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1.
Lymphat Res Biol ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38648290

ABSTRACT

Background: Breast cancer survivors (BCSs) have many lifelong symptoms of anxiety, depression, lymphedema, and fatigue that can be exacerbated by sleep disturbance. However, little is known about unique factors contributing to sleep disturbance among BCSs with lymphedema; this requires further investigation to offer appropriate support and treatment to these individuals. Therefore, the objective of this study was to capture perceptions and experiences of lymphedema and sleep among BCSs with lymphedema. Methods and Results: Qualitative description guided data collection and analysis as part of a mixed-methods investigation to characterize sleep disturbance among BCSs with and without lymphedema. The participants were interviewed one-on-one using a semistructured interview guide. Inductive content analysis was completed using an iterative coding approach, condensing, and categorizing to develop four themes. Seven BCSs with lymphedema participated. From their narratives, four themes were developed: (1) mind and body fatigue are exacerbated by sleep disturbance; (2) fatigue impacted fragile coping and support systems; (3) fatigue influenced self-identity and roles in society; and (4) self-management strategies were used for sleep health. Conclusion: The participants' perceptions of sleep disturbances' impact on their lives endorse further investigation into optimal interventions to improve sleep quality and modify these impactful findings to create a higher quality of life for survivorship.

2.
Lasers Med Sci ; 39(1): 94, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38532146

ABSTRACT

Objective of the study is to assess the effects of wound healing with a commercially available light emitting diode (LED) photo biomodulation (PBM) device that emits three wavelengths (465, 640 and 880nm) after ablative fractional laser (AFL) treatment to healthy skin on the bilateral inner biceps. We conducted a prospective intraindividual randomized controlled study with 25 volunteers. AFL treatment was performed on healthy skin of the bilateral inner biceps. Subjects applied the LED light device for 30 min to the assigned bicep 3 times a week over 4 weeks, beginning on day 0. Subjects were followed up on days 2, 4, 6, 9, 13, 20 and 27 for treatment with the PBM device, clinical digital photography of the test and control sites, and in-person subject assessment, with follow ups on days 34 and 55 for clinical photography and assessment. Three blinded evaluators were asked to determine which bicep healed faster between day 0 to day 13. Pain, discomfort, and itch were also assessed. The three blinded evaluators chose the treatment arm as the faster healed arm in greater than 50% of the images, although the results were not statistically significant. There was no statistically significant difference between test and control arms in terms of pain, discomfort and itch. In conclusion, PBM therapy has the potential to improve wound healing. In this study, a three wavelength PBM device resulted in some subjects achieving faster healing after AFL but the results were not statistically significant.


Subject(s)
Low-Level Light Therapy , Humans , Low-Level Light Therapy/methods , Prospective Studies , Wound Healing , Skin , Pain
3.
Curr Opin HIV AIDS ; 19(2): 79-86, 2024 03 01.
Article in English | MEDLINE | ID: mdl-38169427

ABSTRACT

PURPOSE OF REVIEW: Achieving ART-free remission without the need for lifelong antiretroviral treatment (ART) is a new objective in HIV-1 therapeutics. This review comprehensively examines the literature to evaluate whether the age at ART initiation in children with perinatal HIV-1 influences the size and decay of the HIV-1 reservoir. The insights gathered from this review serve to inform the field on the unique dynamics of HIV-1 reservoir size in perinatal HIV-1 infection as a function of age at ART initiation, as well as inform biomarker profiling and timing of ART-free remission strategies for children living with HIV-1 globally. RECENT FINDINGS: Recent studies demonstrate that initiating very early effective ART in neonates is feasible and limits HIV-1 reservoir size. The clinical relevance of limiting the HIV-1 reservoir size in perinatal infection was recently demonstrated in the Tatelo Study, which investigated a treatment switch from ART to two broadly neutralizing antibodies (bNAbs) in very early treated children. Low proviral reservoir size was associated with sustained virologic control for 24 weeks on bNAbs. SUMMARY: Immediate and early ART initiation for neonates and infants with perinatal HIV-1 is essential to restricting HIV-1 reservoir size that may enable ART-free remission.


