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Background: HOXA1 is a prognostic marker and a potential predictive biomarker for radioresistance in head and neck tumors. Its overexpression has been associated with promoter methylation and a worse prognosis in oral squamous cell carcinoma (OSCC) patients. However, opposite outcomes are also described. The effect of the methylation of this gene on different gene regions, other than the promoter, remains uncertain. We investigated the methylation profile at different genomic regions of HOXA1 in OSCC and correlated differentially methylated CpG sites with clinicopathological data., Methods: The HOXA1 DNA methylation status was evaluated by analyzing data from The Cancer Genome Atlas and three Gene Expression Omnibus datasets. Significant differentially methylated CpG sites were considered with a |∆β| ≥ 0.10 and a Bonferroni-corrected p -value < 0.01. Differentially methylated CpGs were validated by pyrosequencing using two independent cohorts of 15 and 47 OSCC patients, respectively., Results: Compared to normal tissues, we found significantly higher DNA methylation levels in the 3'UTR region of HOXA1 in OSCC. Higher methylation levels in tumor samples were positively correlated with smoking habits and patients' overall survival., Conclusions: Our findings suggest that HOXA1 gene body methylation is a promising prognostic biomarker for OSCC with potential clinical applications in patient monitoring.

Previous studies in mice demonstrated that CD8 T cells exhibit marked veto activity enhancing engraftment in several models for T cell-depleted bone marrow (TDBM) allografting. To reduce the risk of graft-versus-host disease (GVHD) associated with allogeneic CD8 veto T cells, these studies made use of naive CD8 T cells stimulated against third-party stimulators under cytokine deprivation and subsequent expansion in the presence of IL-15. More recently, it was shown that mouse CD8 veto T cells can be generated by stimulating CD8 memory T cells from ovalbumin immunized mice under cytokine deprivation, using ovalbumin as a third-party antigen. These cells also exhibited substantial enhancement of BM allografting without GVHD. In this study, we tested the hypothesis that stimulation and expansion of human CD8 memory T cells under IL-15 and IL-7 deprivation during the early phase of activation against recall viral antigens can lead to substantial loss of alloreactive T clones while retaining marked veto activity. Memory CD8 T cells were enriched by removal of CD45RA + , CD4 + , and CD56 + cells from peripheral blood of cytomegalovirus (CMV)- and Epstein-Barr virus (EBV)-positive donors. In parallel, CD14 + monocytes were isolated; differentiated into mature dendritic cells (mDCs); pulsed with a library of CMV, EBV, adenovirus, and BK virus peptides; and irradiated. The CD8 T cell-enriched fraction was then cultured with the pulsed mDCs in the presence of IL-21 for 3 days, after which IL-15 and IL-7 were added. After 12 days of culture, the cells were tested by limiting dilution analysis for the frequency of alloreactive T cell clones and their veto activity. In preclinical runs using GMP reagents, we established that within 12 days of culture, a large number of highly homogenous CD8 T cells, predominantly expressing a central memory phenotype, could be harvested. These cells exhibited marked veto activity in vitro and >3-log depletion of alloreactivity. Based on these preclinical data, a phase 1-2 clinical trial was initiated to test the safety and efficacy of these antiviral CD8 central memory veto cells in the context of nonmyeloablative (NMA) T cell-depleted haploidentical hematopoietic stem cell transplantation (HSCT). In 2 validation runs and 11 clinical runs using GMP reagents, >1 × 10 10 cells were generated from a single leukapheresis in 12 out of 13 experiments. At the end of 12 days of culture, there were 97 ± 2.5% CD3 + CD8 + T cells, of which 84 ± 9.0% (range, 71.5% to 95.1%) exhibited the CD45RO + CD62L + CM phenotype. Antiviral activity tested by intracellular expression of INF-γ and TNF-α and showed an average of 38.8 ± 19.6% positive cells on 6 hours of stimulation against the viral peptide mixture. Our results demonstrate a novel approach for depleting alloreactive T cell clones from preparations of antiviral CD8 veto cells. Based on these results, a phase 1-2 clinical trial is currently in progress to test the safety and efficacy of these veto cells in the context of NMA haploidentical T cell-depleted HSCT. Studies testing the hypothesis that these non-alloreactive CD8 T cells could potentially offer a platform for off-the-shelf veto chimeric antigen receptor T cell therapy in allogenic recipients, are warranted., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Objective: to analyze the discourses about the care provided by nurses operating in Specialized HIV/Aids Outpatient Services in four public institutions of the city of Fortaleza, Ceará, Brazil., Method: descriptive and exploratory study with a qualitative approach, which used as a method the discourse analysis., Results: when titling the "care as negative", such title came from the analogy proposed by Freud (1912) with the photographic negative, represented by what that care can configure from the unconscious movement, since nurses did not perceive themselves in the care actions developed by supporting the work of other occupational categories, contributing to maintain the ideology of biomedicine., Conclusion: it is necessary to justify and theorize a nursing clinical practice from epistemological issues of the profession, in such a way that nurses can understand their relevance within the care provided.

