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Multiple myeloma is an incurable plasma cell malignancy. Most patients end up relapsing and developing resistance to antineoplastic drugs, like bortezomib. Antibiotic tigecycline has activity against myeloma. This study analyzed tigecycline and bortezomib combination on cell lines and plasma cells from myeloma patients. Apoptosis, autophagic vesicles, mitochondrial mass, mitochondrial superoxide, cell cycle, and hydrogen peroxide were studied by flow cytometry. In addition, mitochondrial antioxidants and electron transport chain complexes were quantified by reverse transcription real-time PCR (RT-qPCR) or western blot. Cell metabolism and mitochondrial activity were characterized by Seahorse and RT-qPCR. We found that the addition of tigecycline to bortezomib reduces apoptosis in proportion to tigecycline concentration. Supporting this, the combination of both drugs counteracts bortezomib in vitro individual effects on the cell cycle, reduces autophagy and mitophagy markers, and reverts bortezomib-induced increase in mitochondrial superoxide. Changes in mitochondrial homeostasis and MYC upregulation may account for some of these findings. These data not only advise to avoid considering tigecycline and bortezomib combination for treating myeloma, but caution on the potential adverse impact of treating infections with this antibiotic in myeloma patients under bortezomib treatment.
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Apoptose , Bortezomib , Mitocôndrias , Mieloma Múltiplo , Espécies Reativas de Oxigênio , Tigeciclina , Bortezomib/farmacologia , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Tigeciclina/farmacologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacosRESUMO
PURPOSE: After the publication of the new standardized nomenclature for the specialty of Otorhinolaryngology in 2021, a joint adaptation was carried out with the Spanish Society of Anesthesiology, Resuscitation and Pain Therapy (SEDAR), creating an executive version. In this version, the Anesthesia groups are added for those procedures that require it and, in addition, the number of acts is reduced to facilitate its implementation in the daily basis healthcare activity. The aim of this article is to update the definitive executive version of the nomenclature for the specialty of Otolaryngology. METHODS: The nomenclature published in 2021 was updated, reducing the number of acts and procedures. For this purpose, a grouping of procedures similar in description and in order and ranking has been made. Those procedures that have been grouped together have received a new description that reflects all the acts included in order to facilitate its coding but respecting the essence of the proposal of the complete version of the 2021 nomenclature. Subsequently, the private medicine committee of SEDAR has assigned the anaesthetic act for those procedures that may require it. In addition, a provisional code has been assigned for those acts that are new with respect to the latest version approved by the OMC, which allows their numerical identification. RESULTS: The executive version of the nomenclature presents a total of 234 medical acts, compared to 395 listed in the 2021 version, which are distributed by OMC classification groups and ENT subspecialties. One-hundred and fourteen procedures maintain the original OMC code, with some modifications in the description of the medical act. Other procedures also performed by ENT but listed elsewhere were kept with their same description and group and assigned OMC codes. The remaining 120 procedures are new proposals made by the scientific society and its subspecialty committees. CONCLUSIONS: The executive version of the new nomenclature of Otorhinolaryngology proposed by the SEORL-CCC and SEDAR updates the one from 2021 and is the only one valid in our specialty for its use in the private healthcare daily practice. The reduction of medical procedures, without losing richness or modifications of the surgical groups, and the allocation of the anesthesia scales, facilitates its implementation, and provides the highest standards of quality and clinical timelines.
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The objective of this article is to compare the amount of intraoperative blood loss during laparoscopic myomectomy when performing bilateral transient clamping of the uterine and utero-ovarian arteries versus no intervention. It´s a randomized controlled prospective study carried out in the Department of Obstetrics and Gynecology Ramón y Cajal University Hospital and HM Montepríncipe-Sanchinarro University Hospital, Madrid, Spain, in women with fibroid uterus undergoing laparoscopic myomectomy. Eighty women diagnosed with symptomatic fibroid uterus were randomly assigned to undergo laparoscopic myomectomy without additional intervention (Group A) or temporary clamping of bilateral uterine and utero-ovarian arteries prior to laparoscopic myomectomy (Group B). Estimated blood loss, operating time, length of hospital stay, and postoperative hemoglobin values were compared in both groups. The number of fibroids removed was similar in both groups (p = 0.77). Estimated blood loss was lower in the group of patients with prior occlusion of uterine arteries (p = 0.025) without increasing operating time (p = 0.17) nor length of stay (p = 0.17). No patient had either intra or postoperative complications. Only two patients (2.5%) required blood transfusion after surgery. We conclude that temporary clamping of bilateral uterine arteries prior to laparoscopic myomectomy is a safe intervention that reduces blood loss without increasing operative time.
