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Purpose: To summarize the results of Chile's 2022 Report Card (RC) on physical activity (PA) for Children and Adolescents. Methods: Chile's 2022 RC included ten core PA indicators common to the Global Matrix 4.0. Evidence from scientific articles, reports, and databases published between 2018 and January 2022 was included for each indicator. The data were collected and analyzed by a national scientific committee, which assigned letter grades (A to F) using a consensus based on benchmarks defined and revised by the Active Healthy Kids Global Alliance. Results: The committee assigned the following grades: Overall PA, D-; Organized Sports and Physical Activity Participation, C-; Active Play, Incomplete; Active Transportation, D; Sedentary Behavior, D-; Physical Fitness, Incomplete; Family and Peers, D; School, C; Community and Environment, D+; Government, A-. Conclusions: Chile's 2022 RC, like its previous versions, shows persistently low grades for most indicators. Overall PA remained nearly unchanged, while Community and Environment scored lower. Slight improvements were seen in Organized Sports, Family and Peers, and School Environment. While Chile has endeavored to increase children's activity levels, policies require implementation through a systemic, coherent framework to promote sustainable changes and reach a larger portion of children and youth.
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The present study evaluated the mechanical behavior of five designs of Morse taper (MT) connections with and without the application of loads. For this, the detorque of the fixing screw and the traction force required to disconnect the abutment from the implant were assessed. A total of 100 sets of implants/abutments (IAs) with MT-type connections were used, comprising five groups (n = 20/group): (1) Group Imp 11.5: IA sets with a cone angulation of 11.5°; (2) Group SIN 11.5: with a cone angulation of 11.5°; (3) Group SIN 16: with a cone angulation of 16°; (4) Group Neo 16: with a cone angulation of 16°; and (5) Group Str 15: with a cone angulation of 15°. All sets received the torque recommended by the manufacturer. After applying the torque, the counter torque of the fixing screws was measured in ten IA sets of each group without the application of cyclic loads (frequencies ≤ 2 Hz, 360,000 cycles, and force at 150 Ncm). The other ten sets of each group were subjected to cyclic loads, after which the detorque was measured. Afterwards, the force for disconnection between the implant and the abutment was measured by traction on all the samples. The untwisting of the abutment fixation screws showed a decrease in relation to the initial torque applied in all groups. In the unloaded samples, it was found to be -25.7% in Group 1, -30.4% in Group 2, -36.8% in Group 3, -29.6% in Group 4, and -25.7% in Group 5. After the applied loads, it was found to be -44% in Group 1, -43.5% in Group 2, -48.5% in Group 3, -47.2% in Group 4, and -49.8% in Group 5. The values for the IA sets were zero for SIN 16 (Group 3) and Neo16 (Group 4), both without and with loads. In the other three groups, without loads, the disconnection value was 56.3 ± 2.21 N (Group 1), 30.7 ± 2.00 N (Group 2), and 26.0 ± 2.52 N (Group 5). After applying loads, the values were 63.5 ± 3.06 N for Group 1, 34.2 ± 2.45 N in Group 2, and 23.1 ± 1.29 N in Group 5. It was concluded that in terms of the mechanical behavior of the five designs of MT IA sets, with and without the application of loads, the Imp 11.5, SIN 11.5, and Srt 15 groups showed better results compared to the SIN 16 and Neo 16 groups, showing that lower values of cone angulation increase the friction between the parts (IA), thus avoiding the need to maintain the torque of the fixing screw to maintain the union of the sets.
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Pancreas transplant (PTx) is the only treatment that establishes normal glucose levels for patients diagnosed with diabetes types 1 and 2. The paper aims to review and analyze graft survival, patient survival, and the impact on diabetic complications. We describe that the graft survival was 82-98% at 1 year, 90% at 5 years, and 75-54% at 10 years for simultaneous pancreas-kidney recipient; 71% pancreas after kidney (PAK), and 62% PTx alone at 1 year. Patient survival: At 1 year for recipients was 96.9% simultaneous pancreas-kidney transplantation (SPK); for PAK transplantation recipients, 96.3%; and for PTx alone recipients, 98.3%. In general, the pancreas transplantation improves and reverses diabetic complications. Finally, the pancreatic transplant is a morbid procedure and emerges as a significant alternative in diabetes management, directly competing with conventional insulin therapies. Results so far suggest that the most effective transplant model is the SPK. While more patients could benefit from this procedure, surgical complications and the need for immunosuppression pose significant challenges.
