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We identified the presence of AIF-1 (allograft inflammatory factor-1) in human peripheral blood mononuclear cells (PBMCs) from normal subjects by immunocytological methods. After isolation of different types of mononuclear cells by FACS (Fluorescence-activated cell sorting) with >95% purity, we studied the transcript levels of AIF-1 using qPCR. We observed the following order of AIF-1 mRNA expression in mononuclear cells: T-lymphocytes ˃ Monocytes ˃ B-lymphocytes ˃ NK. After T cell expansion of isolated PBMCs using anti-CD3-CD28 magnetic beads (Dynabeads®), AIF-1 increased intracellularly in the presence of brefeldin A; this finding, along with an increase in the medium in the absence of the drug, suggests that AIF-1 is processed in the Golgi apparatus and may be secreted extracellularly. In another set of experiments, interleukin-12 and anti-interleukin-4 were added to PBMCs during T cell expansion to promote Th1 polarization and to inhibit Th2 differentiation. In this case, the presence of 6 nM of rhAIF-1 (recombinant human AIF-1) increased the mRNA expression of interferon-ϒ and interleukin-2. In the same set of experiments, the incubation of PBMCs with rhAIF-1 (6 nM) promoted the decrease of mRNA expression of IL-10 and TGF-β, along with the decrease of CD25 and Foxp3 proteins. Furthermore, extracellular rhAIF-1 (6 nM) increased the survival of naive and effector T cells during Th1 polarization by inhibition of apoptosis, without causing changes in cell cycle rate and in retinoblastoma-cyclin-dependent kinase (Rb-CDK) activation. Taken together, rhAIF-1 treatment of PBMCs potentiates Th1 response and inhibits functionally suppressive CD25 + Foxp3 + Treg, which suggests an important immunomodulatory role in governing T cell response.

Background: Antipsychotic medications are the first-line treatment for schizophrenia. However, non-adherence is frequent despite its negative impact on the course of the illness. In response, we aimed to investigate social media posts about antipsychotics to better understand the online environment in this regard.Methods: We collected tweets containing mentions of antipsychotic medications posted between January 1st 2019 and October 31st 2020. The content of each tweet and the characteristics of the users were analyzed as well as the number of retweets and likes generated.Results: Twitter users, especially those identified as patients, showed an interest in antipsychotic medications, mainly focusing on the topics of sexual dysfunction and sedation. Interestingly, paliperidone, despite being among one of the newest antipsychotics, accounted for a low number of tweets and did not generate much interest. Conversely, retweet and like ratios were higher in those tweets asking for or offering help, in those posted by institutions and in those mentioning cognitive complaints. Moreover, health professionals did not have a strong presence in tweet postings, nor did medical institutions. Finally, trivialization was frequently observed.Conclusion: This analysis of tweets about antipsychotic medications provides insights into experiences and opinions related to this treatment. Twitter user perspectives therefore constitute a valuable input that may help to improve clinicians' knowledge of antipsychotic medications and their communication with patients regarding this treatment.

Introduction: Chronic venous disorder (CVeD) has a high prevalence, being commonly diagnosed by the presence of varicose veins. In fact, the development of varicose veins in lower extremities and/or pelvic venous insufficiency (LEPVI) is frequent. However, its potential impact on fetal health has not been investigated. This study aimed to examine whether the presence of varicose veins in women's LEPVI is related to an intrapartum fetal compromise event.Materials: A cross-sectional, national study was conducted using medical administrative records (CMBD) of all vaginal births (n = 256,531) recorded in 2015 in Spain. The independent variable was defined as the presence of varicose veins in the legs, vulva, and perineum or hemorrhoids. A logistic regression model was used to assess the association of interest.Results: Among women with vaginal deliveries, those with varicose veins in their LEPVI have a significantly greater odds of intrapartum fetal compromise (OR = 1.30, 99.55%CI = 1.08–1.54) than their counterparts without varicose veins. After adjustment, this association remained significant (OR = 1.25, 99.5%CI = 1.05–1.50).Conclusions: Our findings of an association between varicose veins in women's lower extremities and/or pelvis and intrapartum fetal compromise suggest that varicose veins may be a novel and important clinical risk factor for fetal well-being and health.

