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1.
PLoS One ; 19(6): e0305391, 2024.
Article in English | MEDLINE | ID: mdl-38885228

ABSTRACT

BACKGROUND: In 2021, Mozambique initiated community-based oral HIV self-testing (HIVST) to increase testing access and uptake among priority groups, including adult males, adolescents, and young adults. Within an HIVST pilot project, we conducted a performance evaluation assessing participants' ability to successfully conduct HIVST procedures and interpret results. METHODS: A cross-sectional study was performed between February-March 2021 among employees, students (18-24 years of age), and community members, using convenience sampling, in two rural districts of Zambézia Province, Mozambique. We quantified how well untrained users performed procedures for the oral HIVST (Oraquick®) through direct observation using a structured checklist, from which we calculated an HIVST usability index (scores ranging 0-100%). Additionally, participants interpreted three previously processed anonymous HIVST results. False reactive and false non-reactive interpretation results were presented as proportions. Bivariate analysis was conducted using Chi-square and Fisher exact tests. RESULTS: A total of 312 persons participated (131[42%] community members, 71[23%] students, 110[35%] employees); 239 (77%) were male; the mean age was 28 years (standard deviation 10). Average usability index scores were 80% among employees, 86% among students, and 77% among community members. Main procedural errors observed included "incorrect tube positioning" (49%), "incorrect specimen collection" (43%), and "improper waiting time for result interpretation" (42%). From the presented anonymous HIVST results, 75% (n = 234) correctly interpreted all three results, while 9 (3%) of study participants failed to correctly interpret any results. Overall, 36 (12%) gave a false non-reactive result interpretation, 21 (7%) a false reactive result interpretation, and 14 (4%) gave both false non-reactive and false reactive result interpretations. Community members generally had lower performance. CONCLUSIONS: Despite some observed testing procedural errors, most users could successfully perform an HIVST. Educational sessions at strategic places (e.g., schools, workplaces), and support via social media and hotlines, may improve HIVST performance quality, reducing the risk of incorrect interpretation.


Subject(s)
HIV Infections , Rural Population , Self-Testing , Humans , Male , Mozambique , Female , Adult , HIV Infections/diagnosis , HIV Infections/epidemiology , Adolescent , Cross-Sectional Studies , Young Adult , HIV Testing/methods
2.
J Biomed Mater Res B Appl Biomater ; 112(2): e35389, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38356168

ABSTRACT

Advances in methodologies to evaluate biomaterials brought an explosive growth of data, ensuing computational challenges to better analyzing them and allowing for high-throughput profiling of biological systems cost-efficiently. In this sense, we have applied bioinformatics tools to better understand the biological effect of different sintering temperatures of hydroxyapatite (abbreviated HA; at 1100, 1150, and 1250°C) on osteoblast performance. To do, we have better analyzed an earlier deposited study, in which the access code is E-MTAB-7219, which the authors have explored different in silico tools on this purpose. In this study, differential gene expression analyses were performed using the gene set variation analysis (GSVA) algorithm from the transcriptomes respecting the thermal changes of HA, which were validated using exclusively in vitro strategies. Furthermore, in silico approaches elected biomarkers during cell behavior in response to different sintering temperatures of HA, and it was further validated using cell culture and qPCR technologies. Altogether, the combination of those strategies shows the capacity of sintered HA at 1250°C to present a better performance in organizing an adequate microenvironment favoring bone regeneration, angiogenesis and material resorption stimulus once it has promoted higher involvement of genes such as CDK2, CDK4 (biomarkers of cell proliferation), p15, Osterix gene (related with osteogenic differentiation), RANKL (related with osteoclastogenesis), VEGF gene (related with angiogenesis), and HIF1α (related with hypoxia microenvironment). Altogether, the combination of in silico and cell culture strategies shows the capacity of sintered HA at 1250°C in guaranteeing osteoblast differentiation and it can be related in organizing an adequate microenvironment favoring bone regeneration, angiogenesis, and material resorption stimulus.


