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1.
Nutr Rev ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38994896

ABSTRACT

CONTEXT: Despite the progress toward gender equality in events like the Olympic Games and other institutionalized competitions, and the rising number of women engaging in physical exercise programs, scientific studies focused on establishing specific nutritional recommendations for female athletes and other physically active women are scarce. OBJECTIVE: This systematic review aimed to compile the scientific evidence available for addressing the question "What dietary strategies, including dietary and supplementation approaches, can improve sports performance, recovery, and health status in female athletes and other physically active women?" DATA SOURCES: The Pubmed, Web of Science, and Scopus databases were searched. DATA EXTRACTION: The review process involved a comprehensive search strategy using keywords connected by Boolean connectors. Data extracted from the selected studies included information on the number of participants and their characteristics related to sport practice, age, and menstrual function. DATA ANALYSIS: A total of 71 studies were included in this review: 17 focused on the analysis of dietary manipulation, and 54 focused on the effects of dietary supplementation. The total sample size was 1654 participants (32.5% categorized as competitive athletes, 30.7% as highly/moderately trained, and 37.2% as physically active/recreational athletes). The risk of bias was considered moderate, mainly for reasons such as a lack of access to the study protocol, insufficient description of how the hormonal phase during the menstrual cycle was controlled for, inadequate dietary control during the intervention, or a lack of blinding of the researchers. CONCLUSION: Diets with high carbohydrate (CHO) content enhance performance in activities that induce muscle glycogen depletion. In addition, pre-exercise meals with a high glycemic index or rich in CHOs increase CHO metabolism. Ingestion of 5-6 protein meals interspersed throughout the day, with each intake exceeding 25 g of protein favors anabolism of muscle proteins. Dietary supplements taken to enhance performance, such as caffeine, nitric oxide precursors, ß-alanine, and certain sport foods supplements (such as CHOs, proteins, or their combination, and micronutrients in cases of nutritional deficiencies), may positively influence sports performance and/or the health status of female athletes and other physically active women. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD480674.

3.
BMJ ; 383: e073980, 2023 10 26.
Article in English | MEDLINE | ID: mdl-37884289

ABSTRACT

Systemic lupus erythematosus (SLE) is a severe multisystem autoimmune disease that can cause injury in almost every body system. While considered a classic example of autoimmunity, it is still relatively poorly understood. Treatment with immunosuppressive agents is challenging, as many agents are relatively non-specific, and the underlying disease is characterized by unpredictable flares and remissions. This State of The Art Review provides a comprehensive current summary of systemic lupus erythematosus based on recent literature. In basic and translational science, this summary includes the current state of genetics, epigenetics, differences by ancestry, and updates about the molecular and immunological pathogenesis of systemic lupus erythematosus. In clinical science, the summary includes updates in diagnosis and classification, clinical features and subphenotypes, and current guidelines and strategies for treatment. The paper also provides a comprehensive review of the large number of recent clinical trials in systemic lupus erythematosus. Current knowns and unknowns are presented, and potential directions for the future are suggested. Improved knowledge of immunological pathogenesis and the molecular differences that exist between patients should help to personalize treatment, minimize side effects, and achieve better outcomes in this difficult disease.


Subject(s)
Lupus Erythematosus, Systemic , Humans , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Immunosuppressive Agents/therapeutic use , Autoimmunity
4.
J Arthroplasty ; 38(11): 2193-2201, 2023 11.
Article in English | MEDLINE | ID: mdl-37778918

ABSTRACT

OBJECTIVE: To develop evidence-based consensus recommendations for the optimal timing of hip and knee arthroplasty to improve patient-important outcomes including, but not limited to, pain, function, infection, hospitalization, and death at 1 year for patients with symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis of the hip or knee who have previously attempted nonoperative therapy, and for whom nonoperative therapy was ineffective, and who have chosen to undergo elective hip or knee arthroplasty (collectively referred to as TJA). METHODS: We developed 13 clinically relevant population, intervention, comparator, outcomes (PICO) questions. After a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence (high, moderate, low, or very low), and evidence tables were created. A Voting Panel, including 13 physicians and patients, discussed the PICO questions until consensus was achieved on the direction (for/against) and strength (strong/conditional) of the recommendations. RESULTS: The panel conditionally recommended against delaying TJA to pursue additional nonoperative treatment including physical therapy, nonsteroidal antiinflammatory drugs, ambulatory aids, and intraarticular injections. It conditionally recommended delaying TJA for nicotine reduction or cessation. The panel conditionally recommended delay for better glycemic control for patients who have diabetes mellitus, although no specific measure or level was identified. There was consensus that obesity by itself was not a reason for delay, but that weight loss should be strongly encouraged, and the increase in operative risk should be discussed. The panel conditionally recommended against delay in patients who have severe deformity or bone loss, or in patients who have a neuropathic joint. Evidence for all recommendations was graded as low or very low quality. CONCLUSION: This guideline provides evidence-based recommendations regarding the optimal timing of TJA in patients who have symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis for whom nonoperative therapy was ineffective to improve patient-important outcomes, including pain, function, infection, hospitalization, and death at 1 year. We acknowledge that the evidence is of low quality primarily due to indirectness and hope future research will allow for further refinement of the recommendations.


Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Hip , Osteoarthritis, Knee , Osteoarthritis , Rheumatology , Surgeons , Humans , Osteoarthritis, Hip/complications , Osteoarthritis, Hip/surgery , Osteoarthritis, Knee/complications , Osteoarthritis, Knee/surgery , Pain , United States
5.
Arthritis Care Res (Hoboken) ; 75(11): 2227-2238, 2023 11.
Article in English | MEDLINE | ID: mdl-37743767

ABSTRACT

OBJECTIVE: To develop evidence-based consensus recommendations for the optimal timing of hip and knee arthroplasty to improve patient-important outcomes including, but not limited to, pain, function, infection, hospitalization, and death at 1 year for patients with symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis of the hip or knee who have previously attempted nonoperative therapy, and for whom nonoperative therapy was ineffective, and who have chosen to undergo elective hip or knee arthroplasty (collectively referred to as TJA). METHODS: We developed 13 clinically relevant population, intervention, comparator, outcomes (PICO) questions. After a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence (high, moderate, low, or very low), and evidence tables were created. A Voting Panel, including 13 physicians and patients, discussed the PICO questions until consensus was achieved on the direction (for/against) and strength (strong/conditional) of the recommendations. RESULTS: The panel conditionally recommended against delaying TJA to pursue additional nonoperative treatment including physical therapy, nonsteroidal antiinflammatory drugs, ambulatory aids, and intraarticular injections. It conditionally recommended delaying TJA for nicotine reduction or cessation. The panel conditionally recommended delay for better glycemic control for patients who have diabetes mellitus, although no specific measure or level was identified. There was consensus that obesity by itself was not a reason for delay, but that weight loss should be strongly encouraged, and the increase in operative risk should be discussed. The panel conditionally recommended against delay in patients who have severe deformity or bone loss, or in patients who have a neuropathic joint. Evidence for all recommendations was graded as low or very low quality. CONCLUSION: This guideline provides evidence-based recommendations regarding the optimal timing of TJA in patients who have symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis for whom nonoperative therapy was ineffective to improve patient-important outcomes, including pain, function, infection, hospitalization, and death at 1 year. We acknowledge that the evidence is of low quality primarily due to indirectness and hope future research will allow for further refinement of the recommendations.


Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Hip , Osteoarthritis, Knee , Osteoarthritis , Rheumatology , Surgeons , Humans , Arthroplasty, Replacement, Knee/adverse effects , Osteoarthritis/therapy , Osteoarthritis, Hip/complications , Osteoarthritis, Hip/surgery , Osteoarthritis, Knee/complications , Osteoarthritis, Knee/therapy , Pain , United States
6.
Arthritis Rheumatol ; 75(11): 1877-1888, 2023 11.
Article in English | MEDLINE | ID: mdl-37746897

ABSTRACT

OBJECTIVE: To develop evidence-based consensus recommendations for the optimal timing of hip and knee arthroplasty to improve patient-important outcomes including, but not limited to, pain, function, infection, hospitalization, and death at 1 year for patients with symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis of the hip or knee who have previously attempted nonoperative therapy, and for whom nonoperative therapy was ineffective, and who have chosen to undergo elective hip or knee arthroplasty (collectively referred to as TJA). METHODS: We developed 13 clinically relevant population, intervention, comparator, outcomes (PICO) questions. After a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence (high, moderate, low, or very low), and evidence tables were created. A Voting Panel, including 13 physicians and patients, discussed the PICO questions until consensus was achieved on the direction (for/against) and strength (strong/conditional) of the recommendations. RESULTS: The panel conditionally recommended against delaying TJA to pursue additional nonoperative treatment including physical therapy, nonsteroidal antiinflammatory drugs, ambulatory aids, and intraarticular injections. It conditionally recommended delaying TJA for nicotine reduction or cessation. The panel conditionally recommended delay for better glycemic control for patients who have diabetes mellitus, although no specific measure or level was identified. There was consensus that obesity by itself was not a reason for delay, but that weight loss should be strongly encouraged, and the increase in operative risk should be discussed. The panel conditionally recommended against delay in patients who have severe deformity or bone loss, or in patients who have a neuropathic joint. Evidence for all recommendations was graded as low or very low quality. CONCLUSION: This guideline provides evidence-based recommendations regarding the optimal timing of TJA in patients who have symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis for whom nonoperative therapy was ineffective to improve patient-important outcomes, including pain, function, infection, hospitalization, and death at 1 year. We acknowledge that the evidence is of low quality primarily due to indirectness and hope future research will allow for further refinement of the recommendations.


Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis , Rheumatology , Surgeons , Humans , Osteoarthritis/therapy , Pain , United States
7.
J Rheumatol ; 50(9): 1103-1113, 2023 09.
Article in English | MEDLINE | ID: mdl-37399470

ABSTRACT

Type I interferon (IFN-I) is thought to play a role in many systemic autoimmune diseases. IFN-I pathway activation is associated with pathogenic features, including the presence of autoantibodies and clinical phenotypes such as more severe disease with increased disease activity and damage. We will review the role and potential drivers of IFN-I dysregulation in 5 prototypic autoimmune diseases: systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, primary Sjögren syndrome, and systemic sclerosis. We will also discuss current therapeutic strategies that directly or indirectly target the IFN-I system.


Subject(s)
Autoimmune Diseases , Interferon Type I , Lupus Erythematosus, Systemic , Humans , Autoimmunity , Interferon Type I/therapeutic use , Autoimmune Diseases/drug therapy , Lupus Erythematosus, Systemic/drug therapy , Interferons/metabolism , Antibodies , Phenotype
8.
Crit Rev Anal Chem ; 53(3): 689-717, 2023.
Article in English | MEDLINE | ID: mdl-34510987

ABSTRACT

Cocoa currently faces differentiation processes toward niches of specialty products, leading to greater competitiveness for producers who must compete with products differentiated by their integral quality regarding their organoleptic characteristics, such as fine-flavor cocoa and their functional characteristics. Quality is influenced by the genetic variety of the cultivars on the one hand, and the correct postharvest processing operations of cocoa seeds, on the other. During the transformation operations, the native chemical compounds of the seeds, especially proteins, carbohydrates, and polyphenols, are transformed and generate other compounds called flavor precursors, which are responsible for defining the product quality. In this sense, the analysis of the most relevant chemical compounds in cocoa is essential to guarantee higher overall quality. Similarly, understanding the fundamental aspects that affect fine-flavor cocoa production is crucial for improving transformation processes. Therefore, reliable and robust analytical techniques are required to detect and quantify these chemical compounds. This review highlights the main techniques used to analyze essential cocoa metabolites and derived products throughout all postharvest transformation stages: from cocoa seeds to chocolate bar, offering an overview of the sample preparation methods and the analytical and imaging methodologies often employed to characterize qualifying cocoa products.


Subject(s)
Cacao , Chocolate , Chocolate/analysis , Cacao/chemistry , Cacao/genetics , Seeds/chemistry
10.
Rev. andal. med. deporte ; 15(1): 22-28, Mar. 2022. tab, ilus
Article in English | IBECS | ID: ibc-209897

ABSTRACT

Objectives: To analyze the effects of core strength training on jump performance in female handball players. Methods: This is a randomized controlled trial. A total of 20 female handball players [age = 19.5 (1.4) years, height = 1.65 (0.05) m, body mass= 61.7 (9.3) kg] were recruited and split in: a core training group and a control group. The core training group participated in 8 weeks in-season of a core strength program (2 times/week). Pre- and post-intervention jump height, contact time and reactive strength index were collected during bilateral and unilateral drop vertical jumps. Frontal knee projection angle was measured only at unilateral drop jumps. Statistical significant difference was set at p ˂0.05. Results: group x time interactions were statistically significant for bilateral and unilateral jump height and for FKPA (<0.05). Core training group increased the bilateral jump height by 18.8% and showed a statistically significant difference in reactive strength index from pre-intervention [0.07 (0.03)] to post-intervention [0.10 (0.04)]. The core training group also improved the unilateral jump height by 20%, but only at the non-dominant leg. This improvement was accompanied by a statistically significant decrease in the frontal knee projection angle from pre-intervention [13.8 (7.4) degrees]to post-intervention [9.3 (6.1) degrees]. Control group did not obtain significant improvements in any of the assessed variables. There were no significant differences between groups in the baseline (p>0.05). Conclusion: A core strength training increased jump performance (drop jump) in female handball players.(AU)


