 nm laser system, including both lasers in combination. Treatment recommendations were also reached for investigational applications with the 1,550 nm laser and 1,927 nm laser. Best practices for using the lasers during the treatment session to achieve optimal outcomes and decrease the post-treatment recovery time were compiled. CONCLUSION: The 1,550 and 1,927 nm dual laser system is effective for a wide range of aesthetic and therapeutic applications, on and off the face and across all Fitzpatrick skin types.

Measuring Nonapoptotic Caspase Activity with a Transgenic Reporter in Mice.

The protease caspase-3 is a key mediator of apoptotic programmed cell death. But weak or transient caspase activity can contribute to neuronal differentiation, axonal pathfinding, and synaptic long-term depression. Despite the importance of sublethal, or nonapoptotic, caspase activity in neurodevelopment and neural plasticity, there has been no simple method for mapping and quantifying nonapoptotic caspase activity (NACA) in rodent brains. We therefore generated a transgenic mouse expressing a highly sensitive and specific fluorescent reporter of caspase activity, with peak signal localized to the nucleus. As a proof of concept, we first obtained evidence that NACA influences neurophysiology in an amygdalar circuit. Then focusing on the amygdala, we were able to quantify a sex-specific persistent elevation in caspase activity in females after restraint stress. This simple in vivo caspase activity reporter will facilitate systems-level studies of apoptotic and nonapoptotic phenomena in behavioral and pathologic models.

Optimizing Outcomes With the 1550/1927 nm Dual Wavelength Non-Ablative Fractional Laser: Experienced User Recommendations.

BACKGROUND: Fractional laser treatment was introduced in 2004 as a non-invasive technique to treat sun-damaged and aging skin. Since then, numerous ablative and non-ablative photothermolysis technologies and devices have been introduced, increasing the options for clinicians and patients but also increasing the complexity regarding which system to use and the techniques to optimize outcomes. No two devices are the same and the user-manuals preset dosimetry does not address many clinical situations, which can create confusion for new and inexperienced users. METHODS: An online survey addressing use of a 1550 nm /1927 nm dual wavelength, non-ablative, fractional laser was sent to eight (8) US board certified dermatologists with extensive experience in the use of the device. The survey included 39 questions, addressing experience, best practices and recommendations for use. RESULTS: The survey data suggests that the device can be used to treat patients of all ages and skin types for indications including photoaging and photodamage, periorbital wrinkles, freckles, (ephelides), solar lentigines, poikiloderma, scarring due to acne or surgery. It can be used on both facial and non-facial areas, including neck, chest, hands, arms, abdomen, legs, and buttocks. Unexpected and adverse effects were rarely reported and those that did were mild and transient. CONCLUSIONS: This position paper provides practical real-world guidelines resulting from a small survey of experienced users, for new and early uses of the novel 1550 nm /1927 nm dual wavelength, non-ablative, fractional laser. J Drugs Dermatol. 2021;20(11):1150-1157. doi:10.36849/JDD.6181.

Racial/Ethnic Variations in Skin Barrier: Implications for Skin Care Recommendations in Skin of Color.

BACKGROUND: Genetic and environmental factors influence stratum corneum (SC) barrier properties and function. Researchers increasingly focus on biophysical studies that may help clinicians provide their patients with an informed choice on tailormade skincare. This literature review on skin barrier properties comparing different ethnic populations aims to offer insights into the information's clinical relevance. METHODS: A literature review followed by panel discussions and an online review process aimed to answer the questions: Are there racial/ethnic differences in the SC barrier structure and healthy skin barrier function? Is there a need for specific cleansers and moisturizers? RESULTS: Ethnic categories based on race and ethnicity are often not well defined and inconsistent across different studies. Studies comparing ethnic groups' physical and biochemical skin barrier properties have reported differences in transepidermal water loss (TEWL), skin lipid levels, pH, and mast cell granule size. However, these studies frequently had methodological flaws, mainly were small, and demonstrated conflicting results. The literature suggests racial/ethnic variations in ceramide content, SC structure, and filaggrin mutations. Furthermore, studies have shown a greater burden of pruritus and atopic dermatitis among Black populations. Data on barrier properties in Hispanic/LatinX and South Asian populations are lacking. CONCLUSION: Robust comparative studies are needed to understand these basic concepts to help tailor skincare and skin of color patients' education. J Drugs Dermatol. 2021;20(9):932-938. doi:10.36849/JDD.6312.

HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase.

HER2-positive breast cancers are among the most heterogeneous breast cancer subtypes. The early amplification of HER2 and its known oncogenic isoforms provide a plausible mechanism in which distinct programs of tumor heterogeneity could be traced to the initial oncogenic event. Here a Cancer rainbow mouse simultaneously expressing fluorescently barcoded wildtype (WTHER2), exon-16 null (d16HER2), and N-terminally truncated (p95HER2) HER2 isoforms is used to trace tumorigenesis from initiation to invasion. Tumorigenesis was visualized using whole-gland fluorescent lineage tracing and single-cell molecular pathology. We demonstrate that within weeks of expression, morphologic aberrations were already present and unique to each HER2 isoform. Although WTHER2 cells were abundant throughout the mammary ducts, detectable lesions were exceptionally rare. In contrast, d16HER2 and p95HER2 induced rapid tumor development. d16HER2 incited homogenous and proliferative luminal-like lesions which infrequently progressed to invasive phenotypes whereas p95HER2 lesions were heterogenous and invasive at the smallest detectable stage. Distinct cancer trajectories were observed for d16HER2 and p95HER2 tumors as evidenced by oncogene-dependent changes in epithelial specification and the tumor microenvironment. These data provide direct experimental evidence that intratumor heterogeneity programs begin very early and well in advance of screen or clinically detectable breast cancer. IMPLICATIONS: Although all HER2 breast cancers are treated equally, we show a mechanism by which clinically undetected HER2 isoforms program heterogenous cancer phenotypes through biased epithelial specification and adaptations within the tumor microenvironment.

Intestinal permeability correlates with behavioural severity in very young children with ASD: A preliminary study.

Systemic inflammation is known to alter behaviour, and since it has been reported that individuals with autism spectrum disorder (ASD) have higher levels of circulating cytokines, it has been hypothesized that systemic inflammation may exacerbate behaviours characteristic of ASD. The acute phase proteins α-2-macroglobulin, C-reactive protein, haptoglobin, serum amyloid P, serum amyloid A, ferritin and tissue plasminogen activator, as well as markers of intestinal permeability (intestinal fatty acid binding protein and lipopolysaccharide) were quantitated in the plasma of very young children with ASD. Behaviour severity was measured using the Autism Diagnostic Interview-Revised (ADI-R), the Autism Diagnostic Observation Schedule (ADOS) and the Vineland Adaptive Behaviour Scale (VABS). An increase in circulating I-FABP correlated with more severe deficits in communication, communication + social interaction as well as maladaptive behaviour. The acute phase protein haptoglobin was associated with more severe social interaction and communication + social interaction. In summary, I-FABP, a marker of intestinal epithelial damage, was associated with more severe behavioural phenotypes in very young children with ASD. In addition, the acute phase protein, haptoglobin, was associated with behaviour.

Symptom trajectories in the first 18 months and autism risk in a prospective high-risk cohort.

BACKGROUND: Although early autism spectrum disorder (ASD) detection strategies tend to focus on differences at a point in time, behavioral symptom trajectories may also be informative. METHODS: Developmental trajectories of early signs of ASD were examined in younger siblings of children diagnosed with ASD (n = 499) and infants with no family history of ASD (n = 177). Participants were assessed using the Autism Observation Scale for Infants (AOSI) from 6 to 18 months. Diagnostic outcomes were determined at age 3 years blind to previous assessments. RESULTS: Semiparametric group-based modeling using AOSI scores identified three distinct trajectories: Group 1 ('Low', n = 435, 64.3%) was characterized by a low level and stable evolution of ASD signs, group 2 ('Intermediate', n = 180, 26.6%) had intermediate and stable levels, and group 3 ('Inclining', n = 61, 9.3%) had higher and progressively elevated levels of ASD signs. Among younger siblings, ASD rates at age 3 varied by trajectory of early signs and were highest in the Inclining group, membership in which was highly specific (94.5%) but poorly sensitive (28.5%) to ASD. Children with ASD assigned to the inclining trajectory had more severe symptoms at age 3, but developmental and adaptive functioning did not differ by trajectory membership. CONCLUSIONS: These prospective data emphasize variable early-onset patterns and the importance of a multipronged approach to early surveillance and screening for ASD.

Air pollution and skin disorders.

