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1.
ASAIO J ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38753559

RESUMEN

Nosocomial infections and thrombosis are frequent complications during extracorporeal membrane oxygenation (ECMO). Preventative measures and close monitoring for early recognition of these complications are imperative in patients supported with ECMO. We report the case of a 41 year old female on veno-venous ECMO awaiting surgical thrombectomy for chronic thromboembolic pulmonary hypertension that developed profound bacteremia leading to gross purulence and thrombosis of the membrane oxygenator. Recannulation in addition to targeted antibiotics, frequent cultures, imaging, and surgery were diagnostic and therapeutic interventions that led to ultimate resolution.

2.
Sci Rep ; 14(1): 10172, 2024 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702411

RESUMEN

The intricate hormonal and physiological changes of the menstrual cycle can influence health on a daily basis. Although prior studies have helped improve our understanding of the menstrual cycle, they often lack diversity in the populations included, sample size, and the span of reproductive and life stages. This paper aims to describe the dynamic differences in menstrual cycle characteristics and associated symptoms by age in a large global cohort of period-tracking application users. This work aims to contribute to our knowledge and understanding of female physiology at varying stages of reproductive aging. This cohort study included self-reported menstrual cycle and symptom information in a sample of Flo application users aged 18-55. Cycle and period length and their variability, and frequency of menstrual cycle symptom logs are described by the age of the user. Based on data logged by over 19 million global users of the Flo app, the length of the menstrual cycle and period show clear age-associated patterns. With higher age, cycles tend to get shorter (Cycle length: D ¯ = 1.85 days, Cohen's D = 0.59) and more variable (Cycle length SD: D ¯ = 0.42 days, Cohen's D = 0.09), until close to the chronological age (40-44) suggesting menopausal transition, when both cycles and periods become longer (Cycle length: D ¯ = 0.86 days, t = 48.85, Cohen's D = 0.26; Period length: D ¯ = 0.08, t = 15.6, Cohen's D = 0.07) and more variable (Cycle length SD: D ¯ = 2.80 days, t = 111.43, d = 0.51; Period length SD: D ¯ = 0.23 days, t = 67.81, Cohen's D = 0.31). The proportion of individuals with irregular cycles was highest in participants aged 51-55 (44.7%), and lowest in the 36-40 age group (28.3%). The spectrum of common menstrual cycle-related symptoms also varies with age. The frequency of logging of cramps and acne is lower in older participants, while logs of headache, backache, stress, and insomnia are higher in older users. Other symptoms show different patterns, such as breast tenderness and fatigue peaking between the ages of 20-40, or mood swings being most frequently logged in the youngest and oldest users. The menstrual cycle and related symptoms are not static throughout the lifespan. Understanding these age-related differences in cycle characteristics and symptoms is essential in understanding how best to care for and improve the daily experience for menstruators across the reproductive life span.


Asunto(s)
Ciclo Menstrual , Humanos , Femenino , Ciclo Menstrual/fisiología , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Estudios de Cohortes , Reproducción/fisiología , Autoinforme , Factores de Edad , Envejecimiento/fisiología
3.
PLoS One ; 19(5): e0302778, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38713687

