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Glucuronidasa , Vigilancia Inmunológica , Células Asesinas Naturales , Invasividad Neoplásica , Humanos , Células Asesinas Naturales/inmunología , Animales , Glucuronidasa/metabolismo , Glucuronidasa/genética , Glucuronidasa/inmunología , Ratones , Neoplasias/inmunología , Neoplasias/patología , Neoplasias/enzimología , Neoplasias/genéticaRESUMEN
PURPOSE: Currently, inguinal hernias are highly prevalent in the Brazilian population, accounting for 75% of all abdominal wall hernias. The recommended treatment to correct them is inguinal herniorrhaphy, which can be performed through open surgery, mainly using the Lichtenstein technique, or laparoscopically, primarily through Transabdominal Preperitoneal Repair (TAPP) or Total Extraperitoneal Repair (TEP) approaches. Like any surgery, these procedures have post-operative complications, with pain being the most common and debilitating. Currently, in European and Brazilian guidelines, the open Lichtenstein and endoscopic inguinal hernia techniques are recommended as best evidence-based options for repair of a primary unilateral hernia providing the surgeon is sufficiently experienced in the specific procedure. In that matter, the surgeon should make a choice based on assessment of the benefits and risks of performing each of them, and practice shared making decision with it patient. Therefore, the objective of this review was to assess the incidence of chronic postoperative pain by comparing the aforementioned surgical approaches to evaluate which procedure causes less disability to the patient. METHODS: The search conducted until May 2024 was performed on Medline (PubMed), Cochrane (CENTRAL), and Lilacs databases. The selection was limited to randomized clinical trials, nonrandomized clinical trials and cohort studies comparing TAPP or TEP to LC, evaluating the incidence of chronic postoperative pain published between 2017 and 2023. Evidence certainty was assessed using the GRADE Pro tool, and bias risk was evaluated with the RoB 2.0 tool and ROBINS I tool. Thirteen studies were included. RESULTS: The meta-analysis showed a significant difference between the groups in both techniques, favoring the laparoscopic approach, which had a lower occurrence of postoperative inguinodynia with a relative risk of 0.49 (95% CI = 0.32, 0.75; I2 = 66% (P = 0.001); Z = 3.28 (P = 0.001) with low certainty of evidence. CONCLUSION: The presence of chronic postoperative pain was lower in laparoscopic TEP/TAPP techniques when compared to the open Lichtenstein technique, meaning that the former can bring more benefits to patients who requires inguinal herniorrhaphy. Nevertheless, further randomized clinical trials are needed to optimize the analysis, minimizing the bias.
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Antibiotic resistance is a major public health threat, and alternatives to antibiotic therapy are urgently needed. Immunotherapy, particularly the blockade of inhibitory immune checkpoints, is a leading treatment option in cancer and autoimmunity. In this study, we used a murine model of Salmonella Typhimurium infection to investigate whether immune checkpoint blockade could be applied to bacterial infection. We found that the immune checkpoint T-cell immunoglobulin and ITIM domain (TIGIT) was significantly upregulated on lymphocytes during infection, particularly on CD4+ T cells, drastically limiting their proinflammatory function. Blockade of TIGIT in vivo using monoclonal antibodies was able to enhance immunity and improve bacterial clearance. The efficacy of anti-TIGIT was dependent on the capacity of the antibody to bind to Fc (fragment crystallizable) receptors, giving important insights into the mechanism of anti-TIGIT therapy. This research suggests that targeting immune checkpoints, such as TIGIT, has the potential to enhance immune responses toward bacteria and restore antibacterial treatment options in the face of antibiotic resistance.
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Ovarian cancer (OC) adjusts energy metabolism in favor of its progression and dissemination. Because melatonin (Mel) has antitumor actions, we investigated its impact on energy metabolism and kinase signaling in OC cells (SKOV-3 and CAISMOV-24). Cells were divided into control and Mel-treated groups, in the presence or absence of the antagonist luzindole. There was a decrease in the levels of HIF-1α, G6PDH, GAPDH, PDH, and CS after Mel treatment even in the presence of luzindole in both OC cells. Mel treatment also reduced the activity of OC-related enzymes including PFK-1, G6PDH, LDH, CS, and GS whereas PDH activity was increased. Lactate and glutamine levels dropped after Mel treatment. Mel further promoted a reduction in the concentrations of CREB, JNK, NF-kB, p-38, ERK1/2, AKT, P70S6K, and STAT in both cell lines. Mel reverses Warburg-type metabolism and possibly reduces glutaminolysis, thereby attenuating various oncogenic molecules associated with OC progression and invasion.
