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1.
bioRxiv ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38979380

ABSTRACT

Integrin α5ß1 is crucial for cell attachment and migration in development and tissue regeneration, and α5ß1 binding proteins could have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo α5ß1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of α5ß1. When immobilized onto titanium surfaces and throughout 3D hydrogels, the NeoNectins outperform native fibronectin and RGD peptide in enhancing cell attachment and spreading, and NeoNectin-grafted titanium implants outperformed fibronectin and RGD-grafted implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine. One-Sentence Summary: A de novo-designed fibronectin substitute, NeoNectin, is specific for integrin α5ß1 and can be incorporated into biomaterials for regenerative medicine.

2.
Mil Med ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829165

ABSTRACT

INTRODUCTION: A light-weight pneumatic-powered knee exoskeleton could augment mobility and lifting capabilities for a variety of occupational settings. However, added weight/bulkiness and artificially produced knee extension torque could compromise sensorimotor characteristics. MATERIALS AND METHODS: Ten healthy participants conducted 3 visits within 10 days to the biomechanics laboratory. Participants were asked to complete the following tasks on each visit: single-leg balance, single-leg drop-landing, and select functional movement tasks. Balance characteristics (the ground reaction forces variability and center-of-pressure velocity) were derived from force plates while knee flexion angles during drop-landing and functional movement tasks were captured using a motion capture system. Descriptive statistics as well as paired t-tests or Wilcoxon signed-rank tests were used to compare between conditions. Significance was set at P < .05 a priori. RESULTS: During single-leg balance, the ground reaction force variabilities were significantly increased (P = .013-.019) and the center of pressure velocity was decreased (P = .001-.017) when wearing knee exoskeleton. During single-leg drop-landing, the exoskeleton condition showed lower knee flexion angles at the initial contact (P = .004-.021) and peak (P = .006-.010). Additionally, the peak vertical ground reaction force was higher in the exoskeleton condition (P = .007). During functional movement tasks, the exoskeleton condition showed less knee flexion range-of-motion during the overhead squat (P = .007-.033) and hurdle step-over (P = .004-.005). CONCLUSIONS: Participants exhibited stiffer landing technique with the exoskeleton. Given that these compromised sensorimotor characteristics have been associated with musculoskeletal injury risk, modifications to exoskeletons to promote softer landing and greater knee flexion range-of-motion during dynamic activities may be warranted.

3.
Neurol Clin Pract ; 14(5): e200332, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38919931

ABSTRACT

Purpose of Review: To summarize the literature on neurologic care for transgender and gender-diverse (TGD) people and provide implications for clinical practice. Recent Findings: There are limited data on the frequency and management of neurologic conditions among TGD people. TGD people have a higher prevalence of various neurologic conditions compared with cisgender or general population cohorts, including migraine, subjective cognitive decline, sleep disturbances, functional disorders, and cerebrovascular disease. Gender-affirming hormone therapy interacts with commonly prescribed neurologic medications and increases stroke risk among transfeminine people. Sex hormones and sex chromosomes may play a role in neurodegeneration and disability progression in neuroimmunologic diseases. Clitoral reduction surgeries on intersex children can cause neurologic disability and sexual dysfunction in adulthood. Socioeconomic disparities among TGD people contribute to health care barriers. Summary: Neurologists should consider the unique experiences and health care needs of TGD people in their clinical practice and research protocols.

4.
Bioconjug Chem ; 35(6): 750-757, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38815180

ABSTRACT

Site-specific installation of non-natural functionality onto proteins has enabled countless applications in biotechnology, chemical biology, and biomaterials science. Though the N-terminus is an attractive derivatization location, prior methodologies targeting this site have suffered from low selectivity, a limited selection of potential chemical modifications, and/or challenges associated with divergent protein purification/modification steps. In this work, we harness the atypically split VidaL intein to simultaneously N-functionalize and purify homogeneous protein populations in a single step. Our method─referred to as VidaL-tagged expression and protein ligation (VEPL)─enables modular and scalable production of N-terminally modified proteins with native bioactivity. Demonstrating its flexibility and ease of use, we employ VEPL to combinatorially install 4 distinct (multi)functional handles (e.g., biotin, alkyne, fluorophores) to the N-terminus of 4 proteins that span three different classes: fluorescent (Enhanced Green Fluorescent Protein, mCherry), enzymatic (ß-lactamase), and growth factor (epidermal growth factor). Moving forward, we anticipate that VEPL's ability to rapidly generate and isolate N-modified proteins will prove useful across the growing fields of applied chemical biology.


