Glucose Load Following Prolonged Fasting Increases Oxidative Stress-Linked Response in Individuals With Diabetic Complications.

OBJECTIVE: Prolonged catabolic states in type 2 diabetes (T2D), exacerbated by excess substrate flux and hyperglycemia, can challenge metabolic flexibility and antioxidative capacity. We investigated cellular responses to glucose load after prolonged fasting in T2D. RESEARCH DESIGN AND METHODS: Glucose-tolerant individuals (CON, n = 10), T2D individuals with (T2D+, n = 10) and without diabetes complications (T2D-, n = 10) underwent oral glucose tolerance test before and after a 5-day fasting-mimicking diet. Peripheral blood mononuclear cells' (PBMC) resistance to ex vivo dicarbonyl methylglyoxal (MG) exposure after glucose load was assessed. Markers of dicarbonyl detoxification, oxidative stress, and mitochondrial biogenesis were analyzed by quantitative PCR, with mitochondrial complex protein expression assessed by western blotting. RESULTS: T2D+ exhibited decreased PBMC resistance against MG, while T2D- resistance remained unchanged, and CON improved postglucose load and fasting (-19.0% vs.-1.7% vs. 12.6%; all P = 0.017). T2D+ showed increased expression in dicarbonyl detoxification (mRNA glyoxalase-1, all P = 0.039), oxidative stress (mRNA glutathione-disulfide-reductase, all P = 0.006), and mitochondrial complex V protein (all P = 0.004) compared with T2D- and CON postglucose load and fasting. Citrate synthase activity remained unchanged, indicating no change in mitochondrial number. Mitochondrial biogenesis increased in T2D- compared with CON postglucose load and fasting (mRNA HspA9, P = 0.032). T2D-, compared with CON, exhibited increased oxidative stress postfasting, but not postglucose load, with increased mRNA expression in antioxidant defenses (mRNA forkhead box O4, P = 0.036, and glutathione-peroxidase-2, P = 0.034), and compared with T2D+ (glutathione-peroxidase-2, P = 0.04). CONCLUSIONS: These findings suggest increased susceptibility to glucose-induced oxidative stress in individuals with diabetes complications after prolonged fasting and might help in diet interventions for diabetes management.

Management of Skin Lesions in Patients with Epidermolysis Bullosa by Topical Treatment: Systematic Review and Meta-Analysis.

Epidermolysis bullosa (EB) is the overarching term for a set of rare inherited skin fragility disorders that result from mutations in at least 20 different genes. Currently, there is no cure for any of the EB subtypes associated with various mutations. Existing therapies primarily focus on alleviating pain and promoting early wound healing to prevent potential complications. Consequently, there is an urgent need for innovative therapeutic approaches. The objective of this research was to assess the efficacy of various topical treatments in patients with EB with the goal of achieving wound healing. A secondary objective was to analyse the efficacy of topical treatments for symptom reduction. A literature search was conducted using scientific databases, including The Cochrane Library, Medline (Pubmed), Web of Science, CINHAL, Embase, and Scopus. The protocol review was registered in PROSPERO (ID: 418790), and inclusion and exclusion criteria were applied, resulting in the selection of 23 articles. Enhanced healing times were observed compared with the control group. No conclusive data have been observed on pain management, infection, pruritus episodes, and cure rates over time. Additionally, evidence indicates significant progress in gene therapies (B-VEC), as well as cell and protein therapies. The dressing group, Oleogel S-10, allantoin and diacerein 1%, were the most represented, followed by fibroblast utilisation. In addition, emerging treatments that improve the patient's innate immunity, such as calcipotriol, are gaining attention. However, more trials are needed to reduce the prevalence of blistering and improve the quality of life of individuals with epidermolysis bullosa.

Placenta Accreta: A Case Report on the Role of Interventional Radiology.

