Downregulation of Caveolae-Associated Proteins in Psoriasis: A Case Series Study.

We have previously identified that a structural membrane protein Caveolin-1 (Cav1) is involved in the regulation of aberrant keratinocyte proliferation and differentiation. The aim of this study was to elucidate the role of Cav1, Caveolin-2 (Cav2), and Cavin-1 in the pathogenesis of psoriasis vulgaris and between psoriasis subtypes. We utilized human biopsies from validated cases of psoriasis vulgaris (n = 21) at the University of Miami Hospital and compared the expression of Cav1, Cav2, and Cavin-1 by immunohistochemistry staining with that in normal healthy age-/sex-/location-matched skin (n = 15) and chronic spongiotic dermatitis skin samples (as control inflammatory skin condition) and quantified using QuPath. Distinct subtypes of psoriasis included guttate, inverse, nail, plaque, palmoplantar, and pustular. All biopsy samples exhibited a trend toward downregulation of Cav1, with nail, plaque, and palmoplantar psoriasis exhibiting the most pronounced effects. Only nail and pustular psoriasis samples exhibited significant downregulation of Cav2 and Cavin-1, suggesting Cav1 to be the main caveolar contributor to the pathogenesis of psoriasis. Together, these data support caveolae as pathophysiological targets in nail and pustular psoriasis, whereas Cav1 seems to be a general biomarker of multiple subtypes of psoriasis.

Toxic Ingredients in Personal Care Products: A Dermatological Perspective.

Environmental dermatology is the study of how environmental factors affect the integumentary system. The environment includes natural and built habitats, encompassing ambient exposure, occupational exposures, and lifestyle exposures secondary to dietary and personal care choices. This review explores common toxins found in personal care products and packaging, such as bisphenols, parabens, phthalates, per- and poly-fluoroalkyl substances, p-phenylenediamine, and formaldehyde. Exposure to these toxins has been associated with carcinogenic, obesogenic, or proinflammatory effects that can potentiate disease. In addition, these compounds have been implicated as endocrine-disrupting chemicals that can worsen dermatological conditions such as acne vulgaris, or dermatitis. Certain pollutants found in personal care products are not biodegradable and have the potential to bioaccumulate in humans. Therefore, even short-term exposure can cause long-lasting issues for communities. The skin is often the first point of contact for environmental exposures and serves as the conduit between environmental toxins and the human body. Therefore, it is important for dermatologists to understand common pollutants and their acute, subacute, and chronic impact on dermatological conditions to better diagnose and manage disease.

Navigating Countertransference in Inpatient Settings: Optimizing Interventions for Patients with Borderline Personality Disorder and Repeated Acute Hospitalizations.

Over the years, the psychiatric inpatient treatment paradigm has shifted to more brief stays focused on acute stabilization and psychopharmacologic-focused interventions, rather than individual psychotherapeutic engagement. Unfortunately, this has allowed patients with complex interpersonal dynamics, particularly borderline personality disorder, to slip through the cracks of effective treatment. This can contribute to repeated inpatient admissions, where both patients and clinicians feel trapped in a maladaptive, unhelpful cycle. In this article, we examine the evolution of inpatient treatment with de-emphasized psychotherapy practices, review the particular dynamics that patients with borderline personality disorder may evoke within an interdisciplinary treatment team, and provide a framework of clinically based vignettes for scenarios that may arise within inpatient treatment of this patient population. With attention to countertransference patterns and common pitfalls of communication, we offer alternative approaches and conversations with the hopes of improving outcomes and alliances in a new landscape of psychiatric practice.

Beliefs and counseling practices among dermatologists regarding sexual and other adverse effects of finasteride.

Finasteride may cause low libido and erectile dysfunction and the product label of finasteride also includes post-marketing reactions of sexual dysfunction that continued after discontinuation of treatment, as well as male infertility and depression. The aim of this study was to evaluate the beliefs and counseling practices among dermatologists regarding adverse effects of finasteride. Anonymous paper surveys were personally distributed to 122 attendees at two annual major dermatology meetings. The participation rate was 82% with 47% women and 77% residents of the United States. 51% of respondents believed that finasteride could cause sexual side effects and 18% believed that it could cause persistent sexual side effects. Fewer than a quarter believed that finasteride could cause depression or lower sperm counts. When initiating finasteride, 69% of respondents counseled at least half of their patients about potential sexual side effects with 52% for persistent sexual side effects and 30% for depression. This study identifies the need for greater awareness of the potential adverse effects of finasteride and identifies opportunities for improvement in counseling practices that reflect finasteride's product labeling.

