Prevalencia de endometritis crónica en mujeres infértiles establecida mediante histeroscopia y biopsia endometrial con CD138 / Prevalence of chronic endometritis in infertile women by hysteroscopy and endometrial biopsy with CD138

Resumen OBJETIVO: Determinar, mediante histeroscopia de evaluación y biopsia de endometrio, con análisis histológico endometrial e identificación de células plasmáticas con inmunohisdtoquímica con CD138 positiva, la prevalencia de endometritis crónica en pacientes infértiles. MATERIALES Y MÉTODOS: Estudio observacional, retrospectivo, efectuado de marzo de 2016 a noviembre del 2021 en el Centro de Reproducción Asistida de Saltillo (CREAS), Coahuila, México, en pacientes que consultaron por infertilidad. El diagnóstico de endometritis crónica se estableció mediante histeroscopia y biopsia de endometrio con inmunohistoquímica CD138. Se analizaron la prevalencia y precisión diagnóstica de la histeroscopia y la biopsia de endometrio. Además, la relación entre las características histeroscópicas específicas y la endometritis crónica confirmada por biopsia con CD138 positiva. RESULTADOS: La prevalencia de endometritis crónica por biopsia de endometrio CD138 positiva en las 170 pacientes estudiadas fue de 36% (n = 62) y por histeroscopia del 48.8% (n = 83), esta última con una sensibilidad del 48.3%, especificidad del 50.9%, valor predictivo positivo y negativo del 36.1 y 63.2%, respectivamente. En relación con las características histeroscópicas, la hiperemia endometrial tuvo una relación estadísticamente significativa con la prevalencia de endometritis crónica (p-value = 0.008; RM = 0.357; IC95%: 0.14-0.81) y con ≥ 2 características sugerentes de endometritis crónica (p-value = 0.015; RM = 3.63; IC95%: 1.15-12.69). CONCLUSIONES: En el procedimiento diagnóstico de la paciente infértil es importante descartar la endometritis crónica. Para ello es decisivo recurrir a herramientas diagnósticas, como la histeroscopia y confirmar el diagnóstico con una biopsia de endometrio con inmunohistoquímica CD138 positiva para que de esta manera pueda dirigirse el tratamiento.

Abstract OBJECTIVE: To determine the prevalence of chronic endometritis in infertile patients by evaluating hysteroscopy and endometrial biopsy with endometrial histologic analysis and identification of plasma cells by CD138-positive immunohistochemistry. MATERIALS AND METHODS: Observational, retrospective study performed from March 2016 to November 2021 at the Center for Assisted Reproduction of Saltillo (CREAS), Coahuila, Mexico, in patients who consulted for infertility. Chronic endometritis was diagnosed by hysteroscopy and endometrial biopsy with CD138 immunohistochemistry. The prevalence and diagnostic accuracy of hysteroscopy and endometrial biopsy were analysed. The association between specific hysteroscopic features and chronic endometritis confirmed by CD138-positive endometrial biopsy was also investigated. RESULTS: The prevalence of chronic endometritis by CD138-positive endometrial biopsy in the 170 patients studied was 36% (n = 62) and by hysteroscopy 48.8% (n = 83), the latter with a sensitivity of 48.3%, specificity of 50.9%, positive and negative predictive values of 36.1 and 63.2%, respectively. In relation to hysteroscopic features, endometrial hyperemia had a statistically significant relationship with the prevalence of chronic endometritis (p-value = 0.008; RM = 0.357; 95%CI: 0.14-0.81) and with ≥ 2 features suggestive of chronic endometritis (p-value = 0.015; RM = 3.63; 95%CI: 1.15-12.69). CONCLUSIONS: In the diagnostic process of infertile patients, it is important to exclude chronic endometritis. It is crucial to use diagnostic tools such as hysteroscopy and to confirm the diagnosis by endometrial biopsy with positive CD138 immunohistochemistry in order to guide treatment.

Lower ΔFosB expression in the dopaminergic system after stevia consumption in rats housed under environmental enrichment conditions.