Placenta accreta spectrum disorder is a pregnancy-related disorder responsible for important post-partum morbimortality, associated with intractable or massive hemorrhage, leading to uterine loss in up to 64% of women. Despite international recommendations advocating planned preterm cesarean hysterectomy for the management of these patients, uterus preservation management is being continuously reported with the implementation of minimally invasive bleeding reduction strategies, such as prophylactic balloon-assisted occlusion. We present the case of a 40-year-old pregnant woman with a previous cesarean, diagnosed with placenta previa and suspected placenta accreta on magnetic resonance after having second-trimester vaginal bleeding. A peri-operative multidisciplinary panel was involved, in collaboration with the interventional radiologist, and the c-section was scheduled for 36 weeks of gestation. The prophylactic balloon-assisted occlusion was successfully performed, minimizing the blood loss and allowing a uterus-preserving approach.

Assessment of main complications of regional anesthesia recorded in an acute pain unit in a tertiary care university hospital: a retrospective cohort

Abstract Background Regional anesthesia has been increasingly used. Despite its low number of complications, they are associated with relevant morbidity. This study aims to evaluate the incidence of complications after neuraxial block and peripheral nerve block. Methods A retrospective cohort study was conducted, and data related to patients submitted to neuraxial block and peripheral nerve block at a tertiary university hospital from January 1, 2011 to December 31, 2017 were analyzed. Results From 10,838 patients referred to Acute Pain Unit, 1093(10.1%) had side effects or complications: 1039 (11.4%) submitted to neuraxial block and 54 (5.2%) to peripheral nerve block. The most common side effects after neuraxial block were sensory (48.5%) or motor deficits (11.8%), nausea or vomiting (17.5%) and pruritus (8.0%); The most common complications: 3 (0.03%) subcutaneous cell tissue hematoma, 3 (0.03%) epidural abscesses and 1 (0.01%) arachnoiditis. 204 of these patients presented sensory or motor deficits at hospital discharge and needed follow-up. Permanent peripheral nerve injury after neuraxial block had an incidence of 7.7:10,000 (0.08%). The most common side effects after peripheral nerve block were sensory deficits (52%) and 21 patients maintained follow-up due to symptoms persistence after hospital discharge. Conclusion Although we found similar incidences of side effects or even lower than those described, major complications after neuraxial block had a higher incidence, particularly epidural abscesses. Despite this, other serious complications, such as spinal hematoma and permanent peripheral nerve injury, are still rare.

Efficacy and safety of FOLFIRI/aflibercept (FA) in an elderly population with metastatic colorectal cancer (mCRC) after failure of an oxaliplatin-based regimen.

BACKGROUND: The VELOUR study showed the benefit of FOLFIRI-Aflibercept (FA) versus FOLFIRI in patients with metastatic colorectal cancer (mCRC) in second-line treatment. However, only 36% of the included patients were ≥65 years. Thus, we seek to evaluate the efficacy and safety of FA in the elderly population in the context of routine practice. MATERIALS AND METHODS: We conducted an observational, retrospective, multicenter, observational study of patients ≥70 years with mCRC treated with FA after progression to oxaliplatin chemotherapy in routine clinical practice in 9 hospitals of the GITuD group. RESULTS: Of 388 patients treated with FA between June 2013 and November 2018, 75 patients ≥70 years were included. The median number of cycles was 10 and the objective response (ORR) and disease control rates (DCR) were 33.8% and 72.0%, respectively. With a median follow-up of 27.1 months, median Progression-free survival (PFS) was 6.6 months and median Overall Survival (OS) was 15.1 months. One third fewer metastasectomies were performed in the ≥75 years' subgroup (24 vs. 52%, p = 0.024) and more initial FOLFIRI dose reductions (68 vs. 36%, p = 0.014). ORR (23.8% vs. 38.3%), DCR (42.8% vs. 85.1%), and PFS (4 vs. 7.8 months; p = 0.017) were significantly less, without difference in OS (9.9 vs. 17.1 months; p = 0.129). The presence of prior hypertension (HT) (PFS 7.9 vs. 5.7 months, p = 0.049) and HT ≥ grade 3 during treatment (PFS 7.6 vs. 6.6 months, p = 0.024) were associated with longer PFS. The most frequent grade 3/4 adverse events were: asthenia (21.3%), neutropenia (14.7%), and diarrhea (14.7%). 57.3% required FOLFIRI dose reduction; 34.7% of aflibercept, including discontinuation (5.3% and 18.7%, respectively). CONCLUSIONS: FA combination is effective in patients ≥70 years. The occurrence of HT is predictive of efficacy. Close monitoring of toxicity and initial dose adjustment is recommended.

Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS): Protocol for a randomized controlled trial.

RATIONALE: Atrial fibrillation causes one-fifth of ischemic strokes, with a high risk of early recurrence. Although long-term anticoagulation is highly effective for stroke prevention in atrial fibrillation, initiation after stroke is usually delayed by concerns over intracranial hemorrhage risk. Direct oral anticoagulants offer a significantly lower risk of intracranial hemorrhage than other anticoagulants, potentially allowing earlier anticoagulation and prevention of recurrence, but the safety and efficacy of this approach has not been established. AIM: Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS) will investigate whether early treatment with a direct oral anticoagulant, within four days of stroke onset, is as effective or better than delayed initiation, 7 to 14 days from onset, in atrial fibrillation patients with acute ischemic stroke. METHODS AND DESIGN: OPTIMAS is a multicenter randomized controlled trial with blinded outcome adjudication. Participants with acute ischemic stroke and atrial fibrillation eligible for anticoagulation with a direct oral anticoagulant are randomized 1:1 to early or delayed initiation. As of December 2021, 88 centers in the United Kingdom have opened. STUDY OUTCOMES: The primary outcome is a composite of recurrent stroke (ischemic stroke or symptomatic intracranial hemorrhage) and systemic arterial embolism within 90 days. Secondary outcomes include major bleeding, functional status, anticoagulant adherence, quality of life, health and social care resource use, and length of hospital stay. SAMPLE SIZE TARGET: A total of 3478 participants assuming event rates of 11.5% in the control arm and 8% in the intervention arm, 90% power and 5% alpha. We will follow a non-inferiority gatekeeper analysis approach with a non-inferiority margin of 2 percentage points. DISCUSSION: OPTIMAS aims to provide high-quality evidence on the safety and efficacy of early direct oral anticoagulant initiation after atrial fibrillation-associated ischemic stroke.Trial registrations: ISRCTN: 17896007; ClinicalTrials.gov: NCT03759938.

Assessment of main complications of regional anesthesia recorded in an acute pain unit in a tertiary care university hospital: a retrospective cohort.

BACKGROUND: Regional anesthesia has been increasingly used. Despite its low number of complications, they are associated with relevant morbidity. This study aims to evaluate the incidence of complications after neuraxial block and peripheral nerve block. METHODS: A retrospective cohort study was conducted, and data related to patients submitted to neuraxial block and peripheral nerve block at a tertiary university hospital from January 1, 2011 to December 31, 2017 were analyzed. RESULTS: From 10,838 patients referred to Acute Pain Unit, 1093(10.1%) had side effects or complications: 1039 (11.4%) submitted to neuraxial block and 54 (5.2%) to peripheral nerve block. The most common side effects after neuraxial block were sensory (48.5%) or motor deficits (11.8%), nausea or vomiting (17.5%) and pruritus (8.0%); The most common complications: 3 (0.03%) subcutaneous cell tissue hematoma, 3 (0.03%) epidural abscesses and 1 (0.01%) arachnoiditis. 204 of these patients presented sensory or motor deficits at hospital discharge and needed follow-up. Permanent peripheral nerve injury after neuraxial block had an incidence of 7.7:10,000 (0.08%). The most common side effects after peripheral nerve block were sensory deficits (52%) and 21 patients maintained follow-up due to symptoms persistence after hospital discharge. CONCLUSION: Although we found similar incidences of side effects or even lower than those described, major complications after neuraxial block had a higher incidence, particularly epidural abscesses. Despite this, other serious complications, such as spinal hematoma and permanent peripheral nerve injury, are still rare.