RESUMEN

INTRODUCTION: Magnetic resonance-guided focused ultrasound (MRgFUS) has been demonstrated to be able to thermally ablate tendons with the aim to non-invasively disrupt tendon contractures in the clinical setting. However, the biomechanical changes of tendons permitting this disrupting is poorly understood. We aim to obtain a dose-dependent biomechanical response of tendons following magnetic resonance-guided focused ultrasound (MRgFUS) thermal ablation. METHODS: Ex vivo porcine tendons (n = 72) were embedded in an agar phantom and randomly assigned to 12 groups based on MRgFUS treatment. The treatment time was 10, 20, or 30s, and the applied acoustic power was 25, 50, 75, or 100W. Following each MRgFUS treatment, tendons underwent biomechanical tensile testing on an Instron machine, which calculated stress-strain curves during tendon elongation. Rupture rate, maximum treatment temperature, Young's modulus and ultimate strength were analyzed for each treatment energy. RESULTS: The study revealed a dose-dependent response, with tendons rupturing in over 50% of cases when energy delivery exceeded 1000J and 100% disruption at energy levels beyond 2000J. The achieved temperatures during MRgFUS were directly proportional to energy delivery. The highest recorded temperature was 56.8°C ± 9.34 (3000J), while the lowest recorded temperate was 18.6°C ± 0.6 (control). The Young's modulus was highest in the control group (47.3 MPa ± 6.5) and lowest in the 3000J group (13.2 MPa ± 5.9). There was no statistically significant difference in ultimate strength between treatment groups. CONCLUSION: This study establishes crucial thresholds for reliable and repeatable disruption of tendons, laying the groundwork for future in vivo optimization. The findings prompt further exploration of MRgFUS as a non-invasive modality for tendon disruption, offering hope for improved outcomes in patients with musculotendinous contractures.


Asunto(s)
Ultrasonido Enfocado de Alta Intensidad de Ablación , Tendones , Animales , Porcinos , Tendones/cirugía , Tendones/fisiología , Tendones/diagnóstico por imagen , Fenómenos Biomecánicos , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Imagen por Resonancia Magnética/métodos , Resistencia a la Tracción , Módulo de Elasticidad
4.
Crit Care Res Pract ; 2024: 9102961, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38716052

RESUMEN

Background: A noninvasive and accurate method of identifying fluid responsiveness in hemodynamically unstable patients has long been sought by physicians. Carotid ultrasound (US) is one such modality previously canvassed for this purpose. The aim of this novel systematic review and meta-analysis is to investigate whether critically unwell patients who are requiring intravenous (IV) fluid resuscitation (fluid responders) can be identified accurately with carotid US. Methods: The protocol was registered with PROSPERO on the 30/11/2022 (ID number: CRD42022380284). Studies investigating carotid ultrasound accuracy in assessing fluid responsiveness in hemodynamically unstable patients were included. Studies were identified through searches of six databases, all run on 4 November 2022, Medline, Embase, Emcare, APA PsycInfo, CINAHL, and Cochrane Library. Risk of bias was assessed using the QUADAS-2 and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines. Results were pooled, meta-analysis was conducted where amenable, and hierarchical summary receiver operating characteristic models were established to compare carotid ultrasound measures. Results: Seventeen studies were included (n = 842), with 1048 fluid challenges. 441 (42.1%) were fluid responsive. Four different carotid US measures were investigated, including change in carotid doppler peak velocity (∆CDPV), carotid blood flow (CBF), change in carotid artery velocity time integral (∆CAVTI), and carotid flow time (CFT). Pooled carotid US had a pooled sensitivity, specificity, and AUROC with 95% confidence intervals (CI) of 0.73 (0.66-0.78), 0.82 (0.72-0.90), and 0.81 (0.78-0.85), respectively. ∆CDPV had sensitivity, specificity, and AUROC with 95% CI of 0.72 (0.64-0.80), 0.87 (0.73-0.94), and 0.82 (0.78-0.85), respectively. CBF had sensitivity, specificity, and AUROC with 95% CI of 0.70 (0.56-0.80), 0.80 (0.50-0.94), and 0.77 (0.78-0.85), respectively. Risk of bias and assessment was undertaken using the QUADAS-2 and GRADE tools. The QUADAS-2 found that studies generally had an unclear or high risk of bias but with low applicability concerns. The GRADE assessment showed that ∆CDPV and CBF had low accuracy for sensitivity and specificity. Conclusion: It appears that carotid US has a limited ability to predict fluid responsiveness in critically unwell patients. ∆CDPV demonstrates the greatest accuracy of all measures analyzed. Further high-quality studies using consistent study design would help confirm this.

