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1.
Nurs Inq ; : e12646, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38838221

RESUMO

Neuropalliative care developed to address the needs of patients living with life-limiting neurologic disease. One critical consideration is that disease-related changes to cognition, communication, and function challenge illness experiences and care practices. We conducted an ethnography to understand neuropalliative care as a phenomenon; how it was experienced, provided, conceptualized. Personhood served as our conceptual framework; with its long philosophical history and important place in nursing theory, we examined the extent to which it captured neuropalliative experiences and concerns. Personhood contextualized complex losses, aligning the impact of functional and relational changes. Cognition, communication, and functional alterations stretched conceptions of personhood, insinuating it can be relational, fluid, adaptive. Although normative conceptions of personhood guided research and decision-making, ethical considerations suggested personhood could be transformed, remade. We consider the implications of our findings through three themes. First, we examine how literature on illness experience fails to integrate the realities of people living with and dying from neurologic disease; we counter this by interrogating the concept of experience. Second, we turn to Ricoeur's work on recognition to illuminate relational conceptions of personhood to inform care practices. Finally, we reflect on how personhood can bridge the gap left by functional changes, enhance relational engagement, and promote dignity at the end of life.

2.
Obes Surg ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38837021

RESUMO

Gastric bypass surgery is a common and effective procedure for obesity and associated comorbidities. However, long-term complications, such as internal hernias, can pose diagnostic and therapeutic challenges. Internal hernias after gastric bypass are rare but can lead to severe complications, including volvulus and bowel ischemia. Understanding the anatomical variations and employing laparoscopic techniques for resolution are crucial in managing these cases.

3.
J Forensic Odontostomatol ; 42(1): 22-29, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38742569

RESUMO

BACKGROUND: The utilization of segmentation method using volumetric data in adults dental age estimation (DAE) from cone-beam computed tomography (CBCT) was further expanded by using current 5-Part Tooth Segmentation (SG) method. Additionally, supervised machine learning modelling -namely support vector regression (SVR) with linear and polynomial kernel, and regression tree - was tested and compared with the multiple linear regression model. MATERIAL AND METHODS: CBCT scans from 99 patients aged between 20 to 59.99 was collected. Eighty eligible teeth including maxillary canine, lateral incisor, and central incisor were used in this study. Enamel to dentine volume ratio, pulp to dentine volume ratio, lower tooth volume ratio, and sex was utilized as independent variable to predict chronological age. RESULTS: No multicollinearity was detected in the models. The best performing model comes from maxillary lateral incisor using SVR with polynomial kernel ( = 0.73). The lowest error rate achieved by the model was given also by maxillary lateral incisor, with 4.86 years of mean average error and 6.05 years of root means squared error. However, demands a complex approach to segment the enamel volume in the crown section and a lengthier labour time of 45 minutes per tooth.


Assuntos
Determinação da Idade pelos Dentes , Tomografia Computadorizada de Feixe Cônico , Aprendizado de Máquina , Humanos , Adulto , Determinação da Idade pelos Dentes/métodos , Masculino , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Esmalte Dentário/diagnóstico por imagem , Dentina/diagnóstico por imagem , Modelos Lineares , Polpa Dentária/diagnóstico por imagem , Máquina de Vetores de Suporte
4.
Artigo em Inglês | MEDLINE | ID: mdl-38693594

RESUMO

The concept of childhood has evolved over the years, inspired by the United Nations Convention on the Rights of the Child in 1989, shifting from developmental models to a conception of childhood that recognizes children as moral agents. This evolution highlights the importance of respecting children's agency and their right to be heard in matters that are related to them. In conventional health research, however, children's voices are often inadequately accessed. In this commentary, we discuss the imperative to recognize children's agency in dental research and a shift from research on children to research with and by children. Moreover, we underscore the importance of actively seeking and listening to children's voices and recognizing their agency in shaping research and healthcare practices in the field of dentistry. Further, we explore the application of participatory research approaches in dental research and provide examples of studies that have involved children in various capacities. We conclude this commentary by emphasizing the potential benefits of participatory research in both qualitative and quantitative dental studies to promote deeper understanding, clearer communication, and stronger advocacy regarding children's interests. Primarily, we call for greater recognition of children's agency in dental research and advocate for more inclusive and child-centred research methodologies.