Subject(s)
Inteins , Green Fluorescent Proteins/chemistry , Green Fluorescent Proteins/metabolism , Green Fluorescent Proteins/genetics , beta-Lactamases/metabolism , beta-Lactamases/chemistry , Luminescent Proteins/chemistry , Epidermal Growth Factor/metabolism , Epidermal Growth Factor/chemistry , Red Fluorescent Protein , Proteins/chemistry
5.
Animals (Basel) ; 14(10)2024 May 15.
Article in English | MEDLINE | ID: mdl-38791686

ABSTRACT

Monitoring vital rates allows managers to estimate trends in growth rates of ungulate populations. However, connecting the influence of nutrition on ungulate demography is challenging. Noninvasive sampling offers a low-cost, low-effort alternative for measuring nutritional indices, allowing for an increased understanding of the mechanistic relationships between environmental factors, nutrition, and specific population vital rates. We examined the temporal influence of intrinsic and extrinsic factors on pronghorn (Antilocapra americana) fawn recruitment. We collected fresh fecal samples from adult female pronghorn in five subpopulations spanning three sampling periods associated with critical maternal life-history stages (late gestation, early lactation, breeding season) for 2 years to investigate both intra- and interannual influences. Intrinsic factors were fecal glucocorticoid metabolites (FGMs), nutritional indices (fecal nitrogen (FN) and 2,6-diaminopimelic acid (DAPA)), and dietary composition (protein intake of forbs, graminoids, legumes, other, shrubs), while the extrinsic factor was vegetative greenness (normalized difference vegetation index (NDVI)). We found variations in DAPA, protein intake of forbs, variation in forb protein intake, and protein intake of legumes during late gestation positively influenced fawn recruitment. Fecal nitrogen during early lactation showed the strongest positive influence on the recruitment of any measured parameter. Finally, breeding season NDVI and the variation in DAPA values positively influenced the subsequent year's fawn recruitment. Our longitudinal study enabled us to investigate which parameter was most important to specific periods of fawn development and recruitment. We combined the results across five subpopulations, but interpretation and subsequent management decisions should be made at the subpopulation level such that pronghorn subpopulations with low recruitment can be positively influenced by increasing nitrogen on the landscape available to adult females during the early lactation period. As the use of noninvasive monitoring methods continues to expand, we believe our methodologies and results can be broadly applied to other ungulate monitoring programs.

6.
bioRxiv ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38766128

ABSTRACT

Hydrogel biomaterials offer great promise for 3D cell culture and therapeutic delivery. Despite many successes, challenges persist in that gels formed from natural proteins are only marginally tunable while those derived from synthetic polymers lack intrinsic bioinstructivity. Towards the creation of biomaterials with both excellent biocompatibility and customizability, recombinant protein-based hydrogels have emerged as molecularly defined and user-programmable platforms that mimic the proteinaceous nature of the extracellular matrix. Here, we introduce PhoCoil, a dynamically tunable recombinant hydrogel formed from a single protein component with unique multi-stimuli responsiveness. Physical crosslinking through coiled-coil interactions promotes rapid shear-thinning and self-healing behavior, rendering the gel injectable, while an included photodegradable motif affords on-demand network dissolution via visible light. PhoCoil gel photodegradation can be spatiotemporally and lithographically controlled in a dose-dependent manner, through complex tissue, and without harm to encapsulated cells. We anticipate that PhoCoil will enable new applications in tissue engineering and regenerative medicine.