Subject(s)
HIV Infections , HIV-1 , Female , Humans , Infant , Infant, Newborn , Pregnancy , Anti-Retroviral Agents/therapeutic use , Broadly Neutralizing Antibodies/therapeutic use , Proviruses/genetics
4.
Cancers (Basel) ; 15(15)2023 Jul 27.
Article in English | MEDLINE | ID: mdl-37568635

ABSTRACT

Neoplasm arising from the keratinocytes or melanocytes in the skin is the most prevalent type of cancer in the United States and worldwide. Since ultraviolet (UV) radiation may be a causing factor for several types of skin cancer, effective strategies to manage skin cancer include preventive measures such as minimizing exposure to UV and applying sunscreens. However, the effect of sunscreen in reducing skin cancer incidence remains uncertain. An alternative approach to prevent skin cancer is chemoprevention, which is defined as using either natural products or synthetic compounds to inhibit, delay, or reverse the development of cancer. Preclinical studies have demonstrated the effectiveness of multiple pharmacological agents and dietary supplements. However, whether preclinical findings can be translated into clinical application is unknown. This review evaluates the state of recent clinical trials investigating chemopreventive agents focusing on skin cancer to compare the target populations, interventions, endpoints, and outcomes of these trials. The ClinicalTrials and PubMed databases were searched for their available literature using the key words "skin cancer" and "chemoprevention". The objective of this review is to provide updated information on the effectiveness and side effects of promising chemopreventive agents in human subjects and to identify research gaps.

5.
J Invest Dermatol ; 143(8): 1388-1396, 2023 08.
Article in English | MEDLINE | ID: mdl-37294242

ABSTRACT

Cutaneous neurofibromas (cNFs) are benign tumors of the skin that affect >95% of adults with neurofibromatosis type 1. Despite their benign histology, cNFs can significantly impact QOL due to disfigurement, pain, and pruritus. There are no approved therapies for cNFs. Existing treatments are limited to surgery or laser-based treatments that have had mixed success and cannot be readily applied to a large number of tumors. We review cNF treatment options that are currently available and under investigation, discuss the regulatory considerations specific to cNFs, and propose strategies to improve cNF clinical trial design and standardize clinical trial endpoints.


Subject(s)
Neurofibroma , Neurofibromatosis 1 , Skin Neoplasms , Adult , Humans , Quality of Life , Neurofibroma/pathology , Neurofibroma/therapy , Neurofibromatosis 1/therapy , Skin Neoplasms/pathology , Pruritus
6.
J Invest Dermatol ; 143(8): 1397-1405, 2023 08.
Article in English | MEDLINE | ID: mdl-37330718

ABSTRACT

A consistent set of measurement techniques must be applied to reliably and reproducibly evaluate the efficacy of treatments for cutaneous neurofibromas (cNFs) in people with neurofibromatosis type 1 (NF1). cNFs are neurocutaneous tumors that are the most common tumor in people with NF1 and represent an area of unmet clinical need. This review presents the available data regarding approaches in use or development to identify, measure, and track cNFs, including calipers, digital imaging, and high-frequency ultrasound sonography. We also describe emerging technologies such as spatial frequency domain imaging and the application of imaging modalities such as optical coherence tomography that may enable the detection of early cNFs and prevention of tumor-associated morbidity.


Subject(s)
Neurofibroma , Neurofibromatosis 1 , Skin Neoplasms , Humans , Neurofibromatosis 1/diagnostic imaging , Neurofibroma/diagnostic imaging , Neurofibroma/pathology , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/pathology , Ultrasonography
7.
mBio ; 14(3): e0047723, 2023 06 27.
Article in English | MEDLINE | ID: mdl-37039646