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Laparoscopia , Leiomioma , Miomectomia Uterina , Neoplasias Uterinas , Feminino , Humanos , Perda Sanguínea Cirúrgica , Laparoscopia/efeitos adversos , Leiomioma/cirurgia , Estudos Prospectivos , Artéria Uterina/cirurgia , Miomectomia Uterina/efeitos adversos , Neoplasias Uterinas/cirurgiaRESUMO
The mammalian telencephalon contains distinct GABAergic projection neuron and interneuron types, originating in the germinal zone of the embryonic basal ganglia. How genetic information in the germinal zone determines cell types is unclear. Here we use a combination of in vivo CRISPR perturbation, lineage tracing and ChIP-sequencing analyses and show that the transcription factor MEIS2 favors the development of projection neurons by binding enhancer regions in projection-neuron-specific genes during mouse embryonic development. MEIS2 requires the presence of the homeodomain transcription factor DLX5 to direct its functional activity toward the appropriate binding sites. In interneuron precursors, the transcription factor LHX6 represses the MEIS2-DLX5-dependent activation of projection-neuron-specific enhancers. Mutations of Meis2 result in decreased activation of regulatory enhancers, affecting GABAergic differentiation. We propose a differential binding model where the binding of transcription factors at cis-regulatory elements determines differential gene expression programs regulating cell fate specification in the mouse ganglionic eminence.
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Desenvolvimento Embrionário , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio , Fatores de Transcrição , Animais , Camundongos , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Desenvolvimento Embrionário/fisiologia , Elementos Facilitadores Genéticos/genética , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/fisiologia , Diferenciação Celular/fisiologia , Interneurônios/metabolismo , Interneurônios/fisiologia , Proteínas com Homeodomínio LIM/metabolismo , Proteínas com Homeodomínio LIM/genética , Neurogênese/fisiologia , Proteínas do Tecido NervosoRESUMO
Chagas disease (CD) is caused by the parasite Trypanosoma cruzi. Although it is endemic in many Latin American (LA) countries, mother-to-child transmission has caused it to expand to other countries and continents. In places where vector transmission is controlled or absent, the epidemiological importance of T. cruzi transmission of the infected mother to her child during pregnancy or childbirth (i.e., perinatal CD) increases. In countries where CD is not endemic, CD screening should be performed in pregnant or fertile women who are native to LA countries or whose mothers are native to LA countries. Diagnosis is established by detecting anti-T. cruzi IgG antibodies in a serum or plasma sample. Antiparasitic treatment cannot be offered during pregnancy, and since the majority of infected newborns are asymptomatic at birth, a diagnosis is made by direct observation or concentration (microhematocrit) or by using molecular testing techniques. Once the infected child receives a diagnosis, it is essential to offer treatment (benznidazole/nifurtimox) as soon as possible, with good tolerance and effectiveness in the first year of life. Even if the diagnosis is negative at birth, the newborn must be followed up for at least the first 9 months of life.
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Doença de Chagas , Trypanosoma cruzi , Gravidez , Recém-Nascido , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Mães , Doença de Chagas/diagnóstico , Doença de Chagas/prevenção & controle , Doença de Chagas/epidemiologiaRESUMO
Introduction: Transvaginal radiofrequency ablation is a relatively noninvasive approach for the treatment of fibroids in patients who do not wish to undergo conventional surgery. Information on potential complications of this novel technique is very scarce. Methods: Retrospective, descriptive, epidemiological study of 115 patients who underwent transvaginal radiofrequency ablation of fibroids and for whom complications were recorded. Results: We performed 115 transvaginal radiofrequency ablation procedures, we recorded a total of 11 complications (9.6%; 95% CI, 3.8-14.8). Of these, 8 (7.0%) were classified as Clavien-Dindo type I, 1 (0.9%,) as type II, and 2 (1.7%) as type IIIb (severe). No other complications were recorded in a year follow-up. Conclusion: Transvaginal radiofrequency ablation is a treatment option that makes it possible to treat fibroids that are difficult to manage using other techniques. Few associated complications have been described, and most of them are mild.
