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1.
Am J Physiol Endocrinol Metab ; 326(5): E567-E576, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38477664

RESUMEN

Signaling through prostaglandin E2 EP3 receptor (EP3) actively contributes to the ß-cell dysfunction of type 2 diabetes (T2D). In T2D models, full-body EP3 knockout mice have a significantly worse metabolic phenotype than wild-type controls due to hyperphagia and severe insulin resistance resulting from loss of EP3 in extra-pancreatic tissues, masking any potential beneficial effects of EP3 loss in the ß cell. We hypothesized ß-cell-specific EP3 knockout (EP3 ßKO) mice would be protected from high-fat diet (HFD)-induced glucose intolerance, phenocopying mice lacking the EP3 effector, Gαz, which is much more limited in its tissue distribution. When fed a HFD for 16 wk, though, EP3 ßKO mice were partially, but not fully, protected from glucose intolerance. In addition, exendin-4, an analog of the incretin hormone, glucagon-like peptide 1, more strongly potentiated glucose-stimulated insulin secretion in islets from both control diet- and HFD-fed EP3 ßKO mice as compared with wild-type controls, with no effect of ß-cell-specific EP3 loss on islet insulin content or markers of replication and survival. However, after 26 wk of diet feeding, islets from both control diet- and HFD-fed EP3 ßKO mice secreted significantly less insulin as a percent of content in response to stimulatory glucose, with or without exendin-4, with elevated total insulin content unrelated to markers of ß-cell replication and survival, revealing severe ß-cell dysfunction. Our results suggest that EP3 serves a critical role in temporally regulating ß-cell function along the progression to T2D and that there exist Gαz-independent mechanisms behind its effects.NEW & NOTEWORTHY The EP3 receptor is a strong inhibitor of ß-cell function and replication, suggesting it as a potential therapeutic target for the disease. Yet, EP3 has protective roles in extrapancreatic tissues. To address this, we designed ß-cell-specific EP3 knockout mice and subjected them to high-fat diet feeding to induce glucose intolerance. The negative metabolic phenotype of full-body knockout mice was ablated, and EP3 loss improved glucose tolerance, with converse effects on islet insulin secretion and content.


Asunto(s)
Diabetes Mellitus Tipo 2 , Intolerancia a la Glucosa , Células Secretoras de Insulina , Animales , Ratones , Secreción de Insulina , Diabetes Mellitus Tipo 2/metabolismo , Dieta Alta en Grasa , Exenatida/farmacología , Intolerancia a la Glucosa/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Obesidad/metabolismo , Glucosa/metabolismo , Ratones Noqueados , Prostaglandinas/metabolismo , Prostaglandinas/farmacología
2.
J Am Acad Dermatol ; 90(2): e43-e56, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37943240

RESUMEN

BACKGROUND: For people with atopic dermatitis (AD) refractory to topical therapies, treatment with phototherapy and systemic therapies can be considered. Multiple biologic therapies and Janus kinase (JAK)inhibitors have been approved since 2014 to treat AD. These guidelines update the 2014 recommendations for management of AD with phototherapy and systemic therapies. OBJECTIVE: To provide evidence-based recommendations on the use of phototherapy and systemic therapies for AD in adults. METHODS: A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic agents, including biologics, oral JAK inhibitors, and other immunomodulatory medications. LIMITATIONS: Most randomized controlled trials of phototherapy and systemic therapies for AD are of short duration with subsequent extension studies, limiting comparative long-term efficacy and safety conclusions. CONCLUSIONS: We make strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib. We make conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids.


Asunto(s)
Dermatitis Atópica , Inhibidores de las Cinasas Janus , Adulto , Humanos , Ciclosporina/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Inhibidores de las Cinasas Janus/uso terapéutico , Metotrexato/uso terapéutico , Fototerapia
3.
J Am Acad Dermatol ; 90(2): 342-345, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37943241

RESUMEN

BACKGROUND: The summarized guidelines update the 2014 recommendations for the management of AD with phototherapy and systemic therapies. METHODS: A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of the evidence and formulating and grading recommendations. RESULTS: The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic therapies, including biologics, oral Janus Kinase inhibitors, and other immunomodulatory medications. CONCLUSIONS: The evidence supported strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib and conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids.