5.
Int J Hyperthermia ; 41(1): 2350759, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38719202

RESUMEN

INTRODUCTION: Magnetic Resonance-guided Focused Ultrasound (MRgFUS) thermal ablation is an effective noninvasive ultrasonic therapy to disrupt in vivo porcine tendon but is prone to inducing skin burns. We evaluated the safety profile of a novel hybrid protocol that minimizes thermal spread by combining long-pulse focused ultrasound followed by thermal ablation. METHODS: In-vivo Achilles tendons (hybrid N = 15, thermal ablation alone N = 21) from 15 to 20 kg Yorkshire pigs were randomly assigned to 6 treatment groups in two studies. The first (N = 21) was ablation (600, 900, or 1200 J). The second (N = 15) was hybrid: pulsed FUS (13.5 MPa peak negative pressure) followed by ablation (600, 900, or 1200 J). Measurements of ankle range of motion, tendon temperature, thermal dose (240 CEM43), and assessment of skin burn were performed in both groups. RESULTS: Rupture was comparable between the two protocols: 1/5 (20%), 5/5 (100%) and 5/5 (100%) for hybrid protocol, compared to 2/7 (29%), 6/7 (86%) and 7/7 (100%) for the ablation-only protocol with energies of 600, 900, and 1200 J, respectively. The hybrid protocol produced lower maximum temperatures, smaller areas of thermal dose, fewer thermal injuries to the skin, and fewer full-thickness skin burns. The standard deviation for the area of thermal injury was also smaller for the hybrid protocol, suggesting greater predictability. CONCLUSION: This study demonstrated a hybrid MRgFUS protocol combining long-pulse FUS followed by thermal ablation to be noninferior and safer than an ablation-only protocol for extracorporeal in-vivo tendon rupture for future clinical application for noninvasive release of contracted tendon.


Asunto(s)
Imagen por Resonancia Magnética , Animales , Porcinos , Imagen por Resonancia Magnética/métodos , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Tendones/diagnóstico por imagen , Terapia por Ultrasonido/métodos
6.
Front Neuroimaging ; 3: 1356713, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38783990

RESUMEN

Purpose: To test the ability of inversion-recovery ultrashort echo time (IR-UTE) MRI to directly detect demyelination in mice using a standard cuprizone mouse model. Methods: Non-aqueous myelin protons have ultrashort T2s and are "invisible" with conventional MRI sequences but can be detected with UTE sequences. The IR-UTE sequence uses an adiabatic inversion-recovery preparation to suppress the long T2 water signal so that the remaining signal is from the ultrashort T2 myelin component. In this study, eight 8-week-old C57BL/6 mice were fed cuprizone (n = 4) or control chow (n = 4) for 5 weeks and then imaged by 3D IR-UTE MRI. The differences in IR-UTE signal were compared in the major white matter tracts in the brain and correlated with the Luxol Fast Blue histochemical marker of myelin. Results: IR-UTE signal decreased in cuprizone-treated mice in white matter known to be sensitive to demyelination in this model, such as the corpus callosum, but not in white matter known to be resistant to demyelination, such as the internal capsule. These findings correlated with histochemical staining of myelin content. Conclusions: 3D IR-UTE MRI was sensitive to cuprizone-induced demyelination in the mouse brain, and is a promising noninvasive method for measuring brain myelin content.

7.
Br J Clin Pharmacol ; 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38784979

RESUMEN

Randomized controlled trials (RCTs) show a reduction in acute kidney injury, renal impairment and acute renal failure after initiation of a sodium glucose cotransporter-2 inhibitor. Observational literature on the association is conflicting, but important to understand for populations with a higher risk of medication-related adverse renal events. We aimed to systematically review the literature to summarize the association between sodium glucose cotransporter-2 inhibitor use and acute kidney injury, renal impairment and acute renal failure in three at-risk groups: older people aged >65 years, people with heart failure and people with reduced renal function. A systematic search of Embase (1974 until 23 February 2024) and PubMed (1946 until 23 February 2024) was performed. RCTs were included if they reported numbers of acute kidney injury or acute renal failure in people using sodium glucose cotransporter-2 inhibitors compared to other diabetic therapies. Studies needed to report results by level of renal function, heart failure status or age. Of 922 results, eight studies were included. The absolute risk of acute kidney injury or acute renal failure was higher in people >65 years compared to those <65 years, higher in people with heart failure (vs without) and higher in people with reduced kidney function (vs preserved kidney function), but insufficient evidence to determine if the relative effect of sodium glucose cotransporter-2 inhibitors on this risk was similar for each group. At-risk cohorts are associated with a higher incidence of acute kidney problems in users of sodium glucose cotransporter-2 inhibitors.

