Sensibilidad al gluten no celiaca: etiología, diagnóstico diferencial y presentación clínica / Non-celiac gluten sensitivity: Clinical presentation, etiology and differential diagnosis

La sensibilidad al gluten no celiaca (SGNC) es la última enfermedad incorporada al grupo de trastornos relacionados con el gluten. Esta revisión aborda la evidencia sobre su etiología, diagnóstico diferencial y sintomatología. Aunque la SGNC se define por una reacción al gluten, se han descrito otros posibles mecanismos etiopatogénicos, como una respuesta inadecuada a otros componentes del trigo o a los FODMAP, extendiéndose últimamente el término sensibilidad al trigo no celiaca. Existen resultados contradictorios sobre la validez del protocolo diagnóstico de los expertos de Salerno. La evidencia sobre biomarcadores diagnóstico para la SGNC escasea, aunque algunos estudios señalan los siguientes: anticuerpos antigliadina, zonulina, prueba ALCAT, micro-ARN, incARN y ciertas citoquinas. En la SGNC, el dolor abdominal y la fatiga son los síntomas más comunes. Además, es frecuente la alteración del estado nutricional. En conclusión, se necesita más investigación sobre la SGNC para mejorar nuestro conocimiento de su etiopatogenia y clínica.(AU)

Non-celiac gluten sensitivity (NCGS) is the latest pathology incorporated into the group of gluten-related disorders. This review addresses the evidence on its etiology, differential diagnosis and symptomatology. Although NCGS is defined by a reaction to gluten, other possible etiopathogenic mechanisms have been described, such as an inadequate response to other components of wheat or to FODMAPs, with the term non-celiac sensitivity to wheat recently being extended. There are contradictory results on the validity of the diagnostic protocol of the Salerno experts. Evidence on diagnostic biomarkers for NCGS is scarce, although some studies indicate the following: antigliadin antibodies, zonulin, ALCAT test, micro-RNA, incRNA and certain cytokines. In NCGS, abdominal pain and fatigue are the most common symptoms. In addition, altered nutritional status is common. In conclusion, more research on NCGS is needed to improve understanding of its etiopathogenesis and clinical features.(AU)

Differences in Psychological Symptoms in Pregnancy and Postpartum before and during COVID-19: A Cross-sectional Study / Las diferencias en los síntomas psicológicos durante el embarazo y el postparto antes y después del COVID-19: un estudio transversal

Rationale: Pregnant women are especially vulnerable to mental health problems, including stress, anxiety, and depression. This risk has been increased during the COVID-19 pandemic and differences in psychological symptoms in pregnancy and postpartum before and during COVID-19 exists. Mental health problems can have adverse effects on both the woman, and the neonate, including miscarriages, premature births, low birth weight, and higher rates of cesarean sections and instrument-assisted deliveries. Aim: To evaluate the prevalence of psychological symptoms of pregnant women before and during the COVID-19 pandemic. Method: A cross-sectional study was carried out to assess the psychological profile in a sample of pregnant women selected before the pandemic and a sample of women studied during the first wave of the pandemic. A total of 122 women were selected prior to the pandemic and 181 women during the COVID-19 outbreak. The Symptom Checklist-90 Revised (SCL-90-R) was used to assess depression and anxiety during pregnancy and in the postpartum period. Results: The prevalence of symptoms of depression and anxiety during pregnancy were higher in the sample of women studied during the pandemic (SCL-90-R: M = 54.6 vs. 42.6 and M = 62.6 vs. 51.7 respectively). In the postpartum the difference between both samples of women was even higher for depression and anxiety (SCL-90-R: M = 50.4 vs. 35.0 and M = 51.3 vs. 36.0 respectively). Being a pregnant woman at the COVID-19 outbreak was directly associated with a higher score of depression symptoms (aOR = 8.67, 95% CI [3.26, 23.02], p < .001). Anxiety during childbirth was more frequently reported by women before the pandemic (aOR = 5.13, 95% CI [2.53, 10.44], p < .001). The variable stage (before /during pandemic) was also associated with having a clinical SCL-90-R score above 70 (aOR = 7.61, 95% CI [2.7, 21.47], p < .001). (AU)