El trasplante de páncreas es el único tratamiento que estabiliza los niveles normales de glucosa en los pacientes diagnosticados con diabetes tipo 1 o tipo 2. En esta revisión se analizan la supervivencia del injerto, la supervivencia del paciente y el impacto en las complicaciones diabéticas. Se describe la supervivencia del injerto: 82-98% al año para los receptores de trasplante simultáneo de páncreas y riñón, 71% para trasplante páncreas después de riñón y 62% para trasplante de páncreas solitario al año. Supervivencia de los pacientes a 1 año: 96.9% para los receptores de trasplante simultáneo de páncreas y riñón, 96.3% para los receptores de trasplante de páncreas después de riñón y 98.3% para los receptores de páncreas solitario. En general, el trasplante de páncreas mejora y revierte las complicaciones diabéticas. Finalmente, el trasplante de páncreas, un procedimiento mórbido, surge como una alternativa significativa en el manejo de la diabetes, compitiendo directamente con las terapias convencionales de insulina. Hasta ahora, los resultados indican que el modelo de trasplante más efectivo es el simultáneo de páncreas y riñón. Aunque más pacientes podrían beneficiarse de este procedimiento, las complicaciones quirúrgicas y la necesidad de inmunosupresión plantean desafíos significativos.
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Diabetes Mellitus Tipo 1 , Supervivencia de Injerto , Trasplante de Riñón , Trasplante de Páncreas , Humanos , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/cirugía , Complicaciones Posoperatorias/etiología , Diabetes Mellitus Tipo 2/complicaciones , Complicaciones de la DiabetesRESUMEN
Coevolutionary antagonism generates relentless selection that can favour genetic exchange, including transfer of antibiotic synthesis and resistance genes among bacteria, and sexual recombination of disease resistance alleles in eukaryotes. We report an unusual link between biological conflict and DNA transfer in bdelloid rotifers, microscopic animals whose genomes show elevated levels of horizontal gene transfer from non-metazoan taxa. When rotifers were challenged with a fungal pathogen, horizontally acquired genes were over twice as likely to be upregulated as other genes - a stronger enrichment than observed for abiotic stressors. Among hundreds of upregulated genes, the most markedly overrepresented were clusters resembling bacterial polyketide and nonribosomal peptide synthetases that produce antibiotics. Upregulation of these clusters in a pathogen-resistant rotifer species was nearly ten times stronger than in a susceptible species. By acquiring, domesticating, and expressing non-metazoan biosynthetic pathways, bdelloids may have evolved to resist natural enemies using antimicrobial mechanisms absent from other animals.
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Transferencia de Gen Horizontal , Rotíferos , Animales , Rotíferos/genética , Rotíferos/metabolismo , Vías Biosintéticas/genética , Péptido Sintasas/genética , Péptido Sintasas/metabolismo , Policétidos/metabolismo , Filogenia , Familia de MultigenesRESUMEN
OBJECTIVE: Approximately half of ischemic strokes (IS) in cancer patients are cryptogenic, with many presumed cardioembolic. We evaluated whether there were specific miRNA and mRNA transcriptome architectures in peripheral blood of IS patients with and without comorbid cancer, and between cardioembolic versus noncardioembolic IS etiologies in comorbid cancer. METHODS: We studied patients with cancer and IS (CS; n = 42), stroke only (SO; n = 41), and cancer only (n = 28), and vascular risk factor-matched controls (n = 30). mRNA-Seq and miRNA-Seq data, analyzed with linear regression models, identified differentially expressed genes in CS versus SO and in cardioembolic versus noncardioembolic CS, and miRNA-mRNA regulatory pairs. Network-level analyses identified stroke etiology-specific responses in CS. RESULTS: A total of 2,085 mRNAs and 31 miRNAs were differentially expressed between CS and SO. In CS, 122 and 35 miRNA-mRNA regulatory pairs, and 5 and 3 coexpressed gene modules, were associated with cardioembolic and noncardioembolic CS, respectively. Complement, growth factor, and immune/inflammatory pathways showed differences between IS etiologies in CS. A 15-gene biomarker panel assembled from a derivation cohort (n = 50) correctly classified 81% of CS and 71% of SO participants in a validation cohort (n = 33). Another 15-gene panel correctly identified etiologies for 13 of 13 CS-cardioembolic and 11 of 11 CS-noncardioembolic participants upon cross-validation; 11 of 16 CS-cryptogenic participants were predicted cardioembolic. INTERPRETATION: We discovered unique mRNA and miRNA transcriptome architecture in CS and SO, and in CS with different IS etiologies. Cardioembolic and noncardioembolic etiologies in CS showed unique coexpression networks and potential master regulators. These may help distinguish CS from SO and identify IS etiology in cryptogenic CS patients. ANN NEUROL 2024;96:565-581.