Linfoma no Hodgkin primario de vagina o cuello uterino. Un diagnóstico en ocasiones incierto: a propósito de un caso / Primary non-Hodgkin´s lymphoma of vagina or cervix. A diagnosis sometimes uncertain: about a case

Resumen ANTECEDENTES: La afectación primaria del aparato genital femenino por un linfoma no Hodgkin es excepcional, se reporta en 0.2 a 1.1% de los casos. Los órganos afectados con más frecuencia son los ovarios, seguidos del cuello uterino; el endometrio y la vagina son los menos aquejados. Debido a su baja frecuencia aún no se llega a un consenso del tratamiento más adecuado de estos linfomas; hasta ahora, por lo general, se ha individualizado para cada caso en concreto. CASO CLÍNICO: Paciente de 29 años que consultó por sangrado genital anómalo e incapacidad para la inserción de tampones vaginales. En la exploración se encontró una masa pélvica, palpable a través de la vagina, que impresionaba al infiltrar toda la luz vaginal y la parte media e izquierda de la vulva. En los estudios de imagen se objetivó una gran masa pélvica de hasta 10 centímetros que parecía depender del cuello del útero y que se extendía e infiltraba el canal vaginal, la vulva y el tercio inferior de la vejiga. El reporte anatomopatológico de la biopsia fue: infiltración de pared vaginal por un linfoma no Hodgkin B difuso de células grandes. Se le indicaron seis ciclos de quimioterapia con ciclofosfamida, vincristina, adriamicina y prednisona con los que se consiguió la remisión metabólica completa. CONCLUSIÓN: El diagnóstico del linfoma genital primario puede resultar complejo por la posibilidad de simular una neoplasia ginecológica. En casos de enfermedad avanzada, la manifestación clínica más frecuente es el sangrado genital anómalo. El esquema de tratamiento más aceptado en la actualidad es con rituximab-ciclofosfamida, vincristina, adriamicina, prednisona seguido de radioterapia de consolidación.

Abstract BACKGROUND: Primary involvement of the female genital tract by non-Hodgkin's lymphoma is exceptional, reported in 0.2 to 1.1% of cases. The most frequently affected organs are the ovaries, followed by the cervix; the endometrium and vagina are the least affected. Due to their low frequency, there is still no consensus on the most appropriate treatment of these lymphomas; until now, it has generally been individualized for each specific case. CLINICAL CASE: A 29-year-old female patient consulted for abnormal genital bleeding and inability to insert vaginal tampons. On examination a pelvic mass was found, palpable through the vagina, which impressed by infiltrating the entire vaginal lumen and the middle and left side of the vulva. Imaging studies showed a large pelvic mass of up to 10 centimeters that appeared to be dependent on the cervix and that extended and infiltrated the vaginal canal, the vulva and the lower third of the bladder. The anatomopathological report of the biopsy was: infiltration of the vaginal wall by diffuse large cell non-Hodgkin's B lymphoma. She was prescribed six cycles of chemotherapy with cyclophosphamide, vincristine, adriamycin and prednisone with which complete metabolic remission was achieved. CONCLUSION: The diagnosis of primary genital lymphoma can be complex because of the possibility of simulating a gynecologic neoplasm. In cases of advanced disease, the most frequent clinical manifestation is abnormal genital bleeding. The most accepted treatment scheme at present is rituximab-cyclophosphamide, vincristine, adriamycin, prednisone followed by consolidation radiotherapy.

Dynamic perspective of the neutrophil-to-lymphocyte ratio in metastatic gastric cancer.

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) is an accessible marker from a routine blood test. This study explored the prognostic and predictive value of a change in NLR (c-NLR) after chemotherapy, baseline NLR (bNLR) and chemotherapy response, in metastatic gastric cancer (mGC) patients. METHODS: A total of 116 mGC patients treated between 2009 to 2019 at seven hospitals from Galician Research Group on Digestive Tumors (GITuD) were reviewed in a multicentre, ambispective and observational study. NLR was calculated and the optimal cut-off was defined as NLR=3.96 based on ROC method. NLR was determined at baseline and after two chemotherapy cycles in first line treatment. Change NLR was calculated as NLR after two chemotherapy cycles minus bNLR. The relation of bNLR and c-NLR to overall survival (OS) was evaluated by Kaplan-Meier method and compared by log-rank test. Dynamic Score (DScore) based on c-NLR and baseline NLR were correlated with OS and radiological response. Univariate, multivariate and chi-square analyses were performed. RESULTS: Median patient age was 68.7 years, and 66% were male. Univariate analysis showed OS correlation for bNLR ≥3.96 (5.97 vs 10.87 months, p=0.001), c-NLR increase (6.63 vs 10.34 months, p=0.021) and DScore (12.74 vs 7.68 vs 2.43 months, p<0.001). High DScore was associated with radiological progression after two cycles (x2=10.26, p=0.006). Multivariate analysis: bNLR ≥3.96 (HR=2.16, p=0.003) and c-NLR increase (HR= 2.36, p=0.003) were prognostic factors of poor OS. CONCLUSION: High bNLR and increased NLR after chemotherapy were associated with worse outcome. Dynamic measurement of NLR provides information for stratifying patients to guide optimal treatment.