Subject(s)
Biocompatible Materials , Durapatite , Biocompatible Materials/pharmacology , Durapatite/pharmacology , Temperature , Osteogenesis , Cell Proliferation , Cell Culture Techniques , Biomarkers
3.
Oncogene ; 43(11): 804-820, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38279062

ABSTRACT

HJURP is overexpressed in several cancer types and strongly correlates with patient survival. However, the mechanistic basis underlying the association of HJURP with cancer aggressiveness is not well understood. HJURP promotes the loading of the histone H3 variant, CENP-A, at the centromeric chromatin, epigenetically defining the centromeres and supporting proper chromosome segregation. In addition, HJURP is associated with DNA repair but its function in this process is still scarcely explored. Here, we demonstrate that HJURP is recruited to DSBs through a mechanism requiring chromatin PARylation and promotes epigenetic alterations that favor the execution of DNA repair. Incorporation of HJURP at DSBs promotes turnover of H3K9me3 and HP1, facilitating DNA damage signaling and DSB repair. Moreover, HJURP overexpression in glioma cell lines also affected global structure of heterochromatin independently of DNA damage induction, promoting genome-wide reorganization and assisting DNA damage response. HJURP overexpression therefore extensively alters DNA damage signaling and DSB repair, and also increases radioresistance of glioma cells. Importantly, HJURP expression levels in tumors are also associated with poor response of patients to radiation. Thus, our results enlarge the understanding of HJURP involvement in DNA repair and highlight it as a promising target for the development of adjuvant therapies that sensitize tumor cells to irradiation.


Subject(s)
Chromatin , Glioma , Humans , Centromere/metabolism , Centromere Protein A/genetics , Centromere Protein A/metabolism , Chromatin/genetics , Chromosomal Proteins, Non-Histone/genetics , Chromosomal Proteins, Non-Histone/metabolism , DNA Repair/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Glioma/genetics
4.
Pathol Res Pract ; 250: 154806, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37738928

ABSTRACT

Prostate cancer (PCa) is the malignant neoplasm that most commonly affects men and is an important cause of death. It can be detected by changes in serum levels of Prostate Specific Antigen (PSA) and digital rectal examination, but often symptoms do not appear until advanced stages and metastases. The C-X-C Motif Chemokine Ligand 12/C-X-C Motif Chemokine Receptor 4 (CXCL12/CXCR4) axis acts in cell migration and may be involved in the metastatic process. In this context, the aim of this study was to evaluate the allelic variants rs1801157 (CXCL12) and rs2228014 (CXCR4) and the immunostaining of CXCR4 protein as candidates for prognostic markers in PCa. Samples (n = 60) were divided according to prognostic parameters (with and without metastasis at diagnosis) in tree groups: better prognosis, worse prognosis with metastasis at diagnosis and worse prognosis without metastasis at diagnosis, and immunostaining was evaluated by indirect immunohistochemistry, considering tumoral and adjacent tissues from the same patient (n = 120). A significant association was found between the C allele of rs2228014 (CXCR4) and the extraprostatic extension. For CXCR4 immunostaining a weak labeling and a cytoplasmic localization predominated, as well as a significant difference between malignant versus adjacent tissue, with higher protein expression in the malignant tissue. A significant association was found between CXCR4 tumor immunostaining with TNM staging (T2b-T2c) and PSA level (> 20 ng/mL). None of the allelic variants affected CXCR4 immunostaining. Prognostic groups did not differ in allelic variant frequency or immunostaining profile. Findings suggest that CXCR4 receptor may be one of the ways to worsen the prognosis of prostatic cancer.

5.
J Toxicol Environ Health A ; 86(21): 803-815, 2023 11 02.
Article in English | MEDLINE | ID: mdl-37565650

ABSTRACT

Nosocomial infections (NIs) appear in patients under medical care in the hospital. The surveillance of the bacterial communities employing high-resolution 16S rRNA profiling, known as metabarcoding, represents a reliable method to establish factors that may influence the composition of the bacterial population during NIs. The present study aimed to utilize high-resolution 16S rRNA profiling to identify high bacterial diversity by analyzing 11 inside and 10 outside environments from the General Hospital of Ribeirão Preto Medical School, Brazil. Our results identified a high bacterial diversity, and among these, the most abundant bacterial genera linked to NIs were Cutibacterium, Streptococcus, Staphylococcus, and Corynebacterium. A Acinetobacter was detected in cafeterias, bus stops, and adult and pediatric intensive care units (ICUs). Data suggest an association between transport and alimentation areas proximal to the hospital ICU environment. Interestingly, the correlation and clusterization analysis showed the potential of the external areas to directly influence the ICU pediatric department microbial community, including the outpatient's clinic, visitor halls, patient reception, and the closest cafeterias. Our results demonstrate that high-resolution 16S rRNA profiling is a robust and reliable tool for bacterial genomic surveillance. In addition, the metabarcoding approach might help elaborate decontamination policies, and consequently reduce NIs.