Objetivos: Analizar los efectos del entrenamiento de la fuerza del core sobre el rendimiento del salto en jugadoras de balonmano. Métodos: Ensayo controlado aleatorio. 20 jugadoras de balonmano [edad = 19.5 (1.4) años, altura = 1.65 (0.05) m, masa corporal = 61.7 (9.3) kg]. Dos grupos: entrenamiento del core y grupo de control. El grupo entrenamiento del core realizó 2 veces por semana (8 semanas) un programa de fortalecimiento específico del core. Fueron registradas pre-post intervención, la altura de salto, el tiempo de contacto, el índice de fuerza reactiva en saltos verticales de caída bilateral y unilateral y el ángulo de proyección frontal de rodilla en saltos con recepción unilateral (p 0.05) ˂0.05. Resultados: las interacciones grupo x tiempo fueron estadísticamente significativas para la altura de salto bilateral y unilateral y la FKPA (p<0.05). El grupo de entrenamiento del core aumentó la altura de salto bilateral en un 18.8% y mostró diferencias significativas en el índice de fuerza reactiva desde la preintervención [0.07 (0.03)] hasta la post-intervención [0.10 (0.04)]. Asimismo, mejoró la altura de salto unilateral en un 20%, en la pierna no dominante. Esta mejora se acompañó de una disminución del ángulo de proyección frontal de la rodilla entre el pre [13.8 (7.4) grados] y el post [9.3 (6.1) grados]. El grupo de control no obtuvo mejoras significativas en las variables evaluadas. No hubo diferencias significativas entre los grupos antes de la intervención (p>0.05). Conclusiones: el fortalecimiento del core ha influido positivamente en el rendimiento del salto (drop jump) en las jugadoras.(AU)


Objetivos: Analisar os efeitos do treino de força central no desempenho de saltos em jogadores de andebol feminino. Métodos: Ensaio controlado aleatorizado. 20 jogadoras de andebol [idade = 19,5 anos (1,4), altura = 1,65m (0,05), massa corporal = 61,7kg (9,3)]. Dois grupos: grupo núcleo de formação e grupo de controlo. O grupo de formação principal realizou 2 vezes por semana (8 semanas) um programa específico de reforço do núcleo. Foram registados a intervenção pré-pós, altura do salto, tempo de contacto, índice de força reativa em saltos verticais bilaterais e unilaterais, e ângulo de projeção do joelho frontal em saltos de captura unilaterais (p ˂0.05). Resultados: As interações grupo x tempo foram estatisticamente significativas para a altura de salto bilateral e unilateral, e FKPA (p<0,05). O grupo de treino principal aumentou a altura do salto bilateral em 18,8% e mostrou diferenças significativas no índice de força reativa desde a pré-intervenção [0,07 (0,03)] até à pós-intervenção [0,10 (0,04)]. Para além disso, a altura do salto unilateral melhorou em 20% na perna não dominante. Esta melhoria foi acompanhada por uma diminuição do ângulo de projecção do joelho frontal entre os pré [13,8 (7,4) graus] e os pós [9,3 (6,1) graus]. O grupo de controlo não teve uma melhoria significativa nas variáveis avaliadas. Não houve diferenças significativas entre os grupos na linha de base (p>0,05). Conclusões: O reforço do núcleo teve um efeito positivo no desempenho dos jogadores no salto de queda.(AU)


Subject(s)
Humans , Female , Young Adult , Athletic Performance , Physical Functional Performance , 51654 , Muscle Strength , Resistance Training , Abdominal Muscles , Pelvis , Buttocks , Sports Medicine , Spain , 28599
11.
Transl Res ; 244: 47-55, 2022 06.
Article in English | MEDLINE | ID: mdl-35114420