Is Supplementation with Micronutrients Still Necessary during Pregnancy? A Review.

INTRODUCTION: Proper nutrition during pregnancy is important to prevent nutritional imbalances that interfere with pregnancy. Micronutrients play critical roles in embryogenesis, fetal growth, and maternal health, as energy, protein, vitamin, and mineral needs can increase during pregnancy. Increased needs can be met by increasing the intake of dietary micronutrients. Severe micronutrient deficiency or excess during pregnancy can have negative effects on fetal growth (intrauterine growth retardation, low birth weight, or congenital malformations) and pregnancy development (pre-eclampsia or gestational diabetes). We investigate whether it is necessary to continue micronutrient supplementation during pregnancy to improve women's health in this stage and whether this supplementation could prevent and control pathologies associated with pregnancy. AIM: The present review aims to summarize evidence on the effects of nutritional deficiencies on maternal and newborn morbidity. METHODS: This aim is addressed by critically reviewing results from published studies on supplementation with different nutrients during pregnancy. For this, major scientific databases, scientific texts, and official webpages have been consulted. PubMed searches using the terms "pregnancy" OR "maternal-fetal health" AND "vitamins" OR "minerals" OR "supplementation" AND "requirement" OR "deficiency nutrients" were performed. RESULTS: There are accepted interventions during pregnancy, such as folic acid supplementation to prevent congenital neural tube defects, potassium iodide supplementation to correct neurodevelopment, and oral iron supplementation during the second half of pregnancy to reduce the risk of maternal anemia and iron deficiency. A number of micronutrients have also been associated with pre-eclampsia, gestational diabetes mellitus, and nausea and vomiting in pregnancy. In general, experimental studies are necessary to demonstrate the benefits of supplementation with different micronutrients and to adjust the recommended daily doses and the recommended periconceptional nutrition for mothers. CONCLUSIONS: Presently, there is evidence of the benefits of micronutrient supplementation in perinatal results, but indiscriminate use is discouraged due to the fact that the side effects of excessive doses are not known. Evidence supports the idea that micronutrient deficiencies negatively affect maternal health and the outcome of pregnancy. No single micronutrient is responsible for the adverse effects; thus, supplementing or correcting one deficiency will not be very effective while other deficiencies exist.

Do Clinical Trials Meet Current Care Needs? Views of Digestive Oncology Specialists in Galicia (Spain) Using the Delphi Method.

Background: In recent years, abundant scientific evidence has been generated based on clinical trials (CT) in the field of oncology. The general objective of this paper is to find out the extent to which decision making is based on knowledge of the most recent CT. Its specific objectives are to pinpoint difficulties with decision making based on the CT performed and find out the motivations patients and clinicians have when taking part in a CT. Methodology: Combined, prospective study, based on the Delphi method. A lack of correspondence between the people who take part in CT and patients who come for consultation has been identified. A need for training in analysing and interpreting CT has also been identified and a lack of trust in the results of CT financed by the pharmaceutical industry itself has been perceived. Conclusions: There is a difficulty in selecting oncological treatment due to the lack of correspondence between the patients included in the CT and patients seen in consultation. In this process, real world data studies may be highly useful, as they may provide this group with greater training in interpreting CT and their results.