Asunto(s)
Dermatitis Atópica , Adulto , Humanos , Ciclosporina/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Metotrexato/uso terapéutico , Fototerapia
4.
J Cutan Pathol ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38837468

RESUMEN

An 11-year-old female was referred from an outside institution after a diagnostic biopsy and subsequent excision of a progressively enlarging reddish-brown nodule demonstrated features concerning for a balloon cell nevus with severe atypia versus a high-grade melanocytoma. Upon review of the initial biopsy specimen and molecular data, we favored the diagnosis to be consistent with a high-grade melanocytoma with balloon cell changes while considering the possibility of balloon cell melanoma due to concerning histopathologic and genetic abnormalities. In this case study, we discuss critical diagnostic considerations in this rare pediatric case and highlight important pathologic and clinical features of melanocytomas and balloon cell melanoma.

5.
Environ Res ; 259: 119475, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38945513

RESUMEN

Avian droppings (combination of fecal matter and urates) provide a non-lethal and non-invasive matrix for measuring pesticide exposures. In the field, droppings may be collected days or weeks after excretion and the persistence of pesticide residues in weathered droppings is not known. Thus, we studied the effects of weathering on pesticide residues in droppings. Domestic chicken (Gallus gallus domesticus) hens were used as a representative species for Order Galliformes. We collected droppings from hens before they were exposed to the pesticides (reference or pre-dose droppings ). Thereafter, the hens were orally administered encapsulated wheat seeds coated with Raxil® PRO Shield (containing the active ingredients imidacloprid, prothioconazole, metalaxyl, and tebuconazole) for consecutive 7 days. During this time, their droppings were collected on days 3, 5, and 8 from the start of the exposure period (post-dose droppings ). The pre-dose and post-dose droppings were weathered for up to 30 days in autumn and spring in shrubsteppe habitat. Droppings were analyzed using HPLC coupled to triple quad LC/MS for parent compound and metabolite residues. No pesticide or its metabolite residues were detected in the weathered reference droppings. No parent pesticide compounds were detected in weathered post-dose droppings but imidacloprid metabolites, imidacloprid-5-hydroxy and imidacloprid-olefin, and the prothioconazole metabolite, desthio-prothioconazole, were detected in all post-dose weathered samples from both seasons. The active ingredients metalaxyl and tebuconazole and their metabolites were not detected in any of the samples. Our results suggest that, depending on the pesticide, its concentration, and the environmental conditions, residues of some pesticides can be detected in droppings weathered for at least 30 days. Knowledge of pesticide persistence in weathered droppings can help refine the quality and quantity of fecal samples that are collected for monitoring pesticide exposures to birds.

6.
Pediatr Dermatol ; 41(3): 461-464, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38378007

RESUMEN

Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disorder impacting children and adults. In this single-center retrospective chart review of pediatric patients with LABD at a large tertiary referral center, we report the unifying and unique clinical features of 10 pediatric patients. Patients typically presented with the "cluster of jewels" sign (n = 6; 60%), mucous membrane involvement (n = 5; 50%) and had a mean disease duration of 38 months; six patients (60%) required inpatient admission for management of their skin disease, including all five patients who had mucous membrane involvement. Our findings suggest that pediatric LABD may be a disease with high morbidity and may be associated with severe complications when mucous membranes are involved.


