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1.
Endocrine ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38963515

RESUMEN

PURPOSE: Alpelisib is a PI3K (Phosphoinositide 3-kinases) inhibitor used for breast cancer which develops hyperglycemia based on its action on glucose metabolism regulation. This study aims to identify potential risk factors predicting hyperglycemia development and the need for multiple treatments for hyperglycemia in patients receiving Alpelisib. METHODS: Fourteen women diagnosed with metastatic hormone receptor-positive breast cancer carrying PI3K mutations who initiated treatment with Alpelisib were monitored through consultations in the Oncology and Endocrinology departments. Non-parametric ROC curves were generated to assess the need for three or more antidiabetic medications to achieve glycemic control. RESULTS: The study population had a median age of 64 years (range:48-69) with a median body mass index (BMI) of 26.6 kg/m2 (range: 22.9-29.4). Overweight was observed in 35.7% of the participants and obesity in 21.4%. Fifty percent of the participants had prediabetes, and 85.7% developed hyperglycemia requiring pharmacological treatment, although none of them needed to discontinue treatment for this reason. Baseline C-peptide levels and BMI were associated with the number of antidiabetic drugs used (Spearman's Rho 0.553, p = 0.040; Spearman's Rho 0.581, p = 0.030, respectively). ROC curve analysis showed and area under the curve (AUC) of 0.819 for the variable risk profile (defined as baseline C-peptide >10.5 ng/ml and BMI > 27 kg/m2), whereas AUC values were 0.556 and 0.514 for HbA1c and baseline glucose, respectively, (p = 0.012). CONCLUSION: A joint follow-up by an Oncology department and a Diabetes Unit can prevent treatment discontinuation in patients under Alpelisib therapy. Baseline BMI and plasma C-peptide levels can predict an increased need for anti-hyperglycemic treatment.

2.
Rheumatol Int ; 44(8): 1381-1393, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38850327

RESUMEN

Rheumatoid arthritis causes progressive joint destruction in the long term, causing a deterioration of the foot and ankle. A clinical practice guideline has been created with the main objective of providing recommendations in the field of podiatry for the conservative management of rheumatoid arthritis. Thus, healthcare professionals involved in foot care of adults with rheumatoid arthritis will be able to follow practical recommendations. A clinical practice guideline was created including a group of experts (podiatrists, rheumatologists, nurses, an orthopaedic surgeon, a physiotherapist, an occupational therapist and patient with rheumatoid arthritis). Methodological experts using GRADE were tasked with systematically reviewing the available scientific evidence and developing the information which serves as a basis for the expert group to make recommendations. Key findings include the efficacy of chiropody in alleviating hyperkeratotic lesions and improving short-term pain and functionality. Notably, custom and standardized foot orthoses demonstrated significant benefits in reducing foot pain, enhancing physical function, and improving life quality. Therapeutic footwear was identified as crucial for pain reduction and mobility improvement, emphasizing the necessity for custom-made options tailored to individual patient needs. Surgical interventions were recommended for cases which were non-responsive to conservative treatments, aimed at preserving foot functionality and reducing pain. Moreover, self-care strategies and education were underscored as essential components for promoting patient independence and health maintenance. A series of recommendations have been created which will help professionals and patients to manage podiatric pathologies derived from rheumatoid arthritis.


Asunto(s)
Artritis Reumatoide , Humanos , Artritis Reumatoide/terapia , Ortesis del Pié , Articulación del Tobillo , Pie , Podiatría/normas , Consenso
3.
Front Vet Sci ; 11: 1359205, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38835898