Justificación: Las mujeres embarazadas son especialmente vulnerables a los problemas de salud mental, como el estrés, la ansiedad y la depresión. Este riesgo se ha incrementado durante la pandemia de COVID-19, habiendo diferencias en los síntomas psicológicos en el embarazo y el puerperio antes y después de la pandemia. Los problemas de salud mental pueden tener efectos perjudiciales tanto en la mujer como en el recién nacido, como abortos espontáneos, partos prematuros, bajo peso al nacer y tasas más altas de cesáreas y partos asistidos. Objetivo: Evaluar la prevalencia de síntomas psicológicos de gestantes antes y durante la pandemia de COVID-19. Método: Se realizó un estudio transversal para evaluar el perfil psicológico en una muestra de mujeres embarazadas seleccionadas antes de la pandemia y una muestra de mujeres estudiadas durante la primera ola de la pandemia. Se seleccionó un total de 122 mujeres antes de la pandemia y 181 mujeres durante el brote de COVID-19. Se utilizó la Inventario de Verificación de Síntomas-90 Revisada (SCL-90-R) para evaluar la depresión y la ansiedad durante el embarazo y el puerperio. Resultados: La prevalencia de síntomas de depresión y ansiedad durante el embarazo fue mayor en la muestra de mujeres estudiadas durante la pandemia (SCL-90-R: M = 54.6 vs. 42.6 y M = 62.6 vs. 51.7 respectivamente). En el postparto la diferencia entre ambas muestras de mujeres fue aún mayor para depresión y ansiedad (SCL-90-R: M = 50.4 vs. 35.0 y M = 51.3 vs. 36.0 respectivamente). Ser mujer embarazada en el brote de COVID-19 se asoció directamente con una mayor puntuación de síntomas de depresión (aOR = 8.67, IC 95% [3.26, 23.02, p < .001). Las mujeres manifestaron ansiedad durante el parto con mayor frecuencia antes de la pandemia (aOR = 5.13, IC 95% 2.53, 10.44], p < .001). La variable estadio (antes/durante la pandemia) también se asoció con tener una puntuación clínica SCL-90-R superior a 70 (aOR = 7.61, IC 95% [2.7, 21.47], p < .001). (AU)

Influencia de la dieta en el riesgo de infección y de gravedad de la COVID-19: una revisión sistemática / Influence of diet in COVID-19 infection and severity risk: a systematic review

Introducción: el riesgo y/o el pronóstico de la COVID-19, causado por el virus SARS-CoV-2, se han relacionado con enfermedades crónicas como obesidad, diabetes mellitus y enfermedades cardiovasculares, siendo la dieta de mala calidad un factor predisponente para estas enfermedades. Objetivo: sintetizar la evidencia científica sobre el efecto de la dieta en el riesgo de infección por SARS-CoV-2 y de COVID-19 grave. Métodos: revisión sistemática realizada siguiendo las guías PRISMA. La búsqueda bibliográfica se hizo en las bases de datos Web of Science, Scopus y Medline (a través del buscador PubMed). El análisis del riesgo de sesgo se realizó mediante las escalas Newcastle-Ottawa y Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies. Resultados: se incluyeron 14 estudios. Una buena adherencia a la dieta mediterránea se asoció con una disminución del riesgo de infección por SARS-CoV-2 (razón de momios RM = 0,44; IC 95 %: 0,22-0,88, para adherencia alta versus baja, y RM significativas de 0,88 y 0,95 en los estudios que analizaron la adherencia de forma cuantitativa) pero no con la gravedad de la COVID-19. Una dieta basada en plantas presentó una asociación protectora frente a la infección y la enfermedad grave. Concretamente, un alto consumo de verdura, legumbres y cereales, y una baja ingesta de lácteos y carnes rojas mostraron un efecto protector frente a la infección y/o la COVID-19 grave, según el estudio. Los suplementos vitamínicos y probióticos también disminuyeron el riesgo de infección. Conclusión: la evidencia disponible sugiere que una dieta saludable, basada en un patrón de dieta mediterránea o en alimentos vegetales, con consumo de lácteos y carnes rojas moderado, ejerce un efecto protector frente a la COVID-19. (AU)

Introduction: the risk and/or prognosis of COVID-19, caused by the SARS-CoV-2 virus, have been related to chronic diseases such as obesity, diabetes mellitus, and cardiovascular diseases, with poor-quality diet being a predisposing factor for these diseases. Objective: to synthesize the scientific evidence on the effect of diet on the risk of SARS-CoV-2 infection and severe COVID-19. Methods: a systematic review was carried out following the PRISMA guidelines. The bibliographic search was made in the databases Web of Science, Scopus and Medline (through the PubMed search engine). Risk of bias analysis was performed using the Newcastle-Ottawa and Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies scales. Results: 14 studies were included. Good adherence to the Mediterranean diet was associated with a decreased risk of SARS-CoV-2 infection (OR = 0.44; 95 % CI, 0.22-0.88, for high versus low adherence, and significant ORs of 0.88 and 0.95 in studies that analyzed adherence quantitatively) but not with the severity of COVID-19. A plant-based diet also had a protective association against both COVID-19 infection and severity. Specifically, a high consumption of vegetables, legumes and cereals, and a low intake of dairy products and red meat showed a protective effect against infection and/or COVID-19 severity, depending on the study. Vitamin and probiotic supplements also lowered the risk of infection. Conclusion: the available evidence suggests that a healthy diet, based on a Mediterranean or plant-based diet, with moderate consumption of dairy and red meat, exerts a protective effect against COVID-19. (AU)