Environmental enrichment (EE) has been proven to reduce drug seeking and the development of addiction-related behaviors in rodent models, but the effects of EE on natural reward acquisition in the form of sweet beverages are poorly understood. Accumulating evidence shows that the intake of sugar, the main ingredient of sweet beverages, alters the dopaminergic system, leading to addiction-related physiological and molecular changes. Sugar in sweet beverages has been replaced with natural sweeteners, such as stevia extract, which has greater sweetener potential but no energy content. Our research group found that sucralose consumption increased the expression of ΔFosB in reward-related nuclei, suggesting activation of the dopaminergic system. The present study assessed the effects of EE on stevia consumption and the expression of ΔFosB in the nucleus accumbens, caudate putamen, and prefrontal cortex. Sixteen male Wistar rats, 21 days old, were randomly assigned to an EE group (n = 8) or standard environment (SE) group (n = 8) and reared for 30 days. On postnatal day 52 (PND52), the brains of four animals in each housing condition were extracted to determine basal ΔFosB levels. Stevia consumption with intermittent access and ΔFosB immunoreactivity were measured for 21 days in the remainder of the rats. Compared with SE animals, EE animals exhibited a reduction of stevia consumption and alterations of ΔFosB immunoreactivity in the reward system. These results indicate that EE reduces stevia consumption and the stevia-induced ΔFosB expression, suggesting addiction-related changes in dopaminergic nuclei, which may be interpreted as a neuroprotective effect.

Creencias sobre la violencia y sus efectos en la prevalencia de la violencia en el noviazgo / Beliefs about violence and its effects on the prevalence of dating violence

Resumen La violencia en el noviazgo es un fenómeno multifactorial que requiere de estudios que profundicen respecto a los efectos que tienen las creencias culturales en el comportamiento tanto del agresor como de la víctima. Teniendo esto en cuenta, el objetivo de la presente investigación fue determinar la relación entre las creencias acerca de la violencia y la prevalencia de la violencia en el noviazgo. Para ello, se contó con una muestra de 420 estudiantes de dos universidades públicas mexicanas que respondieron el Inventario de creencias acerca de la violencia hacia la esposa, el Inventario de conflictos en las relaciones de noviazgo, y un cuestionario de información sociodemográfica. Los datos recolectados fueron examinados por medio de un análisis de correlación canónica, y los resultados mostraron que el modelo en general fue estadísticamente significativo (Wilks X = .654, F(20, 677.54) = 4.626,p < .05); que el tamaño del efecto del modelo general fue de .346, lo que indica que este explicó el 34.6 % de la varianza compartida por los dos conjuntos de variables; y que, específicamente en la primera función, el coeficiente de mayor magnitud fue el de la variable de justificación de la violencia (r2 s = 76.2; h 2 = 90.0), seguido por la del apoyo que se le puede brindar a la víctima (r2 s = 57.1; h2 = 94.5).

Abstract Dating violence is a multifactorial phenomenon that requires in-depth studies regarding the effects that cultural beliefs have on the behavior of both the aggressor and the victim. With this in mind, the objective of this research was to determine the relationship between beliefs about violence and the prevalence of dating violence. To this end, a sample of 420 students from two Mexican public universities answered the Inventory of Beliefs about Wife Violence, the Inventory of Conflicts in Dating Relationships, and a sociodemographic information questionnaire. The data collected were examined through a canonical correlation analysis, and the results showed that the overall model was statistically significant (Wilks X = .654, F (20, 677.54) = 4.626, p < .05); that the effect size of the overall model was .346, indicating that it explained 34. 6 % of the variance shared by the two sets of variables; and that, specifically in the first function, the coefficient of greatest magnitude was that of the variable of justification of the violence (r2 s = 76.2; h2 = 90.0), followed by that of the support that can be given to the victim (r2 s = 57.1; h2 = 94.5).