RESUMEN

Ante-mortem diagnosis of bovine tuberculosis (bTB) is based mainly on the tuberculin skin test (TST) and the ɣ-IFN release assay (IGRA). Some infected animals escape screening tests, thus, limit herd sanitation. Previous reports have suggested a predominant pattern of multi-organ lesions attributable to Mycobacterium bovis (the causative agent of bTB) bacteraemia. A case-control study was conducted to investigate blood PCR as an alternative tool for improving ante-mortem detection of TST false-negative bovines. Cases comprised 70 TST false-negative bovines (cases), which were serology positive, and controls included 81 TST positive bovines; all of them confirmed as infected with M. bovis. Detection of the IS6110 target through touchdown blood-PCR (IS6110 TD-PCR) was performed. The positivity of the blood-PCR was 27.2% in the control group. This performance was similar to the 15% obtained among cases (p = 0.134). Most cases identified by the IS6110 TD-PCR exhibited focalized lesions (p = 0.002). Results demonstrated that blood-PCR could detect TST false-negative cattle, even if they are negative for IGRA. Considering that cases exhibited humoral response to M. bovis, further studies conducted in a pre-serological stage could provide evidence about the real contribution of the technique in herds.

4.
Rev Esp Enferm Dig ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38832588

RESUMEN

We report the case of a 58-year-old male patient presenting with clinical and laboratory findings indicative of acute hepatitis. Abdominal ultrasound excluded biliary tract abnormalities. Two weeks prior, the patient had contracted COVID-19. Viral hepatitis was ruled out, and the presence of autoantibodies was confirmed. Liver biopsy findings were consistent with autoimmune hepatitis and grade 1 fibrosis. Initial treatment with budesonide was ineffective, leading to a switch to prednisone, with maintenance therapy comprising prednisone and azathioprine. COVID-19 infection may act as a trigger for the development of autoimmune hepatitis.

5.
J Clin Med ; 13(11)2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38893020

RESUMEN

Moebius syndrome is a collection of orofacial anomalies with highly variable features affecting many different systems but characterised by bilateral facial palsy and absent eye abduction. We largely regard Moebius syndrome as a diagnosis of exclusion. Lack of awareness and knowledge means that children often fall between services, leading to treatment delays and difficulty interfacing with social care and schools, with long-term impact on physical health and psychosocial development. We developed a multidisciplinary team comprising core clinicians (lead physician, geneticist, speech and language therapist, psychologist and specialist nurse) and an expanded group to encompass the other affected systems. The interactions between our specialties lead to the development of a treatment protocol, which we present. The protocol harnesses the aspects of care of children with a range of other rare diseases at a specialised paediatric centre and synthesises them into a holistic approach for MBS and related conditions. Management is sequenced on an "ABC-style" basis, with airway, feeding, vision and speech taking priority in the early years. We define management priorities as airway stabilisation with swallow assessment, ocular surface protection and maintenance of nutritional support. Management principles for issues such as speech, reflux, drooling and sleep issues are outlined. In later years, psychological support has a prominent role geared towards monitoring and interventions for low mood, self-esteem and bullying.

6.
Int J Mol Sci ; 25(11)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38891922

RESUMEN

Vascular calcification has a global health impact that is closely linked to bone loss. The Receptor Activator of Nuclear Factor Kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system, fundamental for bone metabolism, also plays an important role in vascular calcification. The Leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4), a novel receptor for RANKL, regulates bone remodeling, and it appears to be involved in vascular calcification. Besides RANKL, LGR4 interacts with R-spondins (RSPOs), which are known for their roles in bone but are less understood in vascular calcification. Studies were conducted in rats with chronic renal failure fed normal or high phosphorus diets for 18 weeks, with and without control of circulating parathormone (PTH) levels, resulting in different degrees of aortic calcification. Additionally, vascular smooth muscle cells (VSMCs) were cultured under non-calcifying (1 mM phosphate) and calcifying (3 mM phosphate) media with different concentrations of PTH. To explore the role of RANKL in VSMC calcification, increasing concentrations of soluble RANKL were added to non-calcifying and calcifying media. The effects mediated by RANKL binding to its receptor LGR4 were investigated by silencing the LGR4 receptor in VSMCs. Furthermore, the gene expression of the RANK/RANKL/OPG system and the ligands of LGR4 was assessed in human epigastric arteries obtained from kidney transplant recipients with calcification scores (Kauppila Index). Increased aortic calcium in rats coincided with elevated systolic blood pressure, upregulated Lgr4 and Rankl gene expression, downregulated Opg gene expression, and higher serum RANKL/OPG ratio without changes in Rspos gene expression. Elevated phosphate in vitro increased calcium content and expression of Rankl and Lgr4 while reducing Opg. Elevated PTH in the presence of high phosphate exacerbated the increase in calcium content. No changes in Rspos were observed under the conditions employed. The addition of soluble RANKL to VSMCs induced genotypic differentiation and calcification, partly prevented by LGR4 silencing. In the epigastric arteries of individuals presenting vascular calcification, the gene expression of RANKL was higher. While RSPOs show minimal impact on VSMC calcification, RANKL, interacting with LGR4, drives osteogenic differentiation in VSMCs, unveiling a novel mechanism beyond RANKL-RANK binding.