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Natural killer (NK) cells possess potent cytotoxicity against infected and cancerous cells and hold promise in the development of new immunotherapies. This article for the Highlights of 2023 Series focuses on current advances in NK cell biology in cancerous and infectious settings and highlights opportunities for therapeutic interventions, including engineered NK cell therapies and advancements in feeder cell technologies.
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Ingeniería Celular , Inmunoterapia , Células Asesinas Naturales , Neoplasias , Animales , Humanos , Citotoxicidad Inmunológica , Inmunoterapia/métodos , Inmunoterapia Adoptiva/métodos , Células Asesinas Naturales/inmunología , Neoplasias/terapia , Neoplasias/inmunologíaRESUMEN
BACKGROUND: Natural killer (NK) cells are important innate immunity players and have unique abilities to recognize and eliminate cancer cells, particularly in settings of antibody-opsonization and antibody-dependant cellular cytotoxicity (ADCC). However, NK cell-based responses in bladder cancers to therapeutic antibodies are typically immunosuppressed, and these immunosuppressive mechanisms are largely unknown. METHODS: Single cell RNA sequencing (scRNA-seq) and high-dimensional flow cytometry were used to investigate the phenotype of tumour-infiltrating NK cells in patients with bladder cancer. Further, in vitro, and in vivo models of this disease were used to validate these findings. FINDINGS: NK cells within bladder tumours displayed reduced expression of FcγRIIIa/CD16, the critical Fc receptor involved in ADCC-mediated cytotoxicity, on both transcriptional and protein levels. Transcriptional signatures of transforming growth factor (TGF)-ß-signalling, a pleiotropic cytokine known for its immunosuppressive and tissue residency-inducing effects, were upregulated in tumour-infiltrating NK cells. TGF-ß mediated CD16 downregulation on NK cells, was further validated in vitro, which was accompanied by a transition into a tissue residency phenotype. This CD16 downregulation was also abrogated by TGF-ßR signalling inhibition, which could also restore the ADCC ability of NK cells subject to TGF-ß effects. In a humanized mouse model of bladder cancer, mice treated with a TGF-ß inhibitor exhibited increased ADCC activity compared to mice treated only with antibodies. INTERPRETATION: This study highlights how TGF-ß-rich bladder cancers inhibit NK cell-mediated ADCC by downregulating CD16. TGF-ß inhibition represents new avenues to reverse immunosuppression and enhance the tumoricidal capacity of NK cells in bladder cancer. FUNDING: The Guimaraes Laboratory is funded by a US Department of Defense-Breast Cancer Research Program-Breakthrough Award Level 1 (#BC200025), a grant (#2019485) awarded through the Medical Research Future Fund (MRFF, with the support of the Queensland Children's Hospital Foundation, Microba Life Sciences, Richie's Rainbow Foundation, Translational Research Institute (TRI) and UQ), and a grant (#RSS_2023_085) funded by a Metro South Health Research Support Scheme. J.K.M.W. is funded by a UQ Research Training Program PhD Scholarship and N.O. is funded by a NHMRC Postgraduate Scholarship (#2021932).