The mediating role of emotion regulation strategies in the relationship between family of origin violence and intimate partner violence

Abstract The effects of family of origin violence and intimate partner violence have been extensively documented; however, very few studies have examined the interaction with emotion regulation strategies. Thus, the objective of this research was to analyze whether different types of emotion regulation strategies, both adaptive and maladaptive, mediate the relationship between family of origin violence and intimate partner violence in the Mexican population. A total of 838 participants (45.9% men and 54.1% women) responded to instruments addressing family of origin violence, emotion regulation strategies, and intimate partner violence. The results revealed that both structural models were significant. For women, the model showed an adequate fit X 2 (11, N = 838) = 22.75, p = .288, GFI = .95, AGFI = .91, NFI = .98, CFI = .97, RMSEA = .05. Likewise, we found similar indexes for men X2 (11, N = 838) = 28.20, p = .348, GFI = .97, AGFI = .93, NFI = .97, CFI = .95, RMSEA = .04. Specifically, the direct effects of adaptive strategies on intimate partner violence were statistically significant. Meanwhile, the direct effects of family of origin violence on maladaptive emotion regulation strategies were significant, as were the direct effects of maladaptive strategies on intimate partner violence. In turn, the indirect effects of family of-origin violence were significantly related to intimate partner violence via maladaptive emotion regulation strategies. In addition, the results clearly showed that men reported higher levels of aggression against women. Finally, regarding the selection of emotion regulation strategies, while women employed more adaptive emotion regulation, men showed a more definite tendency to use maladaptive emotion regulation.

Anandamide and sucralose change ΔFosB expression in the reward system.

Food reward has been studied with highly palatable stimuli that come from natural additives such as sucrose. The most common food additive is sucralose, a noncaloric sweetener present in many food products of daily intake. The role of anandamide [N-arachidonylethanolamide (AEA)], an endogenous cannabinoid, has been widely studied in food behavior. Studies have shown that cannabinoids, such as AEA, 2-Arachidonilglycerol, and Tetrahydrocannabinol, can provoke hyperphagia, because they enhance the preference and intake of sweet and high-fat food. Taste perception is mediated by receptors taste type 1 receptor 3 (T1R3); therefore, there could be a synergistic effect between receptors CB1 and T1R3. This could explain why cannabinoids could change sweet taste perception and therefore the activity of neural nuclei involved in taste and reward. In this study, we evaluated the activity of dopaminergic nuclei implicated in food reward after the chronic administration of AEA (0.5 mg/kg bw) and sucralose intake (0.02%). We analyzed the expression of ΔFosB by immunohistochemistry. Our results show that the chronic administration of AEA and sucralose intake induces an overexpression of ΔFosB in the infralimbic cortex (Cx), nucleus accumbens (NAc) core, shell, and central nucleus of amygdala (Amy). These results suggest that the possible interaction between receptors CB1 and T1R3 has consequences not only in taste perception but also that AEA intervenes in the activity of dopaminergic nuclei such as the NAc, and that the chronic administration AEA and sucralose intake induce long-term changes in the reward system.

c-Fos immunoreactivity in the hypothalamus and reward system of young rats after social novelty exposure.

Socialization is an adaptive behavior during the early stages of life because it helps young animals become independent and determines healthy adult social behavior. Therefore, it is probable that the brain areas involved in the processing of social stimuli are more sensitive to social novelty during early life stages. To test this hypothesis, four groups of young male rats were exposed to different socioenvironmental stimuli; nonsocial physical novelty, social familiarity, social novelty, and a control group which received no stimulation. After stimuli exposure, brains were fixed and cut in coronal sections for c-Fos immunohistochemistry. The number of c-Fos-immunoreactive (c-Fos-ir) neurons in the paraventricular nucleus and supraoptic nucleus, the main producers of oxytocin and vasopressin, was compared, as well as in the nucleus accumbens and ventral pallidum, the main areas involved in reinforced behavior. A significantly higher number of c-Fos-ir neurons were found in animals exposed to social novelty in all areas, except in the supraoptic nucleus. In particular, the increase in c-Fos-ir in the paraventricular nucleus seems to be selective in response to social novelty, while the increase of c-Fos-ir in the nucleus accumbens and ventral pallidum suggests that social novelty during youth is a highly rewarding stimulus compared with social familiarity and nonsocial physical novelty.

Enriched environment attenuates nicotine self-administration and induces changes in ΔFosB expression in the rat prefrontal cortex and nucleus accumbens.