Asunto(s)
Músculo Liso Vascular , Ligando RANK , Receptores Acoplados a Proteínas G , Calcificación Vascular , Ligando RANK/metabolismo , Ligando RANK/genética , Animales , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Calcificación Vascular/metabolismo , Calcificación Vascular/patología , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Ratas , Humanos , Masculino , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Osteoprotegerina/metabolismo , Osteoprotegerina/genética , Hormona Paratiroidea/metabolismo , Células Cultivadas , Ratas Sprague-Dawley
8.
Sensors (Basel) ; 24(12)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38931502

RESUMEN

Robotic inspection is advancing in performance capabilities and is now being considered for industrial applications beyond laboratory experiments. As industries increasingly rely on complex machinery, pipelines, and structures, the need for precise and reliable inspection methods becomes paramount to ensure operational integrity and mitigate risks. AI-assisted autonomous mobile robots offer the potential to automate inspection processes, reduce human error, and provide real-time insights into asset conditions. A primary concern is the necessity to validate the performance of these systems under real-world conditions. While laboratory tests and simulations can provide valuable insights, the true efficacy of AI algorithms and robotic platforms can only be determined through rigorous field testing and validation. This paper aligns with this need by evaluating the performance of one-stage models for object detection in tasks that support and enhance the perception capabilities of autonomous mobile robots. The evaluation addresses both the execution of assigned tasks and the robot's own navigation. Our benchmark of classification models for robotic inspection considers three real-world transportation and logistics use cases, as well as several generations of the well-known YOLO architecture. The performance results from field tests using real robotic devices equipped with such object detection capabilities are promising, and expose the enormous potential and actionability of autonomous robotic systems for fully automated inspection and maintenance in open-world settings.

9.
Viruses ; 16(6)2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38932245

RESUMEN

BACKGROUND: Respiratory viruses significantly impact global morbidity and mortality, causing more disease in humans than any other infectious agent. Beyond pathogens, various viruses and bacteria colonize the respiratory tract without causing disease, potentially influencing respiratory diseases' pathogenesis. Nevertheless, our understanding of respiratory microbiota is limited by technical constraints, predominantly focusing on bacteria and neglecting crucial populations like viruses. Despite recent efforts to improve our understanding of viral diversity in the human body, our knowledge of viral diversity associated with the human respiratory tract remains limited. METHODS: Following a comprehensive search in bibliographic and sequencing data repositories using keyword terms, we retrieved shotgun metagenomic data from public repositories (n = 85). After manual curation, sequencing data files from 43 studies were analyzed using EVEREST (pipEline for Viral assEmbly and chaRactEriSaTion). Complete and high-quality contigs were further assessed for genomic and taxonomic characterization. RESULTS: Viral contigs were obtained from 194 out of the 868 FASTQ files processed through EVEREST. Of the 1842 contigs that were quality assessed, 8% (n = 146) were classified as complete/high-quality genomes. Most of the identified viral contigs were taxonomically classified as bacteriophages, with taxonomic resolution ranging from the superkingdom level down to the species level. Captured contigs were spread across 25 putative families and varied between RNA and DNA viruses, including previously uncharacterized viral genomes. Of note, airway samples also contained virus(es) characteristic of the human gastrointestinal tract, which have not been previously described as part of the lung virome. Additionally, by performing a meta-analysis of the integrated datasets, ecological trends within viral populations linked to human disease states and their biogeographical distribution along the respiratory tract were observed. CONCLUSION: By leveraging publicly available repositories of shotgun metagenomic data, the present study provides new insights into viral genomes associated with specimens from the human respiratory tract across different disease spectra. Further studies are required to validate our findings and evaluate the potential impact of these viral communities on respiratory tract physiology.


