Genetic Variant of DNAM-1 rs763361 C>T Is Associated with Ankylosing Spondylitis in a Mexican Population.

DNAM-1 (CD226) is an activating receptor expressed in CD8+ T cells, NK cells, and monocytes. It has been reported that two SNPs in the DNAM-1 gene, rs763361 C>T and rs727088 G>A, have been associated with different autoimmune diseases; however, the role of DNAM-1 in ankylosing spondylitis has been less studied. For this reason, we focused on the study of these two SNPs in association with ankylosing spondylitis. For this, 34 patients and 70 controls were analyzed using endpoint PCR with allele-specific primers. Our results suggest that rs763361 C>T is involved as a possible protective factor under the CT co-dominant model (OR = 0.34, 95% CI = 0.13-0.88, p = 0.022) and the CT + TT dominant model (OR = 0.39, 95% CI = 0.17-0.90, p = 0.025), while rs727088 G>A did not show an association with the disease in any of the inheritance models. When analyzing the relationships of the haplotypes, we found that the T + A haplotype (OR = 0.31, 95% CI = 0.13-0.73, p = 0.0083) is a protective factor for developing the disease. In conclusion, the CT and CT + TT variants of rs763361 C>T and the T + A haplotype were considered as protective factors for developing ankylosing spondylitis.

El manejo multidisciplinar mejora el diagnóstico genético de las enfermedades renales hereditarias en la era de next generation sequencing (NGS) / Multidisciplinary management improves the genetic diagnosis of hereditary kidney diseases in the next generation sequencing (NGS) era

Antecedentes y objetivo Las enfermedades renales hereditarias (ERH) son una causa frecuente de enfermedad renal crónica, habiéndose incrementado su diagnóstico desde la introducción de la secuenciación masiva (NGS). En 2018 se fundó la Unidad multidisciplinar de Enfermedades Renales Hereditarias de la Región de Murcia basándose en el estudio genético de las ERH mediante panel de genes. El objetivo de este estudio es analizar los resultados obtenidos en los primeros tres años de funcionamiento, así como analizar los factores clínicos que se asocian a la obtención de un diagnóstico genético final. Materiales y métodos Se incluyeron los pacientes estudiados mediante panel de genes de ERH y se compararon las características entre los que obtuvieron un diagnóstico genético final y los que no. Resultados Se estudiaron un total de 360 pacientes, detectándose variantes genéticas en 164 pacientes (45,6%) no relacionados familiarmente. Cuarenta y cinco de estas variantes eran de significado clínico incierto precisando estudio de cosegregación familiar, facilitado por la unidad multidisciplinar. Globalmente, considerando los resultados obtenidos con el panel de NGS realizado en el CBGC y los estudios genómicos ampliados, se consiguió un rendimiento diagnóstico final de ERH del 33,3% (120/360), contando hallazgos incidentales, del 35,6% (128/360). Se estudiaron 223 pacientes con sospecha de síndrome de Alport, confirmándose el diagnóstico en un 28,5% (gen más frecuente COL4A4), los cuales eran con más frecuencia mujeres, y con clara historia familiar compatible. También tenían con más frecuencia microhematuria, aunque 5 pacientes sin microhematuria confirmaron diagnóstico. No hubo diferencias en la edad, proteinuria, función renal, hipoacusia o alteraciones oftalmológicas (AU)