Asunto(s)
Dermatosis Bullosa IgA Lineal , Humanos , Estudios Retrospectivos , Dermatosis Bullosa IgA Lineal/tratamiento farmacológico , Dermatosis Bullosa IgA Lineal/diagnóstico , Dermatosis Bullosa IgA Lineal/patología , Masculino , Femenino , Niño , Preescolar , Adolescente , Lactante
7.
Pediatr Dermatol ; 41(1): 46-50, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38014569

RESUMEN

BACKGROUND: Bier anemic spots, cyanosis with urticaria-like eruption (BASCULE) syndrome is a recently described entity with episodic urticarial lesions and white anemic halos on a background of erythrocyanosis, commonly affecting the lower extremities. Possible association with autonomic dysfunction remains poorly understood. Existing publications are limited, but the condition is suggested as highly underrecognized. OBJECTIVE: To further characterize clinical and epidemiologic data for BASCULE syndrome. METHODS: We performed an IRB-approved retrospective chart review on patients with BASCULE syndrome evaluated at Mayo Clinic from April 2021 to November 2022. RESULTS: A total of 17 patients were identified (13 female, 4 male). Median age of onset was 12 years (range 9-17). Lower extremities were involved in all patients (17). Most patients were symptomatic with pruritus (8) or burning pain (8); three were asymptomatic. Triggers were standing (11), hot showers or hot environments (7), or no clear trigger (4). Autonomic dysfunction was present in 10 patients. Treatment responses were observed from propranolol (3) and high-dose cetirizine (1). CONCLUSION: Novel epidemiologic data from 17 pediatric and young adult patients with BASCULE syndrome further supports an association with autonomic dysfunction and suggests a higher prevalence than previously acknowledged.


Asunto(s)
Enfermedades del Sistema Nervioso Autónomo , Exantema , Urticaria , Adulto Joven , Humanos , Masculino , Femenino , Niño , Adolescente , Estudios Retrospectivos , Urticaria/diagnóstico , Urticaria/tratamiento farmacológico , Urticaria/epidemiología , Síndrome , Cianosis
8.
J Pharmacol Exp Ther ; 386(2): 169-180, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36918276

RESUMEN

Type 2 diabetes (T2D) is a rising pandemic worldwide. Diet and lifestyle changes are typically the first intervention for T2D. When this intervention fails, the biguanide metformin is the most common pharmaceutical therapy. Yet its full mechanisms of action remain unknown. In this work, we applied an ultrahigh resolution, mass spectrometry-based platform for untargeted plasma metabolomics to human plasma samples from a case-control observational study of nondiabetic and well-controlled T2D subjects, the latter treated conservatively with metformin or diet and lifestyle changes only. No statistically significant differences existed in baseline demographic parameters, glucose control, or clinical markers of cardiovascular disease risk between the two T2D groups, which we hypothesized would allow the identification of circulating metabolites independently associated with treatment modality. Over 3000 blank-reduced metabolic features were detected, with the majority of annotated features being lipids or lipid-like molecules. Altered abundance of multiple fatty acids and phospholipids were found in T2D subjects treated with diet and lifestyle changes as compared with nondiabetic subjects, changes that were often reversed by metformin. Our findings provide direct evidence that metformin monotherapy alters the human plasma lipidome independent of T2D disease control and support a potential cardioprotective effect of metformin worthy of future study. SIGNIFICANCE STATEMENT: This work provides important new information on the systemic effects of metformin in type 2 diabetic subjects. We observed significant changes in the plasma lipidome with metformin therapy, with metabolite classes previously associated with cardiovascular disease risk significantly reduced as compared to diet and lifestyle changes. While cardiovascular disease risk was not a primary outcome of our study, our results provide a jumping-off point for future work into the cardioprotective effects of metformin, even in well-controlled type 2 diabetes.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Metformina , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Metformina/farmacología , Metformina/uso terapéutico , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Lipidómica , Control Glucémico , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/tratamiento farmacológico , Preparaciones Farmacéuticas , Biomarcadores , Glucemia/metabolismo
9.
J Am Acad Dermatol ; 89(1): 106-113, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36739091