Asunto(s)
Genoma Viral , Metagenómica , Sistema Respiratorio , Viroma , Virus , Humanos , Metagenómica/métodos , Sistema Respiratorio/virología , Virus/genética , Virus/clasificación , Virus/aislamiento & purificación , Metagenoma , Simulación por Computador , Filogenia , Biología Computacional/métodos , Microbiota , Bacteriófagos/genética , Bacteriófagos/clasificación , Bacteriófagos/aislamiento & purificación
10.
Tuberculosis (Edinb) ; 147: 102516, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38735123

RESUMEN

Although studies on non-tuberculous mycobacteria have increased in recent years because they cause a considerable proportion of infections, their cellulolytic system is still poorly studied. This study presents a characterization of the cellulolytic activities of environmental mycobacterial isolates derived from soil and water samples from the central region of Argentina, aimed to evaluate the conservation of the mechanism for the degradation of cellulose in this group of bacteria. The molecular and genomic identification revealed identity with Mycolicibacterium septicum. The endoglucanase and total cellulase activities were assessed both qualitatively and quantitatively and the optimal enzymatic conditions were characterized. A specific protein of around 56 kDa with cellulolytic activity was detected in a zymogram. Protein sequences possibly arising from a cellulase were identified by mass spectrometry-based shotgun proteomics. Results showed that M. septicum encodes for cellulose- and hemicellulose-related degrading enzymes, including at least an active ß-1,4 endoglucanase enzyme that could be useful to improve its survival in the environment. Given the important health issues related to mycobacteria, the results of the present study may contribute to the knowledge of their cellulolytic system, which could be important for their ability to survive in many different types of environments.


Asunto(s)
Proteínas Bacterianas , Celulasa , Celulosa , Microbiología del Suelo , Celulosa/metabolismo , Celulasa/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Argentina , Microbiología del Agua , Proteómica/métodos , Mycobacteriaceae/genética , Mycobacteriaceae/enzimología
11.
Arq Bras Cardiol ; 121(4): e20240113, 2024 Feb.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-38695411
12.
Orthop J Sports Med ; 12(5): 23259671241249123, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38751852

RESUMEN

Background: Greater trochanteric pain syndrome (GTPS) is characterized by gluteal enthesopathy involving the peritrochanteric space and associated with chronic pain and functional impairment. A corticosteroid injection in the trochanteric bursa is the usual palliative treatment for pain. However, it is important to investigate treatment options that will relieve pain in the peritrochanteric space. Purpose: To compare the clinical efficacy of subfascial platelet-rich plasma (PRP) injection and enthesis needling for GTPS. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 92 patients (90% women; mean age, 55 years old; mean body mass index, 25.3 kg/m2) were randomly divided into a subfascial PRP injection group and an enthesis needling group. Descriptive data and radiographic measurements of the pelvis-including leg-length difference, pelvic width difference, and pelvic trochanteric index-were recorded. The primary outcome measures were the Hip Outcome Score (HOS) activities of daily living (HOS-ADL) and sports-specific (HOS-SS) subscales and the visual analog scale for pain at 3, 6, and 12 months posttreatment. In addition, we evaluated the presence or absence of ultrasound characteristics (fascia nodules, trochanteric bursa distension, and calcium deposits) over time in response to treatment. Results: Baseline demographic and radiological characteristics were similar between the groups. The PRP group saw significantly greater improvement from baseline to 12 months posttreatment on the HOS-SS subscore compared with the needling group (32.09 [95% CI, 28.99-40.20] vs 20.52 [95% CI, 11.99-29.05]; P = .048). At 3 months, 60% of patients in the PRP group versus 33.3% in the needling group had a reduction in pain compared with a baseline of >20% (P = .040). After subfascial PRP injection, fewer patients had a fascia nodule over the trochanter and/or bursa distension (P = .006 and P = .004, respectively). The pelvic trochanteric index was predictive of HOS-ADL and HOS-SS outcomes (P = .011 and P = .022, respectively). The interaction between treatment modality and fascia nodule influenced HOS-ADL and HOS-SS outcomes (P = .021 and P = .023) as well as the interactions of treatment modality, fascia nodules, and calcifications (P = .027). Conclusion: Both subfascial PRP injection and enthesis needling resulted in clinical improvements, but the improvement in the HOS-SS was greater in the PRP group. Registration: NCT04231357 (ClinicalTrials.gov identifier).