ABSTRACT

Type I interferon (IFN) is critical in our defense against viral infections. Increased type I IFN pathway activation is a genetic risk factor for systemic lupus erythematosus (SLE), and a number of common risk alleles contribute to the high IFN trait. We hypothesized that these common gain-of-function IFN pathway alleles may be associated with protection from mortality in acute COVID-19. We studied patients admitted with acute COVID-19 (756 European-American and 398 African-American ancestry). Ancestral backgrounds were analyzed separately, and mortality after acute COVID-19 was the primary outcome. In European-American ancestry, we found that a haplotype of interferon regulatory factor 5 (IRF5) and alleles of protein kinase cGMP-dependent 1 (PRKG1) were associated with mortality from COVID-19. Interestingly, these were much stronger risk factors in younger patients (OR = 29.2 for PRKG1 in ages 45-54). Variants in the IRF7 and IRF8 genes were associated with mortality from COVID-19 in African-American subjects, and these genetic effects were more pronounced in older subjects. Combining genetic information with blood biomarker data such as C-reactive protein, troponin, and D-dimer resulted in significantly improved predictive capacity, and in both ancestral backgrounds the risk genotypes were most relevant in those with positive biomarkers (OR for death between 14 and 111 in high risk genetic/biomarker groups). This study confirms the critical role of the IFN pathway in defense against COVID-19 and viral infections, and supports the idea that some common SLE risk alleles exert protective effects in antiviral immunity.


Subject(s)
COVID-19 , Lupus Erythematosus, Systemic , Aged , Alleles , Antiviral Agents , COVID-19/genetics , Genetic Predisposition to Disease , Humans , Interferon Regulatory Factors/genetics , Interferon Regulatory Factors/metabolism , Interferon-alpha/genetics , Lupus Erythematosus, Systemic/genetics , Middle Aged , Polymorphism, Single Nucleotide
12.
Transl Res ; 245: 1-17, 2022 07.
Article in English | MEDLINE | ID: mdl-35158097

ABSTRACT

The complement system plays crucial roles in homeostasis and host defense against microbes. Deficiency of early complement cascade components has been associated with increased susceptibility to systemic lupus erythematosus (SLE), whereas excessive complement consumption is a hallmark of this disease. Although enhanced classical pathway activation by immune complexes was initially thought to be the main contributor to lupus nephritis (LN) pathogenesis, an increasing body of evidence has suggested the alternative and the lectin pathways are also involved. Therapeutic agents targeting complement activation have been used in LN patients and clinical trials are ongoing. We review the mechanisms by which complement system dysregulation contributes to renal injury in SLE and summarize the latest evidence on the use of anticomplement agents to manage this condition.


Subject(s)
Lupus Erythematosus, Systemic , Lupus Nephritis , Complement Inactivator Proteins/therapeutic use , Complement System Proteins , Humans , Kidney/pathology , Lupus Erythematosus, Systemic/complications
13.
J Invest Dermatol ; 142(3 Pt B): 793-803, 2022 03.
Article in English | MEDLINE | ID: mdl-35016780

ABSTRACT

Dysregulated IFN-1 responses play crucial roles in the development of multiple forms of autoimmunity. Many patients with lupus, systemic sclerosis, Sjogren's syndrome, and dermatomyositis demonstrate enhanced IFN-1 signaling. IFN-1 excess is associated with disease severity and autoantibodies and could potentially predict response to newer therapies targeting IFN-1 pathways. In this review, we provide an overview of the signaling pathway and immune functions of IFN-1s in health and disease. We also review the systemic autoimmune diseases classically associated with IFN-1 upregulation and current therapeutic strategies targeting the IFN-1 system.


Subject(s)
Interferon Type I , Lupus Erythematosus, Systemic , Scleroderma, Systemic , Sjogren's Syndrome , Autoimmunity , Humans , Interferon Type I/metabolism , Signal Transduction
14.
Arthritis Rheumatol ; 74(2): 284-294, 2022 02.
Article in English | MEDLINE | ID: mdl-34347939

ABSTRACT

OBJECTIVE: To evaluate seroreactivity and disease flares after COVID-19 vaccination in a multiethnic/multiracial cohort of patients with systemic lupus erythematosus (SLE). METHODS: Ninety SLE patients and 20 healthy controls receiving a complete COVID-19 vaccine regimen were included. IgG seroreactivity to the SARS-CoV-2 spike receptor-binding domain (RBD) and SARS-CoV-2 microneutralization were used to evaluate B cell responses; interferon-γ (IFNγ) production was measured by enzyme-linked immunospot (ELISpot) assay in order to assess T cell responses. Disease activity was measured by the hybrid SLE Disease Activity Index (SLEDAI), and flares were identified according to the Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI flare index. RESULTS: Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS-CoV-2 spike RBD compared to fully vaccinated controls. Twenty-six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti-double-stranded DNA antibody level prior to vaccination were associated with decreased vaccine responses. IgG seroreactivity to the SARS-CoV-2 spike RBD strongly correlated with the SARS-CoV-2 microneutralization titers and correlated with antigen-specific IFNγ production determined by ELISpot. In a subset of patients with poor antibody responses, IFNγ production was similarly diminished. Pre- and postvaccination SLEDAI scores were similar in both groups. Postvaccination flares occurred in 11.4% of patients; 1.3% of these were severe. CONCLUSION: In a multiethnic/multiracial study of SLE patients, 29% had a low response to the COVID-19 vaccine which was associated with receiving immunosuppressive therapy. Reassuringly, severe disease flares were rare. While minimal protective levels remain unknown, these data suggest that protocol development is needed to assess the efficacy of booster vaccination.


