Integrated Behavioral Health Prevention for Infants in Pediatric Primary Care: A Mixed-Methods Pilot Study.

OBJECTIVE: Pediatric primary care is a promising setting in which to deliver preventive behavioral health services to young children and their families. Integrated behavioral health care models typically emphasize treatment rather than prevention. This pilot study examined the efficacy of an integrated behavioral health preventive (IBH-P) intervention delivered by psychologists and focused on supporting parenting in low-income mothers of infants as part of well-child visits in the first 6 months of life. METHODS: Using a mixed-methods approach that included a pilot randomized clinical trial and post-intervention qualitative interviews, 137 mothers were randomly assigned to receive IBH-P or usual care. Self-report measures of parenting, child behavior, and stress were obtained at pre- and/or post-intervention. Direct observation of mother-infant interactions was conducted at post-intervention. RESULTS: No differences between groups were found on maternal attunement, knowledge of child development, nurturing parenting, or infant behavior. A secondary analysis on a subsample with no prior exposure to IBH-P with older siblings found that mothers in IBH-P reported increased self-efficacy relative to controls. In the qualitative interviews, mothers stated that they valued IBH-P, learning about their baby, liked the integration in primary care, and felt respected and comfortable with their provider. CONCLUSIONS: Findings are discussed in terms of the next steps in refining IBH-P approaches to prevention in primary care.

Oral Baricitinib in the Treatment of Cutaneous Lichen Planus.

Background: Cutaneous lichen planus (LP) is a recalcitrant, difficult-to-treat, inflammatory skin disease characterized by pruritic, flat-topped, violaceous papules on the skin. Baricitinib is an oral Janus kinase (JAK) 1/2 inhibitor that interrupts the signaling pathway of interferon (IFN)-γ, a cytokine implicated in the pathogenesis of LP. Methods: In this phase II trial, twelve patients with cutaneous LP received baricitinib 2 mg daily for 16 weeks, accompanied by in-depth spatial, single-cell, and bulk transcriptomic profiling of pre-and post-treatment samples. Results: An early and sustained clinical response was seen with 83.3% of patients responsive at week 16. Our molecular data identified a unique, oligoclonal IFN-γ, CD8+, CXCL13+ cytotoxic T-cell population in LP skin and demonstrate a rapid decrease in interferon signature within 2 weeks of treatment, most prominent in the basal layer of the epidermis. Conclusion: This study demonstrates the efficacy and molecular mechanisms of JAK inhibition in LP. Trial Registration Number : NCT05188521.

Community health worker navigation to improve allostatic load: The Integrated Population Health (IPOP) study.

Background: Social determinants of health (SDOH) and cumulative stress contribute to chronic disease development. The physiological response to repeated stressors typical of lower-income environments can be measured through allostatic load - a composite measure of cardiovascular, metabolic, and immune variables. Healthcare systems have employed patient navigation for social and medical needs to improve SDOH that has demonstrated limited impact on chronic disease outcomes. This study evaluates a novel community health worker navigation intervention developed using behavioral theories to improve access to social and medical services and provide social support for poverty stressed adults. Methods: The Integrated Population Health Study (IPOP) study is a randomized, parallel two arm study evaluating community health worker navigation in addition to an existing integrated population health program (IPOP CHW) as compared to Usual Care (population health program only, IPOP) on allostatic load and chronic disease risk factors. IPOP CHW participants receive a 10-month navigation intervention. Results: From 381 screened individuals, a total of 202 participants (age 58.15 ± 12.03 years, 74.75 % female, 79.21 % Black/African American, 17.33 % Hispanic) were enrolled and randomized to IPOP CHW (n = 100) or IPOP Only (n = 102). Conclusion: This study will evaluate whether CHW navigation, using a structured intervention based on health behavior theories, can effectively guide poverty stressed individuals to address social and medical needs to improve allostatic load-a composite of cumulative stress and physiological responses. Healthcare systems, nonprofit organizations, and governmental entities are interested in addressing SDOH to improve health, thus developing evidence-based interventions could have broad clinical and policy implications.

Different drug loading methods and antibiotic structure modulate the efficacy of polydopamine nanoparticles as drug nanocarriers.

The inefficient delivery of antimicrobials to their target is a significant factor contributing to antibiotic resistance. As such, smart nanomaterials that respond to external stimuli are extensively explored for precise drug delivery. Here, we investigate how drug loading methods and the structure of antibiotics impact the effectiveness of photothermally active polydopamine nanoparticles (PDNPs) as a laser-responsive drug delivery system. We examine two loading methods: in-synthesis and post-synthesis, and evaluate how laser irradiation affects drug release. Density functional theory calculations are also performed to gain deeper insights into the drug-PDNP interactions. Our findings point to the critical role of antibiotic structure and drug loading method in the laser-responsive capabilities of PDNPs as drug nanocarriers. Our study offers valuable insights for optimizing the design and efficiency of PDNP-based drug delivery systems.