14.
Oral Dis ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693647

RESUMEN

OBJECTIVE: To analyze the clinicopathological and evolutionary profile of the main locations of oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: This is a retrospective study on 133 patients treated for OSCC. The group was composed of 48 women and 85 men, with a mean age 63.9 ± 12.73 years. Most cases involved the lingual border of tongue (63), followed by the gingiva (36) and the floor of mouth (34). A comparative analysis was performed using multinomial regression. RESULTS: There were significant differences regarding age, sex, tobacco and alcohol consumption, liver pathology, oral potentially malignant disorders, and bone and perineural invasion. In multivariate regression, tobacco consumption, and bone invasion remained significant. There were no significant differences in relation to prognosis. CONCLUSION: The location of OSCC is an important factor in the clinicopathological assessment of this neoplasm. The main locations of OSCC show differential etiopathogenic and clinicopathological aspects. Tobacco consumption has a great relevance in the floor of mouth; nonetheless, it is less important in the tongue border and the gum, which suggests other pathogenic factors. It is necessary to consider the anatomical location of OSCC in preventive protocols, with the aim of reducing its high mortality.

15.
PLoS One ; 19(5): e0297731, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38809861

RESUMEN

Individuals are increasingly exposed to news and opinion from beyond national borders. This news and opinion are often concentrated in clusters of ideological homophily, such as political parties, factions, or interest groups. But how does exposure to cross-border information affect the diffusion of ideas across national and ideological borders? Here, we develop a non-linear mathematical model for the cross-border spread of two ideologies. First, we describe the standard deterministic model where the populations of each country are assumed to be constant and homogeneously mixed. We solve the system of differential equations numerically by the Runge-Kutta method and show how small changes in the influence of a minority ideology can trigger shifts in the global political equilibrium. Second, we simulate recruitment as a stochastic differential process for each political affiliation and fit model solutions to population growth rates and voting populations in US presidential elections from 1932 to 2020. We also project the dynamics of several possible scenarios from 2020 to the end of the century. We show that cross-border influence plays a fundamental role in determining election outcomes. An increase in foreign support for a national party's ideas could change the election outcome, independent of domestic recruitment capacity. One key finding of our study suggests that voter turnout in the US will grow at a faster rate than non-voters in the coming decades. This trend is attributed to the enhanced recruitment capabilities of both major parties among non-partisans over time, making political disaffection less prominent. This phenomenon holds true across all simulated scenarios.


Asunto(s)
Política , Humanos , Modelos Teóricos , Estados Unidos
16.
Nutrients ; 16(9)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38732624