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Redes Reguladoras de Genes , Accidente Cerebrovascular Isquémico , MicroARNs , Neoplasias , ARN Mensajero , Humanos , Masculino , Femenino , ARN Mensajero/sangre , MicroARNs/sangre , MicroARNs/genética , Persona de Mediana Edad , Accidente Cerebrovascular Isquémico/genética , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/epidemiología , Anciano , Neoplasias/genética , Neoplasias/sangre , Neoplasias/complicaciones , Comorbilidad , TranscriptomaRESUMEN
Background/Objectives: Heart failure (HF) is a highly prevalent clinical syndrome with serious morbidity and mortality. Furthermore, acute heart failure (AHF) is the main cause of hospital admission in people aged 65 years or more. Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) have been shown to improve the survival and quality of life in patients with HF regardless of left ventricular ejection fraction (LVEF). Our aims were to describe the characteristics of adults with multiple pathologies admitted with acute heart failure as the main diagnosis and of the population treated with SGLT2is, as well as to evaluate if their use was associated with lower readmission and mortality rates. Methods: A prospective study of patients from the PROFUND-IC registry who were admitted with AHF as the main diagnosis was conducted. Clinical and analytical characteristics were analyzed, as well as readmissions and mortality. Descriptive and bivariate analyses of the sample between those taking SGLT2is and those who were not were performed, using the chi-square test for qualitative variables and Welch's test for quantitative measures, as well as the Fisher and Wilcoxon tests as indicated for nonparametric tests. Kaplan-Meier curves were constructed to analyze the readmission and mortality of patients at 12 months based on SGLT2i treatment. Finally, a propensity score matching was performed, guaranteeing that the observed effect of the drug was not influenced by the differences in the characteristics between the groups. Results: There were 750 patients included: 58% were women, and the mean age was 84 years. Functional class II according to the NYHA scale predominated (54%), and the mean LVEF was 51%. SGLT2 inhibitors were prescribed to only 28% of patients. Most of the patients were men (48.6% vs. 39.8%, p = 0.029), they were younger (82 vs. 84 years, p = 0.002), and their LVEF was lower (48% vs. 52%, p < 0.001). Lower mortality was observed in the group treated with SGLT2is, both during baseline admission (2.4% vs. 6.9%, p = 0.017) and at the 12-month follow-up (6.2% vs. 13%, p = 0.023); as well as a lower readmission rate (23.8% vs. 38.9%, p < 0.001). After the propensity score matching, a decrease in the 12-month readmission rate continued to be observed in the group treated with SGLT2is (p = 0.03). Conclusions: SGLT2is use was associated with lower readmission rates at the 12-month follow-up in older adults with multiple pathologies admitted with acute heart failure.
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OBJECTIVE: To analyze the success rate of external cephalic version (ECV) in pregnant women with a history of previous cesarean section, as well as to describe the rate of complications associated with the procedure. METHODS: A retrospective cohort study of women who were offered an ECV at "Virgen de la Arrixaca" Clinic University Hospital (Murcia, Spain) between January 2014 and December 2023. We collected data for previous cesarean delivery, obstetric history, fetal presentation, amniotic fluid volume, ECV success rate, complications related to ECV, mode of delivery, and neonatal outcomes. The study confidently performed ECV under sedation with propofol and tocolysis with ritodrine. Univariate and multivariate analyses were conducted to compare the success rate of ECV, ECV complications, and mode of delivery between women with and without previous cesarean sections. RESULTS: Of 1116 pregnant women who were offered ECV, 911 were included in the study, with 42 having a previous cesarean section. The success rate of ECV in pregnant women with a previous cesarean section was 78.6% (adjusted odds ratio 1.18; 95% confidence interval 0.49-2.86; P = 0.708), with a low complication rate of 9.5%, such as non-reassuring fetal heart rate (7.1%) or major vaginal bleeding (2.4%). Of the women who attempted a vaginal delivery after ECV, 80.8% were successful. CONCLUSIONS: These findings support that ECV is a safe and effective option for women with a previous cesarean section, with success rates comparable to those in women without a previous cesarean section.