Environment enrichment conditions have important consequences on subsequent vulnerability to drugs of abuse. The present work examined whether exposure to an enriched environment (EE) decreases oral self-consumption of nicotine. Wistar rats were housed either in a standard environment (SE, four rats per standard cage) or in an EE during 60 days after weaning. EE consisted of eight animals housed in larger cages containing a variety of objects such as boxes, toys, and burrowing material that were changed three times a week. After this period, animals were exposed to nicotine for 3 weeks, where animals chose freely between water and a nicotine solution (0.006% in water). Fluid consumption was evaluated on a daily basis. ΔFosB immunohistochemistry in the prefrontal cortex and nucleus accumbens was also performed. Rats of the EE group consumed less nicotine solution (0.25±0.04 mg/kg/day) than SE rats (0.54±0.05 mg/kg/day). EE increased the number of ΔFos-immunoreactive (ΔFos-ir) cells in the nucleus accumbens core and shell and in the prefrontal cortex, compared with animals in the standard condition. However, rats exposed to nicotine in the SE showed higher ΔFos-ir cells in the nucleus accumbens core and shell than nonexposed rats. Nicotine consumption did not modify ΔFos-ir cells in these brain areas in EE animals. These results support the idea of a possible protective effect of the EE on reward sensitivity and the development of an addictive behavior to nicotine.

Origin, functional role, and clinical impact of Fanconi anemia FANCA mutations.

Fanconi anemia is characterized by congenital abnormalities, bone marrow failure, and cancer predisposition. To investigate the origin, functional role, and clinical impact of FANCA mutations, we determined a FANCA mutational spectrum with 130 pathogenic alleles. Some of these mutations were further characterized for their distribution in populations, mode of emergence, or functional consequences at cellular and clinical level. The world most frequent FANCA mutation is not the result of a mutational "hot-spot" but results from worldwide dissemination of an ancestral Indo-European mutation. We provide molecular evidence that total absence of FANCA in humans does not reduce embryonic viability, as the observed frequency of mutation carriers in the Gypsy population equals the expected by Hardy-Weinberg equilibrium. We also prove that long distance Alu-Alu recombination can cause Fanconi anemia by originating large interstitial deletions involving FANCA and 2 adjacent genes. Finally, we show that all missense mutations studied lead to an altered FANCA protein that is unable to relocate to the nucleus and activate the FA/BRCA pathway. This may explain the observed lack of correlation between type of FANCA mutation and cellular phenotype or clinical severity in terms of age of onset of hematologic disease or number of malformations.

Chromosome fragility in patients with Fanconi anaemia: diagnostic implications and clinical impact.

BACKGROUND: Fanconi anaemia (FA) is a rare syndrome characterized by bone marrow failure, malformations and cancer predisposition. Chromosome fragility induced by DNA interstrand crosslink (ICL)-inducing agents such as diepoxybutane (DEB) or mitomycin C (MMC) is the 'gold standard' test for the diagnosis of FA. OBJECTIVE: To study the variability, the diagnostic implications and the clinical impact of chromosome fragility in FA. METHODS: Data are presented from 198 DEB-induced chromosome fragility tests in patients with and without FA where information on genetic subtype, cell sensitivity to MMC and clinical data were available. RESULTS: This large series allowed quantification of the variability and the level of overlap in ICL sensitivity among patients with FA and the normal population. A new chromosome fragility index is proposed that provides a cut-off diagnostic level to unambiguously distinguish patients with FA, including mosaics, from non-FA individuals. Spontaneous chromosome fragility and its correlation with DEB-induced fragility was also analysed, indicating that although both variables are correlated, 54% of patients with FA do not have spontaneous fragility. The data reveal a correlation between malformations and sensitivity to ICL-inducing agents. This correlation was also statistically significant when the analysis was restricted to patients from the FA-A complementation group. Finally, chromosome fragility does not correlate with the age of onset of haematological disease. CONCLUSIONS: This study proposes a new chromosome fragility index and suggests that genome instability during embryo development may be related to malformations in FA, while DEB-induced chromosome breaks in T cells have no prognostic value for the haematological disease.

Cytotoxic effects of new trans-2,4-diaryl-r-3-methyl-1,2,3,4-tetrahydroquinolines and their interaction with antitumoral drugs gemcitabine and paclitaxel on cellular lines of human breast cancer.