An aging-susceptible circadian rhythm controls cutaneous antiviral immunity.

Aged skin is prone to viral infections, but the mechanisms responsible for this immunosenescent immune risk are unclear. We observed that aged murine and human skin expressed reduced levels of antiviral proteins (AVPs) and circadian regulators, including Bmal1 and Clock. Bmal1 and Clock were found to control rhythmic AVP expression in skin, and such circadian control of AVPs was diminished by disruption of immune cell IL-27 signaling and deletion of Bmal1/Clock genes in mouse skin, as well as siRNA-mediated knockdown of CLOCK in human primary keratinocytes. We found that treatment with the circadian-enhancing agents nobiletin and SR8278 reduced infection of herpes simplex virus 1 in epidermal explants and human keratinocytes in a BMAL1/CLOCK-dependent manner. Circadian-enhancing treatment also reversed susceptibility of aging murine skin and human primary keratinocytes to viral infection. These findings reveal an evolutionarily conserved and age-sensitive circadian regulation of cutaneous antiviral immunity, underscoring circadian restoration as an antiviral strategy in aging populations.

Granulomatous Panniculitis as a Complication of Subcutaneous Testosterone Pellet Therapy.

A 51-year-old man with a 3-year history of exogenous testosterone pellet injections to the left buttock presented for routine skin examination. While the patient reported recurrent drainage from the site of testosterone replacement therapy (TRT) injections, he continued to receive repeated implantations every 6 months. On physical examination, a 12-mm irregular, brown macule was identified within a poorly demarcated, ecchymotic, and fluctuant subcutaneous plaque on the left buttock with a sinus tract draining serosanguinous fluid. The pigmented lesion was biopsied, revealing malignant melanoma in situ; hence, a wide local excision was scheduled. During the procedure, necrotic subcutaneous fat was observed surrounding the site of biopsy, and a region measuring 18 cm2 approximately was debrided and submitted for pathologic evaluation. Histopathologic examination revealed a diffused subcutaneous granulomatous infiltrate with septal and lobular panniculitis and fat necrosis as well as peripherally palisading histiocytes and hemosiderin deposition (Figures 1A and B). Similar findings were observed in another specimen from the same segment of debrided tissue, compatible with granulomatous panniculitis. Periodic acid-Schiff (PAS), Gram's, and acid-fast bacilli (AFB) stains revealed no microorganisms. During surgical exploration, six foreign bodies were discovered and identified as undissolved testosterone pellets. The patient was referred to a wound care center, but ultimately lost to follow-up.

School Challenges and Services Related to Executive Functioning for Fully Included Middle Schoolers with Autism.

The educational services available for fully included middle schoolers with autism spectrum disorder (ASD) in the general education setting are not well known. Even less is known about how the executive functioning (EF) deficits of such youth are addressed in the classroom. The current study sought to identify the challenges, including EF, that middle schoolers with ASD face and the services that they receive on their Individualized Education Program (IEP), and also explore specific strategies used to build EF skills at school. A convenience data sample was obtained from focus groups with educational personnel (n = 15), and qualitative analyses of IEPs were conducted in middle schoolers with ASD with EF deficits (n = 23). Results confirmed that social communication and EF challenges are common. Multiple services and accommodations were identified, although EF challenges were rarely targeted on IEPs. Factors that may facilitate the success of EF strategies in the classroom are discussed.

An Aging-Susceptible Circadian Rhythm Controls Cutaneous Antiviral Immunity.

Aged skin is prone to viral infections, but the mechanisms responsible for this immunosenescent immune risk are unclear. We observed that aged murine and human skin expressed reduced antiviral proteins (AVPs) and circadian regulators including Bmal1 and Clock. Bmal1 and Clock were found to control rhythmic AVP expression in skin and such circadian-control of AVPs was diminished by disruption of immune cell interleukin 27 signaling and deletion of Bmal1/Clock genes in mouse skins, as well as siRNA-mediated knockdown of CLOCK in human primary keratinocytes. We found that treatment of circadian enhancing agents, nobiletin and SR8278, reduced infection of herpes simplex virus 1 (HSV1) in epidermal explants and human keratinocytes in a Bmal1/Clock-dependent manner. Circadian enhancing treatment also reversed susceptibility of aging murine skin and human primary keratinocytes to viral infection. These findings reveal an evolutionarily conserved and age-sensitive circadian regulation of cutaneous antiviral immunity, underscoring circadian restoration as an antiviral strategy in aging populations.