RESUMEN

BACKGROUND: Pemphigoid gestationis (PG) and polymorphic eruption of pregnancy (PEP) may be similar morphologically but confer different maternal and fetal risks. Direct immunofluorescence is the gold standard test used to differentiate between the 2 diagnoses but is not always available. OBJECTIVE: To develop and validate a clinical scoring system to differentiate PG from PEP. METHODS: After developing a scoring system based on differentiating clinical factors reported in existing literature, we tested its diagnostic accuracy in a retrospective international multicenter validation study in collaboration with the European Academy of Dermatology and Venereology's Skin Diseases in Pregnancy Taskforce. RESULTS: Nineteen pregnancies (16 patients) affected by PG and 39 pregnancies (39 patients) affected by PEP met inclusion criteria. PG had a mean score of 4.6 (SD, 2.5) and PEP had a mean score of -0.3 (SD, 2.0). The area under the curve was 0.93 (95% CI, 0.86-1.00). Univariate analysis revealed that almost all criteria used in the scoring system were significantly different between the groups (P < .05), except for skip pregnancy and multiple gestations, which were then removed from the final scoring system. LIMITATIONS: Small retrospective study. CONCLUSION: The Pregnancy Dermatoses Clinical Scoring System may be useful to differentiate PG from PEP in resource-limited settings.


Asunto(s)
Exantema , Penfigoide Gestacional , Complicaciones del Embarazo , Femenino , Embarazo , Humanos , Penfigoide Gestacional/diagnóstico , Estudios Retrospectivos , Prurito/diagnóstico , Complicaciones del Embarazo/diagnóstico
10.
J Am Acad Dermatol ; 89(1): e1-e20, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36641009

RESUMEN

BACKGROUND: New evidence has emerged since the 2014 guidelines that further informs the management of atopic dermatitis (AD) with topical therapies. These guidelines update the 2014 recommendations for management of AD with topical therapies. OBJECTIVE: To provide evidence-based recommendations related to management of AD in adults using topical treatments. METHODS: A multidisciplinary workgroup conducted a systematic review and applied the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: The workgroup developed 12 recommendations on the management of AD in adults with topical therapies, including nonprescription agents and prescription topical corticosteroids (TCS), calcineurin inhibitors (TCIs), Janus kinase (JAK) inhibitors, phosphodiesterase-4 inhibitors (PDE-4), antimicrobials, and antihistamines. LIMITATIONS: The pragmatic decision to limit the literature review to English-language randomized trials may have excluded data published in other languages and relevant long-term follow-up data. CONCLUSIONS: Strong recommendations are made for the use of moisturizers, TCIs, TCS, and topical PDE-4 and JAK inhibitors. Conditional recommendations are made for the use of bathing and wet wrap therapy and against the use of topical antimicrobials, antiseptics, and antihistamines.


Asunto(s)
Antiinfecciosos Locales , Dermatitis Atópica , Fármacos Dermatológicos , Adulto , Humanos , Dermatitis Atópica/tratamiento farmacológico , Inhibidores de la Calcineurina/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Administración Tópica , Glucocorticoides/uso terapéutico , Antiinfecciosos Locales/uso terapéutico , Antagonistas de los Receptores Histamínicos/uso terapéutico
11.
J Am Acad Dermatol ; 89(1): 128-129, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36623556

RESUMEN

These guidelines update the 2014 recommendations for management of atopic dermatitis in adults with topical therapies. A multidisciplinary workgroup employed best practices for guideline development, including a systematic review of the evidence and application of the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading recommendations. The evidence on atopic dermatitis treatment supported strong recommendations for the use of nonprescription moisturizers, topical calcineurin inhibitors, topical corticosteroids, and topical PDE-4 and JAK inhibitors. Conditional recommendations are made for the use of bathing and wet wrap therapy and against the use of topical antimicrobials, antiseptics, and antihistamines.