In cirrhosis, intestinal dysbiosis, intestinal barrier impairment, and systemic immune system abnormalities lead to gut bacterial translocation (GBT) and bacterial infection. However, intestinal immune system dysfunction and its contribution to barrier damage are poorly understood. This study correlates immune system dysregulation in the intestines of rats at different stages of CCl4 -induced cirrhosis with barrier function and pathogenic microbiota. The following variables were addressed in the small intestine: intraepithelial lymphocyte (IEL) and lamina propria lymphocyte (LPL) activation status and cytokine production (flow cytometry), cytokine mRNA and protein expression (quantitative real-time PCR and immunofluorescence), microbiota composition of ileum content (16S recombinant DNA massive sequencing), permeability (fecal albumin loss), and epithelial junctions (immunohistochemistry and immunofluorescence). The intestinal mucosa in rats with cirrhosis showed a proinflammatory pattern of immune dysregulation in IELs and LPLs, which featured the expansion of activated lymphocytes, switch to a T helper 1 (Th1) regulatory pattern, and Th17 reduction. In rats with cirrhosis with ascites, this state was associated with epithelial junction protein disruption, fecal albumin loss, and GBT. Direct correlations (P < 0.01) were observed between elevated interferon gamma (IFNγ)-expressing T cytotoxic LPLs and fecal albumin and between inflammatory taxa abundance and IFNγ-producing immune cells in the ileum. Bowel decontamination led to redistributed microbiota composition, reduced proinflammatory activation of mucosal immune cells, normalized fecal albumin levels, and diminished GBT; but there were no modifications in Th17 depletion. Conclusion: The intestinal mucosa of rats with cirrhosis acquires a proinflammatory profile of immune dysregulation that parallels the severity of cirrhosis; this impaired intestinal immune response is driven by gut dysbiosis and leads to disrupted barrier function, promoting GBT.

Diabetes mellitus causes severe impairment in the cutaneous wound healing process, which has led to extensive research striving to establish new treatments. In this work, we describe the effects of chitosan hydrogels functionalized with either unfractionated heparin or bemiparin (a low molecular weight heparin, LMWH) as topical treatments in an experimental diabetic wound healing model. Although wound morphometry showed similar values at the end of the study, microscopic analyses revealed impaired healing in diabetic animals in terms of inflammation and tissue formation. However, both types of loaded hydrogels accelerated inflammation resolution and improved the epithelialization process, while showing a neodermal thickness similar to that of nondiabetic animals. Immunohistochemistry analyses revealed an intermediate response in macrophage evolution between diabetic and nondiabetic controls in the treated groups, as well as enhanced collagenization and myofibroblast progression patterns. However, these changes were not accompanied by differences among groups in collagen I, III and TGF-β1 gene expression. Functionalized hydrogels improved diabetes-associated impaired wound healing, thus promoting the progression of the process and inducing the formation of high-quality cicatricial tissue. Although the beneficial healing effect observed after topical treatment with chitosan hydrogels loaded with bemiparin or unfractionated heparin was similar, the chitosan hydrogel loaded with bemiparin is the preferred choice as it exhibited high-quality tissue in the neoformed dermal tissue., This research did not receive any other specific grant from funding agencies in the public, commercial, or not-for-profit sectors. This study was supported by Community of Madrid, Spain (B2017/BMD-3804 MITIC-CM) and cofinanced by the European Development Regional Fund “A way to achieve Europe’’ (ERDF). AC was a recipient of a FPIUAH gran

Simple Summary Mitochondrial microRNAs (mitomiRs) are an emerging field of study in a wide range of tumours including breast cancer. By targeting mitochondrial, or non-mitochondrial products, mitomiRs are able to regulate the functions of this organelle, thus controlling multiple carcinogenic processes. The knowledge of this system may provide a novel approach for targeted therapies, as potential biomarkers or helping in the diagnosis of such a complex malignancy. Abstract Breast cancer is the most prevalent and incident female neoplasm worldwide. Although survival rates have considerably improved, it is still the leading cause of cancer-related mortality in women. MicroRNAs are small non-coding RNA molecules that regulate the posttranscriptional expression of a wide variety of genes. Although it is usually located in the cytoplasm, several studies have detected a regulatory role of microRNAs in other cell compartments such as the nucleus or mitochondrion, known as “mitomiRs”. MitomiRs are essential modulators of mitochondrion tasks and their abnormal expression has been linked to the aetiology of several human diseases related to mitochondrial dysfunction, including breast cancer. This review aims to examine basic knowledge of the role of mitomiRs in breast cancer and discusses their prospects as biomarkers or therapeutic targets.