Background and objective Hereditary kidney diseases (HKD) are a frequent cause of chronic kidney disease, and their diagnosis has increased since the introduction of next generation sequencing (NGS). In 2018, the Multidisciplinary Unit for Hereditary Kidney Diseases of the Region of Murcia (UMERH-RM) was founded based on the genetic study of HKD. The objective of this study is to analyze the results obtained in the first 3 years of operation, and to analyze the clinical factors associated to a final genetic diagnosis. Materials and methods All the patients studied with the HKD gene panel were included. The characteristics between those who obtained a final genetic diagnosis and those who did not were compared. Results A total of 360 patients were studied, detecting genetic variants in 164 not related patients (45.6%). 45 of these were variants of uncertain significance requiring a family co-segregation study, which was facilitated by the multidisciplinary unit. Overall, considering the results obtained with the NGS panel and the extended genomic studies, a final diagnostic yield of HRD of 33.3% (120/360) was achieved, and including incidental findings 35.6% (128/360). Two hundred and twenty-three patients with suspected Alport syndrome were studied. Diagnosis was confirmed in 28.5% (COL4A4 most frequent gene), more frequently women with an obvious compatible family history. They also had frequently microhematuria, although 5 patients without microhematuria confirmed the diagnosis. There were no differences in age, proteinuria, renal function, hearing loss, or ophthalmologic abnormalities. The most frequent finding in the renal biopsy was mesangial proliferation. We estimate that 39 patients avoided renal biopsy (AU)

Multidisciplinary management improves the genetic diagnosis of hereditary kidney diseases in the next generation sequencing (NGS) era.

BACKGROUND AND OBJECTIVE: Hereditary kidney diseases (HKD) are a frequent cause of chronic kidney disease, and their diagnosis has increased since the introduction of next generation sequencing (NGS). In 2018, the Multidisciplinary Unit for Hereditary Kidney Diseases of the Region of Murcia (UMERH-RM) was founded based on the genetic study of HKD. The objective of this study is to analyze the results obtained in the first 3 years of operation, and to analyze the clinical factors associated to a final genetic diagnosis. MATERIALS AND METHODS: All the patients studied with the HKD gene panel were included. The characteristics between those who obtained a final genetic diagnosis and those who did not were compared. RESULTS: A total of 360 patients were studied, detecting genetic variants in 164 not related patients (45.6%). 45 of these were variants of uncertain significance requiring a family co-segregation study, which was facilitated by the multidisciplinary unit. Overall, considering the results obtained with the NGS panel and the extended genomic studies, a final diagnostic yield of HRD of 33.3% (120/360) was achieved, and including incidental findings 35.6% (128/360). Two hundred and twenty-three patients with suspected Alport syndrome were studied. Diagnosis was confirmed in 28.5% (COL4A4 most frequent gene), more frequently women with an obvious compatible family history. They also had frequently microhematuria, although 5 patients without microhematuria confirmed the diagnosis. There were no differences in age, proteinuria, renal function, hearing loss, or ophthalmologic abnormalities. The most frequent finding in the renal biopsy was mesangial proliferation. We estimate that 39 patients avoided renal biopsy. A total of 101 patients with suspected PKD were also studied, 49.5% had a conclusive genetic result (most frequent gene PKD1), more frequently women, with larger kidney sizes (although 9 patients with normal kidney size confirmed diagnosis). Again, the most predictive characteristic of genetic outcome was family history. CONCLUSIONS: The implementation of an NGS panel for HKD, together with the multidisciplinary approach to cases, has improved the diagnostic performance of HKD. In our sample, autosomal dominant Alport syndrome is of highest incidence. Ophthalmological and auditory examinations did not contribute to the diagnosis. We have seen a significant decrease in the indication of renal biopsies thanks to molecular diagnosis. The multidisciplinary approach, with the active participation of nephrologists, paediatricians, clinical and molecular geneticists, with insistence on adequate patient phenotyping and review of their family history, offers a better interpretation of genetic variants, allowing reclassification of the diagnosis of some nephropathies, thus improving their management and genetic advice.

Ocular cicatricial pemphigoid: is there an association with autoimmune diseases?