Objective: to know the social representations of sexuality for the elderly, based on the Social Representation Theory., Method: study performed in a Basic Family Health Unit in Maracanau-CE, Brazil, with 30 elderly adults. Data were collected from March through April of 2013, using the free word evocation technique. Data were organized and processed using the EVOC 2000.software, Results: the subjects evoked 150 words associated with the evocator word "sexuality". Out of these, 43 were different. At the possible core of the representation of sexuality for the elderly, the following words were found: love, affection and respect. Sex, companionship, understanding and coexistence composed the intermediate elements of representation., Conclusion: the performed analyses pointed to love, respect and affection as central elements that structured and organized the social representation of sexuality in the elder years for the group studied.

Intact RNA from exosomes/microvesicles (collectively referred to as microvesicles) has sparked much interest as potential biomarkers for the non-invasive analysis of disease. Here we use the Illumina Genome Analyzer to determine the comprehensive array of nucleic acid reads present in urinary microvesicles. Extraneous nucleic acids were digested using RNase and DNase treatment and the microvesicle inner nucleic acid cargo was analyzed with and without DNase digestion to examine both DNA and RNA sequences contained in microvesicles. Results revealed that a substantial proportion (∼87%) of reads aligned to ribosomal RNA. Of the non-ribosomal RNA sequences, ∼60% aligned to non-coding RNA and repeat sequences including LINE, SINE, satellite repeats, and RNA repeats (tRNA, snRNA, scRNA and srpRNA). The remaining ∼40% of non-ribosomal RNA reads aligned to protein coding genes and splice sites encompassing approximately 13,500 of the known 21,892 protein coding genes of the human genome. Analysis of protein coding genes specific to the renal and genitourinary tract revealed that complete segments of the renal nephron and collecting duct as well as genes indicative of the bladder and prostate could be identified. This study reveals that the entire genitourinary system may be mapped using microvesicle transcript analysis and that the majority of non-ribosomal RNA sequences contained in microvesicles is potentially functional non-coding RNA, which play an emerging role in cell regulation.

This study aimed to analyze the proposal of educational plan organized through the Nursing Process, using the International Classification for Nursing Practice (ICNP®), based on the Theory of Modeling and Role Modeling, to one group of women in Maracanaú-CE, Brazil. A case study was carried out in an educational group of women. A qualitative approach conducted the data production guided by the Creative and Sensitive Method. Two main diagnoses emerged from the needs presented by the group: compromised health and adequate knowledge, as well as formulation of results and nursing interventions. This study indicates the possibility of Nursing Process supported by INCP® and educational activities based on the Theory of Modeling and Role Modeling.