Further tests of sequence-sensitive models in a modified garner task using separable dimensions.

In the study of perceptual categorization, a key distinction is made between separable and integral dimensions. Separable dimensions are easy to attend in isolation, while integral dimensions are not. Little et al. (2016) showed that when trial-by-trial responses are analyzed, a consistent pattern of sequential effects was found in a modified Garner paradigm using integral-dimension stimuli. The present experiments investigated whether these pronounced sequential effects are also found with separable-dimension stimuli. Four experiments using two different types of separable dimensions were conducted. The results indicated that similar patterns of sequential effects were present for separable-dimension stimuli, but, unlike for integral dimensions, the effect of a change in the irrelevant dimension in the filtering task was not found. Further, for separable dimensions, the overall pattern of sequential effects did not vary between the Garner tasks (i.e., control, correlated, and filtering). To explain these results, we fit a sequence-sensitive exemplar model and compared the fits of this model to a novel sequence-sensitive feature model, in which only the relevant feature influences the categorization decision. We found that the full exemplar model provided a more compelling account of both our separable dimension data and the integral dimension data of Little et al. (2016). These findings provide a more complete understanding of perceptual categorization and add to the growing body of literature on the prevalence and critical implications of strong sequential effects in cognitive tasks. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Insurance delays in the approval of biologic medications for patients with psoriasis and psoriatic arthritis.

Biologics are the most effective treatment for moderate-to-severe psoriasis. Insurance approval and need for prior authorization continue to be a barrier to care for many patients with psoriasis and psoriatic arthritis. We sought to determine whether race/ethnicity, insurance type, and provider specialty affect biologic approval times. Records from the University of Miami Health System were reviewed, and 101 patients were included. Need for a prior authorization was significantly associated with long waits (p = 2.4 × 10-5). We did not identify a significant difference in wait times between non-Hispanic Whites and non-Whites. The average wait time for biologic approval for Whites was 29.7 days and for non-Whites was 27.2 days. Biologics were approved the same day for 23.7% of HMO carriers, 11.5% of PPO carriers, 63% of Medicare carriers, and 40% of Medicaid carriers (p < 0.001). There was no difference in the biologic type prescribed based on insurance type. Medicaid (p < 0.05) and the need for prior authorization (p = 2.4 × 10-5) significantly predicted approval wait time in our multilinear regression model. Patients with Medicare had the shortest wait time with a mean of 7.3 days. Medicaid patients waited a mean of 11.3 days. Private insurance patients waited the longest, regardless of whether they had a PPO (37 days) or HMO (41.3 days).

Drugs targeting epithelial-mesenchymal transition molecules for treatment of lichen planopilaris.

Primary cicatricial alopecia (PCA), also known as scarring alopecia, comprises a diverse group of hair disorders that cause permanent destruction of the pilosebaceous unit, resulting in disappearance of the follicular ostia. Lichen planopilaris (LPP) is a subtype of primary lymphocytic cicatricial alopecia. There is an urgent need to identify novel molecules that successfully target specific pathogenic pathways in LPP to inhibit and reverse disease progression. Recent studies into LPP pathogenesis have discovered that follicular stem cells undergo epithelial-mesenchymal transition (EMT). We sought to identify drugs that target molecules involved in EMT to repurpose these drugs for treatment of LPP. We identified 8 molecules and 15 drugs that target these EMT molecules. Only four of these drugs (pioglitazone, tofacitinib, barcitinib and apremilast) have been reported in individual cases or case series of patients with LPP and controlled studies are missing. We describe each drug and mechanism of action target EMT in detail. Although previous studies have demonstrated the efficacy of EMT inhibitors in anticancer therapy, there are, to our knowledge, no studies using EMT-attenuating drugs for the treatment of LPP. The treatment molecules discussed in this paper provide a new platform for clinical studies and controlled trials in LPP.

Documented Reasons of Cancellation and Rescheduling of Telehealth Appointments During the Pandemic.