Tumor de células de Sertoli-Leydig: a propósito de un caso y revisión de la literatura reciente / Ovarian Sertoli-Leydig cell tumour: a clinical case and recent basic literature review

INTRODUCCIÓN: Los tumores de células de Sertoli-Leydig son neoplasias de ovario infrecuentes, lo que dificulta su diagnóstico y tratamiento. OBJETIVO: Revisar y sintetizar el manejo actual de los tumores de células de Sertoli-Leydig. MÉTODO: Se realizó una revisión de la literatura reciente sobre tumores de células de Sertoli-Leydig, a propósito de un caso en nuestro centro. RESULTADOS: Los tumores de las células de Sertoli-Leydig son infrecuentes, con mayor incidencia en edades tempranas. Ante una paciente joven con una lesión anexial unilateral y signos de virilización deberán considerarse estos tumores dentro del diagnóstico diferencial. En los estadios iniciales y en pacientes jóvenes podrá plantearse un tratamiento quirúrgico que preserve la fertilidad, y la asociación de tratamiento adyuvante dependerá de la diferenciación y del estadiaje del tumor.

INTRODUCTION: Sertoli-Leydig cell tumors are infrequent ovarian neoplasms, which difficults their diagnosis and treatment. Objective: To review and synthesize the current management of the Sertoli-Leydig cell tumor. METHOD: A review of the recent literature regarding the Sertoli-Leydig cell tumor was carried out, regarding a case in our center. RESULTS: Sertoli-Leydig cell tumors are an infrequent entity, with a higher incidence in early ages. In a young patient with a unilateral adnexal lesion and signs of virilization, these tumors should be considered within the differential diagnosis. In early stages and young patients, a surgical treatment that preserves fertility may be considered, and the association of adjuvant treatment will depend on the differentiation and staging of the tumor.

Behavioral impact of experience based on environmental enrichment: Influence of age and duration of exposure in male NMRI mice.

Prior studies have suggested that short periods of exposure to environmental enrichment (EE) in rodents induce physiological and behavioral effects. In the present study, our aim was to evaluate if the impact of experiences based on EE could be modulated by the age of onset and the developmental period of exposure. NMRI male mice (n = 64) were exposed to EE or standard environment (SE) and behavioral changes (anxiety, exploration, memory and social interaction) were evaluated. Groups compared were: (a) SE: exposure to SE on post-natal day (PND) 28 and lasting 6 months; (b) EE-6: exposure to EE on PND 28 and lasting 6 months; (c) EE-4: exposure to EE on PND 91 and lasting 4 months; (d) EE-2: exposure to EE on PND 154 and lasting 2 months. Results indicated that in the hole-board task the decrease in exploratory behavior reached significance when EE was initiated at adolescence whereas anxiolytic effects in the elevated plus-maze tend to diminish after a longer period of EE. No significant effects of EE on aggressive behavior or novel object recognition were obtained. Taking these results into account, further studies are needed in order to determine the possible modulating role of age and duration of exposure to enriched environments on behavior. Results obtained could explain some discrepancies reported in previous studies, providing new evidence that could contribute to the design of future research related to the benefits of complex and enriched environments.

Michaelis-Menten Kinetics Measurements of Aldo-Keto Reductases for Various Substrates in Murine Tissue.

Aldo-keto reductases (AKRs) are responsible for the detoxification of harmful aldehydes. Due to the large number of isotypes, the physiological relevance of AKRs cannot be obtained using mRNA or protein quantification, but only through the use of enzymatic assays to demonstrate functionality. Here, we present a fast and simple protocol to determine the important Michaelis-Menten kinetics of AKRs, which includes various aldehyde substrates of interest such as 4-hydroxynonenal, methylglyoxal, and malondialdehyde. For complete details on the use and execution of this protocol, please refer to Morgenstern et al. (2017) and Schumacher et al. (2018).

The Glyoxalase System-New Insights into an Ancient Metabolism.