As AIDS advances in Brazil, the Ministry of Health felt the need to sensitize and to train health professionals to work with questions provoked by this infection or by the disease. The implantation of counseling centers and support serological support (CTA) arose and became the main reference in counseling. The HIV / AIDS counseling is a device used by health professionals seeking to work information, guidance, risk assessment and support in accomplish the anti-HIV serology. However, it is necessary that this strategy have theoretical and philosophical fundaments that serve to underpin the counselor's clinical practice. Therefore, this article aimed to present the main presuppositions of some psychological counseling theories and its relation to the practice of HIV/AIDS counseling. It is believed that these reflections can contribute to substantiate theoretically the professionals who perform HIV/AIDS counseling, configuring it as a device for health promotion.

The study aims to examine how the nursing consultation is developed by the nurses workimg in in Outpatient Specialized Services on HIV / AIDS in the city of Fortaleza-CE. This is an exploratory and descriptive study with a qualitative approach that used content analysis as a technique for data analysis. To perform the nursing consultation, listening was reported by nurses as the main mechanism that enables the construction of empathy and trust relationship with the patient, allowing them to express their doubts, fears and anxieties. It also enables the spread of information and guidance about the pathology, as well as the convening of the subject for an active participation in the care process, trying to make them aware about the importance of the adherence to drug treatment. Nursing consultation configure itself as an educational moment, opportune for knowledge exchange and bonding.

A major breakthrough in AIDS treatment occurred with the advent of antiretroviral therapy. However, several vulnerabilities may be present in the path experienced by patients during treatment. This study aimed to analyze the vulnerabilities of patients with HIV / AIDS in treatment failure. It is a qualitative study, involving seven users with AIDS considered in treatment failure in an Outpatient Service Unit on HIV / AIDS, in Fortaleza-CE. To interpret the data, it was used the technique of content analysis. In the speeches, it was realized that the deponents faced conflicts in the family and, difficult relationships with people and stigma at work. It was observed that patients had experienced various situations that made them more susceptible to HIV infection and illness.

The study aims to understand the patients' perception regarding the nursing consultation at an outpatient clinic for Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) in the city of Fortaleza-CE (State of Ceará). This is an exploratory and descriptive qualitative approach. Data was collected through semi-structured interviews with fifteen patients of this institution and analyzed with the support of content analysis. The nursing consultation was reported by patients as a learning moment, focused onproviding information. The trust and emotional support provided by the professional act as a support to the conflicts experienced by the patients, allowing the construction of a new perspective of the disease. We believe that the implementation of the nursing consultation in a dialogic perspective can provide a new meaning to the conflicts surrounding the patients' illness.

The study aims to discuss the concepts of caring and education and propose a strategy for health education as a possibility for clinical nursing care for women in menopause based on the educational principles of Paulo Freire. Over the years, different paradigms of Health Education are conditioned by different strategies, many of them reductionists, which require questioning and implementation of more integral and participatory actions. From this thought, we seek an opportunity for education that includes the "Other" in their complexity, enabling the women in their climacteric phase can also be assisted in full. In this scenario, we visualize the principles of Paulo Freire as a framework to guide this development; it shows a dialectic education, solidarity, without arrogance, articulating the scientific knowledge and popular knowledge, translating his method in a collective work.

This is a reflective article, which aims to discuss the concept of vulnerability and its implications for clinical nursing. Were discussed theoretical concept and how this fits into the area of health as possible to prevent AIDS. We realized that to understand the forms of illness of the subjects, we must understand them as well as biological aspects and take into account cultural, psychological, socio-economic and political, that is, any kind of situation which results in susceptibility to illness. We propose the use of the concept of vulnerability as a useful tool in nursing consultation. This should be at an opportune time for an exchange of knowledge and narrowing of the ties.