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BACKGROUND: Ultrasound features help to differentiate benign from malignant masses, and some of them are included in the ultrasound (US) scores. The main aim of this work is to describe the ultrasound features of certain adnexal masses of difficult classification and to analyse them according to the most frequently used US scores. METHODS: Retrospective studies of adnexal lesions are difficult to classify by US scores in women undergoing surgery. Ultrasound characteristics were analysed, and masses were classified according to the Subjective Assessment of the ultrasonographer (SA) and other US scores (IOTA Simple Rules Risk Assessment-SRRA, ADNEX model with and without CA125 and O-RADS). RESULTS: A total of 133 adnexal masses were studied (benign: 66.2%, n:88; malignant: 33.8%, n:45) in a sample of women with mean age 56.5 ± 7.8 years. Malignant lesions were identified by SA in all cases. Borderline ovarian tumors (n:13) were not always detected by some US scores (SRRA: 76.9%, ADNEX model without and with CA125: 76.9% and 84.6%) nor were serous carcinoma (n:19) (SRRA: 89.5%), clear cell carcinoma (n:9) (SRRA: 66.7%) or endometrioid carcinoma (n:4) (ADNEX model without CA125: 75.0%). While most teratomas and serous cystadenomas have been correctly differentiated, other benign lesions were misclassified because of the presence of solid areas or papillae. Fibromas (n:13) were better identified by SA (23.1% malignancy), but worse with the other US scores (SRRA: 69.2%, ADNEX model without and with CA125: 84.6% and 69.2%, O-RADS: 53.8%). Cystoadenofibromas (n:10) were difficult to distinguish from malignant masses via all scores except SRRA (SA: 70.0%, SRRA: 20.0%, ADNEX model without and with CA125: 60.0% and 50.0%, O-RADS: 90.0%). Mucinous cystadenomas (n:12) were misdiagnosed as malignant in more than 15% of the cases in all US scores (SA: 33.3%, SRRA: 16.7%, ADNEX model without and with CA125: 16.7% and 16.7%, O-RADS:41.7%). Brenner tumors are also difficult to classify using all scores. CONCLUSION: Some malignant masses (borderline ovarian tumors, serous carcinoma, clear cell carcinoma, endometrioid carcinomas) are not always detected by US scores. Fibromas, cystoadenofibromas, some mucinous cystadenomas and Brenner tumors may present solid components/papillae that may induce confusion with malignant lesions. Most teratomas and serous cystadenomas are usually correctly classified.
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ISG20L2, a 3' to 5' exoribonuclease previously associated with ribosome biogenesis, is identified here in activated T cells as an enzyme with a preferential affinity for uridylated miRNA substrates. This enzyme is upregulated in T lymphocytes upon TCR and IFN type I stimulation and appears to be involved in regulating T cell function. ISG20L2 silencing leads to an increased basal expression of CD69 and induces greater IL2 secretion. However, ISG20L2 absence impairs CD25 upregulation, CD3 synaptic accumulation and MTOC translocation towards the antigen-presenting cell during immune synapsis. Remarkably, ISG20L2 controls the expression of immunoregulatory molecules, such as AHR, NKG2D, CTLA-4, CD137, TIM-3, PD-L1 or PD-1, which show increased levels in ISG20L2 knockout T cells. The dysregulation observed in these key molecules for T cell responses support a role for this exonuclease as a novel RNA-based regulator of T cell function.