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African swine fever (ASF) is a deadly disease of swine currently causing a worldwide pandemic, leading to severe economic consequences for the porcine industry. The control of disease spread is hampered by the limitation of available effective vaccines. Live attenuated vaccines (LAVs) are currently the most advanced vaccine prototypes, providing strong protection against ASF. However, the significant advances achieved using LAVs must be complemented with further studies to analyze vaccine-induced immunity. Here, we characterized the onset of cross-protective immunity triggered by the LAV candidate BA71ΔCD2. Intranasally vaccinated pigs were challenged with the virulent Georgia 2007/1 strain at days 3, 7 and 12 postvaccination. Only the animals vaccinated 12 days before the challenge had effectively controlled infection progression, showing low virus loads, minor clinical signs and a lack of the unbalanced inflammatory response characteristic of severe disease. Contrarily, the animals vaccinated 3 or 7 days before the challenge just showed a minor delay in disease progression. An analysis of the humoral response and whole blood transcriptome signatures demonstrated that the control of infection was associated with the presence of virus-specific IgG and a cytotoxic response before the challenge. These results contribute to our understanding of protective immunity induced by LAV-based vaccines, encouraging their use in emergency responses in ASF-affected areas.
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Despite significant efforts from government and industry, enteric foodborne diseases continue to pose a substantial public health challenge worldwide [...].
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Background: Accurately assessing the severity and frequency of fluctuating motor symptoms is important at all stages of Parkinson's disease management. Contrarily to time-consuming clinical testing or patient self-reporting with uncertain reliability, recordings with wearable sensors show promise as a tool for continuously and objectively assessing PD symptoms. While wearables-based clinical assessments during standardised and scripted tasks have been successfully implemented, assessments during unconstrained activity remain a challenge. Methods: We developed and implemented a supervised machine learning algorithm, trained and tested on tremor scores. We evaluated the algorithm on a 67-hour database comprising sensor data and clinical tremor scores for 24 Parkinson patients at four extremities for periods of about 3 hours. A random 25% subset of the labelled samples was used as test data, the remainder as training data. Based on features extracted from the sensor data, a Support Vector Machine was trained to predict tremor severity. Due to the inherent imbalance in tremor scores, we applied dataset rebalancing techniques. Results: Our classifier demonstrated robust performance in detecting tremor events with a sensitivity of 0.90 on the test-portion of the resampled dataset. The overall classification accuracy was high at 0.88. Conclusion: We implemented an accurate classifier for tremor monitoring in free-living environments that can be trained even with modestly sized and imbalanced datasets. This advancement offers significant clinical value in continuously monitoring Parkinson's disease symptoms beyond the hospital setting, paving the way for personalized management of PD, timely therapeutic adjustments, and improved patient quality of life.
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Background: Excessive sedentary time has been negatively associated with several health outcomes, and physical activity alone does not seem to fully counteract these consequences. This panorama emphasizes the essential of sedentary time interruption programs. "The Up Project" seeks to assess the effectiveness of two interventions, one incorporating active breaks led by a professional and the other utilizing a computer application (self-led), of both equivalent duration and intensity. These interventions will be compared with a control group to evaluate their impact on physical activity levels, sedentary time, stress perception, occupational pain, and cardiometabolic risk factors among office workers. Methods: This quasi-experimental study includes 60 desk-based workers from universities and educational institutes in Valparaiso, Chile, assigned to three groups: (a) booster breaks led by professionals, (b) computer prompts that are unled, and (c) a control group. The intervention protocol for both experimental groups will last 12 weeks (only weekdays). The following measurements will be performed at baseline and post-intervention: cardiometabolic risk based on body composition (fat mass, fat-free mass, and bone mass evaluated by DXA), waist circumference, blood pressure, resting heart rate, and handgrip strength. Physical activity and sedentary time will be self-reported and device-based assessed using accelerometry. Questionnaires will be used to determine the perception of stress and occupational pain. Discussion: Governments worldwide are addressing health issues associated with sedentary behavior, particularly concerning individuals highly exposed to it, such as desk-based workers. Despite implementing certain strategies, there remains a noticeable gap in comprehensive research comparing diverse protocols. For instance, studies that contrast the outcomes of interventions led by professionals with those prompted by computers are scarce. This ongoing project is expected to contribute to evidence-based interventions targeting reduced perceived stress levels and enhancing desk-based employees' mental and physical well-being. The implications of these findings could have the capacity to lay the groundwork for future public health initiatives and government-funded programs.