Urinary exosomes or microvesicles are being studied intensively to identify potential new biomarkers for renal disease. We sought to identify whether these microvesicles contain nucleic acids. We isolated microvesicles from human urine in the same density range as that previously described for urinary exosomes and found them to have an RNA integrity profile similar to that of kidney tissue, including 18S and 28S rRNA. This profile was better preserved in urinary microvesicles compared with whole cells isolated from urine, suggesting that microvesicles may protect RNA during urine passage. We were able to detect mRNA in the human urinary microvesicles encoding proteins from all regions of the nephron and the collecting duct. Further, to provide a proof of principle, we found that microvesicles isolated from the urine of the V-ATPase B1 subunit knockout mice lacked mRNA of this subunit while containing a normal amount of the B2 subunit and aquaporin 2. The microvesicles were found to be contaminated with extraneous DNA potentially on their surface; therefore, we developed a rapid and reliable means to isolate nucleic acids from within urine microvesicles devoid of this extraneous contamination. Our study provides an experimental strategy for the routine isolation and use of urinary microvesicles as a novel and non-invasive source of nucleic acids to further renal disease biomarker discovery.

The vacuolar-type H(+)-ATPase (V-ATPase) is a multisubunit proton pump that is involved in both intra- and extracellular acidification processes throughout the body. Multiple homologs and splice variants of V-ATPase subunits are thought to explain its varied spatial and temporal expression pattern in different cell types. Recently subunit nomenclature was standardized with a total of 22 subunit variants identified. However this standardization did not accommodate the existence of splice variants and is therefore incomplete. Thus, we propose here an extension of subunit nomenclature along with a literature and sequence database scan for additional V-ATPase subunits. An additional 17 variants were pulled from a literature search while 4 uncharacterized potential subunit variants were found in sequence databases. These findings have been integrated with the current V-ATPase knowledge base to create a new V-ATPase subunit catalogue. It is envisioned this catalogue will form a new platform on which future studies into tissue- and organelle-specific V-ATPase expression, localization and function can be based.

The purpose of this study was to compare the agar dilution and broth microdilution methods for determining the minimum inhibitory concentration (MIC) of fluconazole, itraconazole, ketoconazole, griseofulvin and terbinafine for 60 dermatophyte samples belonging to the species Trichophyton rubrum, Trichophyton mentagrophytes and Microsporum canis. The percentage agreement between the two methods, for all the isolates with < 2 dilutions that were tested was 91.6% for ketoconazole and griseofulvin, 88.3% for itraconazole, 81.6% for terbinafine and 73.3% for fluconazole. One hundred percent agreement was obtained for Trichophyton mentagrophytes isolates evaluated with ketoconazole and griseofulvin. Thus, until a reference method for testing the in vitro susceptibility of dermatophytes is standardized, the similarity of the results between the two methods means that the agar dilution method may be useful for susceptibility testing on these filamentous fungi.

The antifungal activities of fluconazole, itraconazole, ketoconazole, terbinafine and griseofulvin were tested by broth microdilution technique, against 60 dermatophytes isolated from nail or skin specimens from Goiania city patients, Brazil. In this study, the microtiter plates were incubated at 28 masculineC allowing a reading of the minimal inhibitory concentration (MIC) after four days of incubation for Trichophyton mentagrophytes and five days for T. rubrum and Microsporum canis. Most of the dermatophytes had uniform patterns of susceptibility to the antifungal agents tested. Low MIC values as 0.03 microg/mL were found for 33.3%, 31.6% and 15% of isolates for itraconazole, ketoconazole and terbinafine, respectively.

This reflection intended to analyze the counselling starting from the vision of the Freire's pedagogy visualizing it in a wider way, as an education activity, an intervention act for the subject's autonomy. The counselling is an activity developed by a Health professional, properly, and it is destined to who has indication of accomplishing the anti-HIV. In the ambit of the epidemic of HIV/AIDS, the counselling contains three components: the emotional support to the customer; educational support; and evaluation of risks, that propitiates the reflection on values, attitudes and conducts. In that way, they will avoid to be he turned into a no obligation 'chat' and led according to the counselor's will.

The study aimed to investigate the strategies health professionals use in HIV/AIDS counseling. This study is a qualitative research, based on Paulo Freire's theory and practice. Bardin's content analysis was used as the analysis technique. For the studied group, the counseling is focused on cognition, although new concepts permeating this subject are emerging. The main difficulties in counseling are related to the clients and the institution. The main facility is related to the team, which according to the group has a good relationship. Counseling represents a moment of distress, especially because it brings up existential questions to the counselor. It can be inferred that counseling is a special moment, but it does not constitute an educational moment yet. To obtain this goal, a counseling methodology is proposed, based on Paulo Freire's principles and concepts.