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Ativação Linfocitária , MicroRNAs , Células Apresentadoras de Antígenos , Endonucleases , MicroRNAs/genética , HumanosRESUMO
BACKGROUND: Several ultrasound (US) features help ultrasound experts in the classification of benign vs. malignant adnexal masses. US scores serve in this differentiation, but they all have misdiagnoses. The main objective of this study is to evaluate what ultrasound characteristics are associated with malignancy influencing ultrasound scores. METHODS: This is a retrospective analysis of ultrasound features of adnexal lesions of women managed surgically. Ultrasound characteristics were analyzed, and masses were classified by subjective assessment of the ultrasonographer (SA) and other ultrasound scores (IOTA Simple Rules Risk Assessment SRRA, ADNEX model, and O-RADS). RESULTS: Of a total of 187 adnexal masses studied, 134 were benign (71.7%) and 53 were malignant (28.3%). SA, IOTA SRRA, ADNEX model with or without CA125 and O-RADS had high levels of sensitivity (93.9%, 81.1%, 94.3%, 88.7%, 98.1%) but lower specificity (80.2%, 82.1%, 82.8%, 77.6%, 73.1%) with similar AUC (0.87, 0.87, 0.92, 0.90, 0.86). Ultrasound features significantly related with malignancy were the presence of irregular contour, absence of acoustic shadowing, vascularized solid areas, ≥1 papillae, vascularized septum, and moderate-severe ascites. CONCLUSION: IOTA SRRA, ADNEX model, and O-RADS can help in the classification of benign and malignant masses. Certain ultrasound characteristics studied in ultrasound scores are associated with malignancy.
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The vertebrate appendage comprises three primary segments, the stylopod, zeugopod and autopod, each separated by joints. The molecular mechanisms governing the specification of joint sites, which define segment lengths and thereby limb architecture, remain largely unknown. Existing literature suggests that reciprocal gradients of retinoic acid (RA) and fibroblast growth factor (FGF) signaling define the expression domains of the putative segment markers Meis1, Hoxa11 and Hoxa13. Barx1 is expressed in the presumptive joint sites. Our data demonstrate that RA-FGF signaling gradients define the expression domain of Barx1 in the first presumptive joint site. When misexpressed, Barx1 induces ectopic interzone-like structures, and its loss of function partially blocks interzone development. Simultaneous perturbations of RA-FGF signaling gradients result in predictable shifts of Barx1 expression domains along the proximo-distal axis and, consequently, in the formation of repositioned joints. Our data suggest that during early limb bud development in chick, Meis1 and Hoxa11 expression domains are overlapping, whereas the Barx1 expression domain resides within the Hoxa11 expression domain. However, once the interzone is formed, the expression domains are refined and the Barx1 expression domain becomes congruent with the border of these two putative segment markers.
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Articulações , Fatores de Transcrição , Animais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Articulações/metabolismo , Proteína Meis1/genética , Proteína Meis1/metabolismo , Vertebrados/genética , Vertebrados/metabolismo , Extremidades , Regulação da Expressão Gênica no DesenvolvimentoRESUMO
Background: The diagnosis of pelvic congestion syndrome (PCS) remains a challenge given the lack of universally accepted criteria. Although venography (VG) is the current gold standard for the diagnosis of PCS, non-invasive techniques like transvaginal ultrasonography (TVU) appear to be a valid alternative. The aim of this study was to design a predictive model for the venographic diagnostic of PCS using the parameters identified by TVU in patients with clinical suspicion of PCS, in order to individually assess the need to perform an invasive diagnostic and therapeutic technique such as VG. Methods: An observational and cross-sectional prospective study was conducted including 61 consecutively recruited patients with clinical suspicion of PCS, who were referred by the Pelvic Floor, Gynecology and Vascular Surgery Units, who were distributed in two groups: 18 belonging to the normal group and 43 to the PCS's group. We implemented and compared 19 binary logistic regression models, including the parameters that showed statistical significance in the prior univariate analysis. We evaluated individual predictive values with a receiver operating characteristic (ROC) curve and the area under the curve (AUC). Results: The selected model, based on the presence of pelvic veins or venous plexus of 8 mm or larger, observed by transvaginal ultrasound, had an AUC of 0.79 (95% CI: 0.63-0.96; P<0.001), with a sensitivity of 0.90 and specificity of 0.69, while the VG had a sensitivity of 86.05%, a specificity of 66.67%, and a positive predictive value of 86.05%. Conclusions: This assessment presents a feasible alternative that could potentially be added to our usual gynecological practice.