[Influence of diet in COVID-19 infection and severity risk: a systematic review]. / Influencia de la dieta en el riesgo de infección y de gravedad de la COVID-19: una revisión sistemática.

Introduction: Introduction: the risk and/or prognosis of COVID-19, caused by the SARS-CoV-2 virus, have been related to chronic diseases such as obesity, diabetes mellitus, and cardiovascular diseases, with poor-quality diet being a predisposing factor for these diseases. Objective: to synthesize the scientific evidence on the effect of diet on the risk of SARS-CoV-2 infection and severe COVID-19. Methods: a systematic review was carried out following the PRISMA guidelines. The bibliographic search was made in the databases Web of Science, Scopus and Medline (through the PubMed search engine). Risk of bias analysis was performed using the Newcastle-Ottawa and Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies scales. Results: 14 studies were included. Good adherence to the Mediterranean diet was associated with a decreased risk of SARS-CoV-2 infection (OR = 0.44; 95 % CI, 0.22-0.88, for high versus low adherence, and significant ORs of 0.88 and 0.95 in studies that analyzed adherence quantitatively) but not with the severity of COVID-19. A plant-based diet also had a protective association against both COVID-19 infection and severity. Specifically, a high consumption of vegetables, legumes and cereals, and a low intake of dairy products and red meat showed a protective effect against infection and/or COVID-19 severity, depending on the study. Vitamin and probiotic supplements also lowered the risk of infection. Conclusion: the available evidence suggests that a healthy diet, based on a Mediterranean or plant-based diet, with moderate consumption of dairy and red meat, exerts a protective effect against COVID-19.

Introducción: Introducción: el riesgo y/o el pronóstico de la COVID-19, causado por el virus SARS-CoV-2, se han relacionado con enfermedades crónicas como obesidad, diabetes mellitus y enfermedades cardiovasculares, siendo la dieta de mala calidad un factor predisponente para estas enfermedades. Objetivo: sintetizar la evidencia científica sobre el efecto de la dieta en el riesgo de infección por SARS-CoV-2 y de COVID-19 grave. Métodos: revisión sistemática realizada siguiendo las guías PRISMA. La búsqueda bibliográfica se hizo en las bases de datos Web of Science, Scopus y Medline (a través del buscador PubMed). El análisis del riesgo de sesgo se realizó mediante las escalas Newcastle-Ottawa y Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies. Resultados: se incluyeron 14 estudios. Una buena adherencia a la dieta mediterránea se asoció con una disminución del riesgo de infección por SARS-CoV-2 (razón de momios RM = 0,44; IC 95 %: 0,22-0,88, para adherencia alta versus baja, y RM significativas de 0,88 y 0,95 en los estudios que analizaron la adherencia de forma cuantitativa) pero no con la gravedad de la COVID-19. Una dieta basada en plantas presentó una asociación protectora frente a la infección y la enfermedad grave. Concretamente, un alto consumo de verdura, legumbres y cereales, y una baja ingesta de lácteos y carnes rojas mostraron un efecto protector frente a la infección y/o la COVID-19 grave, según el estudio. Los suplementos vitamínicos y probióticos también disminuyeron el riesgo de infección. Conclusión: la evidencia disponible sugiere que una dieta saludable, basada en un patrón de dieta mediterránea o en alimentos vegetales, con consumo de lácteos y carnes rojas moderado, ejerce un efecto protector frente a la COVID-19.

Non-celiac gluten sensitivity: Clinical presentation, etiology and differential diagnosis. / Sensibilidad al gluten no celiaca: etiología, diagnóstico diferencial y presentación clínica.