Background and Objective: The COVID-19 pandemic increased the use of telehealth around the world. The aim is to minimize health care service disruption as well as reducing COVID-19 exposure. However, one of the major operational concerns is cancellations and rescheduling (C/Rs). C/Rs may create additional burden and cost to the patient, provider, and the health system. Our aim is to understand the reasons for C/Rs of the telehealth session after the scheduled start time. Materials and Methods: We reviewed electronic health records (EHRs) to identify the C/R reasons for behavioral health and speech language pathology departments. Documented C/Rs in the medical charts were identified from EHR by using a keyword-based and Natural Language Processing (NLP)-supported EHR search engine. From the search results, we randomly selected 200 notes and conducted a thematic analysis. Results: We identified four themes explaining C/R reasons. Most frequent theme was "technicality" (47, 36%), followed by "engagement" (34, 25%), "scheduling" (31, 24%), and "unspecified" (20, 15%). The findings showed that technical reasons are the leading cause of C/Rs, constituting 36% of the cases (95% confidence interval [CI]: 29-43%). Notably, "engagement" constituted a sizeable 25% (95% CI: 19-31%) of C/Rs, as a result of the inability to engage a patient to complete the telehealth session. Conclusions: The study shows that engagement is one of the new challenges to the pediatric telehealth visits. Future studies of new engagement models are needed for the success of telehealth. Our findings will help fill the literature gaps and may help with enhancing the digital experience for both caregivers and providers, reducing wasted time and resources due to preventable C/Rs, improving clinical operation efficiency, and treatment adherence.

Multilevel Self-Attention Model and its Use on Medical Risk Prediction.

Various deep learning models have been developed for different healthcare predictive tasks using Electronic Health Records and have shown promising performance. In these models, medical codes are often aggregated into visit representation without considering their heterogeneity, e.g., the same diagnosis might imply different healthcare concerns with different procedures or medications. Then the visits are often fed into deep learning models, such as recurrent neural networks, sequentially without considering the irregular temporal information and dependencies among visits. To address these limitations, we developed a Multilevel Self-Attention Model (MSAM) that can capture the underlying relationships between medical codes and between medical visits. We compared MSAM with various baseline models on two predictive tasks, i.e., future disease prediction and future medical cost prediction, with two large datasets, i.e., MIMIC-3 and PFK. In the experiments, MSAM consistently outperformed baseline models. Additionally, for future medical cost prediction, we used disease prediction as an auxiliary task, which not only guides the model to achieve a stronger and more stable financial prediction, but also allows managed care organizations to provide a better care coordination.

The Relationship between Metformin and Obstructive Sleep Apnea.

OBJECTIVES: This study aimed to assess if metformin had any associations with the prevalence of obstructive sleep apnea in an adult type 2 diabetes population in the Midwest. HYPOTHESIS: Use of metformin is associated with decreased prevalence of obstructive sleep apnea in a adult type 2 diabetes population. METHODS: A retrospective secondary database analysis was carried out with metformin use by patients with type 2 diabetes as the primary variable of interest and obstructive sleep apnea status as the primary outcome. A sample population of 9,853 type 2 diabetes patients with one year of follow-up was used. Other variables that were analyzed included age, gender, race, hypertension, Congestive Heart Failure, Hemoglobin A1c (HbA1c), and Body Mass Index. A p-value of <0.01 was considered significant. RESULTS: Metformin usage was not significantly associated with obstructive sleep apnea prevalence (Odds Ratio: 1.17, Confidence Interval: 1.00-1.36, p = 0.049), but trended in the direction where metformin usage was associated with having obstructive sleep apnea. Lower HbA1c was found to be significantly associated with lower prevalence of obstructive sleep apnea (p <0.001). The rest of the variables followed previously published associations. CONCLUSIONS: Metformin therapy may improve sleep quality, but it may not be through methods that reduce the likelihood of developing obstructive sleep apnea. Future studies that can prove causation about this association should be considered.

Advanced multivariate analysis to assess remediation of hydrocarbons in soils.

Accurate monitoring of degradation levels in soils is essential in order to understand and achieve complete degradation of petroleum hydrocarbons in contaminated soils. We aimed to develop the use of multivariate methods for the monitoring of biodegradation of diesel in soils and to determine if diesel contaminated soils could be remediated to a chemical composition similar to that of an uncontaminated soil. An incubation experiment was set up with three contrasting soil types. Each soil was exposed to diesel at varying stages of degradation and then analysed for key hydrocarbons throughout 161 days of incubation. Hydrocarbon distributions were analysed by Principal Coordinate Analysis and similar samples grouped by cluster analysis. Variation and differences between samples were determined using permutational multivariate analysis of variance. It was found that all soils followed trajectories approaching the chemical composition of the unpolluted soil. Some contaminated soils were no longer significantly different to that of uncontaminated soil after 161 days of incubation. The use of cluster analysis allows the assignment of a percentage chemical similarity of a diesel contaminated soil to an uncontaminated soil sample. This will aid in the monitoring of hydrocarbon contaminated sites and the establishment of potential endpoints for successful remediation.