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Subjective ultrasound assessment by an expert examiner is meant to be the best option for the differentiation between benign and malignant adnexal masses. Different ultrasound scores can help in the classification, but whether one of them is significantly better than others is still a matter of debate. The main aim of this work is to compare the diagnostic performance of some of these scores in the evaluation of adnexal masses in the same set of patients. This is a retrospective study of a consecutive series of women diagnosed as having a persistent adnexal mass and managed surgically. Ultrasound characteristics were analyzed according to IOTA criteria. Masses were classified according to the subjective impression of the sonographer and other ultrasound scores (IOTA simple rules -SR-, IOTA simple rules risk assessment -SRRA-, O-RADS classification, and ADNEX model -with and without CA125 value-). A total of 122 women were included. Sixty-two women were postmenopausal (50.8%). Eighty-one women had a benign mass (66.4%), and 41 (33.6%) had a malignant tumor. The sensitivity of subjective assessment, IOTA SR, IOTA SRRA, and ADNEX model with or without CA125 and O-RADS was 87.8%, 66.7%, 78.1%, 95.1%, 87.8%, and 90.2%, respectively. The specificity for these approaches was 69.1%, 89.2%, 72.8%, 74.1%, 67.9%, and 60.5%, respectively. All methods with similar AUC (0.81, 0.78, 0.80, 0.88, 0.84, and 0.75, respectively). We concluded that IOTA SR, IOTA SRRA, and ADNEX models with or without CA125 and O-RADS can help in the differentiation of benign and malignant masses, and their performance is similar to the subjective assessment of an experienced sonographer.
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BACKGROUND: The use of transvaginal ultrasound guided biopsy and puncture of pelvic lesions is a minimally invasive technique that allows for accurate diagnosis. It has many advantages compared to other more invasive (lower complication rate) or non-invasive techniques (accurate diagnosis). Furthermore, it offers greater availability, it does not radiate, enables the study of pelvic masses accessible vaginally with ultrasound control in real time, and it is possible to use the colour Doppler avoiding puncturing large vessels among others. The main aim of the work is to describe a standardized ambulatory technique and to determine its usefulness. METHODS: This is a retrospective study of ultrasound transvaginal punctures (core needle biopsies and cytologies) and drainages of pelvic lesions performed on an outpatient basis during the last two years. The punctures were made with local anesthesia, under transvaginal ultrasound guidance with an automatic or semi-automatic 18G biopsy needle with a length of 20-25 cm and a penetration depth of 12 or 22 mm. The material obtained was sent for anatomopathological, cytological and/or microbiological study if necessary. RESULTS: A total of 42 women were recruited in two centers. Fifty procedures (nine punctures, seven drains, and 34 biopsies) were performed. In five cases the punction and drain provided clinical relief in benign pelvic masses. Regarding material of the biopsies performed, 15 were vaginal in women previously histerectomized, finding 10 carcinomas, eight were ovarian tumours in advanced stages or peritoneal carcinomatosis obtaining the appropriate histology in each case, seven were suspicious cervical biopsies finding carcinomas in five of them, three were myometrial biopsies including one breast carcinoma metastasis in the miometrium and a benign placental nodule, and a periurethral biopsy was performed on a woman with a history of endometrial cancer confirming recurrence. The pathological diagnosis was satisfactory in all cases, confirming the nature of the lesion (25 malignant-ten vaginal recurrences of previous gynaecological cancers, eight cases of primary ovarian/peritoneal carcinoma, four new diagnosis of cervical malignant masses, one cervical metastasis of lymphoma, one periurethral recurrence of endometrial carcinoma and one recurrence of breast cancer in the myometrium-and 23 benign). The tolerance was excellent and no complications were detected. CONCLUSION: The ambulatory ultrasound transvaginal puncture and drainage technique is useful for obtaining a sample for pathological and microbiological diagnosis with excellent tolerance that can be used to rule out the recurrence of malignant lesions or progression of the disease, diagnose masses not accessible to gynecological exploration (vaginal vault, myometrium or cervix) and for early histologic diagnosis in cases of advanced peritoneal carcinomatosis or ovarian carcinoma as well as drainage and cytological study of cystic pelvic masses.