Background Health awareness initiatives are frequent but their efficacy is a matter of controversy. We have investigated the effect of the Eating Disorder Awareness Week and Wake Up Weight Watchers campaigns on Twitter. Objective We aimed to examine whether the Eating Disorder Awareness Week and Wake Up Weight Watchers initiatives increased the volume and dissemination of Twitter conversations related to eating disorders and investigate what content generates the most interest on Twitter. Methods Over a period of 12 consecutive days in 2018, we collected tweets containing the hashtag #wakeupweightwatchers and hashtags related to Eating Disorder Awareness Week (#eatingdisorderawarenessweek, #eatingdisorderawareness, or #EDAW), with the hashtag #eatingdisorder as a control. The content of each tweet was rated as medical, testimony, help offer, awareness, pro-ana, or anti-ana. We analyzed the number of retweets and favorites generated, as well as the potential reach and impact of the hashtags and the characteristics of contributors. Results The number of #wakeupweightwatchers tweets was higher than that of Eating Disorder Awareness Week and #eatingdisorder tweets (3900, 2056, and 1057, respectively). The content of tweets was significantly different between the hashtags analyzed (P Conclusions Both awareness campaigns effectively promoted tweeting about eating disorders. The majority of tweets did not promote any specific preventive or help-seeking behaviors.

Chronic venous disease (CVeD) has a remarkable prevalence, with an estimated annual incidence of 2%. It has been demonstrated how the loss of homeostatic mechanisms in the vein wall can take part in the physiopathology of CVeD. In this regard, it has been described how different axis, such as IGF-1/PAPP-A/STC-2 axis, may play an essential role in tissue homeostasis. The aim of this research is to study both genetic and protein expressions of the IGF-1/PAPP-A/STC-2 axis in CVeD patients. It is a cross-sectional study in which genetic (RT-qPCR) and protein (immunohistochemistry) expression analysis techniques were accomplished in saphenous veins from CVeD patients ( n = 35 ) in comparison to individuals without vascular pathology (HV). Results show a significant increase in both genetic and protein expressions of PAPP-A and IGF-1, and a decrement STC-2 expression at the same time in CVeD patients. Our study is a pioneer for demonstrating that the expression of the different components of the IGF-1/PAPP-A/STC-2 axis is altered in CVeD patients. This fact can be a part of the loss of homeostatic mechanisms of the venous tissue. Further research should be destined to deepen into alterations of this axis, as well as to evaluate the usage of these components as therapeutic targets for CVeD.

Pregnancy is a period in a woman’s life in which changes can occur that affect different physiological processes. Common conditions during this period include vascular changes, such as lower extremity venous insufficiency (VI). This is an observational, analytical, and prospective cohort study in which 114 pregnant women were analyzed, of which 62 were clinically diagnosed with VI. In parallel, 52 control patients without VI (HC) were studied. The aim of this study was to observe changes in angiogenesis and inflammation markers as well as the presence of calcium deposits. The expression of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and pigment epithelium-derived factor (PEDF) was analyzed by immunohistochemistry and RT-qPCR. The presence of calcium deposits was revealed using the von Kossa method. In the placentas of mothers with VI, gene expression of VEGF (34.575 [32.380–36.720] VI vs 32.965 [30.580–36.320] HC) and PEDF (25.417 [24.459–27.675] VI vs 24.400 [23.102–30.223] HC) significantly increased, as was protein expression in the placental villi. An increase in calcium deposits was observed in the placentas of women with VI (72.58% VI/53.84% HC). This study revealed the existence of cellular damage in the placental villi of mothers with VI with tissue implications such as increased calcification.