Subject(s)
Antirheumatic Agents/therapeutic use , COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Immunocompromised Host , Immunogenicity, Vaccine , Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , 2019-nCoV Vaccine mRNA-1273/therapeutic use , Ad26COVS1/therapeutic use , Adult , Antibodies, Viral/immunology , B-Lymphocytes/immunology , BNT162 Vaccine/therapeutic use , COVID-19 Vaccines/immunology , Case-Control Studies , Cohort Studies , Enzyme-Linked Immunospot Assay , Female , Glucocorticoids/therapeutic use , Humans , Immunoglobulin G/immunology , Interferon-gamma/immunology , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/physiopathology , Male , Middle Aged , Neutralization Tests , Prednisone/therapeutic use , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology , Symptom Flare Up
15.
medRxiv ; 2021 Nov 02.
Article in English | MEDLINE | ID: mdl-34751274

ABSTRACT

Type I interferon (IFN) is critical in our defense against viral infections. Increased type I IFN pathway activation is a genetic risk factor for systemic lupus erythematosus (SLE), and a number of common risk alleles contribute to the high IFN trait. We hypothesized that these common gain-of-function IFN pathway alleles may be associated with protection from mortality in acute COVID-19. We studied patients admitted with acute COVID-19 (756 European-American and 398 African-American ancestry). Ancestral backgrounds were analyzed separately, and mortality after acute COVID-19 was the primary outcome. In European-American ancestry, we found that a haplotype of interferon regulatory factor 5 (IRF5) and alleles of protein kinase cGMP-dependent 1 (PRKG1) were associated with mortality from COVID-19. Interestingly, these were much stronger risk factors in younger patients (OR=29.2 for PRKG1 in ages 45-54). Variants in the IRF7 and IRF8 genes were associated with mortality from COVID-19 in African-American subjects, and these genetic effects were more pronounced in older subjects. Combining genetic information with blood biomarker data such as C-reactive protein, troponin, and D-dimer resulted in significantly improved predictive capacity, and in both ancestral backgrounds the risk genotypes were most relevant in those with positive biomarkers (OR for death between 14 and 111 in high risk genetic/biomarker groups). This study confirms the critical role of the IFN pathway in defense against COVID-19 and viral infections, and supports the idea that some common SLE risk alleles exert protective effects in anti-viral immunity. BACKGROUND: We find that a number of IFN pathway lupus risk alleles significantly impact mortality following COVID-19 infection. These data support the idea that type I IFN pathway risk alleles for autoimmune disease may persist in high frequency in modern human populations due to a benefit in our defense against viral infections. TRANSLATIONAL SIGNIFICANCE: We develop multivariate prediction models which combine genetics and known biomarkers of severity to result in greatly improved prediction of mortality in acute COVID-19. The specific associated alleles provide some clues about key points in our defense against COVID-19.

16.
Rheum Dis Clin North Am ; 47(3): 379-393, 2021 08.
Article in English | MEDLINE | ID: mdl-34215369

ABSTRACT

T-cell dysregulation has been implicated in the loss of tolerance and overactivation of B cells in systemic lupus erythematosus (SLE). Recent studies have identified T-cell subsets and genetic, epigenetic, and environmental factors that contribute to pathogenic T-cell differentiation, as well as disease pathogenesis and clinical phenotypes in SLE. Many therapeutics targeting T-cell pathways are under development, and although many have not progressed in clinical trials, the recent approval of the calcineurin inhibitor voclosporin is encouraging. Further study of T-cell subsets and biomarkers of T-cell action may pave the way for specific targeting of pathogenic T-cell populations in SLE.