7.
bioRxiv ; 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38645065

ABSTRACT

Biomechanical contributions of the ECM underpin cell growth and proliferation, differentiation, signal transduction, and other fate decisions. As such, biomaterials whose mechanics can be spatiotemporally altered - particularly in a reversible manner - are extremely valuable for studying these mechanobiological phenomena. Herein, we introduce a poly(ethylene glycol) (PEG)-based hydrogel model consisting of two interpenetrating step-growth networks that are independently formed via largely orthogonal bioorthogonal chemistries and sequentially degraded with distinct bacterial transpeptidases, affording reversibly tunable stiffness ranges that span healthy and diseased soft tissues (e.g., 500 Pa - 6 kPa) alongside terminal cell recovery for pooled and/or single-cell analysis in a near "biologically invisible" manner. Spatiotemporal control of gelation within the primary supporting network was achieved via mask-based and two-photon lithography; these stiffened patterned regions could be subsequently returned to the original soft state following sortase-based secondary network degradation. Using this approach, we investigated the effects of 4D-triggered network mechanical changes on human mesenchymal stem cell (hMSC) morphology and Hippo signaling, as well as Caco-2 colorectal cancer cell mechanomemory at the global transcriptome level via RNAseq. We expect this platform to be of broad utility for studying and directing mechanobiological phenomena, patterned cell fate, as well as disease resolution in softer matrices.

8.
Psychol Rep ; : 332941241248607, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38637012

ABSTRACT

Grit, characterized by passion and perseverance in the pursuit of long-term goals, may be associated with enhanced quality of life and reduced levels of perceived chronic stress. We hypothesized that reduced levels of perceived stress may mediate the association between facets of grit (i.e., Perseverance and Consistency) and healthy functioning. We conducted two studies, one with college students and one with community adults, to test this hypothesis (cumulative N = 600). In both studies, facets of grit were assessed using the Short Grit Scale, levels of perceived chronic stress were assessed via the Perceived Stress Scale, and health-related quality of life was measured using selected questions from the Medical Outcome Study Short Form-36. Consistent with our hypothesis, perceived stress levels significantly mediated the relation between Grit-Perseverance and health-related quality of life in both college students and community adults. Our data suggest that individuals with high Grit-Perseverance experience lower perceived stress, which may result in improved health-related quality of life. Additionally, perceived stress partially mediated the relation between Grit-Consistency and health-related quality of life, but only in community adults. These novel findings suggest that the association between Grit-Perseverance and perceived chronic stress may differ for college students and community adults. Overall, our work indicates that perceived stress may be a key mediator through which facets of grit are related to healthy functioning in college students and community adults.

9.
Epilepsy Behav ; 155: 109669, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38663142

ABSTRACT

The purpose of this study was to systematically examine three different surgical approaches in treating left medial temporal lobe epilepsy (mTLE) (viz., subtemporal selective amygdalohippocampectomy [subSAH], stereotactic laser amygdalohippocampotomy [SLAH], and anterior temporal lobectomy [ATL]), to determine which procedures are most favorable in terms of visual confrontation naming and seizure relief outcome. This was a retrospective study of 33 adults with intractable mTLE who underwent left temporal lobe surgery at three different epilepsy surgery centers who also underwent pre-, and at least 6-month post-surgical neuropsychological testing. Measures included the Boston Naming Test (BNT) and the Engel Epilepsy Surgery Outcome Scale. Fisher's exact tests revealed a statistically significant decline in naming in ATLs compared to SLAHs, but no other significant group differences. 82% of ATL and 36% of subSAH patients showed a significant naming decline whereas no SLAH patient (0%) had a significant naming decline. Significant postoperative naming improvement was seen in 36% of SLAH patients in contrast to 9% improvement in subSAH patients and 0% improvement in ATLs. Finally, there were no statistically significant differences between surgical approaches with regard to seizure freedom outcome, although there was a trend towards better seizure relief outcome among the ATL patients. Results support a possible benefit of SLAH in preserving visual confrontation naming after left TLE surgery. While result interpretation is limited by the small sample size, findings suggest outcome is likely to differ by surgical approach, and that further research on cognitive and seizure freedom outcomes is needed to inform patients and providers of potential risks and benefits with each.