8.
bioRxiv ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38746396

RESUMEN

Cancer-associated mutations have been documented in normal tissues, but the prevalence and nature of somatic copy number alterations and their role in tumor initiation and evolution is not well understood. Here, using single cell DNA sequencing, we describe the landscape of CNAs in >42,000 breast epithelial cells from women with normal or high risk of developing breast cancer. Accumulation of individual cells with one or two of a specific subset of CNAs (e.g. 1q gain and 16q, 22q, 7q, and 10q loss) is detectable in almost all breast tissues and, in those from BRCA1 or BRCA2 mutations carriers, occurs prior to loss of heterozygosity (LOH) of the wildtype alleles. These CNAs, which are among the most common associated with ductal carcinoma in situ (DCIS) and malignant breast tumors, are enriched almost exclusively in luminal cells not basal myoepithelial cells. Allele-specific analysis of the enriched CNAs reveals that each allele was independently altered, demonstrating convergent evolution of these CNAs in an individual breast. Tissues from BRCA1 or BRCA2 mutation carriers contain a small percentage of cells with extreme aneuploidy, featuring loss of TP53 , LOH of BRCA1 or BRCA2 , and multiple breast cancer-associated CNAs in addition to one or more of the common CNAs in 1q, 10q or 16q. Notably, cells with intermediate levels of CNAs are not detected, arguing against a stepwise gradual accumulation of CNAs. Overall, our findings demonstrate that chromosomal alterations in normal breast epithelium partially mirror those of established cancer genomes and are chromosome- and cell lineage-specific.

10.
ACS Nano ; 18(19): 12477-12488, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38699877

RESUMEN

Progress in the design and synthesis of nanostructured self-assembling systems has facilitated the realization of numerous nanoscale geometries, including fibers, ribbons, and sheets. A key challenge has been achieving control across multiple length scales and creating macroscopic structures with nanoscale organization. Here, we present a facile extrusion-based fabrication method to produce anisotropic, nanofibrous hydrogels using self-assembling peptides. The application of shear force coinciding with ion-triggered gelation is used to kinetically trap supramolecular nanofibers into aligned, hierarchical macrostructures. Further, we demonstrate the ability to tune the nanostructure of macroscopic hydrogels through modulating phosphate buffer concentration during peptide self-assembly. In addition, increases in the nanostructural anisotropy of fabricated hydrogels are found to enhance their strength and stiffness under hydrated conditions. To demonstrate their utility as an extracellular matrix-mimetic biomaterial, aligned nanofibrous hydrogels are used to guide directional spreading of multiple cell types, but strikingly, increased matrix alignment is not always correlated with increased cellular alignment. Nanoscale observations reveal differences in cell-matrix interactions between variably aligned scaffolds and implicate the need for mechanical coupling for cells to understand nanofibrous alignment cues. In total, innovations in the supramolecular engineering of self-assembling peptides allow us to decouple nanostructure from macrostructure and generate a gradient of anisotropic nanofibrous hydrogels. We anticipate that control of architecture at multiple length scales will be critical for a variety of applications, including the bottom-up tissue engineering explored here.