RESUMEN

INTRODUCTION: Nutritional management plays a crucial role in treating patients with type 2 diabetes (T2D), working to prevent and control the progression of chronic non-communicable diseases. OBJECTIVES: To evaluate the effects of individualized nutritional interventions on weight, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting blood glucose (FBG), hemoglobin A1c (HbA1c), total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglycerides (TGs), systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR)} over 12 months and subsequently at follow-up (15 months). METHODS: This longitudinal experimental study (without randomization and blinding) enrolled 84 sedentary participants with T2D (both sexes, aged 18-80 years). They were divided into a control group of 40 participants who received only medical consultations, and an intervention group of 44 participants who received the same medical care along with a nutritional assessment. Consultations occurred quarterly from August 2020 to November 2022 (first-twelfth month), with six to nine patients per session. Subsequently, a follow-up was conducted from December 2022 to November 2023, during which the intervention group had only medical care (during the 12th-15th months). Personalized dietary planning was inspired by the Mediterranean/DASH diets adapted to Brazilian foods and socioeconomic cultures. STATISTICAL ANALYSIS: Normal variables were compared between groups for each time point and also within each group across different time points using a two-way ANOVA (repeated measures for intragroup) followed by the Sídák post hoc test. Non-normal variables were compared between groups for each time point using Kruskal-Wallis followed by the Dunn post hoc test, and within each group across different time points using Friedman followed by the Dunn post hoc test. Data with a Gaussian distribution were presented as mean ± standard deviation (SD), and data with a non-Gaussian distribution were presented as median ± interquartile range (IQR). For all cases, α < 0.05 and p < 0.05 were adopted. RESULTS: In the intervention group, significant reductions were observed between the first and twelfth month for all parameters (p < 0.05), (except for TC), along with an increase in HDL-C (p = 0.0105). Conversely, in the control group, there was a significant increase in HbA1c, weight, BMI, FBG, and WHR (p < 0.05) between the first and twelfth months. Regarding the comparison between groups, there was a significant difference for all analyzed parameters (p < 0.05) from the first to the twelfth month. In the follow-up, differences were also observed (p < 0.05), except for BMI (p > 0.05). CONCLUSION: The individualized nutritional intervention improved eating habits, anthropometric, biochemical, and cardiovascular markers in T2D over 12 months, with sustained results during follow-up. The dietary plan inspired by the Mediterranean and DASH diets demonstrated good adaptation to the Brazilian food culture and the patients' socioeconomic contexts. Consistent monitoring and personalized nutritional management are essential for optimizing long-term outcomes. However, more clinical trials are necessary in order to optimize the level of evidence for longitudinal interventions.


Asunto(s)
Glucemia , Diabetes Mellitus Tipo 2 , Control Glucémico , Humanos , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/sangre , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Control Glucémico/métodos , Estudios Longitudinales , Glucemia/metabolismo , Factores de Riesgo de Enfermedad Cardiaca , Hemoglobina Glucada/metabolismo , Enfermedades Cardiovasculares/prevención & control , Anciano de 80 o más Años , Adulto Joven , Índice de Masa Corporal , Adolescente , Presión Sanguínea , Biomarcadores/sangre , Relación Cintura-Cadera , Circunferencia de la Cintura , Terapia Nutricional/métodos
18.
Am J Transplant ; 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38692412

RESUMEN

In this proof-of-concept study, spatial transcriptomics combined with public single-cell ribonucleic acid-sequencing data were used to explore the potential of this technology to study kidney allograft rejection. We aimed to map gene expression patterns within diverse pathologic states by examining biopsies classified across nonrejection, T cell-mediated acute rejection, interstitial fibrosis, and tubular atrophy. Our results revealed distinct immune cell signatures, including those of T and B lymphocytes, monocytes, mast cells, and plasma cells, and their spatial organization within the renal interstitium. We also mapped chemokine receptors and ligands to study immune cell migration and recruitment. Finally, our analysis demonstrated differential spatial enrichment of transcription signatures associated with kidney allograft rejection across various biopsy regions. Interstitium regions displayed higher enrichment scores for rejection-associated gene expression patterns than tubular areas, which had negative scores. This implies that these signatures are primarily driven by processes unfolding in the renal interstitium. Overall, this study highlights the value of spatial transcriptomics for revealing cellular heterogeneity and immune signatures in renal transplant biopsies and demonstrates its potential for studying the molecular and cellular mechanisms associated with rejection. However, certain limitations must be borne in mind regarding the development and future applications of this technology.

19.
Ecohealth ; 21(1): 71-82, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38727761

RESUMEN

Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex (MTC) and non-tuberculous Mycobacteria (NTM), may infect wild and domestic mammals, including humans. Although cattle are the main hosts and spreaders of M. bovis, many wildlife hosts play an important role worldwide. In Argentina, wild boar and domestic pigs are considered important links in mammalian tuberculosis (mTB) transmission. The aim of this work was to investigate the presence of M. bovis in wild pigs from different regions of Argentina, to characterize isolates of M. bovis obtained, and to compare those with other previously found in vertebrate hosts. A total of 311 samples from wild pigs were obtained, and bacteriological culture, molecular identification and genotyping were performed, obtaining 63 isolates (34 MTC and 29 NTM). Twelve M. bovis spoligotypes were detected. Our findings suggest that wild pigs have a prominent role as reservoirs of mTB in Argentina, based on an estimated prevalence of 11.2 ± 1.8% (95% CI 8.0-14.8) for MTC and the frequency distribution of spoligotypes shared by cattle (75%), domestic pigs (58%) and wildlife (50%). Argentina has a typical scenario where cattle and pigs are farm-raised extensively, sharing the environment with wildlife, creating conditions for effective transmission of mTB in the wildlife-livestock-human interface.