The objectives of this study were to investigate the frequency of pityriasis versicolor occurrence and to identify yeasts of the genus Malassezia in patients at the mycology laboratory of the Federal University of Goiás, in Goiânia, State of Goiás. Ninety-five cases of pityriasis versicolor were diagnosed, and four species of Malassezia were identified: Malassezia furfur, Malassezia sympodialis, Malassezia globosa and Malassezia obtusa.

We present rna22, a method for identifying microRNA binding sites and their corresponding heteroduplexes. Rna22 does not rely upon cross-species conservation, is resilient to noise, and, unlike previous methods, it first finds putative microRNA binding sites in the sequence of interest, then identifies the targeting microRNA. Computationally, we show that rna22 identifies most of the currently known heteroduplexes. Experimentally, with luciferase assays, we demonstrate average repressions of 30% or more for 168 of 226 tested targets. The analysis suggests that some microRNAs may have as many as a few thousand targets, and that between 74% and 92% of the gene transcripts in four model genomes are likely under microRNA control through their untranslated and amino acid coding regions. We also extended the method's key idea to a low-error microRNA-precursor-discovery scheme; our studies suggest that the number of microRNA precursors in mammalian genomes likely ranges in the tens of thousands.

Oropharyngeal candidiasis is the most common opportunistic fungal infection in individuals infected with human immunodeficiency virus. CD4+ lymphocytes count and the quantification of viral RNA in blood plasma have been found to be the main markers of HIV disease progression. The present study was conducted to evaluate Candida sp. diversity in the oral cavity of HIV-infected patients and to determine whether there was association of CD4+ cell count and viral load with asymptomatic oral Candida carriage. Out of 99 HIV-positive patients studied, 62 (62.6%) had positive culture for Candida (oral carriage) and 37 patients (37.4%) had Candida negative culture (no oral carriage). The etiologic agents most common were C. albicans and C. tropicalis. The range of CD4+ was 6-2305 cells/mm3 in colonized patients and 3-839 cells/mm3 for non-colonized patients, while the viral load was 60-90016 copies/mL for colonized patients and 75-110488 copies/mL for non colonized patients. The viral load was undetectable in 15 colonized patients and in 12 non colonized patients. Our results showed that there was no significant difference of the variables CD4+ cell count and viral load between oral candida carriage and no oral candida carriage patients.

Application of a computational membrane organization prediction pipeline, MemO, identified putative type II membrane proteins as proteins predicted to encode a single alpha-helical transmembrane domain (TMD) and no signal peptides. MemO was applied to RIKEN's mouse isoform protein set to identify 1436 non-overlapping genomic regions or transcriptional units (TUs), which encode exclusively type II membrane proteins. Proteins with overlapping predicted InterPro and TMDs were reviewed to discard false positive predictions resulting in a dataset comprised of 1831 transcripts in 1408 TUs. This dataset was used to develop a systematic protocol to document subcellular localization of type II membrane proteins. This approach combines mining of published literature to identify subcellular localization data and a high-throughput, polymerase chain reaction (PCR)-based approach to experimentally characterize subcellular localization. These approaches have provided localization data for 244 and 169 proteins. Type II membrane proteins are localized to all major organelle compartments; however, some biases were observed towards the early secretory pathway and punctate structures. Collectively, this study reports the subcellular localization of 26% of the defined dataset. All reported localization data are presented in the LOCATE database (http://www.locate.imb.uq.edu.au).