Asunto(s)
Hidrogeles , Nanofibras , Péptidos , Nanofibras/química , Péptidos/química , Hidrogeles/química , Humanos , Materiales Biocompatibles/química , Materiales Biocompatibles/síntesis química , Anisotropía , Animales
11.
medRxiv ; 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38699333

RESUMEN

INTRODUCTION: Transcriptome-wide Association Studies (TWAS) extend genome-wide association studies (GWAS) by integrating genetically-regulated gene expression models. We performed the most powerful AD-TWAS to date, using summary statistics from cis -eQTL meta-analyses and the largest clinically-adjudicated Alzheimer's Disease (AD) GWAS. METHODS: We implemented the OTTERS TWAS pipeline, leveraging cis -eQTL data from cortical brain tissue (MetaBrain; N=2,683) and blood (eQTLGen; N=31,684) to predict gene expression, then applied these models to AD-GWAS data (Cases=21,982; Controls=44,944). RESULTS: We identified and validated five novel gene associations in cortical brain tissue ( PRKAG1 , C3orf62 , LYSMD4 , ZNF439 , SLC11A2 ) and six genes proximal to known AD-related GWAS loci (Blood: MYBPC3 ; Brain: MTCH2 , CYB561 , MADD , PSMA5 , ANXA11 ). Further, using causal eQTL fine-mapping, we generated sparse models that retained the strength of the AD-TWAS association for MTCH2 , MADD , ZNF439 , CYB561 , and MYBPC3 . DISCUSSION: Our comprehensive AD-TWAS discovered new gene associations and provided insights into the functional relevance of previously associated variants.

12.
Artículo en Inglés | MEDLINE | ID: mdl-38700375

RESUMEN

INTRODUCTION: Little research has been done on how people mentally simulate future suicidal thoughts and urges, a process we term suicidal prospection. METHODS: Participants were 94 adults with recent suicidal thoughts. Participants completed a 42-day real-time monitoring study and then a follow-up survey 28 days later. Each night, participants provided predictions for the severity of their suicidal thoughts the next day and ratings of the severity of suicidal thoughts over the past day. We measured three aspects of suicidal prospection: predicted levels of desire to kill self, urge to kill self, and intent to kill self. We generated prediction errors by subtracting participants' predictions of the severity of their suicidal thoughts from their experienced severity. RESULTS: Participants tended to overestimate (although the average magnitude was small and the modal error was zero) the severity of their future suicidal thoughts. The best fitting models suggested that participants used both their current suicidal thinking and previous predictions of their suicidal thinking to generate predictions of their future suicidal thinking. Finally, the average severity of predicted future suicidal thoughts predicted the number of days participants thought about suicide during the follow-up period. CONCLUSIONS: This study highlights prospection as a psychological process to better understand suicidal thoughts and behaviors.

13.
JMIR Mhealth Uhealth ; 12: e54124, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38696773

RESUMEN

BACKGROUND: Reproductive health literacy and menstrual health awareness play a crucial role in ensuring the health and well-being of women and people who menstruate. Further, awareness of one's own menstrual cycle patterns and associated symptoms can help individuals identify and manage conditions of the menstrual cycle such as premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). Digital health products, and specifically menstrual health apps, have the potential to effect positive change due to their scalability and ease of access. OBJECTIVE: The primary aim of this study was to measure the efficacy of a menstrual and reproductive health app, Flo, in improving health literacy and health and well-being outcomes in menstruating individuals with and without PMS and PMDD. Further, we explored the possibility that the use of the Flo app could positively influence feelings around reproductive health management and communication about health, menstrual cycle stigma, unplanned pregnancies, quality of life, work productivity, absenteeism, and body image. METHODS: We conducted 2 pilot, 3-month, unblinded, 2-armed, remote randomized controlled trials on the effects of using the Flo app in a sample of US-based (1) individuals who track their cycles (n=321) or (2) individuals who track their cycles and are affected by PMS or PMDD (n=117). RESULTS: The findings revealed significant improvements at the end of the study period compared to baseline for our primary outcomes of health literacy (cycle tracking: D̄=1.11; t311=5.73, P<.001; PMS or PMDD: D̄=1.20; t115=3.76, P<.001) and menstrual health awareness (D̄=3.97; t311=7.71, P<.001), health and well-being (D̄=3.44; t311=5.94, P<.001), and PMS or PMDD symptoms burden (D̄=-7.08; t115=-5.44, P<.001). Improvements were also observed for our secondary outcomes of feelings of control and management over health (D̄=1.01; t311=5.08, P<.001), communication about health (D̄=0.93; t311=2.41, P=.002), menstrual cycle stigma (D̄=-0.61; t311=-2.73, P=.007), and fear of unplanned pregnancies (D̄=-0.22; t311=-2.11, P=.04) for those who track their cycles, as well as absenteeism from work and education due to PMS or PMDD (D̄=-1.67; t144=-2.49, P=.01). CONCLUSIONS: These pilot randomized controlled trials demonstrate that the use of the Flo app improves menstrual health literacy and awareness, general health and well-being, and PMS or PMDD symptom burden. Considering the widespread use and affordability of the Flo app, these findings show promise for filling important gaps in current health care provisioning such as improving menstrual knowledge and health. TRIAL REGISTRATION: OSF Registries osf.io/pcgw7; https://osf.io/pcgw7 ; OSF Registries osf.io/ry8vq; https://osf.io/ry8vq.