ABSTRACT

Despite the extensive research on CD4 T cells within the context of Mycobacterium tuberculosis (Mtb) infections, few studies have focused on identifying and investigating the profile of Mtb-specific T cells within lung granulomas. To facilitate the identification of Mtb-specific CD4 T cells, we identified immunodominant epitopes for two Mtb proteins, namely, Rv1196 and Rv0125, using a Mauritian cynomolgus macaque model of Mtb infection, thereby providing data for the synthesis of MHC class II tetramers. Using tetramers, we identified Mtb-specific cells within different immune compartments, postinfection. We found that granulomas were enriched sites for Mtb-specific cells and that tetramer+ cells had increased frequencies of the activation marker CD69 as well as the transcription factors T-bet and RORγT, compared to tetramer negative cells within the same sample. Our data revealed that while the frequency of Rv1196 tetramer+ cells was positively correlated with the granuloma bacterial burden, the frequency of RORγT or T-bet within tetramer+ cells was inversely correlated with the granuloma bacterial burden, thereby highlighting the importance of having activated, polarized, Mtb-specific cells for the control of Mtb in lung granulomas. IMPORTANCE Tuberculosis, caused by the bacterial pathogen Mycobacterium tuberculosis, kills 1.5 million people each year, despite the existence of effective drugs and a vaccine that is given to infants in most countries. Clearly, we need better vaccines against this disease. However, our understanding of the immune responses that are necessary to prevent tuberculosis is incomplete. This study seeks to understand the functions of T cells that are specific for M. tuberculosis at the site of the disease in the lungs. For this, we developed specialized tools called MHC class II tetramers to identify those T cells that can recognize M. tuberculosis and applied the tools to the study of this infection in nonhuman primate models that mimic human tuberculosis. We demonstrate that M. tuberculosis-specific T cells in lung lesions are associated with control of the bacteria only when those T cells are expressing certain functions, thereby highlighting the importance of combining the identification of specific T cells with functional analyses. Thus, we surmise that these functions of specific T cells are critical to the control of infection and should be considered as a part of the development of vaccines against tuberculosis.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Animals , Humans , Mycobacterium tuberculosis/physiology , CD4-Positive T-Lymphocytes , Nuclear Receptor Subfamily 1, Group F, Member 3/genetics , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , Tuberculosis/microbiology , Granuloma , Macaca fascicularis , Transcription Factors/metabolism
8.
Front Clin Diabetes Healthc ; 4: 1026402, 2023.
Article in English | MEDLINE | ID: mdl-37008275

ABSTRACT

Background: Comorbidity between depression and type 2 diabetes is thought to arise from the joint effects of psychological, behavioral, and biological processes. Studies of monozygotic twins may provide a unique opportunity for clarifying how these processes inter-relate. This paper describes the rationale, characteristics, and initial findings of a longitudinal co-twin study aimed at examining the biopsychosocial mechanisms linking depression and risk of diabetes in mid-life. Methods: Participants in the Mood and Immune Regulation in Twins (MIRT) Study were recruited from the Mid-Atlantic Twin Registry. MIRT consisted of 94 individuals who do not have diabetes at baseline, representing 43 twin pairs (41 monozygotic and 2 dizygotic), one set of monozygotic triplets, and 5 individuals whose co-twin did not participate. A broad set of variables were assessed including psychological factors (e.g., lifetime history major depression (MD)); social factors (e.g., stress perceptions and experiences); and biological factors, including indicators of metabolic risk (e.g., BMI, blood pressure (BP), HbA1c) and immune functioning (e.g., pro- and anti-inflammatory cytokines), as well as collection of RNA. Participants were re-assessed 6-month later. Intra-class correlation coefficients (ICC) and descriptive comparisons were used to explore variation in these psychological, social, and biological factors across time and within pairs. Results: Mean age was 53 years, 68% were female, and 77% identified as white. One-third had a history of MD, and 18 sibling sets were discordant for MD. MD was associated with higher systolic (139.1 vs 132.2 mmHg, p=0.05) and diastolic BP (87.2 vs. 80.8 mmHg, p=0.002) and IL-6 (1.47 vs. 0.93 pg/mL, p=0.001). MD was not associated with BMI, HbA1c, or other immune markers. While the biological characteristics of the co-twins were significantly correlated, all within-person ICCs were higher than the within-pair correlations (e.g., HbA1c within-person ICC=0.88 vs. within-pair ICC=0.49; IL-6 within-person ICC=0.64 vs. within-pair=0.54). Among the pairs discordant for MD, depression was not substantially associated with metabolic or immune markers, but was positively associated with stress. Conclusions: Twin studies have the potential to clarify the biopsychosocial processes linking depression and diabetes, and recently completed processing of RNA samples from MIRT permits future exploration of gene expression as a potential mechanism.