Two tetrahydroquinoline compounds, called DM8 and DM12, from a new series of the cis-2,4-diaryl-r-3-methyl-1,2,3,4-tetrahydroquinolines, were selected for cytotoxic effects studies on cellular lines of human breast cancer. The synergistic, additive and antagonistic effects in combination of these compounds with anticancer drugs, such as paclitaxel and gemcitabine, were studied. The isobolograms and their analysis demonstrated models of synergism, additivity and antagonism of these tetrahydroquinolines in the presence of paclitaxel and gemcitabine. Results showed that compounds DM8 and DM12 individually induced growth inhibition on breast cancer cell lines MCF-7 and SKBR3, and the addition of paclitaxel and gemcitabine intensified their cytotoxic activity on both cell lines at conc. below 1 µg/mL. During these studies the compound DM12 was identified as new, perspective and safe agent for adjuvant therapy.

Cytotoxic activity of seco-entkaurenes from Croton caracasana on human cancer cell lines.

In the course of searching for bioactive compounds from Croton species from Venezuela, two seco-entkaurenes isolated from flowers of Croton caracasana were evaluated in vitro for their effect on cell viability by the standard MTT assay in nine human cancer cell lines of different origins and one primary culture. Both compounds induced cytotoxicity in the range of 2 to 25 microM for caracasine and 0.8 to 12 microM for caracasine acid. However, for the normal fibroblasts and the cell lines, HeLa, MCF-7, PC-3, LoVo, X-17, Jurkat E6.1 and Jurkat JCaM1.6, the IC50 values of caracasine acid were lower than their counterparts. Interestingly, no differences in IC50 were recorded for the leukemic cell lines U937 and K562. It can be concluded that the acid moiety in the structure enhances the cytotoxic effect of caracasine by a pathway which seems not to be activated in the leukemic cell lines tested.

Sleep-inducing factors.

Kuniomi Ishimori and Henri Piéron were the first researchers to introduce the concept and experimental evidence for a chemical factor that would presumably accumulate in the brain during waking and eventually induce sleep. This substance was named hypnotoxin. Currently, the variety of substances which have been shown to alter sleep includes peptides, cytokines, neurotransmitters and some substances of lipidic nature, many of which are well known for their involvement in other biological activities. In this chapter, we describe the sleep-inducing properties of the vasoactive intestinal peptide, prolactin, adenosine and anandamide.

Allogeneic stem cell transplantation for myelodysplastic syndromes in children: a report from the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON).

INTRODUCTION: Experience with the use of allogeneic hemopoietic stem transplantation (AHSCT) in pediatric myelodisplastic syndrome (MDS) in Spain is reviewed. METHODS AND PATIENTS: Twenty-four children with MDS were analyzed retrospectively. Median age of the patients was 10 years. Twenty patients received a bone marrow graft and 4 an unrelated cord blood (UCB) transplant; 12 bone marrow grafts were from a matched related donor (MRD) and 8 from a matched unrelated donor (MUD). Conditioning regimen consisted of chemotherapy alone in 17 patients (busulfan and cyclophosphamide +/- melfalan) Seven patients received TBI and cyclophosphamide. RESULTS: Ten patients died from transplant-related toxicity and 4 had relapse or disease progression post-AHSCT. Nine patients are alive and event-free with a median follow-up of 120 months. EFS rate in the MRD group was 0.48 (SE 0.13) versus 0.25 (SE 0.12) in the MUD/UCB group (p = .07). Lansky score in survivors is >or=90%. CONCLUSIONS: In this historical series of children with MDS, in spite of severe transplant-related toxicity, encouraging EFS outcomes have been achieved after AHSCT with good quality of life.

Long-term results of the Spanish Protocol SO-95 for the treatment of non-metastatic high-grade osteosarcoma of the extremities in children.