Asunto(s)
Dermatitis Atópica , Fármacos Dermatológicos , Dermatología , Adulto , Humanos , Dermatitis Atópica/tratamiento farmacológico , Inhibidores de la Calcineurina/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Glucocorticoides
12.
J Cutan Pathol ; 50(4): 358-363, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36357351

RESUMEN

BACKGROUND: Pemphigoid gestationis (PG) and polymorphic eruption of pregnancy (PEP) are pregnancy-related dermatoses. Definitive diagnosis often relies upon histopathology and direct immunofluorescence (DIF). PG is associated with fetal and neonatal risks, while PEP confers minimal risk. OBJECTIVE: We aimed to compare histopathologic features to determine key differentiators. METHODS: A retrospective cohort study of PG and PEP cases, with accompanying DIF, conducted from 1995 to 2020. Skin biopsies were examined independently in a blinded fashion by two dermatopathologists for a list of histopathological features. RESULTS: Twenty-one cases of PG and 10 cases of PEP were identified. PG had significantly denser eosinophils than PEP (mean 155 vs. 48 cells/5 hpf; p < 0.018). PG was also noted to have eosinophilic spongiosis and eosinophils at the dermal-epidermal junction more frequently compared to PEP (80% PG vs. 10% PEP; p < 0.001). A mean cutoff value of 86 eosinophils and a mean optimal sensitivity and specificity of 81% and 83%, respectively, for eosinophils density's diagnostic power of PEP versus PG were achieved. Subepithelial separation was exclusively seen in PG (40% vs. 0%; p < 0.007). CONCLUSION: Eosinophilic spongiosis, eosinophilic epitheliotropism, and dense superficial dermal eosinophils were diagnostic of PG. Given overlapping clinicopathologic features, however, DIF results with clinicopathologic correlation, remain the gold standard.


Asunto(s)
Enfermedades Autoinmunes , Exantema , Penfigoide Gestacional , Complicaciones del Embarazo , Enfermedades de la Piel , Embarazo , Femenino , Recién Nacido , Humanos , Penfigoide Gestacional/diagnóstico , Penfigoide Gestacional/patología , Estudios Retrospectivos , Complicaciones del Embarazo/patología , Prurito/diagnóstico , Enfermedades de la Piel/patología
13.
Pediatr Dermatol ; 40(1): 84-89, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36373243

RESUMEN

BACKGROUND/OBJECTIVES: Pediatric lichen planus (LP) is rare with variable prevalence and atypical presentations compared to adults. Data on LP are lacking for the pediatric population in the United States. We present demographics, presentations, and treatments for a pediatric LP cohort. METHODS: We reviewed 26 patients diagnosed with LP at 20 years or younger. Treatment responses were defined as no response, partial response, and complete response. RESULTS: Demographics included 54% females and median diagnosis age of 16 years (range 6-20). Most patients presented with cutaneous LP (65%), with fewer having associated oral (23%), nail (7.7%), or genital (3.8%) involvement. Some had cutaneous-only LP (38%) or strictly mucosal LP (oral-only 19% and genital-only 15%). LP lesions were pruritic (50%), painful (19%), and/or asymptomatic (35%). Complete/partial responses occurred with medium-potency topical corticosteroids in cutaneous (n = 7; 64%), oral (n = 3; 75%), and genital LP (n = 3; 100%), with high/ultra-high potency topical corticosteroids in oral LP (n = 6; 86%), and with topical calcineurin inhibitors in genital LP (n = 2; 100%). Side effects were clobetasol-related oral candidiasis and biopsy-related penile depressed scar. Most patients with available follow-up achieved remission (n = 17; 81%). CONCLUSIONS: Pediatric LP usually presents in adolescence with cutaneous involvement and is symptomatic. However, patients frequently can have oral, genital, or nail lesions or may be asymptomatic, so they need thorough examinations and follow-up. Long-term remission is common due to treatment or natural disease course. Medium-potency corticosteroids are recommended for cutaneous, oral, and genital LP. Various other local and systemic therapies exist with successful treatment responses.