Subject(s)
Cross Infection , Microbiota , Adult , Child , Humans , Cross Infection/epidemiology , Cross Infection/microbiology , RNA, Ribosomal, 16S/genetics , Bacteria/genetics , Hospitals
6.
Int J Mol Sci ; 24(13)2023 Jun 28.
Article in English | MEDLINE | ID: mdl-37445965

ABSTRACT

Breast cancer is responsible for 25% of all cancers that affect women. Due to its high heterogeneity pattern in clinical diagnosis and its molecular profile differences, researchers have been seeking new targets and therapies, with more specificity and fewer side effects. Thus, one compound that has garnered our attention is trans-chalcone, which is naturally occurring in various plants and possesses promising biological properties, including antitumor effects. MiRNA is an extensive class of non-coding small, endogenous, and single-stranded RNAs, and it is involved in post-translational gene regulation. Therefore, the objective of this study was to investigate the effects of TChal on miRNAs expression and its relationship with anticancer activity against MCF-7. Initially, the trans-chalcone IC50 value was established by MTT assay for MCF-7and HaCat (non-cancer cell), in which we found out that it was 53.73 and 44.18 µM, respectively. Subsequently, we treated MCF-7 cells with trans-chalcone at its IC50 concentration and performed Mi-seq analysis, which unveiled 23 differentially expressed miRNAs. From this set, we selected five miRNAs (miR-25-5p, miR-27a-3p, miR-891a, miR-449a, and miR-4485) for further validation using qRT-PCR, guided by in silico analysis and their known association with tumorigenesis. In conclusion, our research provides valuable insights into the potential use of TChal to reveal MicroRNAs molecular targets that can be applied in breast cancer therapy.


Subject(s)
Breast Neoplasms , Chalcones , MicroRNAs , Humans , Female , MicroRNAs/genetics , MicroRNAs/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , MCF-7 Cells , Chalcones/pharmacology , Chalcones/therapeutic use , Gene Expression Regulation, Neoplastic
7.
Sci Total Environ ; 872: 162234, 2023 May 10.
Article in English | MEDLINE | ID: mdl-36791854

ABSTRACT

Complexation of dissolved organic matter (DOM) with cations and minerals contributes to the stabilization of carbon in soils, and can enable the transport of metals in the environment. Hence, a proper understanding of mechanisms that control DOM binding properties in the soil is important for major environmental challenges, such as climate change and stream pollution. However, the role of DOM source in those mechanisms remains understudied. Here, we consider poorly drained tropical Podzols as a model environment to isolate effects of aluminium and DOM on sorption and desorption processes in podzolisation. We collected E- and Bh-horizons from a Brazilian coastal Podzol under tropical rainforest to conduct a column experiment, and percolated the columns with DOM collected from a stream (Stream), peat water (Peat), litter (Litter) and charred litter (Char). To quantify sorption and desorption from the columns, leachates were analysed for DOC content, aluminium content, pH, and the amount of fulvic acid relative to humic acid. The results showed large differences in DOC retention between DOM-types, which were consistent over all columns. Retention of DOC in the column varied between 25 % and 92 % for DOM-type Stream, between 33 % and 63 % for DOM-type Peat, between 22 % and 47 % for DOM-type Litter, and between 8 % and 49 % for DOM-type Char. Similarly, desorption from columns with B-horizon material highly differed between DOM-types. Percolation with DOM-types Stream and Peat caused a release of native DOC from B columns that was higher than in those percolated with water only. On the other hand, percolation of B columns with DOM-types Litter and Char caused a net DOC retention. These differences reflect that certain DOM-types hindered desorption, while other DOM-types caused active desorption. The large differences in sorption/desorption between DOM-types implies that changes in environmental conditions may highly influence the fate of soil carbon in Podzols.

