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1.
Ann R Coll Surg Engl ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39224958

RESUMO

INTRODUCTION: The Scoliosis Research Society 22r (SRS-22r) questionnaire is a proven tool in assessing healthcare-related quality of life (HRQoL) in idiopathic scoliosis and is the adopted patient-reported outcome measure for the deformity pathway recorded into the British Spinal Registry (BSR). Surgery for adolescent idiopathic scoliosis (AIS) is performed frequently in teenagers; however, patients also present with curves in the surgical range into adulthood. This work aimed to assess HRQoL differences between patients following surgery for AIS performed in adolescence and adulthood using SRS-22r data collected from the BSR. METHODS: An anonymised BSR search of pre- and postoperative SRS-22r scores for patients with diagnoses of AIS and adult idiopathic scoliosis was conducted. Data from all subdomains were compared preoperatively and at the two-year postoperative timepoint. RESULTS: Preoperative SRS-22r scores were analysed for 1,912 patients with AIS and 65 with adult idiopathic scoliosis. Patients with adult idiopathic scoliosis had significantly lower preoperative SRS-22r scores in all subdomains (p<0.05). By two years postoperatively, both groups of patients had improved SRS-22r scores significantly compared with baseline in all subdomains (p<0.001). A cross-group analysis revealed patients with AIS had significantly better function scores years postoperatively than their adult counterparts (p=0.005). CONCLUSIONS: This work confirms there are benefits following surgery for AIS in improving HRQoL, but has also provided HRQoL data in adult patients, who again show similar improvements following surgery from baseline. This is of value when counselling patients regarding anticipated benefits of surgery performed in childhood and adulthood.

2.
J Am Chem Soc ; 146(37): 25397-25402, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39250821

RESUMO

Phototriggered release of various cargos, including soluble protein factors and small molecules, has the potential to correct aberrant biological events by offering spatiotemporal control over local therapeutic levels. However, the poor penetration depth of light historically limits implementation to subdermal regions, necessitating alternative methods of light delivery to achieve the full potential of photodynamic therapeutic release. Here, we introduce a strategy exploiting bioluminescence resonance energy transfer (BRET)-an energy transfer process between light-emitting Nanoluciferase (NLuc) and a photosensitive acceptor molecule-to drive biomolecule release from hydrogel biomaterials. Through a facile, one-pot, and high-yielding synthesis (60-70%), we synthesized a heterobifunctional ruthenium cross-linker bearing an aldehyde and an azide (CHO-Ru-N3), a compound that we demonstrate undergoes predictable exchange of the azide-bearing ligand under blue-green light irradiation (>550 nm). Following site-specific conjugation to NLuc via sortase-tag enhanced protein ligation (STEPL), the modified protein was covalently attached to a poly(ethylene glycol) (PEG)-based hydrogel via strain-promoted azide-alkyne cycloaddition (SPAAC). Leveraging the high photosensitivity of Ru compounds, we demonstrate rapid and equivalent release of epidermal growth factor (EGF) via either direct illumination or via BRET-based bioluminolysis. As NLuc-originated luminescence can be controlled equivalently throughout the body, we anticipate that this unique protein release strategy will find use for locally triggered drug delivery following systemic administration of a small molecule.


Assuntos
Materiais Biocompatíveis , Materiais Biocompatíveis/química , Azidas/química , Rutênio/química , Processos Fotoquímicos , Hidrogéis/química , Hidrogéis/síntese química , Técnicas de Transferência de Energia por Ressonância de Bioluminescência , Luciferases/metabolismo , Luciferases/química , Luz , Polietilenoglicóis/química
3.
Adv Mater ; : e2404880, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39240007

RESUMO

Biomechanical contributions of the extracellular matrix 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, a poly(ethylene glycol) (PEG)-based hydrogel model consisting of two interpenetrating step-growth networks is introduced that are independently formed via largely orthogonal bioorthogonal chemistries and sequentially degraded with distinct recombinant sortases, 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 is achieved via mask-based and two-photon lithography; these stiffened patterned regions can be subsequently returned to the original soft state following sortase-based secondary network degradation. Using this approach, the effects of 4D-triggered network mechanical changes on human mesenchymal stem cell morphology and Hippo signaling, as well as Caco-2 colorectal cancer cell mechanomemory using transcriptomics and metabolic assays are investigated. This platform is expected to be of broad utility for studying and directing mechanobiological phenomena, patterned cell fate, and disease resolution in softer matrices.