Asunto(s)
Liquen Plano Oral , Liquen Plano , Adulto , Femenino , Humanos , Niño , Adolescente , Adulto Joven , Masculino , Estudios de Seguimiento , Estudios Retrospectivos , Liquen Plano/diagnóstico , Liquen Plano/tratamiento farmacológico , Liquen Plano/patología , Liquen Plano Oral/diagnóstico , Liquen Plano Oral/tratamiento farmacológico , Corticoesteroides/uso terapéutico
14.
Am J Transplant ; 22(11): 2571-2585, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35897156

RESUMEN

Allogeneic islet transplantation is a promising experimental therapy for poorly controlled diabetes. Despite pharmacological immunosuppression, long-term islet engraftment remains elusive. Here, we designed a synthetic fusion transgene coupling PD-L1 and indoleamine dioxygenase [hereafter PIDO] whose constitutive expression prevents immune destruction of genetically engineered islet allograft transplanted in immunocompetent mice. PIDO expressing murine islets maintain robust dynamic insulin secretion in vitro and when transplanted in allogeneic hyperglycemic murine recipients reverse pre-existing streptozotocin-induced and autoimmune diabetes in the absence of pharmacological immunosuppression for more than 50 and 8 weeks, respectively, and is dependent on host CD4 competence. Additionally, PIDO expression in allografts preserves endocrine functional viability of islets and promotes a localized tolerogenic milieu characterized by the suppression of host CD8 T cell and phagocyte recruitment and accumulation of FOXP3+ Tregs. Furthermore, in the canine model of xenogeneic islet transplantation, muscle implanted PIDO-expressing porcine islets displayed physiological glucose-responsive insulin secretion competency in euglycemic recipient for up to 20 weeks. In conclusion, the PIDO transgenic technology enables host CD4+ T cell-modulated immune evasiveness and long-term functional viability of islet allo- and xenografts in immune-competent recipients without the need for pharmacological immune suppression and would allow for improved outcomes for tissue transplantation.


Asunto(s)
Diabetes Mellitus Tipo 1 , Trasplante de Islotes Pancreáticos , Islotes Pancreáticos , Animales , Perros , Humanos , Ratones , Aloinjertos , Antígeno B7-H1/metabolismo , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Terapia de Inmunosupresión , Islotes Pancreáticos/metabolismo , Ratones Endogámicos C57BL , Porcinos , Indolamina-Pirrol 2,3,-Dioxigenasa
15.
J Am Acad Dermatol ; 86(6): 1335-1336.e18, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35085682

RESUMEN

BACKGROUND: Studies found associations between atopic dermatitis (AD) and various comorbidities. OBJECTIVE: To appraise evidence of the association between AD and comorbidities among adults. METHODS: Our multidisciplinary work group conducted a systematic review of the association between AD and selected comorbidities. We applied the Grading of Recommendations, Assessment, Development, and Evaluation for prognosis approach for assessing the certainty of the evidence, providing statements of association based on the available evidence. RESULTS: Analysis of the evidence resulted in 32 statements. Clear evidence of the association of AD in adults and select allergic, atopic, immune-mediated mental health and bone health conditions and skin infections was identified. There is some evidence supporting an association between AD and substance use, attention deficit hyperactivity disorder, and elements of metabolic syndrome. Evidence suggests a small association with various cardiovascular conditions. The association between AD in adults and autism spectrum disorders, myocardial infarction, stroke, and metabolic syndrome is inconclusive. LIMITATIONS: This analysis is based on the best available evidence at the time it was conducted. This guideline does not make recommendations for screening or management of comorbidities in adults with AD. CONCLUSIONS: Clinicians should be aware of comorbidities associated with AD. Further research is needed to determine whether screening or management of comorbidities is beneficial for adults with AD.