PURPOSE: To assess the prevalence of autoimmune diseases (ADs) associated with ocular cicatricial pemphigoid (OCP) and analyze clinical, laboratory, and treatment associations between these entities. METHODS: A multicentre cross-sectional study of patients with an OCP diagnosis. The population was divided into two groups according to their association with other ADs or not. Clinical, laboratory and treatment variables were described and compared between groups. A multivariable logistic regression analysis was performed to identify variables that could suggest the association between OCP and ADs. RESULTS: Eighty-eight patients were recruited, with a mean age at diagnosis of 64.3 years (SD 11.9). Biopsy was performed in 86.8% of the patients. There was a median delay of 2 years from the onset of symptoms to diagnosis. Extraocular involvement was evidenced in 11.5%. The group associated with ADs included 24 patients (27.3%). The most prevalent diagnosis was Sjögren´s syndrome. Hypergammaglobulinemia was associated with ADs and OCP, adjusted for age, sex, smoking, skin and mucosal involvement, and erythrocyte sedimentation rate (OR 8.7; 95%CI 1.6-46.8; p = 0.012). CONCLUSIONS: Due to OCP's autoimmune nature, it could coexist with other ADs. This study observed that more than a quarter of the population presented with this association, and hypergammaglobulinemia could suggest it.

Methylation of histone H3 lysine 36 is a barrier for therapeutic interventions of head and neck squamous cell carcinoma.

Approximately 20% of head and neck squamous cell carcinomas (HNSCCs) exhibit reduced methylation on lysine 36 of histone H3 (H3K36me) due to mutations in histone methylase NSD1 or a lysine-to-methionine mutation in histone H3 (H3K36M). Whether such alterations of H3K36me can be exploited for therapeutic interventions is still unknown. Here, we show that HNSCC models expressing H3K36M can be divided into two groups: those that display aberrant accumulation of H3K27me3 and those that maintain steady levels of H3K27me3. The former group exhibits reduced proliferation, genome instability, and heightened sensitivity to genotoxic agents like PARP1/2 inhibitors. Conversely, H3K36M HNSCC models with constant H3K27me3 levels lack these characteristics unless H3K27me3 is elevated by DNA hypomethylating agents or inhibiting H3K27me3 demethylases KDM6A/B. Mechanistically, H3K36M reduces H3K36me by directly impeding the activities of the histone methyltransferase NSD3 and the histone demethylase LSD2. Notably, aberrant H3K27me3 levels induced by H3K36M expression are not a bona fide epigenetic mark because they require continuous expression of H3K36M to be inherited. Moreover, increased sensitivity to PARP1/2 inhibitors in H3K36M HNSCC models depends solely on elevated H3K27me3 levels and diminishing BRCA1- and FANCD2-dependent DNA repair. Finally, a PARP1/2 inhibitor alone reduces tumor burden in a H3K36M HNSCC xenograft model with elevated H3K27me3, whereas in a model with consistent H3K27me3, a combination of PARP1/2 inhibitors and agents that up-regulate H3K27me3 proves to be successful. These findings underscore the crucial balance between H3K36 and H3K27 methylation in maintaining genome instability, offering new therapeutic options for patients with H3K36me-deficient tumors.

Methylation of histone H3 lysine 36 is a barrier for therapeutic interventions of head and neck squamous cell carcinoma.

