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1.
Int J Cancer ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38728107

RESUMEN

The COVID-19 pandemic was associated with a profound decline in cancer diagnoses in 2020 in Belgium. Disruption in diagnostic and screening services and patient reluctance to visit health facilities led to fewer new cases and concerns that cancers may be diagnosed at more advanced stages and hence have poorer prognosis. Using data from mandatory cancer registration covering all of Belgium, we predicted cancer incidence, stage distribution and 1-year relative survival for 2020 using a Poisson count model over the preceding years, extrapolated to 2020 for 11 common cancer types. We compared these expected values to the observed values in 2020 to specifically quantify the impact of the COVID-19 pandemic, accounting for background trends. A significantly lower incidence was observed for cervical, prostate, head and neck, colorectal, bladder and breast cancer, with limited or no recovery of diagnoses in the second half of 2020 for these cancer types. Changes in stage distribution were observed for cervical, prostate, bladder and ovarian and fallopian tube tumours. Generally, changes in stage distribution mainly represented decline in early-stage than in late-stage tumours. One-year relative survival was lower than predicted for lung cancer and colorectal cancer. Stage shifts are hypothesised to result from alterations in access to diagnosis, potentially due to prioritisation of symptomatic patients, and patient reluctance to contact a physician. Since there were over 5000 fewer cancer diagnoses than expected by the end of 2020, it is critical to monitor incidence, stage distribution and survival for these cancers in the coming years.

2.
JBJS Case Connect ; 14(2)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38728526

RESUMEN

CASE: A 58-year-old woman with medical history of a left total hip arthroplasty performed by the direct anterior (DA) approach 2 years prior presented with left hip pain. She was found to have sustained a transverse Vancouver C periprosthetic femur fracture and an unstable periprosthetic pelvic fracture. CONCLUSIONS: This patient's case represents a previously not reported injury about a total hip arthroplasty-with disruption distal to the femoral implant and proximal to the acetabular implant, with the implant-to-bone interface unaffected. This case may guide future treatment of similar injuries.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Fracturas Periprotésicas , Humanos , Femenino , Artroplastia de Reemplazo de Cadera/efectos adversos , Persona de Mediana Edad , Fracturas Periprotésicas/cirugía , Fracturas Periprotésicas/etiología , Fracturas Periprotésicas/diagnóstico por imagen , Fracturas del Fémur/cirugía , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/etiología
3.
Nat Commun ; 15(1): 3968, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38729925

RESUMEN

Understanding complex reaction systems is critical in chemistry. While synthetic methods for selective formation of products are sought after, oftentimes it is the full reaction signature, i.e., complete profile of products/side-products, that informs mechanistic rationale and accelerates discovery chemistry. Here, we report a methodology using high-throughput experimentation and multivariate data analysis to examine the full signature of one of the most complicated chemical reactions catalyzed by palladium known in the chemical literature. A model Pd-catalyzed reaction was selected involving functionalization of 2-bromo-N-phenylbenzamide and multiple bond activation pathways. Principal component analysis, correspondence analysis and heatmaps with hierarchical clustering reveal the factors contributing to the variance in product distributions and show associations between solvents and reaction products. Using robust data from experiments performed with eight solvents, for four different reaction times at five different temperatures, we correlate side-products to a major dominant N-phenyl phenanthridinone product, and many other side products.