Air pollution is being shown to play an increasing causation role in our most common skin diseases. Acne, hyperpigmentation, atopic dermatitis, and psoriasis have been shown to be influenced by air pollution. It is important for pollution to be added as a risk factor for these skin disorders, and thus we must discuss mitigating its negative affects with patients. Air pollution is the contamination of outdoor (ambient) and indoor (household) environments by any chemical, physical, or biological agent that modifies the natural characteristics of the atmosphere. Nearly all (90%) of the world's population experience daily pollution. In 2019, air pollution was considered by the World Health Organization to be the biggest environmental health risk to humans, responsible for killing more than 7 million people prematurely every year. Preliminary studies link air pollution to COVID-19 deaths, as there were high death tolls in some of the most globally polluted areas. Air pollution affects many organ systems such as cardiovascular, pulmonary, central nervous, reproductive, and integumentary systems. In this study, we detail the current evidence linking specific skin and health disorders to air pollution.

DNA Methylation of the Oxytocin Receptor Across Neurodevelopmental Disorders.

Many neurodevelopmental disorders (NDDs) share common learning and behavioural impairments, as well as features such as dysregulation of the oxytocin hormone. Here, we examined DNA methylation (DNAm) in the 1st intron of the oxytocin receptor gene, OXTR, in patients with autism spectrum (ASD), attention deficit and hyperactivity (ADHD) and obsessive compulsive (OCD) disorders. DNAm of OXTR was assessed for cohorts of ASD (blood), ADHD (saliva), OCD (saliva), which uncovered sex-specific DNAm differences compared to neurotypical, tissue-matched controls. Individuals with ASD or ADHD exhibiting extreme DNAm values had lower IQ and more social problems, respectively, than those with DNAm within normative ranges. This suggests that OXTR DNAm patterns are altered across NDDs and may be correlated with common clinical outcomes.

The Genomics of Opioid Addiction Longitudinal Study (GOALS): study design for a prospective evaluation of genetic and non-genetic factors for development of and recovery from opioid use disorder.

BACKGROUND: The opioid use disorder and overdose crisis in the United States affects public health as well as social and economic welfare. While several genetic and non-genetic risk factors for opioid use disorder have been identified, many of the genetic associations have not been independently replicated, and it is not well understood how these factors interact. This study is designed to evaluate relationships among these factors prospectively to develop future interventions to help prevent or treat opioid use disorder. METHODS: The Genomics of Opioid Addiction Longitudinal Study (GOALS) is a prospective observational study assessing the interplay of genetic and non-genetic by collecting comprehensive genetic and non-genetic information on 400 participants receiving medication for opioid use disorder. Participants will be assessed at four time points over 1 year. A saliva sample will be collected for large-scale genetic data analyses. Non-genetic assessments include validated surveys measuring addiction severity, depression, anxiety, and adverse childhood experiences, as well as treatment outcomes such as urine toxicology results, visit frequency, and number of pre and post-treatment overdoses extracted from electronic medical records. DISCUSSION: We will use these complex data to investigate the relative contributions of genetic and non-genetic risk factors to opioid use disorder and related treatment outcomes.

Screening for Behavioral Signs of Autism Spectrum Disorder in 9-Month-Old Infant Siblings.

Despite considerable progress in characterizing the early signs of autism spectrum disorder (ASD), more remains to be learned about how symptoms emerge in the first year of life. Parents with a new baby who already had at least one biological child diagnosed with ASD (high-risk) or no family history of ASD (low-risk) completed two measures when their baby was 9 months of age, the Autism Parent Screen for Infants (APSI) questionnaire and the interview-based Parent Concerns Form. Children underwent a blinded independent diagnostic assessment for ASD at age 3 years. Total scores on the APSI and the Parent Concerns Form were both able to independently differentiate high-risk children who were later diagnosed with ASD from other high-risk and low-risk children who were not. Using logistic regression, we found that the total score on the APSI predicted ASD outcomes at age 3 with 70% accuracy, but the Parent Concerns Form did not contribute any unique variance when the APSI was already in the model. The results suggest that the APSI identifies early features predictive of ASD in high-risk infants and can be used to flag them for targeted follow-up and screening.

Assessment of Autism Symptoms From 6 to 18 Months of Age Using the Autism Observation Scale for Infants in a Prospective High-Risk Cohort.