9.
Nanomaterials (Basel) ; 13(5)2023 Mar 03.
Article in English | MEDLINE | ID: mdl-36903807

ABSTRACT

The R-carvedilol enantiomer, present in the racemic mixture of the chiral drug carvedilol, does not bind to the ß-adrenergic receptors, but exhibits skin cancer preventive activity. For skin delivery, R-carvedilol-loaded transfersomes were prepared using various ratios of drug, lipids, and surfactants, and characterized for particle size, zeta potential, encapsulation efficiency, stability, and morphology. Transfersomes were compared for in vitro drug release and ex vivo skin penetration and retention. Skin irritation was evaluated by viability assay on murine epidermal cells and reconstructed human skin culture. Single-dose and repeated-dose dermal toxicity was determined in SKH-1 hairless mice. Efficacy was evaluated in SKH-1 mice exposed to single or multiple ultraviolet (UV) radiations. Transfersomes released the drug at a slower rate, but significantly increased skin drug permeation and retention compared with the free drug. The transfersome with a drug-lipid-surfactant ratio of 1:3:0.5 (T-RCAR-3) demonstrated the highest skin drug retention and was selected for further studies. T-RCAR-3 at 100 µM did not induce skin irritation in vitro and in vivo. Topical treatment with T-RCAR-3 at 10 µM effectively attenuated acute UV-induced skin inflammation and chronic UV-induced skin carcinogenesis. This study demonstrates feasibility of using R-carvedilol transfersome for preventing UV-induced skin inflammation and cancer.

10.
Arch Dermatol Res ; 315(5): 1449-1452, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36456760

ABSTRACT

Cosmetic and laser procedures are increasingly popular among patients and are skills in which dermatologists are regarded as well trained. Most dermatology residents intend to incorporate cosmetic procedures into their practice and prefer to learn such procedures during residency through direct patient care. However, there are notable challenges in optimizing how residents are trained in cosmetic and laser dermatology. To address these barriers and elevate the practice of cosmetic dermatology in academic medicine, the Association of Academic Cosmetic Dermatology (AACD) was founded in 2021 as the lead professional society for dermatologists who direct the education of resident trainees in cosmetic and laser dermatology. The AACD, a group of board-certified dermatologists who teach cosmetic and laser dermatology to residents, aims to improve cosmetic dermatology education through collaboration, research, and advocacy.


Subject(s)
Dermatology , Internship and Residency , Humans , Dermatology/education , Curriculum , Surveys and Questionnaires
11.
Arch Dermatol Res ; 315(6): 1755-1762, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36463367

ABSTRACT

Cosmetic dermatology is a key subspecialty of academic dermatology. As such, academic centers are expected to demonstrate excellence in the teaching of cosmetic dermatology skills to trainees, the clinical delivery of cosmetic dermatology services to patients, and the performance of clinical research that advances knowledge and uncovers new therapies in cosmetic dermatology. The Association of Academic Cosmetic Dermatology (AACD), a newly formed medical professional society, includes as its principal aims the support of all of these areas. AACD is comprised of group of board-certified dermatologists who teach cosmetic and laser dermatology at US dermatology residency programs. An expert panel constituted by the AACD recently convened a workshop to review gaps pertaining to academic cosmetic dermatology. This panel considered needs and potential corrective initiatives in three domains: resident education, patient experience, and clinical research. The work of the panel was used to develop a roadmap, which was adopted by consensus, and which will serve to guide the AACD moving forward.