The glyoxalase system was discovered over a hundred years ago and since then it has been claimed to provide the role of an indispensable enzyme system in order to protect cells from a toxic byproduct of glycolysis. This review gives a broad overview of what has been postulated in the last 30 years of glyoxalase research, but within this context it also challenges the concept that the glyoxalase system is an exclusive tool of detoxification and that its substrate, methylglyoxal, is solely a detrimental burden for every living cell due to its toxicity. An overview of consequences of a complete loss of the glyoxalase system in various model organisms is presented with an emphasis on the role of alternative detoxification pathways of methylglyoxal. Furthermore, this review focuses on the overlooked posttranslational modification of Glyoxalase 1 and its possible implications for cellular maintenance under various (patho-)physiological conditions. As a final note, an intriguing point of view for the substrate methylglyoxal is offered, the concept of methylglyoxal (MG)-mediated hormesis.

Phosphorylation of T107 by CamKIIδ Regulates the Detoxification Efficiency and Proteomic Integrity of Glyoxalase 1.

The glyoxalase system is a highly conserved and ubiquitously expressed enzyme system, which is responsible for the detoxification of methylglyoxal (MG), a spontaneous by-product of energy metabolism. This study is able to show that a phosphorylation of threonine-107 (T107) in the (rate-limiting) Glyoxalase 1 (Glo1) protein, mediated by Ca2+/calmodulin-dependent kinase II delta (CamKIIδ), is associated with elevated catalytic efficiency of Glo1 (lower KM; higher Vmax). Additionally, we observe proteasomal degradation of non-phosphorylated Glo1 via ubiquitination does occur more rapidly as compared with native Glo1. The absence of CamKIIδ is associated with poor detoxification capacity and decreased protein content of Glo1 in a murine CamKIIδ knockout model. Therefore, phosphorylation of T107 in the Glo1 protein by CamKIIδ is a quick and precise mechanism regulating Glo1 activity, which is experimentally linked to an altered Glo1 status in cancer, diabetes, and during aging.

Carcinoma endometrioide sincrónico de ovario y endometrio / Ovarian and endometrial synchronous endometrioid carcinoma

ANTECEDENTES: existe una asociación demostrada entre endometriosis y algunas histologías del carcinoma epitelial de ovario. Por otra parte, se ha observado que hasta un 30% de las neoplasias de ovario se presentan de forma concomitante a neoplasias del endometrio. Para considerar la sincronicidad entre estos tumores, estos deben cumplir criterios anatomopatológicos estrictos como los descritos por scully. OBJETIVO: presentar un caso clínico de carcinoma endometrioide sincrónico de ovario y endometrio sobre focos de endometriosis, así como su diagnóstico y manejo. CASO CLÍNICO: paciente de 27 años que consulta por spotting intermenstrual. En la ecografía endocavitaria se observa un pólipo endometrial. Además, se describe un tumor anexial izquierdo de 42mm, trilobulado, con un polo sólido de 17×15mm. Se somete a una polipectomía histeroscópica y quistectomía ovárica laparoscópica. Asimismo, se reseca implante sospechoso en el fondo de saco posterior. El resultado anatomopatológico de las piezas quirúrgicas fue: pólipo endometrial con hiperplasia compleja con atipias y focos de adenocarcinoma endometrioide grado I; el tumor quístico ovárico izquierdo consistente con quiste endometriósico con focos de adenocarcinoma endometrioide. La lesión peritoneal corresponde a un implante de adenocarcinoma endometrioide grado I. El estudio de las características anatomopatológicas y la presencia del implante peritoneal sugieren el diagnóstico de un carcinoma endometrioide ovárico con origen en una lesión endometriósica sincrónico con un carcinoma endometrioide endometrial. CONCLUSIÓN: el diagnóstico diferencial entre la sincronicidad o diseminación de los tumores de ovario y endometrio de estirpe endometrioide supone un reto para el clínico y es fundamental para el correcto manejo de estas neoplasias.