Intravenous immunoglobulin prophylaxis is associated with decreased rate of infection-related hospitalizations in multiple myeloma patients.

This study explored the efficacy of intravenous immunoglobulin (IVIG) prophylaxis in reducing infection-related hospitalizations (IRHs) in MM patients. This was a retrospective study of MM patients who received IVIG at Taussig Cancer Center between July 2009 and July 2021. The primary endpoint was rate of IRHs per patient-year on-IVIG versus off-IVIG. 108 patients were included. There was a significant difference in the primary endpoint of rate of IRHs per patient-year on-IVIG versus off-IVIG in the overall study population (0.81 vs. 1.08; Mean Difference [MD], -0.27; 95% Confidence Interval [CI], -0.57 to 0.03; p value [P] = 0.04). The subgroup of patients with a 1-year period of continuous IVIG (49, 45.3%), the subgroup with standard-risk cytogenetics (54, 50.0%) and the subgroup with 2 or more IRHs (67, 62.0%) all showed a significant reduction in IRHs while on-IVIG versus off-IVIG (0.48 vs. 0.78; MD, -0.30; 95% CI, -0.59 to 0.002; p = 0.03) and (0.65 vs. 1.01; MD, -0.36; 95% CI, -0.71 to -0.01; p = 0.02) and (1.04 vs. 1.43; MD, -0.39; 95% CI, -0.82 to 0.05; p = 0.04) respectively. IVIG showed significant benefit in reducing IRHs in the overall population and in multiple subgroups.

Laser-responsive sequential delivery of multiple antimicrobials using nanocomposite hydrogels.

Precise control of antimicrobial delivery can prevent the adverse effects of antibiotics. By exploiting the photothermal activity of polydopamine nanoparticles along with the distinct transition temperatures of liposomes, a near-infrared (NIR) laser can be used to control the sequential delivery of an antibiotic and its adjuvant from a nanocomposite hydrogel-preventing bacterial growth.

COVID-19 Vaccine Response in People with Multiple Sclerosis Treated with Dimethyl Fumarate, Diroximel Fumarate, Natalizumab, Ocrelizumab, or Interferon Beta Therapy.

BACKGROUND: Some multiple sclerosis (MS) disease-modifying therapies (DMTs) impair responses to vaccines, emphasizing the importance of understanding COVID-19 vaccine immune responses in people with MS (PwMS) receiving different DMTs. METHODS: This prospective, open-label observational study enrolled 45 participants treated with natalizumab (n = 12), ocrelizumab (n = 16), fumarates (dimethyl fumarate or diroximel fumarate, n = 11), or interferon beta (n = 6); ages 18-65 years inclusive; stable on DMT for at least 6 months. Responder rates, anti-SARS-CoV-2 spike receptor-binding domain IgG (anti-RBD) geometric mean titers (GMTs), antigen-specific T cells, and vaccination-related adverse events were evaluated at baseline and 8, 24, 36, and 48 weeks after first mRNA-1273 (Moderna) dose. RESULTS: At 8 weeks post vaccination, all natalizumab-, fumarate-, and interferon beta-treated participants generated detectable anti-RBD IgG titers, compared to only 25% of the ocrelizumab cohort. At 24 and 36 weeks post vaccination, natalizumab-, fumarate-, and interferon beta-treated participants continued to demonstrate detectable anti-RBD IgG titers, whereas participants receiving ocrelizumab did not. Anti-RBD GMTs decreased 81.5% between 8 and 24 weeks post vaccination for the non-ocrelizumab-treated participants, with no significant difference between groups. At 36 weeks post vaccination, ocrelizumab-treated participants had higher proportions of spike-specific T cells compared to other treatment groups. Vaccine-associated side effects were highest in the ocrelizumab arm for most symptoms. CONCLUSIONS: These results suggest that humoral response to mRNA-1273 COVID-19 vaccine is preserved and similar in PwMS treated with natalizumab, fumarate, and interferon beta, but muted with ocrelizumab. All DMTs had preserved T cell response, including the ocrelizumab cohort, which also had a greater risk of vaccine-related side effects.