Approximately 20% of head and neck squamous cell carcinomas (HNSCC) exhibit reduced methylation on lysine 36 of histone H3 (H3K36me) due to mutations in histone methylase NSD1 or a lysine-to-methionine mutation in histone H3 (H3K36M). Whether such alterations of H3K36me can be exploited for therapeutic interventions is still unknown. Here, we show that HNSCC models expressing H3K36M can be divided into two groups: those that display aberrant accumulation of H3K27me3 and those that maintain steady levels of H3K27me3. The first group shows decreased proliferation, genome instability, and increased sensitivity to genotoxic agents, such as PARP1/2 inhibitors. In contrast, the H3K36M HNSCC models with steady H3K27me3 levels do not exhibit these characteristics unless H3K27me3 levels are elevated, either by DNA hypomethylating agents or by inhibiting the H3K27me3 demethylases KDM6A/B. Mechanistically, we found that H3K36M reduces H3K36me by directly impeding the activities of the histone methyltransferase NSD3 and the histone demethylase LSD2. Notably, we found that aberrant H3K27me3 levels induced by H3K36M expression is not a bona fide epigenetic mark in HNSCC since it requires continuous expression of H3K36M to be inherited. Moreover, increased sensitivity of H3K36M HNSCC models to PARP1/2 inhibitors solely depends on the increased H3K27me3 levels. Indeed, aberrantly high H3K27me3 levels decrease BRCA1 and FANCD2-dependent DNA repair, resulting in higher sensitivity to DNA breaks and replication stress. Finally, in support of our in vitro findings, a PARP1/2 inhibitor alone reduce tumor burden in a H3K36M HNSCC xenograft model with elevated H3K27me3, whereas in a H3K36M HNSCC xenograft model with consistent H3K27me3 levels, a combination of PARP1/2 inhibitors and agents that upregulate H3K27me3 proves to be successful. In conclusion, our findings underscore a delicate balance between H3K36 and H3K27 methylation, essential for maintaining genome stability. This equilibrium presents promising therapeutic opportunities for patients with H3K36me-deficient tumors.

[Monkeypox: the other pandemic, the other challenge]. / Viruela símica: la otra pandemia, el otro reto.

Since the emergence of monkeypox in Europe, this disease has gradually spread throughout the rest of the world. In Mexico, epidemiological notices have been issued with the main guidelines to follow in terms of epidemiological surveillance and official figures have been published regularly on a microsite weeks after the first cases. These sources of information were reviewed and analyzed, based on which observations are issued, in addition to other relevant publications on the subject, with the interest of reinforcing the surveillance of this disease in the country.

Desde el surgimiento de la viruela símica en Europa la enfermedad se ha extendido paulatinamente por el resto del mundo. En México se han emitido avisos epidemiológicos con las principales pautas a seguir en materia de vigilancia epidemiológica y publicado las cifras oficiales de forma regular en un micrositio semanas después de los primeros casos. Se revisaron y analizaron dichas fuentes de información, con base en las cuales se emiten observaciones, además de otras publicaciones relevantes del tema, con el interés de reforzar la vigilancia de esta enfermedad en el país.

Albuminuria, Disease Duration, and Glycated Hemoglobin Are Related With Bone Mineral Density in Type 1 Diabetes: A Cross-sectional Study.

OBJECTIVE: Studies have found a significant decrease in bone mineral density (BMD) in individuals with type 1 diabetes (T1D) compared to healthy controls. Factors associated with this phenomenon have yet to be defined; therefore, this study aimed to explore the association of glycated hemoglobin (HbA1c), disease duration, albuminuria, and glomerular filtration rate with BMD in adults with T1D. METHODS: A cross-sectional study was carried out in tertiary care center. BMD analysis was performed by dual x-ray absorptiometry. Linear models were constructed considering variables associated with BMD. Approval from the ethics committees and informed consent were obtained. RESULTS: We included 128 participants, of whom 59% were women, and 16% had menopause. The median age was 33 (26-42) years. The average age of diabetes diagnosis was 15.3 ± 6.3 years, and the median disease duration was 19.5 (12-27) years. In the adjusted analysis, higher albuminuria (P < .01) and disease duration (P < .05) were associated with a lower BMD in the femoral neck and total hip, independently of age, sex, and body mass index (BMI). Higher HbA1c (P < .01) was associated with a lower spine BMD after adjustment for age, sex, and BMI. CONCLUSION: Studied factors specific to T1D, including albuminuria, disease duration, and HbA1c have an association with BMD regardless of BMI, age, and sex.

Endocrine resistance and breast cancer plasticity are controlled by CoREST.