5.
Anim Reprod Sci ; 264: 107405, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38547815

RESUMO

The aim of this study was to investigate the growth and development of animals produced from demi-embryos and compare them with whole embryos from fetus to adult life. To achieve this, calves produced from fresh demi-embryos and whole embryos were individually transferred and monitored from 60 days of pregnancy until slaughter at 550 days. Ultrasound scans were conducted on fetuses at 60 and 90 days to evaluate the biparietal, abdominal, umbilical cord, orbital, and aorta diameters. Subsequently, morphological traits of newborn calves were measured at 0, 7, and 21 days (N = 18). Live weight was recorded at birth, weaning, and every 30 days thereafter until slaughter at 550 days. The growth curve of each group was modeled using logistic regression, and the factors of the respective functions were compared. As early as 60 days of pregnancy, ultrasound evaluations revealed no morphometric differences between fetuses produced from demi-embryos and those from whole embryos. This lack of differentiation persisted in the morphometric evaluations of newborns up to 21 days of age, as well as in live weight and the growth curve from birth to slaughter. Moreover, there were no significant differences between the groups in terms of rib eye area and fat thickness evolution. Consequently, individuals from demi-embryos exhibited no discernible disparities to those whole embryos in growth and development from 60 days of gestation, through birth, and into adulthood.


Assuntos
Animais Recém-Nascidos , Animais , Bovinos/embriologia , Feminino , Gravidez , Desenvolvimento Fetal/fisiologia , Transferência Embrionária/veterinária , Ultrassonografia Pré-Natal/veterinária , Fertilização in vitro/veterinária , Desenvolvimento Embrionário/fisiologia
6.
World J Urol ; 42(1): 133, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478102

RESUMO

PURPOSE: To report oncologic outcomes of patients undergoing salvage cryotherapy (SCT) for local recurrence of prostate cancer (PCa) and to establish a nadir PSA (nPSA) value that best defines long-term oncologic success. METHODS: Retrospective study of men who underwent SCT for local recurrence of PCa between 2008 and 2020. SCT was performed in men with biochemical recurrence (BCR), after primary treatment and with biopsy-proven PCa local recurrence. Survival analysis with Kaplan-Meier and Cox models was performed. We determined the optimal cutoff nPSA value after SCT that best classifies patients depending on prognosis. RESULTS: Seventy-seven men who underwent SCT were included. Survival analysis showed a 5-year biochemical recurrence-free survival (BRFS), androgen deprivation therapy-free survival (AFS), and metastasis-free survival (MFS) after SCT of 48.4%, 62% and 81.3% respectively. On multivariable analysis for perioperative variables associated with BCR, initial ISUP, pre-SCT PSA, pre-SCT prostate volume and post-SCT nPSA emerged as variables associated with BCR. The cutoff analysis revealed an nPSA < 0.5 ng/ml to be the optimal threshold that best defines success after SCT. 5-year BRFS for patients achieving an nPSA < 0.5 vs nPSA ≥ 0.5 was 64% and 9.5% respectively (p < 0.001). 5-year AFS for men with nPSA < 0.5 vs ≥ 0.5 was 81.2% and 12.2% (p < 0.001). Improved 5-year MFS for patients who achieved nPSA < 0.5 was also obtained (89.6% vs 60%, p = 0.003). CONCLUSION: SCT is a feasible rescue alternative for the local recurrence of PCa. Achieving an nPSA < 0.5 ng/ml after SCT is associated with higher long-term BRFS, AFS and MFS rates.


Assuntos
Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias da Próstata/cirurgia , Crioterapia , Terapia de Salvação , Recidiva Local de Neoplasia/terapia
7.
Morphologie ; 108(362): 100772, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38460321

RESUMO

The permanent left mandibular canines have been used for sexual dimorphism when human identification is necessary. Controversy remains whether the morphology of these teeth is actually useful to distinguish males and females. This study aimed to assess the sexual dimorphism of canines by means of a pioneering artificial intelligence approach to this end. A sample of 13,046 teeth radiographically registered from 5838 males and 7208 females between the ages of 6 and 22.99 years was collected. The images were annotated using Darwin V7 software. DenseNet121 was used and tested based on binary answers regarding the sex (male or female) of the individuals for 17 age categories of one year each (i.e. 6-6.99, 7.7.99… 22.22.99). Accuracy rates, receiver operating characteristic (ROC) curves and confusion matrices were used to quantify and express the artificial intelligence's classification performance. The accuracy rates across age categories were between 57-76% (mean: 68%±5%). The area under the curve (AUC) of the ROC analysis was between 0.58 and 0.77. The best performances were observed around the age of 12 years, while the worst were around the age of 7 years. The morphological analysis of canines for sex estimation should be restricted and allowed in practice only when other sources of dimorphic anatomic features are not available.