8.
Mach Vis Appl ; 34(1): 16, 2023.
Article in English | MEDLINE | ID: mdl-36597466

ABSTRACT

Every year, the VISion Understanding and Machine intelligence (VISUM) summer school runs a competition where participants can learn and share knowledge about Computer Vision and Machine Learning in a vibrant environment. 2021 VISUM's focused on applying those methodologies in fashion. Recently, there has been an increase of interest within the scientific community in applying computer vision methodologies to the fashion domain. That is highly motivated by fashion being one of the world's largest industries presenting a rapid development in e-commerce mainly since the COVID-19 pandemic. Computer Vision for Fashion enables a wide range of innovations, from personalized recommendations to outfit matching. The competition enabled students to apply the knowledge acquired in the summer school to a real-world problem. The ambition was to foster research and development in fashion outfit complementary product retrieval by leveraging vast visual and textual data with domain knowledge. For this, a new fashion outfit dataset (acquired and curated by FARFETCH) for research and benchmark purposes is introduced. Additionally, a competitive baseline with an original negative sampling process for triplet mining was implemented and served as a starting point for participants. The top 3 performing methods are described in this paper since they constitute the reference state-of-the-art for this particular problem. To our knowledge, this is the first challenge in fashion outfit complementary product retrieval. Moreover, this joint project between academia and industry brings several relevant contributions to disseminating science and technology, promoting economic and social development, and helping to connect early-career researchers to real-world industry challenges.

9.
Nat Genet ; 55(2): 209-220, 2023 02.
Article in English | MEDLINE | ID: mdl-36635388

ABSTRACT

Malformations of cortical development (MCD) are neurological conditions involving focal disruptions of cortical architecture and cellular organization that arise during embryogenesis, largely from somatic mosaic mutations, and cause intractable epilepsy. Identifying the genetic causes of MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat condition-related epilepsy. Here we report a genetic landscape from 283 brain resections, identifying 69 mutated genes through intensive profiling of somatic mutations, combining whole-exome and targeted-amplicon sequencing with functional validation including in utero electroporation of mice and single-nucleus RNA sequencing. Genotype-phenotype correlation analysis elucidated specific MCD gene sets associated with distinct pathophysiological and clinical phenotypes. The unique single-cell level spatiotemporal expression patterns of mutated genes in control and patient brains indicate critical roles in excitatory neurogenic pools during brain development and in promoting neuronal hyperexcitability after birth.


Subject(s)
Epilepsy , Malformations of Cortical Development , Humans , Multiomics , Brain/metabolism , Epilepsy/genetics , Mutation , Malformations of Cortical Development/genetics , Malformations of Cortical Development/metabolism
11.
Cell Mol Neurobiol ; 43(2): 813-826, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35366170

ABSTRACT

Medulloblastoma is the most common type of pediatric malignant primary brain tumor, and about one-third of patients die due to disease recurrence and most survivors suffer from long-term side effects. MB is clinically, genetically, and epigenetically heterogeneous and subdivided into at least four molecular subgroups: WNT, SHH, Group 3, and Group 4. We evaluated common differentially expressed genes between a Brazilian RNA-seq GSE181293 dataset and microarray GSE85217 dataset cohort of pediatric MB samples using bioinformatics methodology in order to identify hub genes of the molecular subgroups based on PPI network construction, survival and functional analysis. The main finding was the identification of five hub genes from the WNT subgroup that are tumor suppressors, and whose lower expression is related to a worse prognosis for MB patients. Furthermore, the common genes correlated with the five tumor suppressors participate in important pathways and processes for tumor initiation and progression, as well as development and differentiation, and some of them control cell stemness and pluripotency. These genes have not yet been studied within the context of MB, representing new important elements for investigation in the search for therapeutic targets, prognostic markers or for understanding of MB biology.


Subject(s)
Brain Neoplasms , Cerebellar Neoplasms , Medulloblastoma , Humans , Child , Medulloblastoma/genetics , Medulloblastoma/metabolism , Medulloblastoma/pathology , Prognosis , Cerebellar Neoplasms/genetics , Cerebellar Neoplasms/metabolism , Cerebellar Neoplasms/pathology , Gene Expression Profiling , Biomarkers, Tumor/genetics
12.
J Clin Endocrinol Metab ; 108(6): 1464-1474, 2023 05 17.
Article in English | MEDLINE | ID: mdl-36478070