Subject(s)
Dermatology , Internship and Residency , Humans , Dermatology/education , Patient Care , Societies, Medical
12.
Lasers Surg Med ; 55(1): 46-60, 2023 01.
Article in English | MEDLINE | ID: mdl-36208102

ABSTRACT

BACKGROUND AND OBJECTIVES: Port wine birthmark, also known as port wine stain (PWS) is a skin discoloration characterized by red/purple patches caused by vascular malformation. PWS is typically treated by using lasers to destroy abnormal blood vessels. The laser heating facilitates selective photothermolysis of the vessels and attenuates quickly in the tissue due to high optical scattering. Therefore, residual abnormal capillaries deep in the tissue survive and often lead to the resurgence of PWS. Ultrasound (US) has also been proposed to treat PWS, however, it is nonselective with respect to the vasculature but penetrates deeper into the tissue. We aim to study the feasibility of a hybrid PWS treatment modality combining the advantages of both modalities. MATERIALS AND METHODS: In this manuscript, we propose a photoacoustic (PA) guided US focusing methodology for PWS treatment which combines the optical contrast-based selectivity with US penetration to focus the US energy onto the vasculature. The PA signals collected by the transducers, when time-reversed, amplified, and transmitted, converge onto the PWS, thus minimally affecting the neighboring tissue. We performed two- and three-dimensional simulations that mimic realistic transducers and medium properties in this proof of concept study. RESULTS: The time-reversed PA signals when transmitted from the transducers converged onto the vasculature, as expected, thus reducing the heating of the neighboring tissue. We observed that while the US focus is indeed affected due to experimental factors such as limited-view, large detector separation and finite detection bandwidth, and so forth, the US did focus completely or partially onto the vasculature demonstrating the feasibility of the proposed methodology. CONCLUSION: The results demonstrate the potential of the proposed methodology for PWS treatment. This treatment method can destroy the deeper capillaries while minimally heating the neighboring tissue, thus reducing the chances of the resurgence of PWS and as well as cosmetic scarring.


Subject(s)
Port-Wine Stain , Humans , Port-Wine Stain/diagnostic imaging , Port-Wine Stain/therapy , Feasibility Studies , Lasers , Cicatrix , Spectrum Analysis
13.
Front Hum Neurosci ; 16: 1006027, 2022.
Article in English | MEDLINE | ID: mdl-36405075

ABSTRACT

Port-wine birthmarks (PWBs) are caused by somatic, mosaic mutations in the G protein guanine nucleotide binding protein alpha subunit q (GNAQ) and are characterized by the formation of dilated, dysfunctional blood vessels in the dermis, eyes, and/or brain. Cutaneous PWBs can be treated by current dermatologic therapy, like laser intervention, to lighten the lesions and diminish nodules that occur in the lesion. Involvement of the eyes and/or brain can result in serious complications and this variation is termed Sturge-Weber syndrome (SWS). Some of the biggest hurdles preventing development of new therapeutics are unanswered questions regarding disease biology and lack of models for drug screening. In this review, we discuss the current understanding of GNAQ signaling, the standard of care for patients, overlap with other GNAQ-associated or phenotypically similar diseases, as well as deficiencies in current in vivo and in vitro vascular malformation models.

14.
Pediatr Rev ; 43(9): 507-516, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-36045161

ABSTRACT

Sturge-Weber syndrome (SWS) is a neurocutaneous disorder that classically presents with a triad of vascular anomalies affecting the skin, eyes, and brain. Previously, the trigeminal nerve distribution of a port-wine birthmark (PWB) of the face was used to identify risk of SWS. However, recent evidence has demonstrated that PWBs are vascular, not neurologic, in embryologic origin, and facial PWBs at highest risk for the brain involvement of SWS involve the forehead location. Furthermore, a PWB involving the upper or lower eyelid carries a risk of glaucoma, which requires lifelong monitoring. The gold standard of treatment for PWB is the pulsed dye laser, which has many advantages when started as early as possible in infancy. In this review, we discuss the locations of facial PWBs at risk for neurologic and ophthalmologic complications, the differential diagnosis of facial vascular birthmarks, recommendations for patient referral(s) when needed, and the advantages of early laser therapy when desired for the PWB. We also provide additional resources for pediatricians to support patients and their families.