8.
Pregnancy Hypertens ; 35: 96-102, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38306739

RESUMO

Early diagnosis and efficient treatment of preeclampsia remains a medical challenge and etiological factors converge in a deficient placentation that triggers oxidative stress. There is evidence that statins show antioxidant effects that can improve endothelial function without adverse perinatal effects. We aimed to compare early vs. late pravastatin treatment on the oxidative stress and cardiovascular features of an experimental model of preeclampsia. Female Wistar rats were randomly divided into preeclampsia phenotype rats (PEP) developed by sub renal aortic coarctation (SRAC) and healthy pregnant rats (C). Each group received pravastatin (5 mg/Kg) p.o. either for one week before and during the first week or during the last two weeks of gestation. Blood pressure was determined using the plethysmographic method. Phenylephrine (Phe)-induced contractility was evaluated in isolated thoracic and abdominal aortic rings with or without endothelium. Blood samples were obtained to determine anion superoxide concentration as indicator of NADPH activity. Two-way ANOVA and Bonferroni post hoc tests were used to define statistical significance. Early or late pravastatin treatment decreased hypertension of PEP animals but did not change BP of the healthy pregnant group. Thoracic and abdominal aorta from PEP rats showed increased contractility that was reverted by pravastatin early treatment in endothelium intact rings. Pravastatin did not significantly change contractility neither in the thoracic nor in the abdominal aorta segments from healthy pregnant control rats (C), and decrease anion superoxide concentration by NADPH activity. We conclude pravastatin can improve both blood pressure and endothelium-dependent Phe-induced contractility in an experimental model of preeclampsia by reducing oxidative stress.


Assuntos
Pravastatina , Pré-Eclâmpsia , Gravidez , Humanos , Ratos , Feminino , Animais , Pravastatina/farmacologia , Pravastatina/uso terapêutico , Pré-Eclâmpsia/tratamento farmacológico , Superóxidos/farmacologia , NADP/farmacologia , Ratos Wistar , Estresse Oxidativo , Fenilefrina/farmacologia , Endotélio Vascular
10.
Morphologie ; 108(360): 100723, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37897941

RESUMO

Forensic odontologists use biological patterns to estimate chronological age for the judicial system. The age of majority is a legally significant period with a limited set of reliable oral landmarks. Currently, experts rely on the questionable development of third molars to assess whether litigants can be prosecuted as legal adults. Identification of new and novel patterns may illuminate features more dependably indicative of chronological age, which have, until now, remained unseen. Unfortunately, biased perceptions and limited cognitive capacity compromise the ability of researchers to notice new patterns. The present study demonstrates how artificial intelligence can break through identification barriers and generate new estimation modalities. A convolutional neural network was trained with 4003 panoramic-radiographs to sort subjects into 'under-18' and 'over-18' age categories. The resultant architecture identified legal adults with a high predictive accuracy equally balanced between precision, specificity and recall. Moving forward, AI-based methods could improve courtroom efficiency, stand as automated assessment methods and contribute to our understanding of biological ageing.


Assuntos
Inteligência Artificial , Adulto , Humanos , Movimento Celular
12.
Morphologie ; 108(361): 100758, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38128159

RESUMO

Country-specific systematic reviews and meta-analyses have been proposed to compile the available literature and rank methods based on their performance for a target population. India is a country with a vast scientific literature on dental age estimation. This systematic review aimed to provide evidence to help the decision of experts regarding the method of choice for dental age estimation in India. The research protocol was registered in Open Science Framework. Literature Search was performed in Embase, LILACS, MedLine (via PubMed), SciELO, Scopus and Web of Science. Grey Literature was searched in Google Scholar and ProQuest. Observational cross-sectional studies that compared chronological and estimated ages using Demirjian (original [DEM] and Chaillet's modification [modified-DEM]) and Acharya (ACH) methods were included. JBI tool was used to assess the risk of bias. The search detected 9799 studies, out of which 56 were eligible (n=13,107 panoramic radiographs of Indian individuals). Low risk of bias was registered for 48 studies, while 8 presented a moderate risk of bias. The meta-analysis showed a standardized mean difference between chronological and estimated ages of -0.11 (95%CI: -0.29; 0.07), 0.74 (95%CI: 0.39; 1.09), and -0.01 (95%CI: -0.23; 0.22) years for DEM, modified-DEM and ACH, respectively. High heterogeneity (I2=88-93%) was observed across studies for all the methods, including subgroup analyses based on sex. This study ranked ACH, DEM and modified-DEM (from the best to the worse) performances in the Indian population.