ABSTRACT

CONTEXT: Nicotinamide nucleotide transhydrogenase (NNT) acts as an antioxidant defense mechanism. NNT mutations cause familial glucocorticoid deficiency (FGD). How impaired oxidative stress disrupts adrenal steroidogenesis remains poorly understood. OBJECTIVE: To ascertain the role played by NNT in adrenal steroidogenesis. METHODS: The genotype-phenotype association of a novel pathogenic NNT variant was evaluated in a boy with FGD. Under basal and oxidative stress (OS) induced conditions, transient cell cultures of the patient's and controls' wild-type (WT) mononuclear blood cells were used to evaluate antioxidant mechanisms and mitochondrial parameters (reactive oxygen species [ROS] production, reduced glutathione [GSH], and mitochondrial mass). Using CRISPR/Cas9, a stable NNT gene knockdown model was built in H295R adrenocortical carcinoma cells to determine the role played by NNT in mitochondrial parameters and steroidogenesis. NNT immunohistochemistry was assessed in fetal and postnatal human adrenals. RESULTS: The homozygous NNT p.G866D variant segregated with the FGD phenotype. Under basal and OS conditions, p.G866D homozygous mononuclear blood cells exhibited increased ROS production, and decreased GSH levels and mitochondrial mass than WT NNT cells. In line H295R, NNT knocked down cells presented impaired NNT protein expression, increased ROS production, decreased the mitochondrial mass, as well as the size and the density of cholesterol lipid droplets. NNT knockdown affected steroidogenic enzyme expression, impairing cortisol and aldosterone secretion. In human adrenals, NNT is abundantly expressed in the transition fetal zone and in zona fasciculata. CONCLUSION: Together, these studies demonstrate the essential role of NNT in adrenal redox homeostasis and steroidogenesis.


Subject(s)
Adrenal Cortex Neoplasms , NADP Transhydrogenases , Male , Infant, Newborn , Humans , NADP Transhydrogenases/genetics , NADP Transhydrogenases/metabolism , Antioxidants , Reactive Oxygen Species/metabolism , Mitochondria/metabolism , Adrenal Cortex Neoplasms/genetics
13.
Sci Rep ; 12(1): 20732, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36456605

ABSTRACT

Currently, radiologists face an excessive workload, which leads to high levels of fatigue, and consequently, to undesired diagnosis mistakes. Decision support systems can be used to prioritize and help radiologists making quicker decisions. In this sense, medical content-based image retrieval systems can be of extreme utility by providing well-curated similar examples. Nonetheless, most medical content-based image retrieval systems work by finding the most similar image, which is not equivalent to finding the most similar image in terms of disease and its severity. Here, we propose an interpretability-driven and an attention-driven medical image retrieval system. We conducted experiments in a large and publicly available dataset of chest radiographs with structured labels derived from free-text radiology reports (MIMIC-CXR-JPG). We evaluated the methods on two common conditions: pleural effusion and (potential) pneumonia. As ground-truth to perform the evaluation, query/test and catalogue images were classified and ordered by an experienced board-certified radiologist. For a profound and complete evaluation, additional radiologists also provided their rankings, which allowed us to infer inter-rater variability, and yield qualitative performance levels. Based on our ground-truth ranking, we also quantitatively evaluated the proposed approaches by computing the normalized Discounted Cumulative Gain (nDCG). We found that the Interpretability-guided approach outperforms the other state-of-the-art approaches and shows the best agreement with the most experienced radiologist. Furthermore, its performance lies within the observed inter-rater variability.


Subject(s)
Radiology , Humans , Radiography , Radiologists , Diagnosis, Computer-Assisted , Computers
14.
BMJ Open ; 12(10): e056801, 2022 10 17.
Article in English | MEDLINE | ID: mdl-36253047

ABSTRACT

OBJECTIVE: The Brazilian state of Paraná has suffered from COVID-19 effects, understanding predictors of increased mortality in health system interventions prevent hospitalisation of patients. We selected the best models to evaluate the association of death with demographic characteristics, symptoms and comorbidities based on three levels of clinical severity for COVID-19: non-hospitalised, hospitalised non-ICU ward and ICU ward. DESIGN: Cross-sectional survey using binomial mixed models. SETTING: COVID-19-positive cases diagnosed by reverse transcription-PCR of municipalities located in Paraná State. PATIENTS: Cases of anonymous datasets of electronic medical records from 1 April 2020 to 31 December 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: The best prediction factors were chosen based on criteria after a stepwise analysis using multicollinearity measure, lower Akaike information criterion and goodness-of-fit χ2 tests from univariate to multivariate contexts. RESULTS: Male sex was associated with increased mortality among non-hospitalised patients (OR 1.76, 95% CI 1.47 to 2.11) and non-ICU patients (OR 1.22, 95% CI 1.05 to 1.43) for symptoms and for comorbidities (OR 1.89, 95% CI 1.59 to 2.25, and OR 1.30, 95% CI 1.11 to 1.52, respectively). Higher mortality occurred in patients older than 35 years in non-hospitalised (for symptoms: OR 4.05, 95% CI 1.55 to 10.54; and for comorbidities: OR 3.00, 95% CI 1.24 to 7.27) and in hospitalised over 40 years (for symptoms: OR 2.72, 95% CI 1.08 to 6.87; and for comorbidities: OR 2.66, 95% CI 1.22 to 5.79). Dyspnoea was associated with increased mortality in non-hospitalised (OR 4.14, 95% CI 3.45 to 4.96), non-ICU (OR 2.41, 95% CI 2.04 to 2.84) and ICU (OR 1.38, 95% CI 1.10 to 1.72) patients. Neurological disorders (OR 2.16, 95% CI 1.35 to 3.46), neoplastic (OR 3.22, 95% CI 1.75 to 5.93) and kidney diseases (OR 2.13, 95% CI 1.36 to 3.35) showed the majority of increased mortality for ICU as well in the three levels of severity jointly with heart disease, diabetes and CPOD. CONCLUSIONS: These findings highlight the importance of the predictor's assessment for the implementation of public healthcare policy in response to the COVID-19 pandemic, mainly to understand how non-pharmaceutical measures could mitigate the virus impact over the population.