4.
J Thromb Haemost ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38729576

RESUMEN

BACKGROUND: No study has investigated the perioperative management and clinical outcomes in patients who are receiving rivaroxaban 2.5 mg bid and ASA 81-100 mg daily. METHODS: Sub-analysis of the COMPASS trial to assess perioperative management and clinical outcomes in patients with stable coronary or peripheral artery disease who were randomized to receive rivaroxaban 2.5 mg bid plus ASA 100 mg daily, rivaroxaban 5 mg bid, or ASA 100 mg daily. Patients studied required a surgery/procedure during the trial. The study outcomes, which included myocardial infarction, angina, stroke, acute limb ischemia, bleeding, and death, were assessed according to treatment allocation. RESULTS: There were 2,632 patients studied (mean age, 68 years; 80% male) who had a surgery/procedure, comprising percutaneous coronary interventions (∼43%), carotid or other arterial angioplasty (∼15%), pacemaker or internal cardiac defibrillator implantation (∼9%), and coronary artery bypass graft surgery (∼7%). Perioperative study drug management varied, with about one-third of patients not interrupting study drug and the remainder interrupting it between 1 and ≥10 days pre-procedure. The incidences of adverse outcomes across treatment groups were 12.7% to 15.3% for myocardial ischemia, 0.8% to 1.2% for stroke, 0.1% to 0.2% for venous thromboembolism, and 3.1% to 4.2% for any bleeding. There was no statistically significant difference in outcome rates across treatment groups. CONCLUSION: In patients in the COMPASS trial who required a surgery/procedure, there was no significant difference in perioperative adverse outcomes whether patients were receiving rivaroxaban 2.5 mg bid and ASA 100 mg daily, rivaroxaban 5 mg bid or ASA alone.

5.
Food Res Int ; 186: 114313, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38729689

RESUMEN

Exploring the contribution of common microorganisms to spoilage is of great significance in inhibiting spoilage in lamb. This work investigated the extent of protein degradation and profile changes of free amino acids (FAAs), free fatty acids (FFAs) and volatile organic compounds (VOCs) in lamb caused by single- and co-culture of the common aerobic spoilage bacteria, P. paralactis, Ac. MN21 and S. maltophilia. Meanwhile, some key VOCs produced by the three bacteria during lamb spoilage were also screened by orthogonal partial least square discriminant analysis and difference value in VOCs content between inoculated groups and sterile group. Lamb inoculated with P. paralactis had the higher total viable counts, pH, total volatile base nitrogen and TCA-soluble peptides than those with the other two bacteria. Some FAAs and FFAs could be uniquely degraded by P. paralactis but not Ac. MN21 and S. maltophilia, such as Arg, Glu, C15:0, C18:0 and C18:1n9t. Co-culture of the three bacteria significantly promoted the overall spoilage, including bacterial growth, proteolysis and lipolysis. Key VOCs produced by P. paralactis were 2, 3-octanedione, those by Ac. MN21 were 1-octanol, octanal, hexanoic acid, 1-pentanol and hexanoic acid methyl ester, and that by S. maltophilia were hexanoic acid. The production of extensive key-VOCs was significantly and negatively correlated with C20:0, C23:0 and C18:ln9t degradation. This study can provide a basis for inhibiting common spoilage bacteria and promoting high-quality processing of fresh lamb.


Asunto(s)
Acinetobacter , Técnicas de Cocultivo , Microbiología de Alimentos , Pseudomonas , Carne Roja , Stenotrophomonas maltophilia , Compuestos Orgánicos Volátiles , Animales , Compuestos Orgánicos Volátiles/análisis , Compuestos Orgánicos Volátiles/metabolismo , Pseudomonas/metabolismo , Pseudomonas/crecimiento & desarrollo , Acinetobacter/crecimiento & desarrollo , Acinetobacter/metabolismo , Stenotrophomonas maltophilia/crecimiento & desarrollo , Stenotrophomonas maltophilia/metabolismo , Carne Roja/microbiología , Carne Roja/análisis , Ovinos , Almacenamiento de Alimentos , Frío , Ácidos Grasos no Esterificados/metabolismo , Ácidos Grasos no Esterificados/análisis , Aminoácidos/metabolismo , Aminoácidos/análisis , Oveja Doméstica/microbiología , Proteolisis
7.
J Voice ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38734523