The objectives were to characterize behavioral signs of autism spectrum disorder (ASD) in younger siblings of diagnosed children (high-risk; HR) and examine classification features of the Autism Observation Scale for Infants (AOSI). Participants (501 HR and 180 low-risk [LR]) were assessed between 6 and 18 months using the AOSI and at age 3 for ASD diagnoses. Total AOSI scores differentiated HR infants later diagnosed with ASD starting at 12 months. ROC analyses identified 12- and 18-month cutoff scores associated with 0.52 sensitivity and 0.74 specificity and 0.73 sensitivity and 0.65 specificity, respectively. Although classification accuracy does not support use as a standalone screen, the AOSI identifies features associated with ASD starting at 6 months and differentiates HR infants with ASD by 12 months.

The association between social emotional development and symptom presentation in autism spectrum disorder.

Understanding differences in social-emotional behavior can help identify atypical development. This study examined the differences in social-emotional development in children at increased risk of an autism spectrum disorder (ASD) diagnosis (infant siblings of children diagnosed with the disorder). Parents completed the Brief Infant-Toddler Social-Emotional Assessment (BITSEA) to determine its ability to flag children with later-diagnosed ASD in a high-risk (HR) sibling population. Parents of HR (n = 311) and low-risk (LR; no family history of ASD; n = 127) children completed the BITSEA when their children were 18 months old and all children underwent a diagnostic assessment for ASD at age 3 years. All six subscales of the BITSEA (Problems, Competence, ASD Problems, ASD Competence, Total ASD Score, and Red Flags) distinguished between those in the HR group who were diagnosed with ASD (n = 84) compared to non-ASD-diagnosed children (both HR-N and LR). One subscale (BITSEA Competence) differentiated between the HR children not diagnosed with ASD and the LR group. The results suggest that tracking early social-emotional development may have implications for all HR children, as they are at increased risk of ASD but also other developmental or mental health conditions.

Patient- and Family-Centered Care in the Emergency Department for Children With Autism.

BACKGROUND: Emergency department (ED) care processes and environments impose unique challenges for children with autism spectrum disorder (ASD). The implementation of patient- and family-centered care (PFCC) emerges as a priority for optimizing ED care. In this article, as part of a larger study, we explore PFCC in the context of ASD. Our aims were to examine how elements of PFCC were experienced and applied relative to ED care for children with ASD. METHODS: Qualitative interviews were conducted with parents and ED service providers, drawing on a grounded theory approach. Interviews were audio recorded, transcribed verbatim, and analyzed by using established constant comparison methods. Data were reviewed to appraise the reported presence or absence of PFCC components. RESULTS: Fifty-three stakeholders (31 parents of children with ASD and 22 ED service providers) participated in interviews. Results revealed the value of PFCC in autism-based ED care. Helpful attributes of care were a person-centered approach, staff knowledge about ASD, consultation with parents, and a child-focused environment. Conversely, a lack of staff knowledge and/or experience in ASD, inattention to parent expertise, insufficient communication, insufficient family orientation to the ED, an inaccessible environment, insufficient support, a lack of resources, and system rigidities were identified to impede the experience of care. CONCLUSIONS: Findings amplify PFCC as integral to effectively serving children with ASD and their families in the ED. Resources that specifically nurture PFCC emerge as practice and program priorities.

Tensions in Maternal Care for Children, Youth, and Adults With Autism Spectrum Disorder.

This study explored the experiences of mothers caring for an individual with autism spectrum disorder (ASD) ranging from 5 to 25 years of age, and examined pervasive tensions in caregiving. Guided by ethnographic methods, a retrospective cross-sectional study was conducted. Interviews with 85 mothers were analyzed inductively. Prevalent tensions in maternal caregiving were identified: (a) difficulties obtaining, yet resistance to, an ASD diagnosis; (b) identified giftedness of the child versus notions of deficit imposed by others; (c) disability-related behaviors erroneously interpreted as 'poor parenting'; (d) contradictory considerations in diagnosis disclosure; (e) the invisibility yet pervasiveness of ASD; (f) extensive need for, yet the lack of, accessible services; (g) ASD-related care demands versus other pressing responsibilities; (h) arguments for inclusive versus exclusive services; and (i) aims of nurturing independence versus managing safety risk. Tensions were heightened by insufficient supports relative to need. Implications and recommendations for practice and policy are offered.