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Células Asesinas Naturales , Receptores de IgG , Transducción de Señal , Factor de Crecimiento Transformador beta , Neoplasias de la Vejiga Urinaria , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/metabolismo , Humanos , Animales , Ratones , Factor de Crecimiento Transformador beta/metabolismo , Receptores de IgG/metabolismo , Citotoxicidad Celular Dependiente de Anticuerpos/inmunología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Proteínas Ligadas a GPI/metabolismo , Proteínas Ligadas a GPI/genética , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Análisis de la Célula Individual , FemeninoRESUMEN
BACKGROUND: Polyurethane (PU)-coated breast implants are known for their strong integration into breast tissue and the formation of capsules around them. However, capsular contracture can pose both aesthetic and clinical challenges. OBJECTIVES: To analyze the biological and morphological characteristics of the capsular tissue surrounding PU-coated implants, irrespective of their contracture status, and to assess their potential suitability as a flap in revision breast surgery for capsular contracture. METHODS: A total of 23 tissue samples were harvested from the capsules surrounding PU-coated breast implants in 12 female patients during replacement or revision surgery. We evaluated collagen abundance, cellular and vascular density, inflammation, collagen band types and alignment, synovial metaplasia, capsule thickness, and the expression of inflammatory biomarkers and myofibroblasts using immunohistochemical techniques. Scanning electron microscopy was used to assess implant surface characteristics over time. RESULTS: We found a significant association of capsule contraction with longer implantation durations and greater implant surface roughness (p = 0.018 and p = 0.033, respectively). Synovial metaplasia was significantly more frequent in noncontracted capsules (p = 0.0049). Both capsule types consisted of paucicellular, type I collagen-rich compact fibrous tissue with low vascularization. There was a marked reduction in inflammatory cells within the foreign body granuloma. The expression of inflammatory biomarkers in the capsular tissue was negligible. CONCLUSIONS: Given the reduced levels of inflammatory and vascular components within the dense, fibrous capsular tissue, we consider them to be viable alternatives for use as capsular flaps in revision surgery. This strategy has the potential to mimic the reconstruction achieved with acellular dermal matrix.
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Objectives: Immunotherapies targeting natural killer (NK) cell receptors have shown promise against leukaemia. Unfortunately, cancer immunosuppressive mechanisms that alter NK cell phenotype prevent such approaches from being successful. The study utilises advanced cytometry to examine how cancer immunosuppressive pathways affect NK cell phenotypic changes in clinical samples. Methods: In this study, we conducted a high-dimensional examination of the cell surface expression of 16 NK cell receptors in paediatric patients with acute myeloid leukaemia and acute lymphoblastic leukaemia, as well as in samples of non-age matched adult peripheral blood (APB) and umbilical cord blood (UCB). An unsupervised analysis was carried out in order to identify NK cell populations present in paediatric leukaemias. Results: We observed that leukaemia NK cells clustered together with UCB NK cells and expressed relatively higher levels of the NKG2A receptor compared to APB NK cells. In addition, CD56dimCD16+CD57- NK cells lacking NKG2A expression were mainly absent in paediatric leukaemia patients. However, CD56br NK cell populations expressing high levels of NKG2A were highly represented in paediatric leukaemia patients. NKG2A expression on leukaemia NK cells was found to be positively correlated with the expression of its ligand, suggesting that the NKG2A-HLA-E interaction may play a role in modifying NK cell responses to leukaemia cells. Conclusion: We provide an in-depth analysis of NK cell populations in paediatric leukaemia patients. These results support the development of immunotherapies targeting immunosuppressive receptors, such as NKG2A, to enhance innate immunity against paediatric leukaemia.
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Objectives: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus infection in pregnancy is associated with higher incidence of placental dysfunction, referred to by a few studies as a 'preeclampsia-like syndrome'. However, the mechanisms underpinning SARS-CoV-2-induced placental malfunction are still unclear. Here, we investigated whether the transcriptional architecture of the placenta is altered in response to SARS-CoV-2 infection. Methods: We utilised whole-transcriptome, digital spatial profiling, to examine gene expression patterns in placental tissues from participants who contracted SARS-CoV-2 in the third trimester of their pregnancy (n = 7) and those collected prior to the start of the coronavirus disease 2019 (COVID-19) pandemic (n = 9). Results: Through comprehensive spatial transcriptomic analyses of the trophoblast and villous core stromal cell subpopulations in the placenta, we identified SARS-CoV-2 to promote signatures associated with hypoxia and placental dysfunction. Notably, genes associated with vasodilation (NOS3), oxidative stress (GDF15, CRH) and preeclampsia (FLT1, EGFR, KISS1, PAPPA2) were enriched with SARS-CoV-2. Pathways related to increased nutrient uptake, vascular tension, hypertension and inflammation were also enriched in SARS-CoV-2 samples compared to uninfected controls. Conclusions: Our findings demonstrate the utility of spatially resolved transcriptomic analysis in defining the underlying pathogenic mechanisms of SARS-CoV-2 in pregnancy, particularly its role in placental dysfunction. Furthermore, this study highlights the significance of digital spatial profiling in mapping the intricate crosstalk between trophoblasts and villous core stromal cells, thus shedding light on pathways associated with placental dysfunction in pregnancies with SARS-CoV-2 infection.