Resistance to cancer treatment remains a major clinical hurdle. Here, we demonstrate that the CoREST complex is a key determinant of endocrine resistance and ER+ breast cancer plasticity. In endocrine-sensitive cells, CoREST is recruited to regulatory regions co-bound to ERα and FOXA1 to regulate the estrogen pathway. In contrast, during temporal reprogramming towards a resistant state, CoREST is recruited to AP-1 sites. In reprogrammed cells, CoREST favors chromatin opening, cJUN binding to chromatin, and gene activation by controlling SWI/SNF recruitment independently of the demethylase activity of the CoREST subunit LSD1. Genetic and pharmacological CoREST inhibition reduces tumorigenesis and metastasis of endocrine-sensitive and endocrine-resistant xenograft models. Consistently, CoREST controls a gene signature involved in invasiveness in clinical breast tumors resistant to endocrine therapies. Our studies reveal CoREST functions that are co-opted to drive cellular plasticity and resistance to endocrine therapies and tumorigenesis, thus establishing CoREST as a potential therapeutic target for the treatment of advanced breast cancer.

Reserva contráctil por fracción de eyección sola, o con elastancia. ¿Cuál es el mejor predictor de eventos luego de un Eco Estrés sin isquemia? / Contractile Reserve by Left Ventricular Ejection Fraction Alone, o Considering Elastance. ¿Which is the Best Predictor of Events After a Stress Echo Without Ischemia?

RESUMEN Introducción: El comportamiento de la fracción de eyección del ventrículo izquierdo (FEVI) durante el ejercicio se utiliza para medir la reserva contráctil (RC). La RC medida por elastancia podría tener mayor valor pronóstico. Objetivo: Establecer si la medición de la RC por elastancia añade valor pronóstico a largo plazo en relación al comportamiento aislado de la FEVI en pacientes con un Eco Estrés sin isquemia miocárdica. Material y métodos: Estudio retrospectivo, realizado en 904 pacientes con Eco Estrés con ejercicio sin isquemia. Se valoró la RC por FEVI y por elastancia. Se dividieron en 2 grupos: Grupo 1: RC por FEVI presente (a su vez este grupo se dividió en 2 subgrupos: Grupo 1 A, RC con elastancia presente y Grupo 1B: ausencia de RC por elastancia), y Grupo 2: pacientes con ausencia de RC por FEVI. El seguimiento fue de 17,7 ± 5,4 meses. Se consideraron como eventos: muerte, infarto agudo de miocardio (IAM), accidente cerebrovascular (ACV) y/o internación de causa cardiovascular. Resultados: Del total del Grupo 1 (536 pacientes), 200 (37,3%) se incluyeron en el Grupo 1A y 336 (62,7%) en el Grupo 1B. En el Grupo 2, se incluyeron 368 pacientes. En el seguimiento, los pacientes del Grupo 2 tuvieron más eventos, 30 (8,1%) vs. 22 (2,6%) (HR 3,14, IC95% 1,95-5,9, log rank test p<0,001). Dentro del G1, los pacientes del Grupo 1B presentaron más eventos: 18 (5,3%) vs 4 eventos (2%) (HR 2,46 IC95% 1,06-7,3, log rank test p<0,05). En el modelo de regresión, la elastancia fue la única variable predictora de eventos (HR 3,2, IC95% 1,83-5,6, p<0,001). Conclusiones: En el Eco Estrés ejercicio negativo para isquemia, el comportamiento de la RC evaluada por elastancia permitió identificar un subgrupo de peor pronóstico a largo plazo en pacientes con comportamiento normal de la FEVI.