Non-celiac gluten sensitivity (NCGS) is the latest pathology incorporated into the group of gluten-related disorders. This review addresses the evidence on its etiology, differential diagnosis and symptomatology. Although NCGS is defined by a reaction to gluten, other possible etiopathogenic mechanisms have been described, such as an inadequate response to other components of wheat or to FODMAPs, with the term non-celiac sensitivity to wheat recently being extended. There are contradictory results on the validity of the diagnostic protocol of the Salerno experts. Evidence on diagnostic biomarkers for NCGS is scarce, although some studies indicate the following: antigliadin antibodies, zonulin, ALCAT test, micro-RNA, incRNA and certain cytokines. In NCGS, abdominal pain and fatigue are the most common symptoms. In addition, altered nutritional status is common. In conclusion, more research on NCGS is needed to improve understanding of its etiopathogenesis and clinical features.

Psychological Impact of COVID-19 in the Setting of Dentistry: A Review Article.

The worldwide pandemic has exposed healthcare professionals to a high risk of infection, exacerbating the situation of uncertainty caused by COVID-19. The objective of this review was to evaluate the psychological impact of the COVID-19 pandemic on dental professionals and their patients. A literature review was conducted using Medline-Pubmed, Web of Science, and Scopus databases, excluding systematic reviews, narratives, meta-analyses, case reports, book chapters, short communications, and congress papers. A modified version of the Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the selected studies. The search retrieved 3879 articles, and 123 of these were selected for the review (7 longitudinal and 116 cross-sectional studies). Elevated anxiety levels were observed in dental professionals, especially in younger and female professionals. Except for orthodontic treatments, patients reported a high level of fear that reduced their demand for dentist treatment to emergency cases alone. The results suggest that the COVID-19 pandemic has had psychological and emotional consequences for dental professionals and their patients. Further research is necessary to evaluate the persistence of this problem over time.

Regulation of EAE by spontaneously generated IL-10-secreting regulatory T cells in HLA-DR15/TCR.Ob1A12 double transgenic mice.

Humanized double transgenic mice express both HLA-DR15 (the MHC gene linked to MS) and TCR.Ob1A12 from a multiple sclerosis patient (that recognizes MBP85-99 presented by HLA-DR15), yet they fail to develop autoimmune encephalomyelitis quickly, although 5-10% develop disease at 12 months. These mice were found to express large numbers of IL-10-secreting splenocytes as early as 4 weeks of age. These regulatory T cells appeared spontaneously without prior immunization with the autoantigen MBP85-99. They were of murine origin and had a cytokine secretion profile and surface phenotype similar to that reported for Tr1 cells. Notably, the frequency of disease appeared to increase at 14 months. The diseased mice had small spleens which averaged 47 mg, while the remaining non-diseased mice in our colony killed at ages 14-15 months had splenocytes that averaged 80 mg (ranging from 47-130 mg). Thus, the appearance of disease was associated with diminution in numbers of IL-10-secreting regulatory T cells with age.

Genetically modified hematopoietic stem/progenitor cells that produce IL-10-secreting regulatory T cells.

Random amino acid copolymers used in the treatment of multiple sclerosis in man or experimental autoimmune encephalomyelitis (EAE) in mice [poly(Y,E,A,K)n, known as Copaxone, and poly(Y,F,A,K)n] function at least in part by generation of IL-10-secreting regulatory T cells that mediate bystander immunosuppression. The mechanism through which these copolymers induce Tregs is unknown. To investigate this question, four previously described Vα3.2 Vß14 T cell receptor (TCR) cDNAs, the dominant clonotype generated in splenocytes after immunization of SJL mice, that differed only in their CDR3 sequences were utilized to generate retrogenic mice. The high-level production of IL-10 as well as IL-5 and small amounts of the related cytokines IL-4 and IL-13 by CD4+ T cells isolated from the splenocytes of these mice strongly suggests that the TCR itself encodes information for specific cytokine secretion. The proliferation and production of IL-10 by these Tregs was costimulated by activation of glucocorticoid-induced TNF receptor (GITR) (expressed at high levels by these cells) through its ligand GITRL. A mechanism for generation of cells with this specificity is proposed. Moreover, retrogenic mice expressing these Tregs were protected from induction of EAE by the appropriate autoantigen.

Monitoring peripheral nerve degeneration in ALS by label-free stimulated Raman scattering imaging.