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The utilization of single-cell resolved spatial transcriptomics to delineate immune responses during SARS-CoV-2 infection was able to identify M1 macrophages to have elevated expression of IFI27 in areas of infection.
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COVID-19 , Humanos , SARS-CoV-2 , Perfilación de la Expresión Génica , Macrófagos , Proteínas de la MembranaRESUMEN
Ikaros transcription factors are essential for adaptive lymphocyte function, yet their role in innate lymphopoiesis is unknown. Using conditional genetic inactivation, we show that Ikzf1/Ikaros is essential for normal natural killer (NK) cell lymphopoiesis and IKZF1 directly represses Cish, a negative regulator of interleukin-15 receptor resulting in impaired interleukin-15 receptor signaling. Both Bcl2l11 and BIM levels, and intrinsic apoptosis were increased in Ikzf1-null NK cells, which in part accounts for NK lymphopenia as both were restored to normal levels when Ikzf1 and Bcl2l11 were co-deleted. Ikzf1-null NK cells presented extensive transcriptional alterations with reduced AP-1 transcriptional complex expression and increased expression of Ikzf2/Helios and Ikzf3/Aiolos. IKZF1 and IKZF3 directly bound AP-1 family members and deletion of both Ikzf1 and Ikzf3 in NK cells resulted in further reductions in Jun/Fos expression and complete loss of peripheral NK cells. Collectively, we show that Ikaros family members are important regulators of apoptosis, cytokine responsiveness and AP-1 transcriptional activity.
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Células Asesinas Naturales , Factor de Transcripción AP-1 , Factor de Transcripción AP-1/genética , Células Asesinas Naturales/metabolismo , Receptores de Interleucina-15 , Factor de Transcripción Ikaros/genética , Factor de Transcripción Ikaros/metabolismoRESUMEN
Sarcomas are rare and heterogeneous cancers that arise from bone or soft tissue, and are the second most prevalent solid cancer in children and adolescents. Owing to the complex nature of pediatric sarcomas, the development of therapeutics for pediatric sarcoma has seen little progress in the past decades. Existing treatments are largely limited to chemotherapy, radiation, and surgery. Limited knowledge of the sarcoma tumor microenvironment (TME) and of well-defined target antigens in the different subtypes necessitates an alternative investigative approach to improve treatments. Recent advances in spatial omics technologies have enabled a more comprehensive study of the TME in multiple cancers. In this opinion article we discuss advances in our understanding of the TME of some cancers enabled by spatial omics technologies, and we explore how these technologies might advance the development of precision treatments for sarcoma, especially pediatric sarcoma.
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Sarcoma , Niño , Adolescente , Humanos , Sarcoma/tratamiento farmacológico , Sarcoma/patología , Microambiente TumoralRESUMEN
The development of skin organs for studying developmental pathways, modeling diseases, or regenerative medicine purposes is a major endeavor in the field. Human induced pluripotent stem cells (hiPSCs) are successfully used to derive skin cells, but the field is still far from meeting the goal of creating skin containing appendages, such as hair follicles and sweat glands. Here, the goal is to generate skin organoids (SKOs) from human skin fibroblast or placental CD34+ cell-derived hiPSCs. With all three hiPSC lines, complex SKOs with stratified skin layers and pigmented hair follicles are generated with different efficacies. In addition, the hiPSC-derived SKOs develop sebaceous glands, touch-receptive Merkel cells, and more importantly eccrine sweat glands. Together, physiologically relevant skin organoids are developed by direct induction of embryoid body formation, along with simultaneous inactivation of transforming growth factor beta signaling, activation of fibroblast growth factor signaling, and inhibition of bone morphogenetic protein signaling pathways. The skin organoids created in this study can be used as valuable platforms for further research into human skin development, disease modeling, or reconstructive surgeries.