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Fuerza de la Mano , Lugar de Trabajo , Humanos , Ejercicio Físico/fisiología , Ocupaciones , DolorRESUMEN
The present study compared three different implant and abutment sets of type Morse taper (MT) connection, with- and without-index, were analyzed regarding their mechanical behavior without and with cyclic load application simulating the masticatory function. Ninety implant and abutment (IA) sets were used in the present study, divided into three groups (n = 30 samples per group): Group A, Ideale solid straight abutment (one piece) without index; Group B, Ideale abutment with an angle of 30-degree (two pieces) without index; Group C, Ideale abutment with an angle of 30-degree (two pieces) with index. The abutment stability quotient (ASQ) values, detorque value and rotation angle were measured before and after the cycling load. Twenty IA sets of each group were submitted to mechanical load at 360,000 cycles. The ASQ without load were 64.7 ± 2.49 for the group A, 60.2 ± 2.64 for the group B, 54.4 ± 3.27 for the group C; With load were 66.1 ± 5.20 for the group A, 58.5 ± 6.14 for the group B, 58.9 ± 2.99 for the group C. Detorque values were lower in groups B and C compared to group A (p < 0.05). In conclusion, the presence of the index did not influence the stability values. However, solid straight abutments (group A) showed higher values of stability compared to groups of angled abutments (groups B and C).
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Optical fiber with YPO4:Pr3+ nanocrystals (NCs) is presented for the first time using the glass powder-NCs doping method. The method's advantage is separate preparation of NCs and glass to preserve luminescent and optical properties of NCs once they are incorporated into optical fiber. The YPO4:Pr3+ nanocrystals were synthesized by the co-precipitation and hydrothermal methods, optimized for size (< 100 nm), shape, Pr3+ ions concentration (0.2 mol%), and emission lifetime. The core glass was selected from the non-silica P2O5-containing system with refractive index (n = 1.788) close to the NCs (no = 1.657, ne = 1.838). Optical fiber was drawn by modified powder-in-tube method after pre-sintering of glass powder-YPO4:Pr3+ (wt 3%) mixture to form optical fiber preform. Luminescent properties of YPO4:Pr3+ and optical fiber showed their excellent agreement, including sharp Pr3+ emission at 600 nm (1D2-3H4) and 1D2 level lifetime (τ = 156 ± 5 µs) under 488 nm excitation. The distribution of the YPO4:Pr3+ NCs in optical fiber were analyzed by TEM-EDS in the core region (FIB-SEM-prepared). The successful usage of glass powder-NCs doping method was discussed in the aspect of promising properties of the first YPO4:Pr3+ doped optical fiber as a new way to develop active materials for lasing applications, among others.
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Developing prolonged antigen delivery systems that mimic long-term exposure to pathogens appears as a promising but still poorly explored approach to reach durable immunities. In this study, we have used a simple technology by which His-tagged proteins can be assembled, assisted by divalent cations, as supramolecular complexes with progressive complexity, namely protein-only nanoparticles and microparticles. Microparticles produced out of nanoparticles are biomimetics of secretory granules from the mammalian hormonal system. Upon subcutaneous administration, they slowly disintegrate, acting as an endocrine-like secretory system and rendering the building block nanoparticles progressively bioavailable. The performance of such materials, previously validated for drug delivery in oncology, has been tested here regarding the potential for time-prolonged antigen release. This has been completed by taking, as a building block, a nanostructured version of p30, a main structural immunogen from the African swine fever virus (ASFV). By challenging the system in both mice and pigs, we have observed unusually potent pro-inflammatory activity in porcine macrophages, and long-lasting humoral and cellular responses in vivo, which might overcome the need for an adjuvant. The robustness of both innate and adaptive responses tag, for the first time, these dynamic depot materials as a novel and valuable instrument with transversal applicability in immune stimulation and vaccinology.