Obesity is a condition of rising prevalence worldwide, with important socioeconomic implications, being considered as a growing public health concern. Frequently, obesity brings other complications in addition to itself—like Type 2 Diabetes Mellitus (T2DM)—sharing origin, risk factors and pathophysiological mechanisms. In this context, some authors have decided to include both conditions as a unique entity known as “diabesity”. In fact, understanding diabesity as a single disease is possible to maximise the benefits from therapies received in these patients. Gut microbiota plays a key role in individual’s health, and their alterations, either in its composition or derived products are related to a wide range of metabolic disorders like T2DM and obesity. The present work aims to collect the different changes reported in gut microbiota in patients with T2DM associated with obesity and their possible role in the onset, development, and establishment of the disease. Moreover, current research lines to modulate gut microbiota and the potential clinical translation derived from the knowledge of this system will also be reviewed, which may provide support for a better clinical management of such a complex condition.

Varicose veins are a disease with high incidence and prevalence. In the venous wall, the smooth muscle cells (SMCs) act in the vascular homeostasis that secretes multiple substances in response to stimuli. Any alteration of these cells can modify the function and structure of the other venous layers such as the endothelium, resulting in increases in endothelial permeability and release of substances. Therefore, knowing the cellular and molecular mechanisms of varicose veins is imperative. The aims of this study are to understand how SMCs of patients with varicose veins subjected to saphenectomy of the great saphenous vein react under hypoxic cell conditions and to determine the role of vascular endothelial growth factor (VEGF) in this process. We obtained SMCs from human saphenous vein segments from patients with varicose veins (n=10) and from organ donors (n=6) undergoing surgery. Once expanded, the cells were subjected to hypoxic conditions in specific chambers, and expansion was examined through analyzing morphology and the expression of α-actin. Further gene expression studies of HIF-1α, EGLN3, VEGF, TGF-β1, eNOS, and Tie-2 were performed using RT-qPCR. This study reveals the reaction of venous cells to sustained hypoxia. As significant differential gene expression was observed, we were able to determine how venous cells are sensitive to hypoxia. We hypothesize that venous insufficiency leads to cellular hypoxia with homeostatic imbalance. VEGF plays a differential role that can be related to the cellular quiescence markers in varicose veins, which are possible therapeutic targets. Our results show how SMCs are sensitive to hypoxia with a different gene expression. Therefore, we can assume that the condition of venous insufficiency leads to a situation of sustained cellular hypoxia. This situation may explain the cellular response that occurs in the venous wall as a compensatory mechanism.

Chronic venous insufficiency (CVI) is a multifactorial disease, commonly caused by valvular incompetence (clinically diagnosed by venous reflux) and venous hypertension. The incidence of these factors clearly increases with patient age, and aging is one of the risk factors involved. The activity of the PI3K/Akt/mTOR pathway is considered fundamental in vascular pathologies, and understanding its involvement would help in the development of possible therapeutic targets. This is an observational, analytical, and prospective cohort study that reviewed 110 patients with CVI scheduled to undergo stratified saphenectomy. They were distributed according to the presence (R=81) or absence (NR=29) of valvular incompetence (venous reflux) diagnosed clinically. Each of the groups was further divided according to age, with a cutoff point of 50 years (NR<50=13, NR≥50=16, R<50=32, and R≥50=49). The involvement of the PI3K/Akt/mTOR pathway, as well as that of HIF-1α and HIF-2α and of CD4+, CD8+, and CD19+ cells and mastocytes, was assessed. Saphenous vein tissue samples obtained during surgery were processed for RT-qPCR and immunohistochemistry. Patients with venous reflux showed a significant increase in mRNA and protein expression levels for PI3K/mTOR and HIF-1α/HIF-2α. The number of mast cells was significantly elevated in the R group. In distribution by age, PI3K/Akt/mTOR and HIF-1α were significantly higher in R<50 patients. Furthermore, these patients had a significant increase in the number of CD4+, CD8+, and CD19+ cells and mastocytes in the saphenous vein wall. These findings provide a basis for the possible existence of changes in PI3K/Akt/mTOR pathway expression in young patients, with potential accelerated asynchronous aging that is enhanced by CVI.