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The complement system is a first line of defence against infectious, tumoral or autoimmune processes, and it is constitutively regulated to avoid excessive or unspecific activation. Factor H (FH), a most relevant complement regulator, controls complement activation in plasma and on the cellular surfaces of autologous tissues. FH shares evolutionary origin and structural features with a group of plasma proteins known as FH-Related Proteins (FHRs), which could act as FH functional antagonists. Studies in patient cohorts of atypical Haemolytic-Uraemic Syndrome (aHUS), C3 Glomerulopathy (C3G), and IgA nephropathy (IgAN), have identified rare genetic variants that give rise to severe FH and FHRs dysfunctions, and are major genetic predisposing factors. These patients also have a higher frequency of a few polymorphisms whose relevance as disease risk factors is incompletely understood. In the last years, the availability of specific reagents has allowed a more precise quantitation of FH and FHRs in plasma samples from patients and controls. These studies have revealed that some aHUS, C3G or IgAN risk polymorphisms determine mild changes in FH or FHRs levels that could somehow perturb complement regulation and favour disease pathogenesis.
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Síndrome Hemolítico-Urêmica Atípica , Glomerulonefrite por IGA , Síndrome Hemolítico-Urêmica Atípica/genética , Ativação do Complemento , Fator H do Complemento/genética , Humanos , Rim/patologiaRESUMO
Communication through cell-cell contacts and extracellular vesicles (EVs) enables immune cells to coordinate their responses against diverse types of pathogens. The function exerted by EVs in this context depends on the proteins and nucleic acids loaded into EVs, which elicit specific responses involved in the resolution of infection. Several mechanisms control protein and nucleic acid loading into EVs; in this regard, acetylation has been described as a mechanism of cellular retention during protein sorting to exosomes. HDAC6 is a deacetylase involved in the control of cytoskeleton trafficking, organelle polarity and cell migration, defense against Listeria monocytogenes (Lm) infection and other immune related functions. Here, we show that the protein content of dendritic cells (DCs) and their secreted EVs (DEVs) vary during Lm infection, is enriched in proteins related to antiviral functions compared to non-infected cells and depends on HDAC6 expression. Analyses of the post-translational modifications revealed an alteration of the acetylation and ubiquitination profiles upon Lm infection both in DC lysates and DEVs. Functionally, EVs derived from infected DCs upregulate anti-pathogenic genes (e.g. inflammatory cytokines) in recipient immature DCs, which translated into protection from subsequent infection with vaccinia virus. Interestingly, absence of Listeriolysin O in Lm prevents DEVs from inducing this anti-viral state. In summary, these data underscore a new mechanism of communication between bacteria-infected DC during infection as they alert neighboring, uninfected DCs to promote antiviral responses.
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Vesículas Extracelulares , Listeria monocytogenes , Listeriose , Ácidos Nucleicos , Antivirais/metabolismo , Citocinas/metabolismo , Células Dendríticas , Vesículas Extracelulares/metabolismo , Humanos , Imunidade Inata , Ácidos Nucleicos/metabolismoRESUMO
We want to describe a model that allows the use of transperineal ultrasound to define the probability of experiencing uterine prolapse (UP). This was a prospective observational study involving 107 patients with UP or cervical elongation (CE) without UP. The ultrasound study was performed using transperineal ultrasound and evaluated the differences in the pubis−uterine fundus distance at rest and with the Valsalva maneuver. We generated different multivariate binary logistic regression models using nonautomated methods to predict UP, including the difference in the pubis−uterine fundus distance at rest and with the Valsalva maneuver. The parameters were added progressively according to their simplicity of use and their predictive capacity for identifying UP. We used two binary logistic regression models to predict UP. Model 1 was based on the difference in the pubis−uterine fundus distance at rest and with the Valsalva maneuver and the age of the patient [AUC: 0.967 (95% CI, 0.939−0.995; p < 0.0005)]. Model 2 used the difference in the pubis−uterine fundus distance at rest and with the Valsalva maneuver, age, avulsion and ballooning (AUC: 0.971 (95% CI, 0.945−0.997; p < 0.0005)). In conclusion, the model based on the difference in the pubis−uterine fundus distance at rest and with the Valsalva maneuver and the age of the patient could predict 96.7% of patients with UP.