Subject(s)
COVID-19 , Humans , Male , Brazil/epidemiology , Comorbidity , COVID-19/complications , COVID-19/epidemiology , COVID-19/mortality , COVID-19/therapy , Cross-Sectional Studies , Hospitalization , Intensive Care Units , Pandemics , Female , Risk Factors , Adult , Middle Aged , Aged , Models, Statistical
15.
Cell Rep Phys Sci ; 3(9): 101019, 2022 Sep 21.
Article in English | MEDLINE | ID: mdl-36259071

ABSTRACT

Here, we report photonic nanostructures replicated from the adaxial epidermis of flower petals onto light-polymerized coatings using low-cost nanoimprint lithography at ambient temperature. These multifunctional nanocoatings are applied to confer enhanced light trapping, water repellence, and UV light and environmental moisture protection features in perovskite solar cells. The former feature helps attain a maximum power conversion efficiency of 24.61% (21.01% for the reference cell) without any additional device optimization. Added to these merits, the nanocoatings also enable stable operation under AM 1.5G and UV light continuous illumination or in real-world conditions. Our engineering approach provides a simple way to produce multifunctional nanocoatings optimized by nature's wisdom.

16.
Int J Mol Sci ; 23(19)2022 Sep 29.
Article in English | MEDLINE | ID: mdl-36232817

ABSTRACT

Given the importance of menstrual blood in the pathogenesis of endometriosis and the multifunctional roles of menstrual mesenchymal stem cells (MenSCs) in regenerative medicine, this issue has gained prominence in the scientific community. Moreover, recent reviews highlight how robust the integrated assessment of omics data are for endometriosis. To our knowledge, no study has applied the multi-omics approaches to endometriosis MenSCs. This is a case-control study at a university-affiliated hospital. MenSCs transcriptome and proteome data were obtained by RNA-seq and UHPLC-MS/MS detection. Among the differentially expressed proteins and genes, we emphasize ATF3, ID1, ID3, FOSB, SNAI1, NR4A1, EGR1, LAMC3, and ZFP36 genes and MT2A, TYMP, COL1A1, COL6A2, and NID2 proteins that were already reported in the endometriosis. Our functional enrichment analysis reveals integrated modulating signaling pathways such as epithelial-mesenchymal transition (↑) and PI3K signaling via AKT to mTORC1 (↓ in proteome), mTORC1 signaling, TGF beta signaling, TNFA signaling via NFkB, IL6 STAT3 signaling, and response to hypoxia via HIF1A targets (↑ in transcriptome). Our findings highlight primary changes in the endometriosis MenSCs, suggesting that the chronic inflammatory endometrial microenvironment can modulate these cells, providing opportunities for endometriosis etiopathogenesis. Moreover, they identify challenges for future research leveraging knowledge for regenerative and precision medicine in endometriosis.