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Anastomosis Quirúrgica , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Humanos , Canal Anal/cirugía , Anastomosis Quirúrgica/métodos , Proctectomía/métodos , Neoplasias del Recto/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Grapado Quirúrgico/métodos , Cirugía Endoscópica Transanal/métodosRESUMEN
La propagación vía hematógena de Neisseria gonorrhoeae, patógeno de transmisión sexual, resulta en una enfermedad gonocócica diseminada (EGD), también conocida como síndrome artritis-dermatitis por el desarrollo de lesiones cutáneas, tenosinovitis y artritis. La población que más frecuentemente se ve afetada es la de adultos jóvenes. Describimos el caso de una adolescente que de forma aguda desarrolló lesiones cutáneas, artritis, tenosinovitis y síntomas constitucionales por EGD. La identificación del agente causal fue por cultivo de secreción vaginal y fue tratada con ceftriaxona intravenosa durante 7 días, con recuperación clínica completa. Es importante diferenciar este cuadro clínico de otros tipos de artritis desarrollados en la adolescencia.(AU)
Hematogenous spread of Neisseria gonorrhoeae, a sexually transmitted pathogen, results in disseminated gonococcal disease (DGD), also known as arthritis-dermatitis syndrome, due to the development of skin lesions, tenosynovitis, and arthritis. The most frequently affected population is young adults. We describe the case of an adolescent female who acutely developed skin lesions, arthritis, tenosynovitis, and constitutional symptoms. The causal agent was identified by a culture of vaginal secretion and treated with ceftriaxone for 7 days with complete recovery. It is important to differentiate this clinical picture from other types of arthritis developed in adolescence.(AU)
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Humanos , Femenino , Adolescente , Tenosinovitis , Artritis Reumatoide , Gonorrea , Neisseria gonorrhoeae , Tenosinovitis/complicaciones , Pacientes Internos , Examen Físico , Reumatología , Pediatría , Evaluación de SíntomasRESUMEN
INTRODUCTION AND OBJECTIVES: Vaccines against SARS-CoV-2 have been a major scientific and medical achievement in the control of the COVID-19 pandemic. However, very infrequent cases of inflammatory heart disease have been described as adverse events, leading to uncertainty in the scientific community and in the general population. METHODS: The Vaccine-Carditis Registry has included all cases of myocarditis and pericarditis diagnosed within 30 days after COVID-19 vaccination since August 1, 2021 in 29 centers throughout the Spanish territory. The definitions of myocarditis (probable or confirmed) and pericarditis followed the consensus of the Centers for Disease Control and the Clinical Practice Guidelines of the European Society of Cardiology. A comprehensive analysis of clinical characteristics and 3-month evolution is presented. RESULTS: From August 1, 2021, to March 10, 2022, 139 cases of myocarditis or pericarditis were recorded (81.3% male, median age 28 years). Most cases were detected in the 1st week after administration of an mRNA vaccine, the majority after the second dose. The most common presentation was mixed inflammatory disease (myocarditis and pericarditis). 11% had left ventricular systolic dysfunction, 4% had right ventricular systolic dysfunction, and 21% had pericardial effusion. In cardiac magnetic resonance studies, left ventricular inferolateral involvement was the most frequent pattern (58%). More than 90% of cases had a benign clinical course. After a 3-month follow-up, the incidence of adverse events was 12.78% (1.44% mortality). CONCLUSIONS: In our setting, inflammatory heart disease after vaccination against SARS-CoV-2 predominantly affects young men in the 1st week after the second dose of RNA-m vaccine and presents a favorable clinical course in most cases.