Subject(s)
Glaucoma , Port-Wine Stain , Sturge-Weber Syndrome , Brain , Glaucoma/etiology , Humans , Port-Wine Stain/complications , Port-Wine Stain/diagnosis , Port-Wine Stain/therapy , Risk Assessment , Sturge-Weber Syndrome/diagnosis , Sturge-Weber Syndrome/therapy
15.
JAMA Dermatol ; 158(10): 1193-1201, 2022 Oct 01.
Article in English | MEDLINE | ID: mdl-35976634

ABSTRACT

Importance: Laser-assisted drug delivery (LADD) is used for various medical and cosmetic applications. However, there is insufficient evidence-based guidance to assist clinicians performing LADD. Objective: To develop recommendations for the safe and effective use of LADD. Evidence Review: A systematic literature review of Cochrane Central Register of Controlled Trials, Embase, and MEDLINE was conducted in December 2019 to identify publications reporting research on LADD. A multidisciplinary panel was convened to draft recommendations informed by the systematic review; they were refined through 2 rounds of Delphi survey, 2 consensus meetings, and iterative review by all panelists until unanimous consensus was achieved. Findings: Of the 48 published studies of ablative fractional LADD that met inclusion criteria, 4 were cosmetic studies; 21, oncologic; and 23, medical (not cosmetic/oncologic), and 6 publications of nonablative fractional LADD were included at the request of the expert panel, producing a total of 54 studies. Thirty-four studies (63.0%) were deemed to have low risk of bias, 17 studies (31.5%) had moderate risk, and 3 (5.5%) had serious risk. The key findings that informed the guidelines developed by the expert panel were as follows: LADD is safe in adults and adolescents (≥12 years) with all Fitzpatrick skin types and in patients with immunosuppression; it is an effective treatment for actinic keratosis, cutaneous squamous cell carcinoma in situ, actinic cheilitis, hypertrophic scars, and keloids; it is useful for epidermal and dermal analgesia; drug delivery may be increased through the application of heat, pressure, or occlusion, or by using an aqueous drug solution; laser settings should be selected to ensure that channel diameter is greater than the delivered molecule; antibiotic prophylaxis is not recommended, except with impaired wound healing; antiviral prophylaxis is recommended when treating the face and genitalia; and antifungal prophylaxis is not recommended. The guideline's 15 recommendations address 5 areas of LADD use: (I) indications and contraindications; (II) parameters to report; (III) optimization of drug delivery; (IV) safety considerations; and (V) prophylaxis for bacterial, viral, and fungal infections. Conclusions and Relevance: This systematic review and Delphi consensus approach culminated in an evidence-based clinical practice guideline for safe and effective use of LADD in a variety of applications. Future research will further improve our understanding of this novel treatment technique.


Subject(s)
Carcinoma, Squamous Cell , Skin Neoplasms , Adult , Humans , Adolescent , Pharmaceutical Preparations , Antifungal Agents , Lasers , Antiviral Agents
16.
Commun Biol ; 5(1): 710, 2022 07 16.
Article in English | MEDLINE | ID: mdl-35842455

ABSTRACT

Cerebellar volume is highly heritable and associated with neurodevelopmental and neurodegenerative disorders. Understanding the genetic architecture of cerebellar volume may improve our insight into these disorders. This study aims to investigate the convergence of cerebellar volume genetic associations in close detail. A genome-wide associations study for cerebellar volume was performed in a discovery sample of 27,486 individuals from UK Biobank, resulting in 30 genome-wide significant loci and a SNP heritability of 39.82%. We pinpoint the likely causal variants and those that have effects on amino acid sequence or cerebellar gene-expression. Additionally, 85 genome-wide significant genes were detected and tested for convergence onto biological pathways, cerebellar cell types, human evolutionary genes or developmental stages. Local genetic correlations between cerebellar volume and neurodevelopmental and neurodegenerative disorders reveal shared loci with Parkinson's disease, Alzheimer's disease and schizophrenia. These results provide insights into the heritable mechanisms that contribute to developing a brain structure important for cognitive functioning and mental health.