Subject(s)
Endometriosis , Mesenchymal Stem Cells , Case-Control Studies , Cell Proliferation , Endometriosis/pathology , Female , Humans , Interleukin-6 , Laminin , Mechanistic Target of Rapamycin Complex 1/metabolism , Menstruation , Mesenchymal Stem Cells/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proteome , Proto-Oncogene Proteins c-akt/metabolism , Tandem Mass Spectrometry , Transcriptome , Transforming Growth Factor beta/genetics
17.
Arq. bras. cardiol ; 119(4 supl.1): 263-263, Oct, 2022.
Article in English | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1397465

ABSTRACT

INTRODUCTION: Tricuspid insufficiency (TI) is thought to be a rare complication of blunt,nonpenetrating chest trauma.The right ventricle (RV) is immediately behind the sternum,predisposing it to an anteroposterior compression type of injury,especially during the end diastolic phase. CASE DESCRIPTION: A previously healthy 39-year-old male without cardiac history was admitted to the emergency room with symptoms of heart failure and atrial flutter.Transthoracic echocardiogram showed significant tricuspid regurgitation, with an image suggestive of chordae rupture related to the anterior leaflet,with significant enlargement of the right chambers (right atrium indexed volume 115 ml/m²),moderate RV systolic dysfunction.After clinical stabilization, a history of high-energy automobile trauma occurred 20 years ago was identified,which resulted in traumatic brain injury and blunt abdominal trauma,requering abdominal surgeries; did not have any cardiovascular symptoms.Since then,he has not performed any cardiovascular follow-up.However, about three years ago,after starting to practice intense sports,he noticed of fatigue and dyspnea.He noticed progression of symptoms, seeking care in the emergency room with dyspnea on minimal exertion, palpitations and chest pain.In the heart team it was indicated surgical correction for severe TI.In the intraoperative,rupture of the chordae was observed, with calcification of the related papillary muscle and significant dilation of the tricuspid ring (60 mm);he was underwent valve replacement for a biological prosthesis in the tricuspid position.Postoperative echocardiogram showed the prosthesis in tricuspid position without reflux and maximum gradient of 8 mmHg. CONCLUSION:We report a case of traumatic TI,manifesting symptoms 20 years after the trauma.The interval between the traumatic event and the appearance of symptoms is variable,possibly due to the variability of possible associated valve lesions.While papillary muscle rupture is associated with more severe and acute symptoms (weeks to months), chordae rupture more commonly causes a slower course -10 to 25 years.The timing and appropriate treatment of traumatic TI depends on the natural course of the disease.Most cases do not require surgical intervention in the immediate period after the event. However,in the medium and long term,surgical correction of the tricuspid valve -by replacement or valve repair- is indicated to improve symptoms and avoid permanent impairment of the RV.


Subject(s)
Tricuspid Valve Insufficiency , Heart Failure
18.
J Int AIDS Soc ; 25(6): e25952, 2022 06.
Article in English | MEDLINE | ID: mdl-35718940

ABSTRACT

INTRODUCTION: Mentor Mothers (MM) provide peer support to pregnant and postpartum women living with HIV (PPWH) and their infants with perinatal HIV exposure (IPE) throughout the cascade of prevention of vertical transmission (PVT) services. MM were implemented in Zambézia Province, Mozambique starting in August 2017. This evaluation aimed to determine the effect of MM on PVT outcomes. METHODS: A retrospective interrupted time series analysis was done using routinely collected aggregate data from 85 public health facilities providing HIV services in nine districts of Zambézia. All PPWH (and their IPE) who initiated antiretroviral therapy (ART) from August 2016 through April 2019 were included. Outcomes included the proportion per month per district of: PPWH retained in care 12 months after ART initiation, PPWH with viral suppression and IPE with HIV DNA PCR test positivity by 9 months of age. The effect of MM on outcomes was assessed using logistic regression. RESULTS: The odds of 12-month retention increased 1.5% per month in the pre-MM period, compared to a monthly increase of 7.6% with-MM (35-61% pre-MM, 56-72% with-MM; p < 0.001). The odds of being virally suppressed decreased by 0.9% per month in the pre-MM period, compared to a monthly increase of 3.9% with-MM (49-85% pre-MM, 59-80% with-MM; p < 0.001). The odds of DNA PCR positivity by 9 months of age decreased 8.9% per month in the pre-MM period, compared to a monthly decrease of 0.4% with-MM (0-14% pre-MM, 4-10% with-MM; p < 0.001). The odds of DNA PCR uptake (the proportion of IPE who received DNA PCR testing) by 9 months of age were significantly higher in the with-MM period compared to the pre-MM period (48-100% pre-MM, 87-100% with-MM; p < 0.001). CONCLUSIONS: MM services were associated with improved retention in PVT services and higher viral suppression rates among PPWH. While there was ongoing but diminishing improvement in DNA PCR positivity rates among IPE following MM implementation, this might be explained by increased uptake of HIV testing among high-risk IPE who were previously not getting tested. Additional efforts are needed to further optimize PVT outcomes, and MM should be one part of a comprehensive strategy to address this critical need.