Asunto(s)
Alfabetización en Salud , Aplicaciones Móviles , Humanos , Femenino , Alfabetización en Salud/estadística & datos numéricos , Alfabetización en Salud/normas , Alfabetización en Salud/métodos , Adulto , Proyectos Piloto , Aplicaciones Móviles/normas , Aplicaciones Móviles/estadística & datos numéricos , Persona de Mediana Edad , Calidad de Vida/psicología , Síndrome Premenstrual/psicología , Síndrome Premenstrual/terapia , Encuestas y Cuestionarios , Trastorno Disfórico Premenstrual/psicología , Trastorno Disfórico Premenstrual/terapia
14.
Artículo en Inglés | MEDLINE | ID: mdl-38754005

RESUMEN

BACKGROUND: This study focuses on investigating the risk factors of increased operating room time and patient complication rates after total shoulder arthroplasty cases (both reverse and anatomic). We hypothesize that the use of surgeon-preferred staff will improve operating room efficiency and reduce complication rates while increased staff turnover will decrease efficiency and increase complications. METHODS: This is a single-center, retrospective study focused on determining the effects of staffing on operating room time and efficiency in total shoulder arthroplasty. The study included patients who underwent total shoulder arthroplasty by a single fellowship-trained orthopaedic surgeon from 2018 to 2023. RESULTS: Four hundred twenty-three patients were included in the study from August 2018 to April 2023, 264 of which were reverse total shoulder arthroplasty (rTSA) and 159 were anatomic total shoulder arthroplasty (aTSA). In both rTSA and aTSA, the presence of surgeon-preferred staff markedly decreased operating room time. In rTSA, staff turnover increased risk of 90-day complications. CONCLUSION: Because the presence of surgeon-preferred staff affects operating room time and efficiency, orthopaedic surgeons should train multiple surgical teams so that efficiency is not affected by the loss of personnel during a case. To reduce 90-day complication rates in rTSA, staff breaks and turnover should be minimized as much as possible because this has a direct effect on patient outcomes. Effort from hospital administration and management should be put toward reducing turnover to improve patient outcomes.


Asunto(s)
Artroplastía de Reemplazo de Hombro , Quirófanos , Tempo Operativo , Complicaciones Posoperatorias , Humanos , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Reorganización del Personal , Cirujanos Ortopédicos , Factores de Riesgo
15.
Nat Genet ; 56(5): 889-899, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38741018

RESUMEN

The extent of cell-to-cell variation in tumor mitochondrial DNA (mtDNA) copy number and genotype, and the phenotypic and evolutionary consequences of such variation, are poorly characterized. Here we use amplification-free single-cell whole-genome sequencing (Direct Library Prep (DLP+)) to simultaneously assay mtDNA copy number and nuclear DNA (nuDNA) in 72,275 single cells derived from immortalized cell lines, patient-derived xenografts and primary human tumors. Cells typically contained thousands of mtDNA copies, but variation in mtDNA copy number was extensive and strongly associated with cell size. Pervasive whole-genome doubling events in nuDNA associated with stoichiometrically balanced adaptations in mtDNA copy number, implying that mtDNA-to-nuDNA ratio, rather than mtDNA copy number itself, mediated downstream phenotypes. Finally, multimodal analysis of DLP+ and single-cell RNA sequencing identified both somatic loss-of-function and germline noncoding variants in mtDNA linked to heteroplasmy-dependent changes in mtDNA copy number and mitochondrial transcription, revealing phenotypic adaptations to disrupted nuclear/mitochondrial balance.