Background: The contents of traditional communication media and new internet social media reflect the interests of society. However, certain barriers and a lack of attention towards mental disorders have been previously observed. Objective: The objective of this study is to measure the relevance of influential American mainstream media outlets for the distribution of psychiatric information and the interest generated in these topics among their Twitter followers. Methods: We investigated tweets generated about mental health conditions and diseases among 15 mainstream general communication media outlets in the United States of America between January 2007 and December 2016. Our study strategy focused on identifying several psychiatric terms of primary interest. The number of retweets generated from the selected tweets was also investigated. As a control, we examined tweets generated about the main causes of death in the United States of America, the main chronic neurological degenerative diseases, and HIV. Results: In total, 13,119 tweets about mental health disorders sent by the American mainstream media outlets were analyzed. The results showed a heterogeneous distribution but preferential accumulation for a select number of conditions. Suicide and gender dysphoria accounted for half of the number of tweets sent. Variability in the number of tweets related to each control disease was also found (5998). The number of tweets sent regarding each different psychiatric or organic disease analyzed was significantly correlated with the number of retweets generated by followers (1,030,974 and 424,813 responses to mental health disorders and organic diseases, respectively). However, the probability of a tweet being retweeted differed significantly among the conditions and diseases analyzed. Furthermore, the retweeted to tweet ratio was significantly higher for psychiatric diseases than for the control diseases (odds ratio 1.11, CI 1.07-1.14; P

Objective. The aim of this study was to summarize evidence on the effectiveness of therapeutic exercise in Fibromyalgia Syndrome. Design. Studies retrieved from the Cochrane Plus, PEDro, and Pubmed databases were systematically reviewed. Randomized controlled trials and meta-analyses involving adults with fibromyalgia were included. The primary outcomes considered in this systematic review were pain, global well-being, symptoms of depression, and health-related quality of life. Results. Effects were summarized using standardized mean differences with 95% confidence intervals using a random effects model. This study provides strong evidence that physical exercise reduces pain (−1.11 [95% CI] −1.52; −0.71; overall effect p<0.001), global well-being (−0.67 [95% CI] −0.89, −0.45; p<0.001), and symptoms of depression (−0.40 [95% CI] −0.55, −0.24; p<0.001) and that it improves both components of health-related quality of life (physical: 0.77 [95% CI] 0.47; 1.08; p<0.001; mental: 0.49 [95% CI] 0.27; 0.71; p<0.001). Conclusions. This study concludes that aerobic and muscle strengthening exercises are the most effective way of reducing pain and improving global well-being in people with fibromyalgia and that stretching and aerobic exercises increase health-related quality of life. In addition, combined exercise produces the biggest beneficial effect on symptoms of depression.

In order to determine the relationships between CD2+ lymphocyte subpopulations and tumour mass, the immunophenotype of natural killer (NK) cells and T lymphocyte subsets was studied in 56 B-chronic lymphocytic leukaemia (B-CLL) patients and 38 healthy subjects. The patients were classified according to their blood lymphocyte count (BLC). Forty patients had BLC30x10(9)/l (low BLC, less tumour mass) and 16 patients had BLC30x10(9)/l (high BLC, larger tumour mass). The percentage of CD3- CD56+ cells, as well as of CD8+, CD8+ CD45RO+ and CD3+ CD57+ T subsets in low BLC patients, were higher than those found in high BLC patients. Conversely, the percentages of CD3+ HLA x DR+, CD4+ and CD4+ CD45RO+ lymphocytes were higher in high BLC patients than in low BLC patients. The CD4/CD8 ratio was decreased in low BLC patients while it was increased in high BLC patients and a significant positive correlation was found between their CD4/CD8 ratio and their BLC. We conclude that in low BLC B-CLL patients there is a decreased percentage of activated helper lymphocytes and an increased percentage of NK cells and activated cytotoxic T lymphocytes. These results suggest a role for NK cells, and helper and cytotoxic T lymphocytes in the control of tumour burden in B-CLL patients.

SummaryThe clinical findings of a pregnant woman from Colombia with a triple co-infection caused by dengue, chikungunya, and Zika viruses are described. Weekly obstetric ultrasounds from 14.6 to 29 weeks of gestation were normal. She remains under follow-up and management according to the standard guidelines for the management of Zika virus-infected pregnant women.