Assuntos
Determinação da Idade pelos Dentes , Humanos , Índia , Determinação da Idade pelos Dentes/métodos , Criança , Adolescente , Radiografia Panorâmica , Estudos Transversais , Feminino , Dente/diagnóstico por imagem , Dente/crescimento & desenvolvimento , Dente/anatomia & histologia , Masculino
14.
Mar Environ Res ; 193: 106293, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38103302

RESUMO

Here we provide evidence, along an 8-year period time-series based on multifaceted data from a Mediterranean marine protected area (MPA), whether protection can tackle invasive and range expanding herbivore fishes, and their effects on the algal resource availability, taking into account the population trends of predatory fishes, fisheries catches of herbivore fishes and sea surface temperature (SST) through time. Our findings pointed out that an ineffective in restoring top-down control process MPA may facilitate, rather than alleviate, the sudden and enduring population burst of invasive and range-expanding herbivorous fishes at tipping points of abrupt change. This subsequently results in the deterioration of rocky reef habitats and the depletion of algal resources, with the tipping points of abrupt change for algal and herbivore fish species not overlapping chronologically. As sea temperature increases, ineffective or recently established MPAs may inadvertently facilitate the proliferation of invasive and range-expanding species, posing a significant challenge to management effectiveness and conservation objectives.


Assuntos
Ecossistema , Herbivoria , Animais , Peixes , Pesqueiros , Temperatura , Conservação dos Recursos Naturais
15.
Hosp Pediatr ; 13(10): 954-960, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37667850

RESUMO

BACKGROUND: Children are increasingly discharged directly from the PICU. Transitions have been recognized as a period of increased patient and caregiver stress and risk of adverse events. No study has evaluated patient and caregiver outcomes after direct discharge from the PICU. This study aimed to explore the family's experiences with discharge directly home (DDH) from the PICU. METHODS: This exploratory mixed-methods study was conducted in the PICU of the Institution is Sainte-Justine Hospital from February to July 2021. We included families of children expected to be DDH within 12 hours. Semistructured interviews were conducted at discharge, followed by telephone interviews 7 and 28 days post-PICU discharge. We measured comfort on a 5-point Likert scale and screened for anxiety using the Generalized Anxiety Disorder-7 tool. RESULTS: Families of 25 patients were interviewed. Thematic analysis of the interviews revealed several themes, such as feeling stress and anxiety, feeling confident, anticipating home care, and needing support. These findings complemented the quantitative findings; the median comfort score was 4 (comfortable) (interquartile range 4-5) and 8 (interquartile range 4-12) for the Generalized Anxiety Disorder-7 on the day of discharge, with 16 reporting clinically significant anxiety. In the 28-day study period, 2 patients were readmitted and 6 had visited the emergency department. CONCLUSIONS: Despite feelings of anxiety, many families felt comfortable with DDH from the PICU. Increasing our understanding of the patient and family experiences of discharge from the PICU will help to better support these patients and their families during transition.