Phase II Trial of Pembrolizumab and Anti-CD3 x Anti-HER2 Bispecific Antibody-Armed Activated T Cells in Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: A phase II study was conducted to evaluate the safety and efficacy of the combination of HER2 bispecific antibody (HER2Bi)-armed activated T cells (HER2 BAT) and programmed death 1 inhibitor, pembrolizumab. PATIENTS AND METHODS: Patients with metastatic castration-resistant prostate cancer (mCRPC) with 0 to 1 performance status and normal liver, kidney, and marrow function, pre- or post-docetaxel chemotherapy were eligible. Primary endpoint was 6-month progression-free survival (PFS). Peripheral blood mononuclear cells were obtained by a single apheresis, shipped to University of Virginia, activated with OKT3 and expanded for 14 days in IL2, harvested, and armed with HER2Bi and cryopreserved. HER2 BATs were infused twice weekly for 4 weeks and pembrolizumab was administered every 21 days for a maximum duration of 6 months starting 1 to 3 weeks prior to HER2 BATs infusion. RESULTS: Fourteen patients were enrolled with a median age of 69 (range 57-82 years) and median PSA of 143.4 (range 8.2-4210 ng/dL). Two patients had peritoneal metastases, 1 had lymph node (LN) only metastases and 11 had bone metastases of which 7 had bone and LN metastases. All were pretreated with androgen receptor axis targeted agents and 7 (50%) had prior docetaxel chemotherapy. The toxicities were grade1-2 infusion reactions with fever, chills, headaches, nausea and/or myalgias. Primary endpoint of 6 month PFS was achieved in 5 of 14 patients (38.5%; 95% confidence interval, 19.5%-76.5%). Median PFS was 5 months and median survival was 31.6 months. CONCLUSIONS: The safety and promising efficacy makes this combination worthy of future investigation in mCRPC.

Skin Cancer Knowledge, Attitudes and Sun Protection Practices in the Hispanic Population: A Cross-Sectional Survey.

Hispanics are more likely to be diagnosed with skin cancer at a later stage and experience worse overall survival than Whites. The objective of this cross-sectional study was to assess the skin cancer knowledge, attitudes, perceived risk, and sun protection practices among an underserved population in the Phoenix area. We recruited participants from the greater Phoenix area to undergo skin examination and complete a questionnaire. 208 participants were included. The majority were Hispanic (64.9%). Of this Hispanic group, most were from Mexico (87.9%). The Hispanic cohort had an overall mean skin cancer knowledge score of 3.68/6, the lowest of any other racial/ethnic group, but had the highest desire to learn more about skin cancer (64.6%, "strongly agree"). They were the most concerned about developing skin cancer (50.4%, "very concerned") but had relatively lower rates of sun protection practices (7.9% "always use" sunscreen, 22.0% "always use" sun-protective clothing). Limitations of this study include a small sample size, lack of validation for the skin cancer knowledge score, lack of season as a covariate in the multivariate analysis, lack of follow-up, and lack of robust skin cancer risk assessment. In conclusion, despite poorer skin cancer knowledge and sun protection practices, the Hispanic population had the highest concern for developing skin cancer and desire to learn more about skin cancer. Targeted and culturally relevant skin cancer and sun protection education for this group is needed.

Why does children's temperamental exuberance increase their vulnerability to externalizing symptoms? A process-oriented approach.

This study examined children's exposure to family adversity, hostile reactivity to parental conflict, and negative family representations as mediators of the prospective relation between their temperamental exuberance and externalizing symptoms. Participants included 243 preschool children (Mage = 4.60 years; 56% girls) and parents (48% Black; 16% Latinx) in a multi-method and multi-informant study with three annual measurement occasions. Structural equation model results specifically supported children's hostile reactivity to parental conflict and negative family representations as mediators. Exuberance predicted residualized increases in children's hostile reactivity and negative family representations over a 1-year period. In turn, children's hostile reactivity and negative family representations predicted their greater externalizing symptoms 1 year later after controlling for prior externalizing symptoms. Results are discussed in the context of their relation and refinement of temperamental models of developmental psychopathology.

The intestinal microbiota in colorectal cancer metastasis - Passive observer or key player?

The association between colorectal cancer (CRC) and alterations in intestinal microbiota has been demonstrated by several studies, and there is increasing evidence that bacteria are an important component of the tumour microenvironment. Bacteria may contribute to the development of CRC metastasis by signalling through metabolites, promoting epithelial-mesenchymal transition, creating an immunosuppressive microenvironment and through the impairment of the gut-vascular barrier. Host immunity and intestinal microbiome symbiosis play a key role in determining innate and adaptive immune responses at the local and systemic level. How this gut-systemic axis might contribute to the development of CRC metastasis is however unclear. Several clinical trials are investigating the impact of microbiome-targeted interventions on the systemic inflammatory response, treatment-related complications, and side effects. This review examines pre-clinical and clinical studies which have examined the role of microbes in relation to CRC metastasis, the mechanisms which may contribute to tumour dissemination, and directions for future work.