Subject(s)
Genome-Wide Association Study , Schizophrenia , Brain , Genome-Wide Association Study/methods , Humans , Mental Health , Polymorphism, Single Nucleotide , Schizophrenia/genetics
17.
Front Cardiovasc Med ; 9: 848768, 2022.
Article in English | MEDLINE | ID: mdl-35665255

ABSTRACT

Low socioeconomic status (SES) and living in a disadvantaged neighborhood are associated with poor cardiovascular health. Multiple lines of evidence have linked DNA methylation to both cardiovascular risk factors and social disadvantage indicators. However, limited research has investigated the role of DNA methylation in mediating the associations of individual- and neighborhood-level disadvantage with multiple cardiovascular risk factors in large, multi-ethnic, population-based cohorts. We examined whether disadvantage at the individual level (childhood and adult SES) and neighborhood level (summary neighborhood SES as assessed by Census data and social environment as assessed by perceptions of aesthetic quality, safety, and social cohesion) were associated with 11 cardiovascular risk factors including measures of obesity, diabetes, lipids, and hypertension in 1,154 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). For significant associations, we conducted epigenome-wide mediation analysis to identify methylation sites mediating the relationship between individual/neighborhood disadvantage and cardiovascular risk factors using the JT-Comp method that assesses sparse mediation effects under a composite null hypothesis. In models adjusting for age, sex, race/ethnicity, smoking, medication use, and genetic principal components of ancestry, epigenetic mediation was detected for the associations of adult SES with body mass index (BMI), insulin, and high-density lipoprotein cholesterol (HDL-C), as well as for the association between neighborhood socioeconomic disadvantage and HDL-C at FDR q < 0.05. The 410 CpG mediators identified for the SES-BMI association were enriched for CpGs associated with gene expression (expression quantitative trait methylation loci, or eQTMs), and corresponding genes were enriched in antigen processing and presentation pathways. For cardiovascular risk factors other than BMI, most of the epigenetic mediators lost significance after controlling for BMI. However, 43 methylation sites showed evidence of mediating the neighborhood socioeconomic disadvantage and HDL-C association after BMI adjustment. The identified mediators were enriched for eQTMs, and corresponding genes were enriched in inflammatory and apoptotic pathways. Our findings support the hypothesis that DNA methylation acts as a mediator between individual- and neighborhood-level disadvantage and cardiovascular risk factors, and shed light on the potential underlying epigenetic pathways. Future studies are needed to fully elucidate the biological mechanisms that link social disadvantage to poor cardiovascular health.