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Células Madre Pluripotentes Inducidas , Embarazo , Humanos , Femenino , Placenta , Piel , Folículo Piloso/fisiología , OrganoidesRESUMEN
Tumour necrosis factor (TNF) is a primary mediator of inflammatory processes by facilitating cell death, immune cell activation and triggering of inflammation. In the cancer context, research has revealed TNF as a multifaceted cytokine that can be both pro- or anti-tumorigenic depending on what context is observed. We explore the plethora of ways that TNF and its receptors manipulate the functional and phenotypic characteristics in the tumour microenvironment (TME) on both tumour cells and immune cells, promoting either tumour elimination or progression. Here, we discuss the latest cutting-edge TNF-focused biologics currently in clinical translation that modifies the TME to derive greater immune responses and therapeutic outcomes, and further give perspectives on the future of targeting TNF in the context of cancer by emerging technological approaches.
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Neoplasias , Microambiente Tumoral , Humanos , Inflamación , Factor de Necrosis Tumoral alfa/fisiología , Citocinas , Neoplasias/terapiaRESUMEN
This study assessed the cardiovascular repercussions of two VHI (ventilation hyperinflation) protocols using the volume-controlled mode, one with an inspiratory pause (VHI-P) and the other without an inspiratory pause (VHI-NP), in mechanically ventilated elderly patients. The patients underwent both VHI protocols in a randomized order, and impedance cardiography was used to record cardiovascular variables. During VHI-P, the diastolic blood pressure was lower than during VHI-NP (Δ = 10%; p = 0.009). VHI-NP and VHI-P demonstrated a decrease in cardiac output (CO) during the first and third sets compared to baseline (p < 0.05; ES=0.23 and 0.29, respectively). Arterial oxygen delivery decreased simultaneously with CO compared to baseline values (p < 0.05; ES=0.22 and 0.23, respectively). Five minutes after the intervention, the systolic time ratio values were lower for VHI-P than VHI-NP (Δ = 10%; p = 0.01). Left ventricular ejection time values were consistently lower in VHI-NP compared to VHI-P (Δ = 2%; p = 0.02). In conclusion, our study shows that VHI in volume-controlled mode induces hemodynamic changes in mechanically ventilated elderly patients, albeit with a small effect size and within the normal range.
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The SARS-CoV-2 (COVID-19) virus has caused a devastating global pandemic of respiratory illness. To understand viral pathogenesis, methods are available for studying dissociated cells in blood, nasal samples, bronchoalveolar lavage fluid and similar, but a robust platform for deep tissue characterization of molecular and cellular responses to virus infection in the lungs is still lacking. We developed an innovative spatial multi-omics platform to investigate COVID-19-infected lung tissues. Five tissue-profiling technologies were combined by a novel computational mapping methodology to comprehensively characterize and compare the transcriptome and targeted proteome of virus infected and uninfected tissues. By integrating spatial transcriptomics data (Visium, GeoMx and RNAScope) and proteomics data (CODEX and PhenoImager HT) at different cellular resolutions across lung tissues, we found strong evidence for macrophage infiltration and defined the broader microenvironment surrounding these cells. By comparing infected and uninfected samples, we found an increase in cytokine signalling and interferon responses at different sites in the lung and showed spatial heterogeneity in the expression level of these pathways. These data demonstrate that integrative spatial multi-omics platforms can be broadly applied to gain a deeper understanding of viral effects on cellular environments at the site of infection and to increase our understanding of the impact of SARS-CoV-2 on the lungs.