Speech-evoked auditory brainstem responses reflect familial and cognitive influences.

Cortical function and related cognitive, language, and communication skills are genetically influenced. The auditory brainstem response to speech is linked to language skill, reading ability, cognitive skills, and speech-in-noise perception; however, the impact of shared genetic and environmental factors on the response has not been investigated. We assessed auditory brainstem responses to speech presented in quiet and background noise from (1) 23 pairs of same sex, same learning diagnosis siblings (Siblings), (2) 23 unrelated children matched on age, sex, IQ, and reading ability to one of the siblings (Reading-Matched), and (3) 22 pairs of unrelated children matched on age and sex but not on reading ability to the same sibling (Age/Sex-Matched). By quantifying response similarity as the intersubject response-to-response correlation for sibling pairs, reading-matched pairs, and age- and sex-matched pairs, we found that siblings had more similar responses than age- and sex-matched pairs and reading-matched pairs. Similarity of responses between siblings was as high as the similarity of responses collected from an individual over the course of the recording session. Responses from unrelated children matched on reading were more similar than responses from unrelated children matched only on age and sex, supporting previous data linking variations in auditory brainstem activity with variations in reading ability. These results suggest that auditory brainstem function can be influenced by siblingship and auditory-based communication skills such as reading, motivating the use of speech-evoked auditory brainstem responses for assessing risk of reading and communication impairments in family members.

The development of soil organic matter in restored biodiverse Jarrah forests of South-Western Australia as determined by ASE and GCMS.

BACKGROUND, AIM AND SCOPE: Soil organic matter (SOM) is known to increase with time as landscapes recover after a major disturbance; however, little is known about the evolution of the chemistry of SOM in reconstructed ecosystems. In this study, we assessed the development of SOM chemistry in a chronosequence (space for time substitution) of restored Jarrah forest sites in Western Australia. MATERIALS AND METHODS: Replicated samples were taken at the surface of the mineral soil as well as deeper in the profile at sites of 1, 3, 6, 9, 12, and 17 years of age. A molecular approach was developed to distinguish and quantify numerous individual compounds in SOM. This used accelerated solvent extraction in conjunction with gas chromatography mass spectrometry. A novel multivariate statistical approach was used to assess changes in accelerated solvent extraction (ASE)-gas chromatography-mass spectrometry (GCMS) spectra. This enabled us to track SOM developmental trajectories with restoration time. RESULTS: Results showed total carbon concentrations approached that of native forests soils by 17 years of restoration. Using the relate protocol in PRIMER, we demonstrated an overall linear relationship with site age at both depths, indicating that changes in SOM chemistry were occurring. CONCLUSIONS: The surface soils were seen to approach native molecular compositions while the deeper soil retained a more stable chemical signature, suggesting litter from the developing diverse plant community has altered SOM near the surface. Our new approach for assessing SOM development, combining ASE-GCMS with illuminating multivariate statistical analysis, holds great promise to more fully develop ASE for the characterisation of SOM.

Role of nutrients in the development of neonatal immune response.

Nutrients exert unique regulatory effects in the perinatal period that mold the developing immune system. The interactions of micronutrients and microbial and environmental antigens condition the post-birth maturation of the immune system, influencing reactions to allergens, fostering tolerance towards the emerging gastrointestinal flora and ingested antigens, and defining patterns of host defense against potential pathogens. The shared molecular structures that are present on microbes or certain plants, but not expressed by human cells, are recognized by neonatal innate immune receptors. Exposure to these activators in the environment through dietary intake in early life can modify the immune response to allergens and prime the adaptive immune response towards pathogens that express the corresponding molecular structures.

Cellular dielectric spectroscopy: a powerful new approach to label-free cellular analysis.