RESUMEN

OBJECTIVES: Patients recently diagnosed with a new medical condition frequently search the internet to learn about their diagnosis. We aimed to identify specific questions people ask regarding common laryngological diagnoses by evaluating "People Also Ask" (PAA) questions generated by Google, search volume of these diagnoses, and to determine if the sources accessed were credible. STUDY DESIGN: Descriptive study. METHODS: The terms "subglottic stenosis" (SS), "Zenker's diverticulum" (ZD), "vocal fold paralysis" (VFP), and related terms were entered into Google. PAA questions and associated websites were then extracted using Ahrefs software. Questions were categorized into specific topics. Websites were categorized by type and then assessed using the Journal of the American Medical Association (JAMA) benchmark criteria. A search engine optimization tool was used to determine search volume for individual topics. RESULTS: One hundred and forty-four PAA questions (SS n = 52, ZD n = 49, and VFP n = 43) and their associated websites were extracted. Inquiries were most related to disease etiology (34%), management (27.1%), and signs/symptoms (16.7%). Sources most commonly linked to PAA questions were academic (37.6%), government (25.6%), and commercial (16.2%) websites, while medical practice (7.69%), single surgeon (3.42%), and social media (9.40%) websites were less frequently referenced. JAMA scores were highest for government websites (mean 3.35, standard deviation = 0.54) and lowest for academic websites (mean 0.77, standard deviation = 0.14). CONCLUSIONS: The most asked questions regarding SS, ZD, and VFP are related to etiology and management. Academic medical institution websites are most frequently viewed to answer these questions. Therefore, academic laryngological professionals should ensure the information on their websites is current and accurate.

8.
Influenza Other Respir Viruses ; 18(5): e13299, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38700006

RESUMEN

INTRODUCTION: Traditional surveillance systems may underestimate the burden caused by respiratory syncytial virus (RSV). Capture-recapture methods provide alternatives for estimating the number of RSV-related hospitalizations in a population. METHODS: Capture-recapture methods were used to estimate the number of RSV-related hospitalizations in adults in Middle Tennessee from two independent hospitalization surveillance systems during consecutive respiratory seasons from 2016-2017 to 2019-2020. Data from the Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) and the Emerging Infections Program (EIP) were used. Annual RSV hospitalization rates were calculated using the capture-recapture estimates weighted by hospitals' market share divided by the corresponding census population. RESULTS: Using capture-recapture methods, the estimated overall adult hospitalization rates varied from 8.3 (95% CI: 5.9-15.4) RSV-related hospitalizations per 10,000 persons during the 2016-2017 season to 28.4 (95% CI: 18.2-59.0) hospitalizations per 10,000 persons in the 2019-2020 season. The proportion of hospitalizations that HAIVEN determined ranged from 8.7% to 36.7% of the total capture-recapture estimated hospitalization, whereas EIP detected 23.5% to 52.7% of the total capture-recapture estimated hospitalizations. CONCLUSION: Capture-recapture estimates showed that individual traditional surveillance systems underestimated the hospitalization burden in adults. Using capture-recapture allows for a more comprehensive estimate of RSV hospitalizations.


Asunto(s)
Hospitalización , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Humanos , Infecciones por Virus Sincitial Respiratorio/epidemiología , Hospitalización/estadística & datos numéricos , Adulto , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Persona de Mediana Edad , Tennessee/epidemiología , Adulto Joven , Anciano , Masculino , Femenino , Adolescente , Estaciones del Año , Costo de Enfermedad
10.
Cancer Cell ; 42(5): 833-849.e12, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38701792

RESUMEN

Glucocorticoids have been used for decades to treat lymphomas without an established mechanism of action. Using functional genomic, proteomic, and chemical screens, we discover that glucocorticoids inhibit oncogenic signaling by the B cell receptor (BCR), a recurrent feature of aggressive B cell malignancies, including diffuse large B cell lymphoma and Burkitt lymphoma. Glucocorticoids induce the glucocorticoid receptor (GR) to directly transactivate genes encoding negative regulators of BCR stability (LAPTM5; KLHL14) and the PI3 kinase pathway (INPP5D; DDIT4). GR directly represses transcription of CSK, a kinase that limits the activity of BCR-proximal Src-family kinases. CSK inhibition attenuates the constitutive BCR signaling of lymphomas by hyperactivating Src-family kinases, triggering their ubiquitination and degradation. With the knowledge that glucocorticoids disable oncogenic BCR signaling, they can now be deployed rationally to treat BCR-dependent aggressive lymphomas and used to construct mechanistically sound combination regimens with inhibitors of BTK, PI3 kinase, BCL2, and CSK.