Asunto(s)
Animales Salvajes , Mycobacterium bovis , Enfermedades de los Porcinos , Tuberculosis , Animales , Argentina/epidemiología , Animales Salvajes/microbiología , Tuberculosis/epidemiología , Tuberculosis/veterinaria , Tuberculosis/microbiología , Mycobacterium bovis/aislamiento & purificación , Mycobacterium bovis/genética , Porcinos , Enfermedades de los Porcinos/microbiología , Enfermedades de los Porcinos/epidemiología , Sus scrofa/microbiología , Reservorios de Enfermedades/microbiología , Reservorios de Enfermedades/veterinaria , Prevalencia , Genotipo
20.
Lancet HIV ; 11(6): e389-e405, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38816141

RESUMEN

BACKGROUND: Allogeneic haematopoietic stem-cell transplantation (allo-HSCT) markedly reduces HIV reservoirs, but the mechanisms by which this occurs are only partly understood. In this study, we aimed to describe the dynamics of virological and immunological markers of HIV persistence after allo-HSCT. METHODS: In this prospective observational cohort study, we analysed the viral reservoir and serological dynamics in IciStem cohort participants with HIV who had undergone allo-HSCT and were receiving antiretroviral therapy, ten of whom had received cells from donors with the CCR5Δ32 mutation. Participants from Belgium, Canada, Germany, Italy, the Netherlands, Spain, Switzerland, and the UK were included in the cohort both prospectively and retrospectively between June 1, 2014 and April 30, 2019. In the first 6 months after allo-HSCT, participants had monthly assessments, with annual assessments thereafter, with the protocol tailored to accommodate for the individual health status of each participant. HIV reservoirs were measured in blood and tissues and HIV-specific antibodies were measured in plasma. We used the Wilcoxon signed-rank test to compare data collected before and after allo-HSCT in participants for whom longitudinal data were available. When the paired test was not possible, we used the Mann-Whitney U test. We developed a mathematical model to study the factors influencing HIV reservoir reduction in people with HIV after allo-HSCT. FINDINGS: We included 30 people with HIV with haematological malignancies who received a transplant between Sept 1, 2009 and April 30, 2019 and were enrolled within the IciStem cohort and included in this analysis. HIV reservoirs in peripheral blood were reduced immediately after full donor chimerism was achieved, generally accompanied by undetectable HIV-DNA in bone marrow, ileum, lymph nodes, and cerebrospinal fluid, regardless of donor CCR5 genotype. HIV-specific antibody levels and functionality values declined more slowly than direct HIV reservoir values, decaying significantly only months after full donor chimerism. Mathematical modelling suggests that allogeneic immunity mediated by donor cells is the main viral reservoir depletion mechanism after massive reservoir reduction during conditioning chemotherapy before allo-HSCT (half-life of latently infected replication-competent cells decreased from 44 months to 1·5 months). INTERPRETATION: Our work provides, for the first time, data on the effects of allo-HSCT in the context of HIV infection. Additionally, we raise the question of which marker can serve as the last reporter of the residual viraemia, postulating that the absence of T-cell immune responses might be a more reliable marker than antibody decline after allo-HSCT. FUNDING: amfAR (American Foundation for AIDS Research; ARCHE Program), National Institutes of Health, National Institute of Allergy and Infectious Diseases, and Dutch Aidsfonds.


Asunto(s)
Infecciones por VIH , Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Masculino , Estudios Prospectivos , Femenino , Adulto , Persona de Mediana Edad , VIH-1/inmunología , Trasplante Homólogo , Biomarcadores/sangre , Carga Viral , Anticuerpos Anti-VIH/sangre
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