Subject(s)
Anti-HIV Agents , HIV Infections , Pregnancy Complications, Infectious , Anti-HIV Agents/therapeutic use , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/prevention & control , Humans , Infant , Infectious Disease Transmission, Vertical/prevention & control , Interrupted Time Series Analysis , Mentors , Mothers , Mozambique/epidemiology , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/prevention & control , Retrospective Studies
19.
AIDS Res Hum Retroviruses ; 38(8): 622-630, 2022 08.
Article in English | MEDLINE | ID: mdl-35579964

ABSTRACT

HIV self-testing (HIVST) is a WHO-recommended strategy to increase testing, especially among key populations, men, and young adults. Between May and December 2019, a pilot was implemented in Zambézia province, Mozambique, allowing clients to purchase HIV self-tests in 14 public/private pharmacies. The study assessed the strategy's acceptability and uptake. Pharmacy-based exit surveys were conducted among a random sample of clients, during the first three months of the pilot, independent of HIVST purchase. Another random sample of clients who bought an HIVST completed a survey 1-12 weeks after purchase. Chi-square and Mann-Whitney tests were used for the analysis, comparing clients who purchased an HIVST versus not. A total of 1,139 adults purchased 1,344 tests. Buyers were predominantly male (70%) and younger (52% between 15 and 34 years of age). Surveys were completed by 280 exiting pharmacy clients and 82 clients who purchased an HIVST. Main advantages were confidentiality and lack of need of a health provider visit, with main disadvantages being absence of nearby counseling and fear of results. No differences were seen between buyers and non-buyers for these factors. Among all undergoing HIVST, 71 (92%) perceived the instructions to be clear, however, 29 (38%) stated they would have benefitted from additional pre-test information or counseling. Ten (13%) reported following up at a nearby health facility to confirm results and/or receive care. Offering HIVST at public/private pharmacies was acceptable among people who traditionally tend to have a lower HIV testing coverage, such as men and young adults. However, additional resources and/or enhanced educational materials to address the lack of counseling, and linkage-to-care systems need to be put into place before scaling up this strategy.


Subject(s)
HIV Infections , Pharmacies , Pharmacy , Female , HIV Infections/diagnosis , HIV Testing , Humans , Male , Mass Screening/methods , Mozambique , Self-Testing , Young Adult
20.
Sci Total Environ ; 826: 154144, 2022 Jun 20.
Article in English | MEDLINE | ID: mdl-35227726

ABSTRACT

The sorption of dissolved organic matter (DOM) depends on its interaction with the soil matrix. In hydromorphic podzols, DOM reacts mainly with aluminium (Al), which is responsible for the formation of the Bh-horizon in the subsoil. In this work, we investigated whether the retention of DOM in the soil during the podzolization process is selective in relation to the molecular composition of DOM. A column experiment was conducted to study the selective retention of sorption and desorption processes under controlled conditions. Materials used in the column experiment were representative for Brazilian coastal podzols under tropical rainforest. Materials were collected from this tropical coastal podzol ecosystem, and included soil from E- and Bh-horizons, and DOM from a stream (Stream), peat water (Peat), litter (Litter) and charred litter (Char). To evaluate selective retention of DOM, both the initial DOM and its leachates were analyzed by Fourier transform infrared spectra absorption (FTIR) and pyrolysis gas-chromatography/mass spectrometry (Py-GC/MS). The results showed preferential retention of DOM associated with biopolymers for soil columns with E-horizon material (E), E with Al nitrate (E-n), E with kaolinite (E-k) and E with gibbsite (E-h), except for Char. The composition of leachates after percolation through B horizon columns was mainly determined by desorption, and had a relatively large contribution from phenolic and carboxylic groups associated with Al and low molecular weight aromatic and N-containing pyrolysis products, while products from macromolecular materials such as cellulose were selectively retained in the columns for all DOM types. DOM from the Stream (taken during the rainy season) resembled that of desorbed OM from the B columns, reinforcing substantial desorption in the field as well. Our results suggest that sorption and desorption of OM in the hydromorphic Bh-horizon is continuous and that the selectivity of sorption is dependent on DOM source.


Subject(s)
Dissolved Organic Matter , Adsorption , Ecosystem , Pyrolysis , Soil/chemistry , Spectroscopy, Fourier Transform Infrared
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