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Prolapso de Órgão Pélvico , Prolapso Uterino , Feminino , Humanos , Ultrassonografia , Prolapso Uterino/diagnóstico por imagem , Útero/diagnóstico por imagem , Manobra de ValsalvaRESUMO
Natural killer (NK) cells recognize and kill target cells undergoing different types of stress. NK cells are also capable of modulating immune responses. In particular, they regulate T cell functions. Small RNA next-generation sequencing of resting and activated human NK cells and their secreted extracellular vesicles (EVs) led to the identification of a specific repertoire of NK-EV-associated microRNAs and their post-transcriptional modifications signature. Several microRNAs of NK-EVs, namely miR-10b-5p, miR-92a-3p, and miR-155-5p, specifically target molecules involved in Th1 responses. NK-EVs promote the downregulation of GATA3 mRNA in CD4+ T cells and subsequent TBX21 de-repression that leads to Th1 polarization and IFN-γ and IL-2 production. NK-EVs also have an effect on monocyte and moDCs (monocyte-derived dendritic cells) function, driving their activation and increased presentation and costimulatory functions. Nanoparticle-delivered NK-EV microRNAs partially recapitulate NK-EV effects in mice. Our results provide new insights on the immunomodulatory roles of NK-EVs that may help to improve their use as immunotherapeutic tools.
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Vesículas Extracelulares , MicroRNAs , Animais , Vesículas Extracelulares/metabolismo , Humanos , Células Matadoras Naturais/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Linfócitos T/metabolismoRESUMO
The gold standard for the diagnosis of pelvic congestion syndrome (PCS) is venography (VG), although transvaginal ultrasound (TVU) might be a noninvasive, nonionizing alternative. Our aim is to determine whether TVU is an accurate and comparable diagnostic tool for PCS. An observational prospective study including 67 patients was carried out. A TVU was performed on patients, measuring pelvic venous vessels parameters. Subsequentially, a VG was performed, and results were compared for the test calibration of TVU. Out of the 67 patients included, only 51 completed the study and were distributed in two groups according to VG results: 39 patients belonging to the PCS group and 12 to the normal group. PCS patients had a larger venous plexus diameter (15.1 mm vs. 12 mm; p = 0.009) and higher rates of crossing veins in the myometrium (74.35% vs. 33.3%; p = 0.009), reverse or altered flow during Valsalva (58.9% vs. 25%; p = 0.04), and largest pelvic vein ≥ 8 mm (92.3% vs. 25%). The sensitivity and specificity of TVU were 92.3% (95% CI: 78.03-97.99%) and 75% (95% CI: 42.84-93.31%), respectively. In conclusion, transvaginal ultrasonography, with the described methodology, appears to be a promising tool for the diagnosis of PCS, with acceptable sensitivity and specificity.
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Dor Pélvica , Doenças Vasculares , Feminino , Humanos , Dor Pélvica/diagnóstico por imagem , Pelve/irrigação sanguínea , Pelve/diagnóstico por imagem , Estudos Prospectivos , UltrassonografiaRESUMO
INTRODUCTION: To explore the prevalence of dysphonia in European patients with mild-to-moderate COVID-19 and the clinical features of dysphonic patients. METHODS: The clinical and epidemiological data of 702 patients with mild-to-moderate COVID-19 were collected from 19 European Hospitals. The following data were extracted: age, sex, ethnicity, tobacco consumption, comorbidities, general, and otolaryngological symptoms. Dysphonia and otolaryngological symptoms were self-assessed through a 4-point scale. The prevalence of dysphonia, as part of the COVID-19 symptoms, was assessed. The outcomes were compared between dysphonic and nondysphonic patients. The association between dysphonia severity and outcomes was studied through Bayesian analysis. RESULTS: A total of 188 patients were dysphonic, accounting for 26.8% of cases. Females developed more frequently dysphonia than males (P = 0.022). The proportion of smokers was significantly higher in the dysphonic group (P = 0.042). The prevalence of the following symptoms was higher in dysphonic patients compared with nondysphonic patients: cough, chest pain, sticky sputum, arthralgia, diarrhea, headache, fatigue, nausea, and vomiting. The severity of dyspnea, dysphagia, ear pain, face pain, throat pain, and nasal obstruction was higher in dysphonic group compared with nondysphonic group. There were significant associations between the severity of dysphonia, dysphagia, and cough. CONCLUSION: Dysphonia may be encountered in a quarter of patients with mild-to-moderate COVID-19 and should be considered as a symptom list of the infection. Dysphonic COVID-19 patients are more symptomatic than nondysphonic individuals. Future studies are needed to investigate the relevance of dysphonia in the COVID-19 clinical presentation.