Buffer Components Incorporate into the Framework of Polyserotonin Nanoparticles and Films during Synthesis.

Polyserotonin nanoparticles (PSeNP) and films are bioinspired nanomaterials that have potential in biomedical applications and surface coatings. As studies on polyserotonin (PSe) nanoparticles and films are still in their infancy, synthetic pathways and material development for this new class of nanomaterial await investigation. Here, we sought to determine how different buffers used during the polymerization of serotonin to form nanoparticles and films impact the physicochemical properties of PSe materials. We show that buffer components are incorporated into the polymer matrix, which is also supported by density functional theory calculations. While we observed no significant differences between the elasticity of nanoparticles synthesized in the different buffers, the nanoscale surface properties of PSe films revealed dissimilarities in surface functional groups influenced by solvent molecules. Overall, the results obtained in this work can be used towards the rational design of PSe nanomaterials with tailored properties and for specific applications.

Secukinumab for the treatment of adult-onset pityriasis rubra pilaris: a single-arm clinical trial with transcriptomic analysis.

BACKGROUND: The pathogenesis of pityriasis rubra pilaris (PRP) is not completely understood, but interleukin (IL)-17 has been shown to play a critical role. There are no reliable immunomodulatory agents to treat PRP. We conducted an open-label, single-arm clinical trial of secukinumab, a monoclonal antibody that inhibits IL-17A, for the treatment of PRP. OBJECTIVES: To evaluate the clinical efficacy of secukinumab and define the transcriptomic landscape of PRP and its response to IL-17A blockade. METHODS: Twelve patients with PRP were recruited for an open-label trial of secukinumab. Patients received a 24-week course of secukinumab. The primary endpoint was a ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75) from baseline to week 28. Secondary endpoints included PASI 90, change in Physician's Global Assessment (PGA), and change in Dermatology Life Quality Index (DLQI). RNA sequencing was performed on lesional and nonlesional skin biopsies obtained at baseline and week 2. Sample groups were compared to identify differential gene expression and pathway enrichment. This trial was registered with ClinicalTrials.gov: 'Cosentyx (secukinumab) for the treatment of adult onset pityriasis rubra pilaris' - NCT03342573. RESULTS: At week 28, six of 11 patients (55%) achieved PASI 75, and three patients (27%) achieved PASI 90. PGA (P = 0.008) and DLQI scores (P = 0.010) showed significant improvement with treatment. No serious treatment-related adverse events were encountered. Treatment with secukinumab normalized transcriptional differences between lesional and nonlesional skin. Transcriptomic data from nonresponsive patients suggest that overactivity of innate immune pathways may be driving resistance to secukinumab. CONCLUSIONS: Secukinumab appears to be an effective treatment for PRP and warrants further investigation. PRP is a transcriptionally heterogeneous disease, reflecting its variable response to therapy. Agents targeting other IL-17 isoforms and innate immune mediators should be considered for future clinical trials. What is already known about this topic? The pathogenesis of pityriasis rubra pilaris is incompletely understood. Successful treatment has been reported with a variety of immunomodulatory agents, but disease is often refractory to therapy. Interleukin (IL)-17 is thought to drive keratinocyte proliferation and vascular dysfunction in this disease. A previous trial demonstrated efficacy of the anti-IL-17A drug ixekizumab for pityriasis rubra pilaris. What does this study add? Herein we describe the findings of a clinical trial of secukinumab, an anti-IL-17A monoclonal antibody, for the treatment of pityriasis rubra pilaris. Secukinumab was effective in treating pityriasis rubra pilaris. Our transcriptomic data give new insight into the expressional changes that occur in response to secukinumab and suggest mechanisms of treatment resistance.

Atypical jobs in psychology: Interview of Dr. Ellen Scrivner.

This publication highlights the career of Dr. Ellen Scrivner, a past president of American Psychological Association's (APA's) Division 18 and a pioneer in the specialty of police and public safety psychology. While psychologists' work with police and public safety may be typical now, Dr. Scrivner's journey and work were atypical when she embarked on her academic studies and began her career. Although initially intrigued by the science of changing behavior, she became more interested in changing the behaviors of organizations throughout her time as a psychology major in undergraduate studies. Dr. Scrivner followed this passion through her graduate studies and into her career. As a professional working with police in public safety, having a background in psychology has allowed Dr. Scrivner to better assist organizations in transitioning or creating different, coherent, and more effective patterns or practices. (PsycInfo Database Record (c) 2022 APA, all rights reserved).