Subject(s)
Lupus Erythematosus, Systemic , T-Lymphocytes , B-Lymphocytes , Humans , Lupus Erythematosus, Systemic/drug therapy
17.
Lupus ; 30(10): 1671-1678, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34192954

ABSTRACT

INTRODUCTION: Activation of the complement pathway by immune complexes is a key feature of systemic lupus erythematosus (SLE) and SLE glomerulonephritis, which translates into low levels of C3 and C4 during active disease. C3 glomerulonephritis (C3GN) is part of a broader group of rare renal diseases, the C3 glomerulopathies, characterized by prominent C3 accumulation in the glomeruli with minimal to no immunoglobulin (Ig) deposition secondary to dysregulation of the alternative pathway of the complement system. Distinguishing lupus nephritis from other complement-mediated kidney disorders, including C3GN, represents a diagnostic challenge with potential therapeutic implications. METHODS: We report an unusual case of a 55-year-old woman with SLE and previous biopsy-proven class IV lupus nephritis, subsequently diagnosed with C3GN. Furthermore, we review the available literature published from January 2010-March 2021 on the clinical features and management of C3GN in the setting of SLE. RESULTS: In addition to our case, very few reports exist in the literature regarding C3GN in association with SLE. The underlying pathogenic mechanism of C3GN consists of dysregulation of the alternative pathway of the complement system, either due to genetic variation in complement-related genes or to acquired autoantibodies targeting C3 or C5 convertases; the latter mechanism could explain the occurrence of C3GN in the setting of autoimmune diseases, although it was not definitively identified in our patient or others with SLE. Similar to some of the previous reports, after suboptimal renal response on mycophenolate mofetil and rituximab, our patient has been successfully treated with eculizumab, thus far with >50% improvement in proteinuria. CONCLUSIONS: C3GN represents an additional mechanism of renal injury in SLE mediated by alternative complement pathway dysregulation. Although rare, patients with SLE and persistent proteinuria with very low C3 would benefit from expedited renal biopsy to evaluate for C3GN as well as genetic testing, since this entity could require a different therapeutic approach.


Subject(s)
Glomerulonephritis, Membranoproliferative , Glomerulonephritis , Kidney Diseases , Lupus Erythematosus, Systemic , Lupus Nephritis , Antibodies, Monoclonal, Humanized , Complement C3 , Female , Glomerulonephritis/drug therapy , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Lupus Nephritis/diagnosis , Lupus Nephritis/drug therapy , Middle Aged , Proteinuria
18.
Data Brief ; 37: 107194, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34150964

ABSTRACT

This data article is associated with the research article "Technical and environmental analysis on the power production from residual biomass using hydrogen as energy vector". This paper shows the procedure to calculate the Life Cycle Inventory (LCI) of the foreground system to perform the Life Cycle Assessment (LCA) of the power production from sugarcane press-mud. Said process encompasses four main stages: i) bioethanol production; ii) bioethanol purification; iii) syngas production and purification; and iv) power production. Additionally, other processes such as biomethane production and manufacturing of catalyst were included. Foreground data related to bioethanol production was gathered from experimental procedures at lab-scale. While foreground data, concerning the other processes such as bioethanol purification, syngas production and purification, power production, and biomethane production, was built by using material and energy flows obtained from Aspen Plus®. Lastly, LCI of the catalyst manufacturing was built based on literature review and the approach stated by Ecoinvent. All the inventories are meaningful to carry out future environmental assessments involving sustainable energy systems based on bioethanol, biomethane, or hydrogen.