INTRODUCTION: The long-term results of the Spanish Study Protocol SEOP-SO-95 for treatment of localised osteosarcoma of the extremities in children were evaluated. PATIENTS AND METHODS: One hundred consecutive patients under 18 years of age from 22 institutions were enrolled from January 1995 to December 2000. Immunohistochemical expression of p53, HER/erbB-2 and P-glycoprotein were retrospectively studied in 27 patients. Treatment consisted of: preoperative chemotherapy with doxorubicin, cisplatin, high-dose methotrexate with leucovorin rescue and ifosfamide for 14 weeks; surgery of primary tumour in week 16; postoperative chemotherapy with the above-mentioned drugs for 25 weeks. RESULTS: With a median follow-up of 124 months (range 84-158 months), 69 patients (69%) were continuously event-free survivors; the 10-year probability of event-free survival (EFS) was 62%. Conservative surgery was performed in 85% of patients. Twenty-six patients had local recurrence or distant relapse. The median time to recurrence/ relapse was 27 months (range 17-93 months). The local recurrence rate was 7% (7 of the 100 patients); 4 had wide surgical margins, 2 marginal and 1 intralesional. Four patients died as a result of chemotherapy-related toxicity and 1 developed a second neoplasia (acute myeloid leukaemia). p53 expression and HER2/erbB-2 expression showed no effect on survival or EFS. CONCLUSIONS: This therapeutic protocol achieved good oncologic and orthopaedic results. We observed a significant treatment-related toxicity.

Long-term results of two consecutive trials in childhood acute lymphoblastic leukaemia performed by the Spanish Cooperative Group for Childhood Acute Lymphoblastic Leukemia Group (SHOP) from 1989 to 1998.

INTRODUCTION: The first multi-centric protocol for childhood acute lymphoblastic leukaemia (ALL) treatment in Spain started in 1989 and was conducted by the Spanish Pediatric Hematology and Oncology Societies. MATERIALS AND METHODS: A total of 673 patients were included in two consecutive trials, SHOP-89 (1989-1993) and SHOP- 94 (1994-1998). Approximately 67% of the children diagnosed with ALL in Spain during this period were enrolled in these trials. The 250 eligible patients enrolled in the SHOP- 89 study were stratified to either a standard or a high-risk group. Therapy schedule was based on the central nervous system (CNS) therapy designed by St Jude CRH and the Children's Cancer Group, and the post-induction intensification developed by the BFM group. In the SHOP-94 study, a further high-risk group was included in the stratification of the 423 enrolled patients. The therapeutic protocol was characterised by intensification of systemic chemotherapy and the administration of cranial radiotherapy only to patients at high risk of relapse or with CNS involvement at diagnosis. RESULTS: Event-free survival (EFS) increased from 0.57+/- 0.03 at 15 years in SHOP-89, to 0.68+/-0.03 at 11 years in SHOP-94 (p=0.01). Relapse rate decreased from SHOP-89 to SHOP-94: 0.38 vs. 0.25 (p=0.01). CNS relapse rate was 9.1% in SHOP-89 and 4.6% in SHOP-94 (p=0.001). EFS in patients with T-immunophenotype was 0.40+/-0.08 in SHOP-89 and 0.44+/-0.06 in SHOP-94 (p=ns). CONCLUSIONS: Our therapeutic results evidence a significant improvement in EFS and systemic and CNS relapse rates among the two consecutive trials after modification of patient stratification and intensification of systemic chemotherapy.

A comprehensive strategy for the subtyping of patients with Fanconi anaemia: conclusions from the Spanish Fanconi Anemia Research Network.

BACKGROUND: Fanconi anaemia is a heterogeneous genetic disease, where 12 complementation groups have been already described. Identifying the complementation group in patients with Fanconi anaemia constitutes a direct procedure to confirm the diagnosis of the disease and is required for the recruitment of these patients in gene therapy trials. OBJECTIVE: To determine the subtype of Fanconi anaemia patients in Spain, a Mediterranean country with a relatively high population (23%) of Fanconi anaemia patients belonging to the gypsy race. METHODS: Most patients could be subtyped by retroviral complementation approaches in peripheral blood T cells, although some mosaic patients were subtyped in cultured skin fibroblasts. Other approaches, mainly based on western blot analysis and generation of nuclear RAD51 and FANCJ foci, were required for the subtyping of a minor number of patients. RESULTS AND CONCLUSIONS: From a total of 125 patients included in the Registry of Fanconi Anaemia, samples from 102 patients were available for subtyping analyses. In 89 cases the subtype could be determined and in 8 cases exclusions of common complementation groups were made. Compared with other international studies, a skewed distribution of complementation groups was observed in Spain, where 80% of the families belonged to the Fanconi anaemia group A (FA-A) complementation group. The high proportion of gypsy patients, all of them FA-A, and the absence of patients with FA-C account for this characteristic distribution of complementation groups.