Asunto(s)
Glucocorticoides , Receptores de Antígenos de Linfocitos B , Humanos , Glucocorticoides/farmacología , Receptores de Antígenos de Linfocitos B/metabolismo , Animales , Transducción de Señal/efectos de los fármacos , Receptores de Glucocorticoides/metabolismo , Ratones , Línea Celular Tumoral , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/genética , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patología , Terapia Molecular Dirigida/métodos , Fosfatidilinositol 3-Quinasas/metabolismo , Familia-src Quinasas/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos
11.
Curr Sports Med Rep ; 23(5): 192-198, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38709945

RESUMEN

ABSTRACT: Sport psychology is the scientific study and application of psychological principles to enhance performance and well-being in sport, exercise, and physical activity. It has numerous applications to sports medicine, as psychological factors are associated with sport injury risk, recovery, successful return to play, and overall health. This article addresses how sport psychology is important to sports medicine and what applied sport psychologists do. We discuss several psychological principles and practices relevant to individual performance and well-being, including goal setting, communication, arousal and performance, imagery/mental rehearsal, attention management, managing psychological distress, and behavioral health. We also discuss principles and practices of sport psychology relevant to team performance, including stages of team development, goal setting, communication, arousal and performance, and behavioral health. Sport psychology and applied sport psychology practitioners can be valued assets to sports medicine teams in supporting individual and team performance and injury recovery.


Asunto(s)
Traumatismos en Atletas , Psicología del Deporte , Medicina Deportiva , Humanos , Traumatismos en Atletas/terapia , Traumatismos en Atletas/psicología , Rendimiento Atlético/psicología , Objetivos , Comunicación , Nivel de Alerta , Atención , Volver al Deporte
12.
Ann Otol Rhinol Laryngol ; : 34894241249547, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38712740

RESUMEN

OBJECTIVE: to investigate the ability of mandibular distraction osteogenesis (MDO) to avoid gastrostomy tube (G-tube). DATA SOURCES: PubMed, EBSCOhost, Cochrane, and Embase. REVIEW METHODS: We retrospectively reviewed the number of MDO cases performed at our institution for patients with Robin Sequence (RS) over the past 10 years. In our institutional review, patients were excluded if they had a G-tube already placed at the time of surgery. We also performed a systematic review of the literature. Articles were excluded if they did not detail feeding outcomes after MDO, or if MDO was performed on patients that did not have RS. RESULTS: In our systematic review, 12 articles were included that comprised a total of 209 neonates with RS that underwent MDO. A total of 174 (83.3%) patients avoided a G-tube once MDO was performed. A total of 14 patients met the inclusion criteria at our institution. Of the 14 RS patients, 9 (64%) avoided having a G-tube placed and all (14/14) avoided tracheostomy. The average birth weight of patients avoiding a G-tube was 3.11 kg compared to 2.25 kg (P = .045) in the group requiring a G-tube. In the group avoiding a G-tube, the average weight at time of operation was 3.46 kg compared to 2.83 kg (P = .037) in the group requiring a G-tube. CONCLUSION: MDO may be considered as a surgical option to prevent G-tube placement for neonates with non-syndromic RS who have difficulty with PO feeding but whose airway obstruction is not severe enough to require respiratory support. Based on our institutional experience, a minimum weight of 3.00 kg correlated with higher success rates of PO intake and avoiding a G-tube.