The past decade has seen a number of significant changes in identifying higher quality lead compounds earlier in the drug discovery process. Cell-based assay technologies yielding high-content information have emerged to achieve this goal. Although most of these systems are based on fluorescence detection, this article describes the development and application of an innovative cellular assay technology based on radio frequency spectrometry and bioimpedance measurements. Using this technique, the authors have discovered a link between cellular bioimpedance changes and receptor-mediated signal transduction events. By performing dielectric spectroscopy of cells across as pectrum of frequencies (1 KHz to 110 MHz), a series of receptor-specific, frequency-dependent impedance patterns is collected. These raw data patterns are used to determine the identity of the cellular receptor-signaling pathway being tested and to quantify stimulation endpoints and kinetics. The authors describe the application of this technology to the analysis of ligand-induced cellular responses mediated by the 3 major classes of G-protein-coupled receptors (GPCRs) and protein tyrosine kinase receptors. This single assay platform can be used with ease to monitor G(s), G(i), and G(q) GPCRs without the need for chimeric or promiscuous G-proteins, fluorophors, or tagged proteins. In contrast to other methods of monitoring cellular signal transduction, this approach provides high information content in a simplified, noninvasive, and biologically relevant fashion.

Clinical deterioration in pediatric asthmatic patients after September 11, 2001.

BACKGROUND: New York City residents were exposed to a variety of inhaled substances after the collapse of the World Trade Center. Exposure to these substances might lead to an increase in asthma severity, with residential distance from Ground Zero predictive of the degree of change. OBJECTIVE: We sought to assess the effect of the World Trade Center collapse on local pediatric asthmatic patients. METHODS: We retrospectively reviewed the charts of 205 pediatric patients with established asthma from a clinic in lower Manhattan's Chinatown. Clinical data were obtained for the year before and the year after September 11, 2001. Measurements included numbers of visits, asthma medication prescriptions, oral corticosteroid prescriptions, weekly doses of rescue inhaler, and peak expiratory flow rates. Residential zip codes were used to compare the asthma severity of patients living within and beyond a 5-mile radius of Ground Zero. RESULTS: After September 11, 2001, these children had more asthma-related clinic visits (P = .002) and received more prescriptions for asthma medications (P = .018). No significant differences in oral steroid or rescue inhaler use were noted. Those living within 5 miles had more clinic visits after September 11, 2001 (P = .013); the increase in clinic visits for patients living more than 5 miles from Ground Zero was not significant. Mean percent predicted peak expiratory flow rates decreased solely for those patients living within 5 miles of Ground Zero during the 3 months after September 11, 2001. CONCLUSIONS: Asthma severity worsened after September 11, 2001, in pediatric asthmatic patients living near Ground Zero. Residential proximity to Ground Zero was predictive of the degree of decrease in asthma health.

Cytotoxicity of antiviral nucleotides adefovir and cidofovir is induced by the expression of human renal organic anion transporter 1.

The transport of organic anions in proximal convoluted tubules plays an essential role in the active secretion of a variety of small molecules by the kidney. In addition to other anionic substrates, the human renal organic anion transporter 1 (hOATI) is capable of transporting the nucleotide analogs adefovir and cidofovir. To investigate the involvement of hOATI in the mechanism of nephrotoxicity associated with these two clinically important antiviral agents, Chinese hamster ovary (CHO) cells were stably transfected with hOATI cDNA. The resulting CHOhOAT cells showed probenecid-sensitive and pH-dependent uptake of p-aminohippurate (Km = 15.4 FtM, V,,, ..ax = 20.6 pmol/106 cells min), a prototypical organic anion substrate. In addition, the stably expressed hOATI mediated efficient transport of adefovir (Km, = 23.8 tLM, V, a,, = 46.0 pmol/106 cells min) and cidofovir (K, = 58.0 /iM, Vt,ax = 103 pmol/106 cells * min) such that the levels of intracellular metabolites of both nucleotides were > 1 00-fold higher in CHOh OAT cells than in parental CHO. Consequently, adefovir and cidofovir were approximately 500-fold and 400-fold more cytotoxic, respectively, in CHOh OAT cells compared to CHO. The cytotoxicity of both drugs in CHOh OAT cells was markedly reduced in the presence of hOATI inhibitors. The cyclic prodrug of cidofovir, which exhibits reduced in vivo nephrotoxicity, was a poor substrate for hOATI and showed only marginally increased cytotoxicity in CHOh OAT cells. In conclusion, these studies demonstrate that hOATI plays a critical role in the organ-specific toxicity of adefovir and cidofovir, and indicates that CHOh OAT cells may represent a useful in vitro model to investigate the potential nephrotoxicity of clinically relevant organic anion agents.