4.
Nat Chem Eng ; 1(1): 2-5, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39015819

RESUMO

Focusing on engineering control over cell function and fate, this article examines the critical balance of 'outside-in' and 'inside-out signaling in tissue development and regeneration. It highlights emerging strategies to manipulate these interactions, including biomaterial design and synthetic biology to influence this delicate equilibrium and fine tune cellular responses.

5.
bioRxiv ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38979380

RESUMO

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.

6.
Mil Med ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829165

RESUMO

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.

7.
Neurol Clin Pract ; 14(5): e200332, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38919931

RESUMO

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.

8.
Animals (Basel) ; 14(10)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38791686

RESUMO

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.

9.
bioRxiv ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38766128

RESUMO

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.

10.
Bioconjug Chem ; 35(6): 750-757, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38815180

RESUMO

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.


Assuntos
Inteínas , Proteínas de Fluorescência Verde/química , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Fluorescência Verde/genética , beta-Lactamases/metabolismo , beta-Lactamases/química , Proteínas Luminescentes/química , Fator de Crescimento Epidérmico/metabolismo , Fator de Crescimento Epidérmico/química , Proteína Vermelha Fluorescente , Proteínas/química
11.
Epilepsy Behav ; 155: 109669, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38663142

RESUMO

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.


Assuntos
Lobectomia Temporal Anterior , Epilepsia do Lobo Temporal , Testes Neuropsicológicos , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Resultado do Tratamento , Epilepsia do Lobo Temporal/cirurgia , Estudos Retrospectivos , Lobectomia Temporal Anterior/métodos , Lobectomia Temporal Anterior/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Adulto Jovem , Convulsões/cirurgia , Procedimentos Neurocirúrgicos/métodos , Lobo Temporal/cirurgia
12.
bioRxiv ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38645065

RESUMO

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.

13.
Psychol Rep ; : 332941241248607, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637012

RESUMO

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.

14.
Adv Sci (Weinh) ; 11(24): e2301708, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38477407

RESUMO

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.


Assuntos
Materiais Biocompatíveis , Hidrogéis , Hidrogéis/química , Humanos , Materiais Biocompatíveis/química , Terapia Baseada em Transplante de Células e Tecidos/métodos , Elasticidade , Animais , Viscosidade , Camundongos , Elastina/genética , Elastina/química , Elastina/metabolismo
16.
Proc Natl Acad Sci U S A ; 121(6): e2309457121, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38289949

RESUMO

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.


Assuntos
Materiais Biocompatíveis , Hidrogéis , Animais , Hidrogéis/química , Biopolímeros , Mamíferos
17.
Aesthet Surg J ; 44(6): 612-622, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38284419

RESUMO

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.


Assuntos
Mastectomia , Dispositivos para Expansão de Tecidos , Expansão de Tecido , Humanos , Dispositivos para Expansão de Tecidos/efeitos adversos , Feminino , Mastectomia/efeitos adversos , Mastectomia/métodos , Expansão de Tecido/métodos , Expansão de Tecido/instrumentação , Expansão de Tecido/efeitos adversos , Solução Salina/administração & dosagem , Mamoplastia/métodos , Mamoplastia/efeitos adversos , Mamoplastia/economia , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Implante Mamário/métodos , Implante Mamário/efeitos adversos , Implante Mamário/instrumentação , Neoplasias da Mama/cirurgia , Implantes de Mama/efeitos adversos
18.
Nat Protoc ; 19(4): 1015-1052, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38253657

RESUMO

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.


Assuntos
Escherichia coli , Engenharia de Proteínas , Animais , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas Recombinantes/genética , Engenharia de Proteínas/métodos , Aminoácidos , Mamíferos
19.
Issues Ment Health Nurs ; 45(1): 85-95, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38190426

RESUMO

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.


Assuntos
Recursos Humanos de Enfermagem , Enfermagem Psiquiátrica , Humanos , Preceptoria , Atitude do Pessoal de Saúde , Recursos Humanos de Enfermagem/psicologia , Motivação
20.
Aesthet Surg J ; 44(4): 383-393, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-37757895

RESUMO

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.


Assuntos
Implante Mamário , Implantes de Mama , Neoplasias da Mama , Linfoma Anaplásico de Células Grandes , Humanos , Feminino , Dispositivos para Expansão de Tecidos/efeitos adversos , Implantes de Mama/efeitos adversos , Implante Mamário/efeitos adversos , Mama/cirurgia , Incidência , Linfoma Anaplásico de Células Grandes/epidemiologia , Linfoma Anaplásico de Células Grandes/etiologia , Linfoma Anaplásico de Células Grandes/patologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Neoplasias da Mama/cirurgia
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