13.
Cureus ; 16(4): e57843, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38721181

RESUMEN

The meniscus of the knee serves as a crucial load-bearing structure, and its damage can significantly impact weight distribution. In addressing focal meniscal defects, segmental meniscal allograft transplantation (SMALT) emerges as an innovative solution. Here, we detail a case involving a young, active female who underwent SMALT augmented with osteochondral allograft transplantation (OCA) and bone marrow aspirate concentration (BMAC). The patient, a 40-year-old former Division I volleyball player, previously underwent arthroscopic procedures and presented with knee pain alongside complex lateral meniscus tear evident in magnetic resonance imaging (MRI) findings. Initial arthroscopy revealed multiple tears, including segmental deficiency at the posterior horn-body junction and a horizontal cleavage tear. Despite failed attempts at repair due to the meniscal gap, a second-stage lateral SMALT was performed, with the allograft soaked in the patient's BMAC, supplemented with OCA to the lateral femoral condyle. Rehabilitation protocols tailored to both SMALT and OCA were implemented. This represents the first documented instance of lateral SMALT, extending the scope of viable solutions for segmental meniscal deficiencies, and marking a significant milestone in orthopedic practice.

14.
J Pediatr Genet ; 13(2): 139-143, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38721582

RESUMEN

Townes-Brocks syndrome (TBS) is a rare syndrome characterized by triad of anal, ear, and thumb anomalies. Further malformations/anomalies include congenital heart diseases, foot malformations, sensorineural and/or conductive hearing impairment, genitourinary malformations, and anomalies of eye and nervous system. Definitive diagnosis for TBS is confirmed by molecular analysis for mutations in the SALL1 gene. Only one known case of TBS with absent pulmonary valve syndrome (APVS) has been previously described to our knowledge. Here, we report a newborn diagnosed with TBS with APVS and tetralogy of Fallot (TOF) who was found to carry the most common pathogenic SALL1 gene mutation c.826C > T (p.R276X), with its surgical repair and postoperative follow-up. To our knowledge, this is the first genotyped case of TBS from Turkey to date. TBS should be suspected in the presence of ear, anal, and thumb malformations in a neonate. If a patient with TBS and TOF-APVS needs preoperative ventilation within the first months of life, this implies prolonged postoperative intubation and increased risk of mortality.

15.
Am J Hum Genet ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38723632

RESUMEN

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10-8) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10-5). Fine mapping identified 4,008 CCVs in these regions, of which 1,452 CCVs were located in ovarian cancer-related chromatin marks with significant enrichment in active enhancers, active promoters, and active regions for CCVs from each EOC histotype. Transcriptome-wide association and colocalization analyses across histotypes using tissue-specific and cross-tissue datasets identified 86 candidate susceptibility genes in known EOC risk regions and 32 genes in 23 additional genomic regions that may represent novel EOC risk loci (false discovery rate <0.05). Finally, by integrating genome-wide HiChIP interactome analysis with transcriptome-wide association study (TWAS), variant effect predictor, transcription factor ChIP-seq, and motifbreakR data, we identified candidate gene-CCV interactions at each locus. This included risk loci where TWAS identified one or more candidate susceptibility genes (e.g., HOXD-AS2, HOXD8, and HOXD3 at 2q31) and other loci where no candidate gene was identified (e.g., MYC and PVT1 at 8q24) by TWAS. In summary, this study describes a functional framework and provides a greater understanding of the biological significance of risk alleles and candidate gene targets at EOC susceptibility loci identified by a genome-wide association study.