Subject(s)
Anterior Temporal Lobectomy , Epilepsy, Temporal Lobe , Neuropsychological Tests , Humans , Male , Female , Adult , Middle Aged , Treatment Outcome , Epilepsy, Temporal Lobe/surgery , Retrospective Studies , Anterior Temporal Lobectomy/methods , Anterior Temporal Lobectomy/adverse effects , Minimally Invasive Surgical Procedures/methods , Young Adult , Seizures/surgery , Neurosurgical Procedures/methods , Temporal Lobe/surgery
10.
Adv Sci (Weinh) ; 11(24): e2301708, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38477407

ABSTRACT

While direct cell transplantation holds great promise in treating many debilitating diseases, poor cell survival and engraftment following injection have limited effective clinical translation. Though injectable biomaterials offer protection against membrane-damaging extensional flow and supply a supportive 3D environment in vivo that ultimately improves cell retention and therapeutic costs, most are created from synthetic or naturally harvested polymers that are immunogenic and/or chemically ill-defined. This work presents a shear-thinning and self-healing telechelic recombinant protein-based hydrogel designed around XTEN - a well-expressible, non-immunogenic, and intrinsically disordered polypeptide previously evolved as a genetically encoded alternative to PEGylation to "eXTENd" the in vivo half-life of fused protein therapeutics. By flanking XTEN with self-associating coil domains derived from cartilage oligomeric matrix protein, single-component physically crosslinked hydrogels exhibiting rapid shear thinning and self-healing through homopentameric coiled-coil bundling are formed. Individual and combined point mutations that variably stabilize coil association enables a straightforward method to genetically program material viscoelasticity and biodegradability. Finally, these materials protect and sustain viability of encapsulated human fibroblasts, hepatocytes, embryonic kidney (HEK), and embryonic stem-cell-derived cardiomyocytes (hESC-CMs) through culture, injection, and transcutaneous implantation in mice. These injectable XTEN-based hydrogels show promise for both in vitro cell culture and in vivo cell transplantation applications.


Subject(s)
Biocompatible Materials , Hydrogels , Hydrogels/chemistry , Humans , Biocompatible Materials/chemistry , Cell- and Tissue-Based Therapy/methods , Elasticity , Animals , Viscosity , Mice , Elastin/genetics , Elastin/chemistry , Elastin/metabolism
12.
Nat Protoc ; 19(4): 1015-1052, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38253657

ABSTRACT

The conditional assembly of split-protein pairs to modulate biological activity is commonly achieved by fusing split-protein fragments to dimerizing components that bring inactive pairs into close proximity in response to an exogenous trigger. However, current methods lack full spatial and temporal control over reconstitution, require sustained activation and lack specificity. Here light-activated SpyLigation (LASL), based on the photoregulation of the covalent SpyTag (ST)/SpyCatcher (SC) peptide-protein reaction, assembles nonfunctional split fragment pairs rapidly and irreversibly in solution, in engineered biomaterials and intracellularly. LASL introduces an ortho-nitrobenzyl(oNB)-caged lysine into SC's reactive site to generate a photoactivatable SC (pSC). Split-protein pairs of interest fused to pSC and ST are conditionally assembled via near-ultraviolet or pulsed near-infrared irradiation, as the uncaged SC can react with ST to ligate appended fragments. We describe procedures for the efficient synthesis of the photocaged amino acid that is incorporated within pSC (<5 days) as well as the design and cloning of LASL plasmids (1-4 days) for recombinant protein expression in either Escherichia coli (5-6 days) or mammalian cells (4-6 days), which require some prior expertise in protein engineering. We provide a chemoenzymatic scheme for appending bioorthogonal reactive handles onto E. coli-purified pSC protein (<4 days) that permits LASL component incorporation and patterned protein activation within many common biomaterial platforms. Given that LASL is irreversible, the photolithographic patterning procedures are fast and do not require sustained light exposure. Overall, LASL can be used to interrogate and modulate cell signaling in various settings.