19.
Lancet Rheumatol ; 3(8): e585-e594, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34075358

ABSTRACT

BACKGROUND: Patients with systemic lupus erythematosus (SLE) are at risk of developing COVID-19 due to underlying immune abnormalities and regular use of immunosuppressant medications. We aimed to evaluate the presence of SARS-CoV-2 IgG antibodies in patients with SLE with or without previous COVID-19-related symptoms or RT-PCR-confirmed SARS-CoV-2 infection. METHODS: For this analysis, we included patients with SLE from two cohorts based in New York City: the Web-based Assessment of Autoimmune, Immune-Mediated and Rheumatic Patients during the COVID-19 pandemic (WARCOV) study; and the NYU Lupus Cohort (a prospective registry of patients at NYU Langone Health and NYC Health + Hospitals/Bellevue). Patients in both cohorts were tested for SARS-CoV-2 IgG antibodies via commercially available immunoassays, processed through hospital or outpatient laboratories. Patients recruited from the NYU Lupus Cohort, referred from affiliated providers, or admitted to hospital with COVID-19 were tested for SARS-CoV-2 IgG antibodies as part of routine surveillance during follow-up clinical visits. FINDINGS: 329 patients with SLE were included in this analysis, 146 from the WARCOV study and 183 from the NYU Lupus Cohort, and were tested for SARS-CoV-2 antibodies between April 29, 2020, and Feb 9, 2021. 309 (94%) were women and 91 (28%) were of Hispanic ethnicity. 51 (16%) of 329 patients had a positive SARS-CoV-2 IgG antibody test. Seropositive patients were more likely than seronegative patients to be Hispanic (24 [47%] of 51 vsz 67 [24%] of 278). Other demographic variables, SLE-specific factors, and immunosuppressant use were not associated with SARS-CoV-2 positivity. Of the 29 patients with COVID-19 previously confirmed by RT-PCR, 18 (62%) were on immunosuppressants; 24 (83%) of 29 patients tested positive for SARS-CoV-2 IgG antibodies. Of 17 patients who had symptoms of COVID-19 but negative concurrent RT-PCR testing, one (6%) developed an antibody response. Of 26 patients who had COVID-19-related symptoms but did not undergo RT-PCR testing, six (23%) developed an antibody response. Of 83 patients who had no symptoms of COVID-19 and no RT-PCR testing, four (5%) developed an antibody response. Among 36 patients who were initially SARS-CoV-2 IgG positive, the majority maintained reactivity serially (88% up to 10 weeks, 83% up to 20 weeks, and 80% up to 30 weeks). Seven (70%) of ten patients with confirmed COVID-19 had antibody positivity beyond 30 weeks from disease onset. INTERPRETATION: Most patients with SLE and confirmed COVID-19 were able to produce and maintain a serological response despite the use of a variety of immunosuppressants, providing reassurance about the efficacy and durability of humoral immunity and possible protection against re-infection with SARS-CoV-2. FUNDING: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, and Bloomberg Philanthropies COVID-19 Response Initiative Grant.

20.
Medicine (Baltimore) ; 100(13): e25325, 2021 Apr 02.
Article in English | MEDLINE | ID: mdl-33787627

ABSTRACT

ABSTRACT: Minor salivary gland biopsy (MSGB) is often used in patients lacking specific autoantibodies (seronegative patients) to confirm the presence of focal lymphocytic sialadenitis (FLS), which would suggest a diagnosis of Sjogren syndrome. There are no current guidelines indicating when to refer patients for MSGB. The objective of our study was to ascertain distinguishing clinical and laboratory features among individuals with sicca symptoms based on their serologic and histopathologic status, and to identify factors associated with FLS.Using a cross-sectional study design, patients ages 18 years or older with sicca symptoms who had MSGB performed at the University of Iowa from January 2000 to December 2016 were selected for chart reviews. The clinical and laboratory features of patients with and without FLS were analyzed using exact univariate and multivariable logistic regression, with Bonferroni correction for multiple comparisons.We identified 177 patients who had MSGB performed and available clinical data. A total of 133 patients had FLS, 37 (27.8%) were seropositive (positive-anti-Sjogren syndrome type A [SSA] and/or anti-Sjogren syndrome type B) and 96 (72.2%) were seronegative. Dry eyes (unadjusted odds ratio [OR]: 5.17, 95% confidence interval [CI]: 1.16-26.30; adjusted odds ratio [aOR]: 12.58, 95% CI: 1.70-167.77) and the presence of anti-SSA (OR: 7.16, 95% CI: 1.70-64.24; aOR: 8.82, 95% CI: 1.73-93.93) were associated with FLS. Smoking (aOR 0.27, 95% CI: 0.11-0.63) and antihistamine use (aOR 0.23, 95% CI: 0.08-0.63) were associated with lower odds of FLS.Our study suggests that dry eyes and anti-SSA positivity are associated with FLS. Smoking and antihistamine use were associated with lower odds of FLS. In the appropriate clinical context, seronegative patients with sicca symptoms and no smoking history could be considered for MSGB. A thorough medication and smoking history should be performed in all patients before referral for MSGB.


Subject(s)
Autoantibodies/analysis , Biopsy/methods , Salivary Glands, Minor/pathology , Sialadenitis/diagnosis , Sjogren's Syndrome/diagnosis , Adult , Cross-Sectional Studies , Diagnosis, Differential , Dry Eye Syndromes/diagnosis , Female , Humans , Male , Middle Aged , Odds Ratio , Young Adult
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