ABSTRACT Background: The behavior of left ventricular ejection fraction (LVEF) during exercise is used to measure contractile reserve (CR). CR measured by elastance could have greater prognostic value. Objective: To establish whether the measurement of CR by elastance adds long-term prognostic value to CR measured by LVEF in patients with a Stress Echo without myocardial ischemia. Material and methods: Retrospective study, carried out in 904 patients with an exercise Stress Echo without ischemia. CR was assessed by LVEF and by elastance. Patients were divided into 2 groups: Group 1: presence of CR by LVEF (in turn this group was divided into 2 subgroups: Group 1A, CR with elastance present, and Group 1B: absence of CR by elastance), and Group 2: patients with absence of CR by LVEF. The follow-up was 17,7 ± 5,4 months. Outcomes considered were death, acute myocardial infarction (AMI), stroke, and cardiovascular hospitalization. Results: 536 patients were included in Group 1, 200 (37,3 %) in Group 1A and 336 (62,7%) in Group 1B. In Group 2, 368 patients were included. At follow-up, patients in Group 2 had more events, 30 (8.1%) vs. 22 (2.6%) (HR 3.14, 95% CI 1.95-5.9, log rank test p <0.001). Within G1, patients in Group 1B presented more events: 18(5.3%) vs 4 (2%) (HR 2.46 CI 95% 1.06-7.3, log rank test p <0.05). In the regression model, CR assessed by LVEF and additionally by elastance was the only significant outcome predictor (HR 3.2, 95% CI 1.83-5.6, p <0.001). Conclusions: In an exercise Stress Echo negative for ischemia, CR behavior evaluated by elastance allowed us to identify a subgroup with a worse long-term prognosis in patients with normal LVEF response.

Mala nutrición en población escolar mexicana: factores geográficos y escolares asociados.

OBJETIVOS: Determinar prevalencias de mala nutrición [sobrepeso u obesidad (Sp+O) y talla baja (TB)] en población mexicana de 6 a 12 años de edad de nivel básico de primaria, y su asociación con características geográficas (ámbito, marginación y región del país), y de la escuela (tipo, turno y grado). MÉTODOS: Con información de 10 528 676 escolares, se estimaron prevalencias (e I.C. 95%), a nivel nacional y por características de interés, y su asociación mediante modelos de regresión logística. RESULTADOS: La prevalencia nacional de Sp+O fue 34.4%, 36.5% en ámbito urbano y 40.2% en escuelas privadas. La prevalencia nacional de TB fue 8.7%; en área rural, 13.7% y 28.8% en escuelas tipo indígenas. El Sp+O y la TB se asociaron significativamente con características geográficas y de escuelas. CONCLUSIONES: Existe una polarización nutricional en el contexto escolar del país. Es importante continuar con sistemas de monitoreo y vigilancia nutricional.

Factors leading to satisfaction with counseling for Labor after Cesarean among Latina women in the United States.

BACKGROUND: Cesarean birth, especially repeat cesarean, is associated with significantly higher morbidity than vaginal birth. Appropriately counseling women who are candidates for labor after cesarean (LAC) has the potential to confer significant health benefits for women. Little guidance exists about optimal counseling techniques, especially for Latina women. The aim of this study was to evaluate satisfaction among Latinas about how LAC counseling is performed, specifically as it relates to shared decision making. METHODS: We conducted a qualitative study of pregnant women at several clinics in a Federally Qualified Health Center system in Utah. We interviewed eleven Latina women about satisfaction with recent LAC counseling with a specific aim of obtaining rich, personal narratives rather than reaching data saturation. A codebook representing the most common themes was developed. RESULTS: Three major themes emerged related to LAC counseling including influences on satisfaction, influences on the birth decision process, and preferences surrounding method and timing of counseling. Women experienced greater satisfaction from providers who used jargon-free communication, were perceived as trustworthy, cared about her experiences, and empowered her to make an informed decision. Women's decisions were influenced by prior birth experiences, desire for a safe delivery and easy recovery, and future family planning. CONCLUSIONS: Understanding the aspects of LAC counseling that are most meaningful for Latina women can promote effective communication between patient and provider and improve patient satisfaction. Globally, our findings highlight the importance of evaluating the experiences and preferences of minority groups; majority populations cannot be assumed to speak for minority populations.

Validation and adaptation of the Spanish version of the systemic lupus activity questionnaire (S-SLAQ) in an Argentinean population.