16.
Acta Neuropathol ; 147(1): 80, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714540

RESUMEN

GABAergic interneurons play a critical role in maintaining neural circuit balance, excitation-inhibition regulation, and cognitive function modulation. In tuberous sclerosis complex (TSC), GABAergic neuron dysfunction contributes to disrupted network activity and associated neurological symptoms, assumingly in a cell type-specific manner. This GABAergic centric study focuses on identifying specific interneuron subpopulations within TSC, emphasizing the unique characteristics of medial ganglionic eminence (MGE)- and caudal ganglionic eminence (CGE)-derived interneurons. Using single-nuclei RNA sequencing in TSC patient material, we identify somatostatin-expressing (SST+) interneurons as a unique and immature subpopulation in TSC. The disrupted maturation of SST+ interneurons may undergo an incomplete switch from excitatory to inhibitory GABAergic signaling during development, resulting in reduced inhibitory properties. Notably, this study reveals markers of immaturity specifically in SST+ interneurons, including an abnormal NKCC1/KCC2 ratio, indicating an imbalance in chloride homeostasis crucial for the postsynaptic consequences of GABAergic signaling as well as the downregulation of GABAA receptor subunits, GABRA1, and upregulation of GABRA2. Further exploration of SST+ interneurons revealed altered localization patterns of SST+ interneurons in TSC brain tissue, concentrated in deeper cortical layers, possibly linked to cortical dyslamination. In the epilepsy context, our research underscores the diverse cell type-specific roles of GABAergic interneurons in shaping seizures, advocating for precise therapeutic considerations. Moreover, this study illuminates the potential contribution of SST+ interneurons to TSC pathophysiology, offering insights for targeted therapeutic interventions.


Asunto(s)
Neuronas GABAérgicas , Interneuronas , Esclerosis Tuberosa , Interneuronas/patología , Interneuronas/metabolismo , Esclerosis Tuberosa/patología , Esclerosis Tuberosa/metabolismo , Humanos , Neuronas GABAérgicas/patología , Neuronas GABAérgicas/metabolismo , Masculino , Femenino , Eminencia Media/patología , Eminencia Media/metabolismo , Somatostatina/metabolismo , Niño , Preescolar , Receptores de GABA-A/metabolismo , Adolescente , Eminencia Ganglionar
17.
Vaccine ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38714447

RESUMEN

This study examined short-to-medium term safety of COVID-19 vaccines among adults aged ≥65 years using the Canadian National Vaccine Safety Network active safety surveillance data. Both vaccinated and unvaccinated older adult participants recruited from seven provinces and territories were included in the analysis. Safety was assessed at 7 days after COVID-19 vaccination (dose 1, 2 and 3), and 7 months after dose 1. Multivariable logistic regression was used to examine the association between BNT162b2/mRNA-1273 COVID-19 vaccines and two short-term health events: 1) health event preventing daily activities and/or required medical consultation, 2) serious health events resulting in an emergency department visit and/or hospitalization within 7 days following each dose. We also assessed the rates of serious health events for the period between dose 1 and 2, and 7-months following dose 1. Between December 2020 and February 2022, a total of 173,038, 104,452, and 13,970 older adults completed dose 1, dose 2, and dose 3 surveys, respectively. The control survey was completed by 2,955 unvaccinated older adults. Health events occurred more frequently among recipients after dose 2 homologous mRNA-1273 (adjusted odds ratio [95 % confidence interval]: 2.91 [2.24-3.79]) and dose two heterologous (BNT162b2 followed by mRNA-1273): 1.50 [1.12-2.02] compared to unvaccinated counterparts. There was no difference in event rates after any dose of BNT162b2 and unvaccinated participants. The rates of serious health events following COVID-19 vaccination were very low (≤0.3 %) across all vaccine products and doses, and were not higher compared to unvaccinated controls, and were not associated with an emergency department visit or hospitalization within 7 days following vaccination. Reported symptoms were self-limited and rarely required medical assessment. Our findings further strengthen the current evidence that mRNA COVID-19 vaccines are safe and can be used to inform older adults about expected adverse events following COVID-19 vaccination.