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Vacunas contra la COVID-19 , COVID-19 , Miocarditis , Pericarditis , Adulto , Femenino , Humanos , Masculino , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Progresión de la Enfermedad , Miocarditis/inducido químicamente , Miocarditis/epidemiología , Pericarditis/inducido químicamente , Pericarditis/epidemiología , Sistema de Registros , Vacunación/efectos adversos , EspañaRESUMEN
BACKGROUND: Cryptorchidism is one of the most common congenital disorders in boys and it is associated with a higher risk of sub-fertility and testicular cancer. Testicular descent occurs during embryo-fetal development in two phases, transabdominal and inguino-scrotal. In the latter process, androgens play a leading role. The androgen receptor has in its N-terminal domain, two aminoacidic repeats encoded by polymorphic nucleotide repetitions: (CAG)nCAA and GGN. The number of repetitions of these trinucleotides has been associated with different transactivation capacities and sensitivities of the androgen receptor response. OBJECTIVE: To determine whether pediatric Chilean individuals with idiopathic inguinal cryptorchidism have a different number of CAG and/or GGN repeats polymorphisms compared with controls. MATERIALS AND METHODS: A total of 109 cases with idiopathic inguinal cryptorchidism (26 bilateral and 83 unilateral) were studied by polymerase chain reaction amplification from DNA extracted from peripheral blood, followed by fragment size analysis by capillary electrophoresis, which were compared with 140 controls. RESULTS: The CAG26 repeats allele was increased in the total cases (8.3% vs. 1.4%; p = 0.012; odds ratio = 6.21, 95% confidence interval 1.31-29.4), and in bilateral cases compared to controls (11.5% vs. 1.4%; p = 0.028; odds ratio = 9 CI 95% 1.43-56.8). Similarly, CAG > 22 alleles were increased in the total cases (62.4% vs. 49.3%, p = 0.041), and more significantly in bilateral cases (73.1% vs. 49.3%; p = 0.032; odds ratio = 2.79, 95% confidence interval 1.1-7.1). In addition, CAG < 18 alleles were not observed among cases, but were present in 5.7% of controls (p = 0.01). Regarding the GGN repeats, no differences were observed between cases and controls either when analyzing separately unilateral and bilateral cryptorchidism. The joint analysis of the distribution of CAG and GGN alleles showed that the CAG26 allele was present with GGN23, hence the combination CAG26/GGN23 alleles was equally increased in bilateral cases compared with controls (11.5% vs. 1.4%). In contrast, CAG < 18 was preferably observed in the combination CAG < 18/GGN≠23 and was absent in the total cases (4.3% vs. 0%; p = 0.037). DISCUSSION: These results suggest that greater lengths of CAG alleles may contribute to a diminished androgen receptor function. The CAG26 allele alone or in combination with GGN23 was associated with a higher risk of bilateral cryptorchidism. On the other hand, CAG < 18 and the CAG < 18/GGN≠23 allele combination may reduce the probability of cryptorchidism.
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Criptorquidismo , Neoplasias Testiculares , Niño , Humanos , Masculino , Chile , Criptorquidismo/genética , Receptores Androgénicos/genética , Neoplasias Testiculares/genética , Repeticiones de TrinucleótidosRESUMEN
BACKGROUND: Drug hypersensitivity reactions (DHRs) to platinum-based drugs are heterogenous and restrict their access, and drug desensitization (DD) has provided a ground-breaking procedure for their re-introduction, although the response is heterogeneous. We aimed to identify the phenotypes, endotypes, and biomarkers of reactions to carboplatin and oxaliplatin and their response to DD. METHODS: Seventy-nine patients presenting with DHRs to oxaliplatin (N = 46) and carboplatin (N = 33) were evaluated at the Allergy Departments of two tertiary care hospitals in Spain. Patient symptoms, skin testing, biomarkers, and outcomes of 267 DDs were retrospectively analyzed. RESULTS: Oxaliplatin-reactive patients presented with type I (74%), cytokine release reaction (CRR) (11%), and mixed (Mx) (15%) phenotypes. In contrast, carboplatin reactive patients presented with predominantly type I (85%) and Mx (15%) but no CRRs. Out of 267 DDs, breakthrough reactions (BTRs) to oxaliplatin occurred twice as frequently as carboplatin (32% vs. 15%; p < .05). Phenotype switching from type I to another phenotype was observed in 46% of oxaliplatin DDs compared to 21% of carboplatin DDs. Tryptase was elevated in type I and Mx reactions, and IL-6 in CRR and Mx, indicating different mechanisms and endotypes. CONCLUSION: Carboplatin and oxaliplatin induced three different types of reactions with defined phenotypes and endotypes amendable to DD. Although most of the initial reactions for both were type I, oxaliplatin presented with unique CRR reactions. During DD, carboplatin reactive patients presented mostly type I BTR, while oxaliplatin-reactive patients frequently switched from type I to CRR, providing a critical difference and the need for personalized DD protocols.