OBJECTIVES: To validate the systemic lupus activity questionnaire (SLAQ) in Spanish language. METHODS: The SLAQ questionnaire was translated and adapted in Spanish. Consecutive SLE patients from 8 centers in Argentina were included. A rheumatologist completed a Systemic Lupus Activity Measure (SLAM), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K, and a physician's assessment. Reliability was assessed by internal consistency (Cronbach's alpha), stability by test-retest reliability (intraclass correlation coefficient), and construct validity by evaluating the correlation with clinically relevant scores. Sensitivity and specificity for clinically significant disease activity (SLEDAI ≥6) of different S-SLAQ cut-off points were evaluated. RESULTS: We included 97 patients ((93% female, mean age: 40 years (SD14.7)). Internal consistency was excellent (Cronbach's alpha = 0.84, p < 0.001), and the intraclass correlation coefficient was 0.95 (p < 0.001). Mean score of S-SLAQ was 8.2 (SD 7.31). Correlation of S-SLAQ was moderate with Patient NRS (r= 0.63 p< 0.001), weak with SLAM-no lab (r = 0.42, p <0.001) and SLAM (r = 0.38, p < 0.0001), and very weak with SLEDAI-2K (r = 0.15, p =0.1394). Using the S-SLAQ cutoff of five points, the sensitivity was 72.2% and specificity was 37.9%, for clinically significant disease activity. CONCLUSIONS: The S-SLAQ showed good validity and reliability. A good correlation, similar to the original instrument, was observed with patient´s global disease activity. No correlation was found between S-SLAQ and gold standard disease activity measures like SLEDAI-2K and SLAM. The S-SLAQ cutoff point of 5 showed a good sensitivity to identify the active SLE population and therefore could be an appropriate screening instrument for disease activity in clinical and epidemiological studies.

The influence of the -94 Ins/Del ATTG polymorphism of NFkB on the anti-CCP antibody levels in patients with rheumatoid arthritis.

ABSTRACT: Rheumatoid arthritis (RA) is an autoimmune disease characterized by an inflammatory process that affects mainly synovial tissue in joints, and by the production of cyclic citrullinated peptides (anti-CCP) antibodies. In the inflammatory process the regulation of the nuclear factor kappa B (NFkB) transcription factor activation is a key point in the production of inflammatory cytokines. On the other hand, polymorphisms in several genes could contribute to the promotion of the inflammatory process observed in RA, and the association of the rs28362491 polymorphism in the NFkB gene with RA has been studied in different population. Therefore, it could be one of the interest targets to analyze their association with RA in a Mexican population.This is a case-control study to determine the influence of rs28362491 in the NFkB gene on RA and on clinical features of this disease, such as anti-CCP antibody levels, Disease Activity Score, and Health Assessment Questionnaire-Disability Index.The genotype of rs28362491 in the NFkB gene was determined in 140 RA patients and 135 healthy controls using the polymerase chain reaction-restriction fragment length polymorphism method with the enzyme PflMI. The following clinical variables were also determined: anti-CCP levels, Disease Activity Score, and Spanish version of the Health Assessment Questionnaire Disability-Index.Although no association of the polymorphism as a risk/protection factor with RA was found, the RA patients who carried the Ins/Ins genotype showed higher anti-CCP levels, while those with the Del/Del genotype showed higher Spanish version of the Health Assessment Questionnaire-Disability Index levels, compared to the other genotypes.The NFkB -94 Ins/Del ATTG (rs28362491) polymorphism is, therefore, associated with higher levels of anti-CCP antibodies, though no significant association as a risk or protection factor in RA cases was identified.

Developing a web-based toolkit for new mothers about postpartum pelvic floor health in collaboration with a professional medical association.