Asunto(s)
Núcleo Celular , Variaciones en el Número de Copia de ADN , ADN Mitocondrial , Genoma Mitocondrial , Neoplasias , Análisis de la Célula Individual , Humanos , ADN Mitocondrial/genética , Análisis de la Célula Individual/métodos , Variaciones en el Número de Copia de ADN/genética , Núcleo Celular/genética , Neoplasias/genética , Neoplasias/patología , Línea Celular Tumoral , Animales , Mitocondrias/genética , Secuenciación Completa del Genoma/métodos , Ratones , Heteroplasmia/genética
16.
Adv Radiat Oncol ; 9(4): 101435, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38778830

RESUMEN

Purpose: The COVID-19 pandemic disrupted medical care. Little is known about how radiation therapy (RT) ordering behavior changed during the pandemic. This study examined (1) whether there was a change in the rate at which orders for lumpectomy were followed by orders for RT and (2) whether there was a change in the percentage of RT orders for hypofractionated (HF) RT rather than conventionally fractionated (CF) RT. Methods and Materials: Prior authorization order data from 2019 and 2020, pertaining to patients with commercial and Medicare Advantage health plans, were reviewed to determine whether patients had an order for RT in the 90 days after lumpectomy and if it was for CF or HF RT. Univariate analyses were conducted using χ2 tests, and adjusted analyses were conducted using multivariate logistic regression, controlling for patient age, urbanicity, local median income, region, if the lumpectomy facility was academic, and if the lumpectomy facility was a hospital. Results: In 2019, 47.7% of included lumpectomy orders (2200/4610) were followed by an RT order within 90 days, in contrast to 45.6% (1944/4263) in 2020 (P = .048). Of the RT orders meeting this study's definition of CF or HF, 75.3% of orders placed in 2019 (1387/1843) and 79.0% of orders placed in 2020 (1261/1597) were for HF (P = .011). Adjusted analysis found patients receiving a lumpectomy order in the first quarter of 2020 had significantly reduced odds (odds ratio, 0.84; 95% CI, 0.71-0.99) of receiving an order for RT after lumpectomy, relative to those with orders placed in the first quarter of 2019. Adjusted analysis likewise found significant evidence of increased use of HF RT during the pandemic. Conclusions: In the population examined, physicians were less likely to order RT after lumpectomy in 2020 than in 2019, and if they did, were more likely to order HF RT.

17.
Healthcare (Basel) ; 12(10)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38786431

RESUMEN

Patient-Reported Outcome Measures (PROMs), such as the six-item International Knee Documentation Committee Subjective Knee Form (IKDC-6), play a crucial role in assessing health conditions and guiding clinical decisions. Latent Growth Modeling (LGM) can be employed to understand recovery trajectories in patients post-operatively. Therefore, the purpose of this study was to assess LGM properties of the IKDC-6 in patients with knee pathologies that require surgical intervention and to assess differences between subgroups (i.e., sex and age). A cross-sectional study was conducted using the Surgical Outcome System (SOS) database with patients who had undergone knee arthroscopy. Our results found that preoperative scores did not influence the rate of change overtime. Perceived knee health improved over time, with varying rates among individuals. The adolescent age subgroup and male subgroup exhibited faster recovery rates compared to the older age subgroup and female subgroup. While initial hypotheses suggested IKDC-6 could serve as a prognostic tool, results did not support this. However, results indicated favorable outcomes irrespective of preoperative perceived knee impairment levels. This study provides valuable insights into recovery dynamics following knee surgery, emphasizing the need for personalized rehabilitation strategies tailored to individual patient characteristics.