Subject(s)
Escherichia coli , Protein Engineering , Animals , Escherichia coli/genetics , Escherichia coli/metabolism , Recombinant Proteins/genetics , Protein Engineering/methods , Amino Acids , Mammals
13.
Aesthet Surg J ; 44(6): 612-622, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38284419

ABSTRACT

The most common reconstruction technique following mastectomy is a 2-stage technique that involves tissue expansion followed by definitive implant-based reconstruction (IBR). Tissue expanders (TEs) have classically used saline for initial fill; however, TEs with an initial gas fill (GTE)-including the CO2-based AeroForm (AirXpanders, San Francisco, CA) TE and TEs initially filled with atmospheric air-have been increasingly used in the past decade. We aimed to compare the outcomes in breast reconstruction for tissue expanders initially filled with saline vs gas. PubMed was queried for studies comparing gas- and saline-filled tissue expanders (STEs) used in IBR. A meta-analysis was performed on major postoperative outcomes and the required expansion and definitive reconstruction time. Eleven studies were selected and included in the analysis. No significant differences existed between tissue expansion with GTEs vs STEs for 11 of the 13 postoperative outcomes investigated. Out of the complications investigated, only the risk of infection/cellulitis/abscess formation was significantly lower in the GTE cohort (odds ratio 0.62; 95% CI, 0.47 to 0.82; P = .0009). The time to definitive reconstruction was also significantly lower in the GTE cohort (mean difference [MD], 45.85 days; 95% CI, -57.80 to -33.90; P < .00001). The total time to full expansion approached significance in the GTE cohort (MD, -20.33 days; 95% CI, -41.71 to 1.04; P = .06). A cost analysis considering TE cost and infection risk determined that GTE use saved a predicted $2055.34 in overall healthcare costs. Surgical outcomes for both fill types were predominantly similar; however, GTEs were associated with a significantly decreased risk of postoperative infection compared to saline-filled TEs. GTEs could also reduce healthcare expenditures and require less time until definitive reconstruction after placement.


Subject(s)
Mastectomy , Tissue Expansion Devices , Tissue Expansion , Humans , Tissue Expansion Devices/adverse effects , Female , Mastectomy/adverse effects , Mastectomy/methods , Tissue Expansion/methods , Tissue Expansion/instrumentation , Tissue Expansion/adverse effects , Saline Solution/administration & dosage , Mammaplasty/methods , Mammaplasty/adverse effects , Mammaplasty/economics , Treatment Outcome , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Postoperative Complications/epidemiology , Breast Implantation/methods , Breast Implantation/adverse effects , Breast Implantation/instrumentation , Breast Neoplasms/surgery , Breast Implants/adverse effects
14.
Issues Ment Health Nurs ; 45(1): 85-95, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38190426

ABSTRACT

This study explored the impact of an innovative approach to clinical supervision for mental health nurses which integrates Safewards, named Group Reflective integrated Practice with Safewards - GRiP-S. Qualitative data was collected through 10 individual semi-structured interviews with nursing staff who had participated within the clinical supervision approach. Interviews provided insights into the nursing staff's perception and experience of the clinical supervision approach. Through interpretive phenomenological analysis six themes emerged (i) illuminating embodied practice of Safewards, (ii) building confidence through empowering connections, (iii) creating a culture of positive change, (iv) identifying internal motivation for and external barriers to supervision engagement, (v) navigating a global pandemic, and (vi) the transformative role of reflection. Findings demonstrated that the GRiP-S approach assisted mental health nurses' adoption of Safewards interventions in practice, while supporting the development of a cohesive staff team. The impact of COVID-19 within the study setting was addressed and nurses identified how the Safewards model assisted in navigating challenges during this time. Findings further supported prior research on the role of the supervisor and supervisee relationship. This study supports the integration of Safewards within reflective clinical supervision for mental health nursing staff to assist in Safewards fidelity and nursing staff personal and professional development.