16.
World J Urol ; 41(8): 2091-2097, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37528288

RESUMO

PURPOSE: Determining the frequency and distribution of pathogenic germline variants (PGVs) in Austrian prostate cancer (PCa) patients and to assess the accuracy of different clinical risk scores to correctly predict PGVs. METHODS: This cross-sectional study included 313 men with advanced PCa. A comprehensive personal and family history was obtained based on predefined questionnaires. Germline DNA sequencing was performed between 2019 and 2021 irrespective of family history, metastatic or castration status or age at diagnosis. Clinical risk scores for hereditary cancer syndromes were evaluated and a PCa-specific score was developed to assess the presence of PGVs. RESULTS: PGV presence was associated with metastasis (p = 0.047) and castration resistance (p = 0.011), but not with personal cancer history or with relatives with any type of cancer. Clinical risk scores (Manchester score, PREMM5 score, Amsterdam II criteria or Johns Hopkins criteria) showed low sensitivities (3.3-20%) for assessing the probability of PGV presence. A score specifically designed for PCa patients stratifying patients into low- or high-risk regarding PGV probability, correctly classified all PGV carriers as high-risk, whereas a third of PCa patients without PGVs was classified as low risk of the presence of PGVs. CONCLUSION: Application of common clinical risk scores based on family history are not suitable to identify PCa patients with high PGV probabilities. A PCa-specific score stratified PCa patients into low- or high-risk of PGV presence with sufficient accuracy, and germline DNA sequencing may be omitted in patients with a low score. Further studies are needed to evaluate the score.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Estudos Transversais , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Fatores de Risco , Células Germinativas/patologia , Áustria , Predisposição Genética para Doença
17.
Morphologie ; 107(359): 100607, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37543029

RESUMO

BACKGROUND: The effect of impaction on third molar development is disputable as the scientific literature is not uniform. In parallel, population-specific studies have been encouraged in dental age estimation. This study aimed to investigate the effect of impaction on third molar formation in a sample of Lebanese individuals. MATERIALS AND METHODS: The sample consisted of 518 panoramic radiographs of females (n=229) and males (n=289) between 15 and 23.9 years. Mandibular third molars were classified based on their position as non-impacted and impacted (with horizontal, vertical, mesioangular, and distoangular impaction). Dental development was classified according to Demirjian's 8-level staging system. RESULTS: Most teeth presented mesioangular impaction (#38=29.7%, #48=33%). Developing third molars were predominantly distributed between stages D and G. The mean age of most developmental stages was higher among impacted teeth, meaning that third molar mineralization could be slower in the presence of impaction. In general, the delayed dental development did not have statistically significant effects (P<0.05). However, descriptive data pointed out differences between (impacted and non-impacted) mean ages of >12 months-suggesting a potential clinical significance (despite the lack of a statistical one). Furthermore, differences changed based on sex and side (#38/#48). CONCLUSION: Therefore, dental age estimation from third molars in the selected Lebanese population should preferably be performed in non-impacted third molars whenever available.


Assuntos
Dente Serotino , Dente Impactado , Masculino , Feminino , Humanos , Lactente , Dente Serotino/diagnóstico por imagem , Dente Impactado/diagnóstico por imagem , Dente Impactado/epidemiologia , Mandíbula , Dente Molar , Radiografia Panorâmica
18.
Animal ; 17 Suppl 5: 100809, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37612227

RESUMO

Ruminal tympany (bloat) has long been an issue for large and small livestock operations. Though improvements in feedlot management practices have reduced its occurrence, it is still highly prevalent and is known to detrimentally affect animal performance, welfare, and in many instances, lead to animal death. Current decision support systems and diet formulation software omit the inclusion of bloat prediction based on animal performance. Here, we aim to predict bloat incidence in implanted and non-implanted feedlot steers from performance data comparing linear (LDB) and non-linear decision boundaries. Eighteen crossbred Angus × Hereford steers: BW (491.13 ± 25.78 kg) and age (12 ± 1 mo) were randomly distributed into implanted and non-implanted treatments. All animals were randomly assigned to one of two pens fit with automated monitoring systems for BW, freshwater intake, and water intake behavior: water intake event visit, no water intake event visit (NWIE), and time spent drinking. DM intake (DMI) was individually recorded from all animals through the Calan Gate system for 135 d (30 d adaptation, 105 d experimental diet). Incidences of bloat were recorded as bloat instances regardless of severity to ensure that early onset detection of bloat was recorded and properly identified in predictive models. Logistic regression with a binomial distribution and a logit link function was utilized to predict the incidences of bloat through LDB. Feature selection and penalization of coefficients were explored through L1 (sum of absolute values) and L2 (sum of squares) penalization to avoid overfitting of models. Additional NLDB and a non-parametric LDB are examined for prediction. Accuracy, specificity, and sensitivity were high for the models reported. No significant differences were observed between LDB and NLDB, with the highest specificity (predicting bloat) value of 0.820 for stepwise feature selection algorithms, and a value of 0.832 for the artificial neural network. Highest accuracy was 0.829 for ridge regression, and 0.847 for the random forest with hyperparameter tuning. DM intake, BW, and NWIE were the three most important variables for the prediction of feedlot bloat showing clear drops in DMI and BW and increases in NWIE when animals bloated. The lack of difference in predictive performance between LDB and NLDB highlights the often-overlooked concept that machine learning algorithms are not always the only/best modeling technique. Additionally, the models reported herein carry acceptable predictive performance for inclusion into management decisions that reduce bloat incidences in feedlot cattle.