18.
Artículo en Inglés | MEDLINE | ID: mdl-38717347

RESUMEN

RATIONALE: Bronchiectasis is characterised by acute exacerbations but the biological mechanisms underlying these events is poorly characterised. Objectives To investigate the inflammatory and microbial characteristics of exacerbations of bronchiectasis. METHODS: 120 patients with bronchiectasis were enrolled and presented with acute exacerbations within 12 months. Spontaneous sputum samples were obtained during a period of clinical stability and again at exacerbation prior to receipt of antibiotic treatment. A validated rapid PCR assay for bacteria and viruses was used to classify exacerbations as bacterial, viral or both. Sputum inflammatory assessments included label free Liquid chromography/mass spectrometry and measurement of sputum cytokines and neutrophil elastase activity. 16s rRNA sequencing was used to characterise the microbiome. MEASUREMENTS AND MAIN RESULTS: Bronchiectasis exacerbations showed profound molecular heterogeneity. At least one bacteria was identified in 103 samples (86%) and a high bacterial load (total bacterial load >10(7) copies/g) was observed in 81 patients (68%). Respiratory viruses were identified in 55 (46%) patients with rhinovirus being the most common virus (31%). PCR was more sensitive than culture. No consistent change in the microbiome was observed at exacerbation. Exacerbations were associated with increased neutrophil elastase, proteinase-3, Il-1beta and CXCL8. There markers were particularly associated with bacterial and bacterial+viral exacerbations. Distinct inflammatory and microbiome profiles were seen between different exacerbation subtypes, including bacterial, viral and eosinophilic events in both hypothesis led, and hypothesis-free analysis using integrated microbiome and proteomics, demonstrating 4 subtypes of exacerbation. CONCLUSION: Bronchiectasis exacerbations are heterogeneous events with contributions from bacteria, viruses and inflammatory dysregulation.

19.
Hip Int ; : 11207000241249673, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38700947

RESUMEN

The optimal fixation method in total hip arthroplasty (THA) remains controversial. Initial concerns related to the long-term performance of cement fixation as well as cement disease led to the development of cementless implants, and registry data has indicated that the use of this type of fixation has increased in recent years. However, data from these same registries has not shown any improvement in outcomes when compared to cement fixation. On the contrary, while similar outcomes are seen when comparing these fixation types in younger patients (<70 years of age), cementless fixation has shown increased implant failure and revision rates in elderly patients (>70 years of age). Given the increased projected volume of THA in the United States over the next decade, it is important to utilise available data to make clinical decisions that minimise not only individual patient harm, but also the burden on the healthcare system itself. This review provides an overview of currently available outcomes data comparing cement and cementless fixation, as well as an updated analysis of current trends in fixation use in THA. We furthermore provide a comprehensive technique guide to help surgeons optimise cement fixation of the femoral component for THA and hemiarthroplasty.

20.
Inorg Chem ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38701516

RESUMEN

Photochemical ligand release from metal complexes may be exploited in the development of novel photoactivated chemotherapy agents for the treatment of cancer and other diseases. Highly intriguing photochemical behavior is reported for two ruthenium(II) complexes bearing conformationally flexible 1,2,3-triazole-based ligands incorporating a methylene spacer to form 6-membered chelate rings. [Ru(bpy)2(pictz)]2+ (1) and [Ru(bpy)2(btzm)]2+ (2) (bpy = 2,2'-bipyridyl; pictz = 1-(picolyl)-4-phenyl-1,2,3-triazole; btzm = bis(4-phenyl-1,2,3-triazol-4-yl)methane) exhibit coordination by the triazole ring through the less basic N2 atom as a consequence of chelation and readily undergo photochemical release of the pictz and btzm ligands (ϕ = 0.079 and 0.091, respectively) in acetonitrile solution to form cis-[Ru(bpy)2(NCMe)2]2+ (3) in both cases. Ligand-loss intermediates of the form [Ru(bpy)2(κ1-pictz or κ1-btzm)(NCCD3)]2+ are detected by 1H NMR spectroscopy and mass spectrometry. Photolysis of 1 yields three ligand-loss intermediates with monodentate pictz ligands, two of which form through simple decoordination of either the pyridine or triazole donor with subsequent solvent coordination (4-tz(N2) and 4-py, respectively). The third intermediate, shown to be able to form photochemically directly from 1, arises through linkage isomerism in which the monodentate pictz ligand is coordinated by the triazole N3 atom (4-tz(N3)) with a comparable ligand-loss intermediate with an N3-bound κ1-btzm ligand also observed for 2.

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