Subject(s)
Nursing Staff , Psychiatric Nursing , Humans , Preceptorship , Attitude of Health Personnel , Nursing Staff/psychology , Motivation
15.
Proc Natl Acad Sci U S A ; 121(6): e2309457121, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38289949

ABSTRACT

Relating the macroscopic properties of protein-based materials to their underlying component microstructure is an outstanding challenge. Here, we exploit computational design to specify the size, flexibility, and valency of de novo protein building blocks, as well as the interaction dynamics between them, to investigate how molecular parameters govern the macroscopic viscoelasticity of the resultant protein hydrogels. We construct gel systems from pairs of symmetric protein homo-oligomers, each comprising 2, 5, 24, or 120 individual protein components, that are crosslinked either physically or covalently into idealized step-growth biopolymer networks. Through rheological assessment, we find that the covalent linkage of multifunctional precursors yields hydrogels whose viscoelasticity depends on the crosslink length between the constituent building blocks. In contrast, reversibly crosslinking the homo-oligomeric components with a computationally designed heterodimer results in viscoelastic biomaterials exhibiting fluid-like properties under rest and low shear, but solid-like behavior at higher frequencies. Exploiting the unique genetic encodability of these materials, we demonstrate the assembly of protein networks within living mammalian cells and show via fluorescence recovery after photobleaching (FRAP) that mechanical properties can be tuned intracellularly in a manner similar to formulations formed extracellularly. We anticipate that the ability to modularly construct and systematically program the viscoelastic properties of designer protein-based materials could have broad utility in biomedicine, with applications in tissue engineering, therapeutic delivery, and synthetic biology.


Subject(s)
Biocompatible Materials , Hydrogels , Animals , Hydrogels/chemistry , Biopolymers , Mammals
16.
Nature ; 625(7996): 760-767, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38092039

ABSTRACT

GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a full mechanistic understanding is lacking1-4. Here we report that fetal production of GDF15 and maternal sensitivity to it both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally labelled GDF15 variant, we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants, we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with ß-thalassaemia, a condition in which GDF15 levels are chronically high5, report very low levels of nausea and vomiting of pregnancy. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by prepregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.


Subject(s)
Growth Differentiation Factor 15 , Hyperemesis Gravidarum , Nausea , Vomiting , Animals , Female , Humans , Mice , Pregnancy , beta-Thalassemia/blood , beta-Thalassemia/metabolism , Fetus/metabolism , Growth Differentiation Factor 15/blood , Growth Differentiation Factor 15/metabolism , Hormones/blood , Hormones/metabolism , Hyperemesis Gravidarum/complications , Hyperemesis Gravidarum/metabolism , Hyperemesis Gravidarum/prevention & control , Hyperemesis Gravidarum/therapy , Nausea/blood , Nausea/complications , Nausea/metabolism , Placenta/metabolism , Vomiting/blood , Vomiting/complications , Vomiting/metabolism
17.
Clin Oncol (R Coll Radiol) ; 36(2): 119-127, 2024 02.
Article in English | MEDLINE | ID: mdl-38042669

ABSTRACT

AIMS: Cardiac disease is a dose-limiting toxicity in non-small cell lung cancer radiotherapy. The dose to the heart base has been associated with poor survival in multiple institutional and clinical trial datasets using unsupervised, voxel-based analysis. Validation has not been undertaken in a cohort with individual patient delineations of the cardiac base or for the endpoint of cardiac events. The purpose of this study was to assess the association of heart base radiation dose with overall survival and the risk of cardiac events with individual heart base contours. MATERIALS AND METHODS: Patients treated between 2015 and 2020 were reviewed for baseline patient, tumour and cardiac details and both cancer and cardiac outcomes as part of the NI-HEART study. Three cardiologists verified cardiac events including atrial fibrillation, heart failure and acute coronary syndrome. Cardiac substructure delineations were completed using a validated deep learning-based autosegmentation tool and a composite cardiac base structure was generated. Cox and Fine-Gray regressions were undertaken for the risk of death and cardiac events. RESULTS: Of 478 eligible patients, most received 55 Gy/20 fractions (96%) without chemotherapy (58%), planned with intensity-modulated radiotherapy (71%). Pre-existing cardiovascular morbidity was common (78% two or more risk factors, 46% one or more established disease). The median follow-up was 21.1 months. Dichotomised at the median, a higher heart base Dmax was associated with poorer survival on Kaplan-Meier analysis (20.2 months versus 28.3 months; hazard ratio 1.40, 95% confidence interval 1.14-1.75, P = 0.0017) and statistical significance was retained in multivariate analyses. Furthermore, heart base Dmax was associated with pooled cardiac events in a multivariate analysis (hazard ratio 1.75, 95% confidence interval 1.03-2.97, P = 0.04). CONCLUSIONS: Heart base Dmax was associated with the rate of death and cardiac events after adjusting for patient, tumour and cardiovascular factors in the NI-HEART study. This validates the findings from previous unsupervised analytical approaches. The heart base could be considered as a potential sub-organ at risk towards reducing radiation cardiotoxicity.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Heart Diseases , Lung Neoplasms , Radiotherapy, Intensity-Modulated , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Heart , Radiotherapy, Intensity-Modulated/adverse effects , Heart Diseases/epidemiology , Heart Diseases/etiology , Radiation Dosage
18.
Aesthet Surg J ; 44(4): 383-393, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-37757895