Assuntos
Ração Animal , Dieta , Bovinos , Animais , Ração Animal/análise , Dieta/veterinária , Coleta de Dados
19.
Rev Clin Esp (Barc) ; 223(8): 499-509, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37507048

RESUMO

Acute heart failure (AHF) is associated with significant morbidity and mortality and it stands as the primary cause of hospitalization for individuals over the age of 65 in Spain. This document outlines the main recommendations as follows: (1) Upon admission, it is crucial to conduct a comprehensive assessment, taking into account the patient's standard treatment and comorbidities, as these factors determine the prognosis of the disease. (2) During the initial hours of hospital care, prioritizing decongestive treatment is essential. It is recommended to adopt an early staged diuretic therapeutic approach based on the patient's response. (3) In order to manage patients in the stable phase, it is advisable to consider initiating and/or adjusting evidence-based drug treatments such as sacubitril/valsartan or angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta blockers, aldosterone antagonists, and SGLT2 inhibitors. (4) Upon hospital discharge, utilizing a checklist is recommended to optimize the patient's management and identify the most efficient options for ensuring continuity of care post-discharge.


Assuntos
Assistência ao Convalescente , Insuficiência Cardíaca , Humanos , Consenso , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Alta do Paciente , Insuficiência Cardíaca/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Hospitalização , Hospitais , Resultado do Tratamento
20.
Front Immunol ; 14: 1206099, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37404829

RESUMO

Introduction: Osteoclasts play a crucial role in bone resorption, and impairment of their differentiation can have significant implications for bone density, especially in individuals with HIV who may be at risk of altered bone health. The present study aimed to investigate the effects of HIV infection on osteoclast differentiation using primary human monocyte-derived macrophages as precursors. The study focused on assessing the impact of HIV infection on cellular adhesion, cathepsin K expression, resorptive activity, cytokine production, expression of co-receptors, and transcriptional regulation of key factors involved in osteoclastogenesis. Methods: Primary human monocyte-derived macrophages were utilized as precursors for osteoclast differentiation. These precursors were infected with HIV, and the effects of different inoculum sizes and kinetics of viral replication were analyzed. Subsequently, osteoclastogenesis was evaluated by measuring cellular adhesion, cathepsin K expression, and resorptive activity. Furthermore, cytokine production was assessed by monitoring the production of IL-1ß, RANK-L, and osteoclasts. The expression levels of co-receptors CCR5, CD9, and CD81 were measured before and after infection with HIV. The transcriptional levels of key factors for osteoclastogenesis (RANK, NFATc1, and DC-STAMP) were examined following HIV infection. Results: Rapid, massive, and productive HIV infection severely impaired osteoclast differentiation, leading to compromised cellular adhesion, cathepsin K expression, and resorptive activity. HIV infection resulted in an earlier production of IL-1ß concurrent with RANK-L, thereby suppressing osteoclast production. Infection with a high inoculum of HIV increased the expression of the co-receptor CCR5, as well as the tetraspanins CD9 and CD81, which correlated with deficient osteoclastogenesis. Massive HIV infection of osteoclast precursors affected the transcriptional levels of key factors involved in osteoclastogenesis, including RANK, NFATc1, and DC-STAMP. Conclusions: The effects of HIV infection on osteoclast precursors were found to be dependent on the size of the inoculum and the kinetics of viral replication. These findings underscore the importance of understanding the underlying mechanisms to develop novel strategies for the prevention and treatment of bone disorders in individuals with HIV.


Assuntos
Infecções por HIV , HIV-1 , Humanos , Osteoclastos/metabolismo , Catepsina K , HIV-1/metabolismo , Infecções por HIV/metabolismo , Fatores de Transcrição NFATC/metabolismo , Macrófagos/metabolismo , Proteínas de Transporte/metabolismo , Citocinas/metabolismo
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