BACKGROUND: there is a demonstrated association between endometriosis and some epithelial ovarian carcinoma histologies. On the other hand, it has been observed that up to 30% of ovarian neoplasms present concomitantly with endometrial neoplasms. To consider synchronicity between these neoplasms, they must meet strict pathological criteria such as those described by scully. OBJECTIVE: to introduce a case of an ovarian and endometrial synchronous endometrioid carcinoma implanted on endometriosis sites, as well as its diagnosis and management. CLINICAL CASE: a 27-year-old patient who consulted because of an intermenstrual spotting. The ultrasound image showed an endometrial polyp. Furthermore, a 42 mm left adnexal trilobal tumor with a 17×15mm solid pole was described. She underwent a hysteroscopic polypectomy and laparoscopic ovarian cystectomy. Likewise, resection of a suspicious implant in the posterior vaginal fornix was done. The pathological result of the surgical pieces was: endometrial polyp with complex hyperplasia with atypia and focal points of grade I endometrioid adenocarcinoma; the left ovarian cystectomy: endometriotic cyst with focal points of endometrioid adenocarcinoma. The peritoneal lesion corresponded to a grade I endometrioid adenocarcinoma implant. The study of the pathological characteristics and the presence of the peritoneal implant suggest the diagnosis of endometrioid ovarian carcinoma originated in a synchronous endometriotic lesion with endometrial endometrioid carcinoma. CONCLUSION: differential diagnosis between the synchronicity or spread of ovarian and endometrial endometrioid cell line carcinomas, is a great challenge and it is essential for the correct management of these neoplasms

The Mediational Role of Burden and Perceived Stress in Subjective Memory Complaints in Informal Cancer Caregivers.

The role of informal caregiver of cancer patients is considered a situation of chronic stress that could have impact on cognitive functioning. Our aim was to evaluate differences in perceived stress, subjective memory complaints, self-esteem, and resilience between caregivers and non-caregivers, as well as the possible mediational role of burden in caregivers. The sample was composed of 60 participants divided into two groups: (1) Primary informal caregivers of a relative with cancer (CCG) (n = 34); and (2) non-caregiver control subjects (Non-CG) (n = 26). All participants were evaluated through a battery of tests: Socio-demographic questionnaire, subjective memory complaints questionnaire (MFE-30), Rosenberg Self-Esteem Scale, resilience (CD-RISC-10), and perceived stress scale (PSS). The CCG group also completed the Zarit burden interview. Results indicated that CCG displayed higher scores than Non-CG in MFE-30 (p = 0.000) and PSS (p = 0.005). In the CCG group, Pearson correlations indicated that PSS showed a negative relationship with resilience (p = 0.000) and self-esteem (p = 0.002) and positive correlation with caregiver's burden (p = 0.015). In conclusion, CCG displayed higher number of subjective memory complaints and higher perceived stress than Non-CG, whereas no significant differences were obtained on self-esteem and resilience. These results could aid in designing new intervention strategies aimed to diminish stress, burden, or cognitive effects in informal caregivers of cancer patients.

Physical activity and environmental enrichment: Behavioural effects of exposure to different housing conditions in mice.

Enriched environments and exercise provide complex environmental stimulation that can induce emotional and cognitive changes; however, few studies have evaluated the effects of these two components on other behaviours, such as novelty seeking or pain sensitivity. The aim of the present study was to investigate the influence of voluntary physical activity provided through different housing conditions on anxiety, locomotor activity, pain sensitivity, and exploration. Male mice at postnatal day (PND) 21 and were randomly assigned to one of four different conditions on PND 28: Marlau cages (MC), a standardized cage designed to provide a complex environment; physical exercise in large groups (PE­8); physical exercise in small groups (PE­4); or a standard environment (SE). After seven weeks, animals were evaluated in the hole­board task, the elevated zero maze, actimeter, and hot plate test. In the hole­board task, MC animals displayed more exploration than animals in the PE­8 and PE­4 groups, but no significant differences were observed between groups in the actimeter. In the elevated zero maze, MC and PE­8 animals exhibited an anxiogenic­like profile as compared to the SE group. When pain sensitivity was evaluated, the PE­8 group displayed a higher sensitivity to noxious thermal stimuli than the SE group. These data suggest that the complexity of the environment in which physical activity and environmental stimulation are provided can influence animal behaviours such as novelty seeking, emotional response, and pain sensitivity. These animal models could be useful for designing more personalized interventions that include physical, social, and cognitive stimulation to promote a more active lifestyle in humans. Such interventions could be useful in the prevention and treatment of aging­related decline or neurodegenerative diseases.