ABSTRACT

BACKGROUND: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a type of non-Hodgkin lymphoma first linked with breast implants in 2011. The correlation between BIA-ALCL and textured devices has led to increased use of smooth devices. However, much of the data surrounding smooth and textured devices investigates breast implants specifically and not tissue expanders. OBJECTIVES: We performed a systematic review and a meta-analysis to compare surgical outcomes for smooth tissue expanders (STEs) and textured tissue expanders (TTEs). METHODS: A search was performed on PubMed, including articles from 2016 to 2023 (n = 419). Studies comparing TTEs and STEs and reported complications were included. A random-effects model was utilized for meta-analysis. RESULTS: A total of 5 articles met inclusion criteria, representing 1709 patients in the STE cohort and 1716 patients in the TTE cohort. The mean duration of tissue expansion with STEs was 221.25 days, while TTEs had a mean time of tissue expansion of 220.43 days.Our meta-analysis found no differences in all surgical outcomes except for explantation risk. STE use was associated with increased odds of explantation by over 50% compared to TTE use (odds ratio = 1.53; 95% CI = 1.15 to 2.02; P = .003). CONCLUSIONS: Overall, STEs and TTEs had similar complication profiles. However, STEs had 1.5 times higher odds of explantation. The incidence of BIA-ALCL is low, and only a single case of BIA-ALCL has been reported with TTEs. This indicates that TTEs are safe and may lower the risk of early complications requiring explantation. Further studies are warranted to further define the relationship between tissue expanders and BIA-ALCL.


Subject(s)
Breast Implantation , Breast Implants , Breast Neoplasms , Lymphoma, Large-Cell, Anaplastic , Humans , Female , Tissue Expansion Devices/adverse effects , Breast Implants/adverse effects , Breast Implantation/adverse effects , Breast/surgery , Incidence , Lymphoma, Large-Cell, Anaplastic/epidemiology , Lymphoma, Large-Cell, Anaplastic/etiology , Lymphoma, Large-Cell, Anaplastic/pathology , Breast Neoplasms/epidemiology , Breast Neoplasms/etiology , Breast Neoplasms/surgery
20.
Cogn Emot ; 38(2): 256-266, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37987770

ABSTRACT

Trait mindfulness confers emotional benefits and encourages skillful emotion regulation, in part because it helps people more deliberately attend to internal experiences and external surroundings. Such heightened attentional control might help skillfully deploy one's attention towards certain kinds of stimuli, which may in turn help regulate emotions, but this remains unknown. Testing how trait mindful people deploy attention when regulating their emotions could help uncover the specific mechanisms of mindfulness that confer its emotional benefits. The present study aimed to determine whether high trait mindfulness is associated with sustained attention biases to (i.e. longer gaze at) emotional scenes, when all participants are given the emotion regulation goal of staying in a positive mood. To measure this, we used eye tracking to assess selective attention to positive, neutral, and negative photographs. Higher trait mindfulness was associated with both a stronger attention bias for positive (vs. neutral and vs. negative) images, as well as greater success staying in a positive mood during viewing. Surprisingly, this attention bias towards the positive images did not mediate the relationship between mindfulness and maintenance of positive mood. Future work should compare visual attention to other emotion regulation strategies that may maximise positive affect for mindful people.


Subject(s)
Emotional Regulation , Mindfulness , Humans , Mindfulness/methods , Goals , Emotions/physiology , Affect
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