18.
Healthcare (Basel) ; 12(10)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38786432

RESUMEN

The Hip Dysfunction and Osteoarthritis Outcome Score for Joint Replacement (HOOS-JR) was developed as a short-form survey to measure progress after total hip arthroplasty (THA). However, the longitudinal validity of the scale structure pertaining to the modified five-item HOOS-JR has not been assessed. Therefore, the purpose of this study was to evaluate the structural validity, longitudinal invariance properties, and latent growth curve (LGC) modeling of the modified five-item HOOS-JR in a large multi-site sample of patients who underwent a THA. A longitudinal study was conducted using data from the Surgical Outcome System (SOS) database. Confirmatory factor analyses (CFAs) were conducted to assess the structural validity and longitudinal invariance across five time points. Additionally, LGC modeling was performed to assess the heterogeneity of the recovery patterns for different subgroups of patients. The resulting CFAs met most of the goodness-of-fit indices (CFI = 0.964-0.982; IFI = 0.965-0.986; SRMR = 0.021-0.035). Longitudinal analysis did not meet full invariance, exceeding the scalar invariance model (CFIDIFF = 0.012; χ2DIFF test = 702.67). Partial invariance requirements were met upon release of the intercept constraint associated with item five (CFIDIFF test = 0.010; χ2DIFF = 1073.83). The equal means model did not pass the recommended goodness-of-fit indices (CFIDIFF = 0.133; χ2DIFF = 3962.49). Scores significantly changed over time, with the highest scores identified preoperatively and the lowest scores identified at 2- and 3-years postoperatively. Upon conclusion, partial scalar invariance was identified within our model. We identified that patients self-report most improvements in their scores within 6 months postoperatively. Females reported more hip disability at preoperative time points and had faster improvement as measured by the scores of the modified five-item HOOS-JR.

19.
Sports (Basel) ; 12(5)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38786992

RESUMEN

Background: Popular movement-based injury risk screens were shown to lack predictive precision, leading to interest in multifactorial models. Furthermore, there is a lack of research regarding injury risk assessment for those currently or planning to be recreationally active. This study aims to provide injury risk insights by analyzing multifactorial injury risk models and associated clinical measures in the U.S. population. Methods: Data related to injury, inflammatory markers, physical functioning, body composition, physical activity, and other variables from 21,033 respondents were extracted from NHANES. Odds ratios for self-reported injury were calculated for single predictors and risk models. Case-control and principal component analyses (PCA) were conducted to elucidate confounders and identify risk factor clusters, respectively. Receiver operating characteristic analysis was used to test the precision of a risk factor cluster to identify pain points and functional difficulties. Results: Sociodemographic, individual, and lifestyle factors were strongly associated with higher odds of injury. Increases in fibrinogen and C-reactive protein were significantly associated with all risk groups. Membership to the high-risk group (age over 40, obesity, no muscle-strengthening activities, sedentary lifestyle, and low back pain) predicted at least one functional difficulty with 67.4% sensitivity and 87.2% specificity. In the injury group, bone turnover markers were higher, yet confounded by age, and there was a significantly higher prevalence of self-reported osteoporosis compared to the control. In males, low testosterone was associated with injury, and high estradiol was associated with pain and functional difficulties. In females, high follicle-stimulating hormone was associated with functional difficulties. PCA revealed four high-risk profiles, with markers and activities showing distinct loadings. Conclusions: A comprehensive approach to injury risk assessment should consider the nexus of aging, lifestyle, and chronic disease to enhance tailored injury prevention strategies, fostering safe and effective physical activity participation and reducing the burden of musculoskeletal disorders.

20.
New J Chem ; 48(17): 7548-7551, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38689796

RESUMEN

We report the synthesis of 4-nitrophenyl (4-NP) functionalised Pt(iv) complexes as a colorimetric strategy for monitoring Pt(iv) reduction in aqueous solution. Treatment of each 4-NP functionalised Pt(iv) complex with the biological reductant sodium ascorbate led to a colour change from clear to yellow, which was attributed to the reduction of Pt(iv) to Pt(ii) and simultaneous release of 4-nitroaniline. Trends in reduction profiles and a photocatalysed reduction for each Pt(iv) complex were observed.

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