The study of amyotrophic lateral sclerosis (ALS) and potential interventions would be facilitated if motor axon degeneration could be more readily visualized. Here we demonstrate that stimulated Raman scattering (SRS) microscopy could be used to sensitively monitor peripheral nerve degeneration in ALS mouse models and ALS autopsy materials. Three-dimensional imaging of pre-symptomatic SOD1 mouse models and data processing by a correlation-based algorithm revealed that significant degeneration of peripheral nerves could be detected coincidentally with the earliest detectable signs of muscle denervation and preceded physiologically measurable motor function decline. We also found that peripheral degeneration was an early event in FUS as well as C9ORF72 repeat expansion models of ALS, and that serial imaging allowed long-term observation of disease progression and drug effects in living animals. Our study demonstrates that SRS imaging is a sensitive and quantitative means of measuring disease progression, greatly facilitating future studies of disease mechanisms and candidate therapeutics.

Liaison between natural killer cells and dendritic cells in human gestation.

A successful pregnancy relies on immunological adaptations that allow the fetus to grow and develop in the uterus, despite being recognized by maternal immune cells. Among several immunocompetent cell types present within the human maternal/fetal interface, DC-SIGN(+) dendritic cells (DCs) and CD56(+) natural killer (NK) cells are of major importance for early pregnancy maintenance, not only generating maternal immunological tolerance but also regulating stromal cell differentiation. Previous reports show the presence of NK-DC cell conjugates in first trimester human decidua, suggesting that these cells may play a role in the modulation of the local immune response within the uterus. While effective immunity is necessary to protect the mother from harmful pathogens, some form of tolerance must be activated to avoid an immune response against fetal antigens. This review article discusses current evidence concerning the functions of DC and NK cells in pregnancy and their liaison in human decidua.

Profiling Lgals9 splice variant expression at the fetal-maternal interface: implications in normal and pathological human pregnancy.

Disruption of fetal-maternal tolerance mechanisms can contribute to pregnancy complications, including spontaneous abortion. Galectin-9 (LGALS9), a tandem repeat lectin associated with immune modulation, is expressed in the endometrium during the mid and late secretory phases and in decidua during human early pregnancy. However, the role of LGALS9 during pregnancy remains poorly understood. We used real-time PCR and immunohistochemical staining to analyze the expression of Lgals9/LGALS9 during mouse gestation as well as in human tissues obtained from normal pregnancy and spontaneous abortions. In mice, three Lgals9 splice variants were detected, the expression of which was differentially regulated during gestation. Furthermore, decidual Lgals9 expression was deregulated in a mouse model of spontaneous abortion, whereas placental levels did not change. We further found that the LGALS9 D5 isoform suppresses interferon gamma production by decidual natural killer cells. In human patients, six Lgals9 splice variants were detected, and a decrease in Lgals9 D5/10 was associated with spontaneous abortion. Altogether, these results show a differential regulation of Lgals9 isoform expression during normal and pathological pregnancies and designate Lgals9 as a potential marker for adverse pregnancy outcomes.

Expression of the vasoactive proteins AT1, AT2, and ANP by pregnancy-induced mouse uterine natural killer cells.

Angiotensin II receptor type 1 (AT1) activation leads to vasoconstriction and type 2 receptor (AT2) leads to vasodilation. Atrial natriuretic peptide (ANP) antagonizes the effects of AT1. In human and murine pregnancies, uterine natural killer (uNK) cells closely associate with decidual blood vessels. Protein localization of AT1, AT2, and ANP to mouse uNK cells was examined between gestation days (gds) 6 and 12, the interval of uNK cell expansion. Percentages of uNK cells expressing AT1 or AT2 changed between gd6 and gd10. Atrial natriuretic peptide did not localize to uNK cells at gd6 or 8, but did colocalize to uNK cells at gd10 and 12, times immediately after spiral arterial modification. This is the first report of AT1, AT2, and ANP expression in uterine immune cells. Expression of these molecules suggests that uNK cells have the potential to contribute to the changes in blood pressure that occur between days 5 and 12 of pregnancy in mice.

Uterine NK cells, spiral artery modification and the regulation of blood pressure during mouse pregnancy.

Reproductive success in mammals involves coordinated changes in the immune and cardiovascular as well as in the neuroendocrine and reproductive systems. This review addresses studies that identify potential links for NK cells and T cells with the local and systemic cardiovascular adaptations of pregnancy. The studies reviewed have utilized immunohistochemisty and in vivo analyses of vascular parameters by ultrasound, chronic monitoring of hemodynamics via radiotelemetric recording and intravital microscopy. At the uterine level, functional subsets of uterine natural killer cells were identified. These included subsets expressing molecules important for vasoregulation, in addition to those previously identified for angiogenesis. Spiral arteries showed conducted responses that could account for conceptus control of vasoactivity and mouse gestational blood pressure 5-phase pattern. Vascular immunology is an emerging transdisciplinary field, critical for both reproductive immunology and cardiovascular disease.