18.
Br J Dermatol ; 187(5): 730-742, 2022 11.
Article in English | MEDLINE | ID: mdl-35762296

ABSTRACT

BACKGROUND: There is limited evidence on the best available treatment options for capillary malformations (CMs), mainly due to the absence of uniform outcome measures in trials on therapies. A core outcome set (COS) enables standard reporting of trial outcomes, which facilitates comparison of treatment results. OBJECTIVES: To develop a core outcome domain set (CDS), as part of a core outcome set (COS), for clinical research on CMs. METHODS: Sixty-seven potentially relevant outcome subdomains were recognized based on the literature, focus group sessions, and input from the COSCAM working group. These outcome subdomains were presented in an online Delphi study to CM experts (medical specialists and authors of relevant literature) and (parents of) patients with CM (international patient associations). During three e-Delphi study rounds, the participants repeatedly scored the importance of these outcome subdomains on a seven-point Likert scale. Participants could also propose other relevant outcome subdomains. Consensus was defined as ≥ 80% agreement as to the importance of an outcome subdomain among both stakeholder groups. The CDS was finalized during an online consensus meeting. RESULTS: In total 269 participants from 45 countries participated in the first e-Delphi study round. Of these, 106 were CM experts from 32 countries, made up predominantly of dermatologists (59%) and plastic surgeons (18%). Moreover, 163 (parents of) patients with CM from 28 countries participated, of whom 58% had Sturge-Weber syndrome. During the two subsequent e-Delphi study rounds, 189 and 148 participants participated, respectively. After the entire consensus process, consensus was reached on 11 outcome subdomains: colour/redness, thickness, noticeability, distortion of anatomical structures, glaucoma, overall health-related quality of life, emotional functioning, social functioning, tolerability of intervention, patient satisfaction with treatment results, and recurrence. CONCLUSIONS: We recommend the CDS to be used as a minimum reporting standard in all future trials of CM therapy. Our next step will be to select suitable outcome measurement instruments to score the core outcome subdomains. What is already known about this topic? Besides physical and functional sequelae, capillary malformations (CMs) often cause emotional and social burden. The lack of uniform outcome measures obstructs proper evaluation and comparison of treatment strategies. As a result, there is limited evidence on the best available treatment options. The development of a core outcome set (COS) may improve standardized reporting of trial outcomes. What does this study add? A core outcome domain set (CDS), as part of a COS, was developed for clinical research on CMs. International consensus was reached on the recommended core outcome subdomains to be measured in CM trials: colour/redness, thickness, noticeability, distortion of anatomical structures, glaucoma, overall health-related quality of life, emotional functioning, social functioning, tolerability of intervention, patient satisfaction with treatment results, and recurrence. This CDS enables the next step in the development of a COS, namely to reach consensus on the core outcome measurement instruments to score the core outcome subdomains. What are the clinical implications of this work? The obtained CDS will facilitate standardized reporting of treatment outcomes, thereby enabling proper comparison of treatment results. This comparison is likely to provide more reliable information for patients about the best available treatment options.


Subject(s)
Glaucoma , Quality of Life , Humans , Consensus , Delphi Technique , Outcome Assessment, Health Care , Research Design , Treatment Outcome , Clinical Trials as Topic
19.
J Invest Dermatol ; 142(5): 1243-1252.e1, 2022 05.
Article in English | MEDLINE | ID: mdl-35461534

ABSTRACT

Over the past few years, high-resolution optical imaging technologies such as optical coherence tomography (OCT), reflectance confocal microscopy (RCM), and multiphoton microscopy (MPM) have advanced significantly as new methodologies for clinical research and for real-time detection, diagnosis, and therapy monitoring of skin diseases. Implementation of these technologies into clinical research and practice requires clinicians to have an understanding of their capabilities, benefits, and limitations. This concise review provides insights on the application of OCT, RCM, and MPM for clinical skin imaging through images acquired in vivo from the same lesions. The presented data are limited to pigmented lesions and basal cell carcinoma.


Subject(s)
Carcinoma, Basal Cell , Skin Neoplasms , Biopsy , Carcinoma, Basal Cell/diagnostic imaging , Carcinoma, Basal Cell/pathology , Humans , Microscopy, Confocal/methods , Research Design , Skin/diagnostic imaging , Skin/pathology , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/pathology , Tomography, Optical Coherence
20.
J Immigr Minor Health ; 24(2): 360-367, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34052978

ABSTRACT

This study investigated whether anti-immigrant sentiment leading up to the 2016 election increased risk of major depression among older U.S. immigrants. Drawing data from the Health and Retirement Study, we tested whether there was a disproportionate increase in major depression among U.S. immigrants than non-immigrants from 2014 to 2016 using a Difference in Difference approach. Older immigrants had a higher relative change in major depression from 2014 to 2016 than non-immigrants (RRR 1.35; 95% CI 1.06, 1.73). This relationship was driven by associations among those who are White (RRR 2.07; 95% CI 1.26, 3.41) or Hispanic (RRR 1.55; 95% CI 0.99, 2.40). Anti-immigrant sentiment leading up to the 2016 election was associated with an increase in major depression among older U.S. immigrants. Findings may help identify high-risk groups in future election years and inform treatment strategies for major depression that consider the influence of sociopolitical factors.


Subject(s)
Depressive Disorder, Major , Emigrants and Immigrants , Depression/epidemiology , Health Status , Hispanic or Latino , Humans , United States/epidemiology
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