Asunto(s)
Dermatitis Atópica , Dermatología , Síndrome Metabólico , Infarto del Miocardio , Adulto , Comorbilidad , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/epidemiología , Humanos , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Estados Unidos/epidemiología
16.
Pediatr Dermatol ; 39(5): 713-717, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35574616

RESUMEN

BACKGROUND/OBJECTIVES: Basal cell nevus syndrome (BCNS) is an autosomal dominant skin cancer predisposition syndrome associated with abnormal mineral metabolism, a risk factor for urinary stone disease (USD). However, no research investigating the association between BCNS and USD or other manifestations of abnormal mineral metabolism has been conducted. The objective of this study is to investigate the association between BCNS and conditions associated with disordered mineral metabolism including USD, hypothyroidism, and osteoporosis and compare them to prevalence in the general population to elucidate potential unknown manifestations of the condition. METHODS: This retrospective study examined medical records of adult and pediatric patients with confirmed BCNS from the Mayo Clinic database from 1 January 1995 to 12 January 2020. Records were surveyed for evidence of USD and other comorbidities potentially related to BCNS. The studied cohort included 100 adult patients and 5 pediatric patients. RESULTS: A total of 105 patients were included in this analysis, 10 of whom experienced confirmed USD, representing a prevalence of 10%. Six adult patients were identified with a diagnosis of osteoporosis, representing a prevalence of 6%. Thirteen adult patients were identified with a diagnosis of hypothyroidism, representing a prevalence of 13%. CONCLUSIONS: This study identified a prevalence of USD in BCNS patients comparable to estimates of national prevalence, indicating that known abnormalities in mineral metabolism likely do not increase the incidence of USD in BCNS patients. Additional findings included increased prevalence of hypothyroidism and decreased prevalence of osteoporosis in the BCNS cohort compared to national averages.


Asunto(s)
Síndrome del Nevo Basocelular , Hipotiroidismo , Osteoporosis , Neoplasias Cutáneas , Cálculos Urinarios , Enfermedades Urológicas , Adulto , Síndrome del Nevo Basocelular/complicaciones , Niño , Humanos , Hipotiroidismo/complicaciones , Hipotiroidismo/epidemiología , Osteoporosis/complicaciones , Osteoporosis/epidemiología , Estudios Retrospectivos , Neoplasias Cutáneas/diagnóstico , Cálculos Urinarios/complicaciones
17.
Mo Med ; 119(3): 208-212, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36035560

RESUMEN

Terminology Incarcerated is a nonspecific term which refers to a person confined to a jail, prison, or other institution. Inmate (preferred term: incarcerated person) refers to a person confined in a correctional facility (jail or prison). Individuals who are classified as being on probation, parole, or supervised release, remain under court supervision and are allowed to serve some or all of their sentence while residing in the community.2 Jails are under municipal or county jurisdictions and house persons awaiting trial, sentencing, or transfer to another facility; those who have violated parole or probation; and some individuals who have been sentenced to less than a year in custody.3 State and federal prisons generally house persons who have been sentenced to greater than one year in custody.3.


Asunto(s)
Prisiones , Justicia Social , Humanos
18.
J Proteome Res ; 20(1): 463-473, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33054244

RESUMEN

Metabolomics-the endpoint of the omics cascade-is increasingly recognized as a preferred method for understanding the ultimate responses of biological systems to stress. Flow injection electrospray (FIE) mass spectrometry (MS) has advantages for untargeted metabolic fingerprinting due to its simplicity and capability for high-throughput screening but requires a high-resolution mass spectrometer to resolve metabolite features. In this study, we developed and validated a high-throughput and highly reproducible metabolomics platform integrating FIE with ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) MS for analysis of both polar and nonpolar metabolite features from plasma samples. FIE-FTICR MS enables high-throughput detection of hundreds of metabolite features in a single mass spectrum without a front-end separation step. Using plasma samples from genetically identical obese mice with or without type 2 diabetes (T2D), we validated the intra and intersample reproducibility of our method and its robustness for simultaneously detecting alterations in both polar and nonpolar metabolite features. Only 5 min is needed to acquire an ultra-high resolution mass spectrum in either a positive or negative ionization mode. Approximately 1000 metabolic features were reproducibly detected and annotated in each mouse plasma group. For significantly altered and highly abundant metabolite features, targeted tandem MS (MS/MS) analyses can be applied to confirm their identity. With this integrated platform, we successfully detected over 300 statistically significant metabolic features in T2D mouse plasma as compared to controls and identified new T2D biomarker candidates. This FIE-FTICR MS-based method is of high throughput and highly reproducible with great promise for metabolomics studies toward a better understanding and diagnosis of human diseases.