This study aimed at verifying the expectations of patients with HIV serum-positive patients, regarding to nursing care. This is a study with qualitative approach developed in the inpatient unit of a state public hospital in the municipal district of Fortaleza, CE. Data were collected in the period of September to October of 2003 through semi-structured interview, applied to 12 patients, randomly selected among the patients with diagnosis of HIV/AIDS. For data analysis it was used the Collective Subject's Speech (DSC) through emission of central ideas and/or key-expression. It was conclude that the patients expectations are for a more human care, more attention, contact verbal, more affectivity of the nursing team, a qualified and worthy attention. Besides their needs they should be informed daily about the vulnerabilities that they are submitted during the hospitalization.

The authors present some biographical data about Paulo Freire, his main works and his most important production, showing the fertility of his legacy. This article aims to discuss the articulation of some concepts used by Freire in nursing practice and education, offering reflections for turning professional practice more critical and creative on the basis of this Brazilian educator's ideas.

E-cadherin-catenin complexes mediate cell-cell adhesion on the basolateral membrane of epithelial cells. The cytoplasmic tail of E-cadherin supports multiple protein interactions, including binding of beta-catenin at the C terminus and of p120ctn to the juxtamembrane domain. The temporal assembly and polarized trafficking of the complex or its individual components to the basolateral membrane are not fully understood. In Madin-Darby canine kidney cells at steady state and after treatment with cycloheximide or temperature blocks, E-cadherin and beta-catenin localized to the Golgi complex, but p120ctn was found only at the basolateral plasma membrane. We previously identified a dileucine sorting motif (Leu586-Leu587, termed S1) in the juxtamembrane domain of E-cadherin and now show that it is required to target full-length E-cadherin to the basolateral membrane. Removal of S1 resulted in missorting of E-cadherin mutants (EcadDeltaS1) to the apical membrane; beta-catenin was simultaneously missorted and appeared at the apical membrane. p120ctn was not mistargeted with EcadDeltaS1, but could be recruited to the E-cadherin-catenin complex only at the basolateral membrane. These findings help define the temporal assembly and sorting of the E-cadherin-catenin complex and show that membrane recruitment of p120ctn in polarized cells is contextual and confined to the basolateral membrane.

We have developed a computational strategy to identify the set of soluble proteins secreted into the extracellular environment of a cell. Within the protein sequences predominantly derived from the RIKEN representative transcript and protein set, we identified 2033 unique soluble proteins that are potentially secreted from the cell. These proteins contain a signal peptide required for entry into the secretory pathway and lack any transmembrane domains or intracellular localization signals. This class of proteins, which we have termed the mouse secretome, included >500 novel proteins and 92 proteins <100 amino acids in length. Functional analysis of the secretome included identification of human orthologs, functional units based on InterPro and SCOP Superfamily predictions, and expression of the proteins within the RIKEN READ microarray database. To highlight the utility of this information, we discuss the CUB domain-containing protein family.

E-cadherin is a major adherens junction protein of epithelial cells, with a central role in cell-cell adhesion and cell polarity. Newly synthesized E-cadherin is targeted to the basolateral cell surface. We analyzed targeting information in the cytoplasmic tail of E-cadherin by utilizing chimeras of E-cadherin fused to the ectodomain of the interleukin-2alpha (IL-2alpha) receptor expressed in Madin-Darby canine kidney and LLC-PK(1) epithelial cells. Chimeras containing the full-length or membrane-proximal half of the E-cadherin cytoplasmic tail were correctly targeted to the basolateral domain. Sequence analysis of the membrane-proximal tail region revealed the presence of a highly conserved dileucine motif, which was analyzed as a putative targeting signal by mutagenesis. Elimination of this motif resulted in the loss of Tac/E-cadherin basolateral localization, pinpointing this dileucine signal as being both necessary and sufficient for basolateral targeting of E-cadherin. Truncation mutants unable to bind beta-catenin were correctly targeted, showing, contrary to current understanding, that beta-catenin is not required for basolateral trafficking. Our results also provide evidence that dileucine-mediated targeting is maintained in LLC-PK(1) cells despite the altered polarity of basolateral proteins with tyrosine-based signals in this cell line. These results provide the first direct insights into how E-cadherin is targeted to the basolateral membrane.