BACKGROUND: Few electronic resources are available for new mothers with concerns about changes in their pelvic floor following childbirth. Patients may struggle when seeking authoritative information regarding pelvic floor conditions online given the sensitivity of the topic as well as the inadvertent connection to obscene or demeaning content found online. A health sciences librarian partnered with the Motherhood and Pelvic Health Study, an interdisciplinary research group, to provide expert searching skills for a particularly challenging health condition that patients struggle to find useful information on. CASE PRESENTATION: A custom rubric was developed to evaluate existing information products, which included criteria for cultural sensitivity, conflicts of interest, and other red flags. This evaluation process enabled the research team to identify top-tier evidence-based materials that were culturally congruent. This collaborative evaluation process led to the creation of a web-based toolkit resource for new mothers concerned about changes in their pelvic floor. The toolkit connects women to pertinent information on a national health organization's patient portal, supplemented by videos created by the team to serve as models of communication for women and health care providers. CONCLUSION: When developing a web-based resource, health sciences libraries can partner with research teams to find, evaluate, and disseminate information. Culturally congruent toolkits such as this one can improve access to health information and lead to improved health outcomes. To ensure that the information highlighted in toolkits is both culturally congruent and authoritative, research teams should form advisory committees and partner with relevant professional medical associations.

Trajectories of Pelvic Floor Symptoms and Support After Vaginal Delivery in Primiparous Women Between Third Trimester and 1 Year Postpartum.

OBJECTIVES: The objectives of this study were to describe trajectories of pelvic floor symptoms and support from the third trimester to 1 year postpartum in primiparous women after vaginal delivery and to explore factors associated with their resolution between 8 weeks postpartum and 1 year postpartum. METHODS: Five hundred ninety-seven nulliparous women 18 years or older who gave birth vaginally at term completed the Epidemiology of Prolapse and Incontinence Questionnaire and the Pelvic Organ Prolapse Quantification examination at the third trimester, 8 weeks postpartum, and 1 year postpartum. RESULTS: At 1 year postpartum, 41%, 32%, and 23% of participants reported stress urinary incontinence, nocturia, and flatus incontinence, respectively, and 9% demonstrated maximal vaginal descent (MVD) ≥ 0 cm. For more common symptoms, incidence rates between the third trimester and 8 weeks postpartum ranged from 6% for urinary frequency to 22% for difficult bowel movements, and resolution rates between 8 weeks postpartum and 1 year postpartum ranged from 23% for stress urinary incontinence to 73% for pain. Between the third trimester and 8 weeks postpartum, 13% demonstrated de novo MVD ≥ 0 cm. For most symptoms, the presence of the same symptom before delivery decreased the probability of resolution between 8 weeks postpartum and 1 year. However, the sensitivities of predelivery vaginal bulge and MVD of 0 cm or greater for those outcomes at 1 year postpartum was overall low (10-12%). CONCLUSIONS: One year postpartum, urinary and bowel symptoms are common in primiparous women who gave birth vaginally. A substantial portion of this burden is represented by symptoms present before delivery, while most of the prevalence of worse anatomic support is accounted for by de novo changes after delivery.

The Polycomb protein RING1B enables estrogen-mediated gene expression by promoting enhancer-promoter interaction and R-loop formation.

Polycomb complexes have traditionally been prescribed roles as transcriptional repressors, though increasing evidence demonstrate they can also activate gene expression. However, the mechanisms underlying positive gene regulation mediated by Polycomb proteins are poorly understood. Here, we show that RING1B, a core component of Polycomb Repressive Complex 1, regulates enhancer-promoter interaction of the bona fide estrogen-activated GREB1 gene. Systematic characterization of RNA:DNA hybrid formation (R-loops), nascent transcription and RNA Pol II activity upon estrogen administration revealed a key role of RING1B in gene activation by regulating R-loop formation and RNA Pol II elongation. We also found that the estrogen receptor alpha (ERα) and RNA are both necessary for full RING1B recruitment to estrogen-activated genes. Notably, RING1B recruitment was mostly unaffected upon RNA Pol II depletion. Our findings delineate the functional interplay between RING1B, RNA and ERα to safeguard chromatin architecture perturbations required for estrogen-mediated gene regulation and highlight the crosstalk between steroid hormones and Polycomb proteins to regulate oncogenic programs.