Asunto(s)
Diabetes Mellitus Tipo 2 , Espectrometría de Masas en Tándem , Animales , Metabolómica , Ratones , Plasma , Reproducibilidad de los Resultados
19.
Am J Physiol Renal Physiol ; 321(1): F82-F92, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-34121451

RESUMEN

We used male BTBR mice carrying the Lepob mutation, which are subject to severe and progressive obesity and diabetes beginning at 6 wk of age, to examine the influence of one specific manifestation of sleep apnea, intermittent hypoxia (IH), on male urinary voiding physiology and genitourinary anatomy. A custom device was used to deliver continuous normoxia (control) or IH to wild-type and Lepob/ob (mutant) mice for 2 wk. IH was delivered during the 12-h inactive (light) period in the form of 90 s of 6% O2 followed by 90 s of room air. Continuous room air was delivered during the 12-h active (dark) period. We then evaluated genitourinary anatomy and physiology. As expected for the type 2 diabetes phenotype, mutant mice consumed more food and water, weighed more, and voided more frequently and in larger urine volumes. They also had larger bladder volumes but smaller prostates, seminal vesicles, and urethras than wild-type mice. IH decreased food consumption and increased bladder relative weight independent of genotype and increased urine glucose concentration in mutant mice. When evaluated based on genotype (normoxia + IH), the incidence of pathogenic bacteriuria was greater in mutant mice than in wild-type mice, and among mice exposed to IH, bacteriuria incidence was greater in mutant mice than in wild-type mice. We conclude that IH exposure and type 2 diabetes can act independently and together to modify male mouse urinary function. NEW & NOTEWORTHY Metabolic syndrome and obstructive sleep apnea are common in aging men, and both have been linked to urinary voiding dysfunction. Here, we show that metabolic syndrome and intermittent hypoxia (a manifestation of sleep apnea) have individual and combined influences on voiding function and urogenital anatomy in male mice.


Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Hipoxia/metabolismo , Síndrome Metabólico/metabolismo , Obesidad/metabolismo , Animales , Diabetes Mellitus Tipo 2/genética , Modelos Animales de Enfermedad , Hipoxia/genética , Resistencia a la Insulina/fisiología , Hígado/metabolismo , Masculino , Síndrome Metabólico/genética , Ratones , Obesidad/genética
20.
J Am Acad Dermatol ; 84(2): 432-470, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32738429

RESUMEN

Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the United States population. This guideline addresses important clinical questions that arise in psoriasis management and care and provides recommendations based on the available evidence. The treatment of psoriasis with topical agents and with alternative medicine will be reviewed, emphasizing treatment recommendations and the role of dermatologists in monitoring and educating patients regarding benefits as well as risks that may be associated. This guideline will also address the severity assessment methods of psoriasis in adults.


Asunto(s)
Terapias Complementarias/métodos , Fármacos Dermatológicos/administración & dosificación , Dermatología/métodos , Psoriasis/terapia , Academias e Institutos/normas , Administración Cutánea , Terapia Combinada/métodos , Terapia Combinada/normas , Terapias Complementarias/normas , Dermatología/normas , Medicina Basada en la Evidencia/métodos , Medicina Basada en la Evidencia/normas , Fundaciones/normas , Humanos , Educación del Paciente como Asunto/normas , Psoriasis/diagnóstico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Estados Unidos
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