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BACKGROUND: Metastatic cancer cells exploit Epithelial-mesenchymal-transition (EMT) to enhance their migration, invasion, and resistance to treatments. Recent studies highlight that elevated levels of copper are implicated in cancer progression and metastasis. Clinical trials using copper chelators are associated with improved patient survival; however, the molecular mechanisms by which copper depletion inhibits tumor progression and metastasis are poorly understood. This remains a major hurdle to the clinical translation of copper chelators. Here, we propose that copper chelation inhibits metastasis by reducing TGF-ß levels and EMT signaling. Given that many drugs targeting TGF-ß have failed in clinical trials, partly because of severe side effects arising in patients, we hypothesized that copper chelation therapy might be a less toxic alternative to target the TGF-ß/EMT axis. RESULTS: Our cytokine array and RNA-seq data suggested a link between copper homeostasis, TGF-ß and EMT process. To validate this hypothesis, we performed single-cell imaging, protein assays, and in vivo studies. Here, we used the copper chelating agent TEPA to block copper trafficking. Our in vivo study showed a reduction of TGF-ß levels and metastasis to the lung in the TNBC mouse model. Mechanistically, TEPA significantly downregulated canonical (TGF-ß/SMAD2&3) and non-canonical (TGF-ß/PI3K/AKT, TGF-ß/RAS/RAF/MEK/ERK, and TGF-ß/WNT/ß-catenin) TGF-ß signaling pathways. Additionally, EMT markers of MMP-9, MMP-14, Vimentin, ß-catenin, ZEB1, and p-SMAD2 were downregulated, and EMT transcription factors of SNAI1, ZEB1, and p-SMAD2 accumulated in the cytoplasm after treatment. CONCLUSIONS: Our study suggests that copper chelation therapy represents a potentially effective therapeutic approach for targeting TGF-ß and inhibiting EMT in a diverse range of cancers.
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BACKGROUND: Chest physiotherapy for hospitalized patients with COVID-19 has been poorly reported. Although recommendations were published to guide physiotherapists, practice might have differed depending on education and training. OBJECTIVE: To analyze the differences in chest physiotherapy applied for hospitalized patients with COVID-19 between certified specialists and non-certified specialists. METHODS: An online questionnaire survey was developed for physiotherapists involved in the management of hospitalized patients with COVID-19. The questionnaire inquired about professional information and characteristics of physiotherapy practice. RESULTS: There were 485 respondents, yielding a completion rate of 76%. Of these, 61 were certified specialists and 424 non-certified specialists. The certified specialists were older, had more years of professional experience, were more qualified, and had better job conditions. For mechanically ventilated patients, the certified specialists used the ventilator hyperinflation maneuver more frequently (50.4% vs 35.1%, p = 0.005), and the hard/brief expiratory rib cage compression (ERCC) (26.9% vs 48.3%, p = 0.016), soft/long ERCC (25.2% vs 39.1%, p = 0.047), and manual chest compression-decompression (MCCD) maneuver (22.4% vs 35.6%, p = 0.001) less often. For spontaneously breathing patients, the certified specialists used the active cycle of breathing technique (30.8% vs 67.1%, p<0.001), autogenic drainage (7.7% vs 20.7%, p = 0.017), and MCCD maneuver (23.1% vs 41.4%, p = 0.018) less frequently. CONCLUSIONS: Certified specialists with higher levels of expertise seem to prefer the use of chest physiotherapy techniques that are applied with the mechanical ventilator over manual techniques. Furthermore, they use techniques that could potentially increase the work of breathing less frequently, mitigating the risk of exacerbating respiratory conditions in patients with COVID-19.
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COVID-19 , Humanos , Brasil/epidemiología , COVID-19/epidemiología , Modalidades de Fisioterapia , Terapia Respiratoria/efectos adversos , Terapia Respiratoria/métodosRESUMEN
Killer cell immunoglobulin-like receptors (KIR) exhibit extensive diversity, giving rise to different KIR profiles in populations worldwide. This study aimed to investigate the distribution of KIR genes and HLA ligands in a population from Campinas, southeastern Brazil (n = 292), and to compare their results with other populations. A comprehensive analysis of population-specific genes, genotype, and haplotype frequencies of KIR may facilitate a better understanding of their evolution and role in immunity. The genotyping of 16 KIR genes and HLA class I alleles was performed by the reverse sequence-specific oligonucleotide methodology using the Luminex platform (One Lambda, Inc., Canoga Park, CA). The framework genes were present in all individuals, with the most common non-framework KIR genes detected being KIR2DP1(96.6%), KIR2DL1(95.5%), KIR3DL1(94.5%), KIR2DS4(93.8%) and KIR2DL3(87.3%). KIR2DS1, KIR2DS3, KIR2DS5, and KIR3DS1 presented frequencies below 40%. KIR2DL2, KIR2DL5, and KIR2DS2 showed intermediate frequencies (between53% and 58%). The activating gene KIR2DS5 was the least common in this population (30.8%). Forty-five KIR profiles were found with the commonest being the homozygous A haplotype (27.4%). The distribution of KIR genes in the Brazilian population is similar to Caucasian European and Euro-descendant populations.