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1.
RSC Adv ; 14(11): 7459-7467, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38440266

RESUMEN

The present work investigated the effect of destabilization time on the mechanical properties and microstructure evolution of high chromium cast iron, and scanning electron microscopy and electron probe microanalysis techniques were employed. The results show that the hardness of hypoeutectic high chromium cast iron is related to the size and volume fraction of secondary carbides precipitated from the matrix. The hardness of the alloy continues to rise due to the continuous increase of the volume fraction of the secondary carbide at the initial stage of destabilization. The alloy reaches its peak hardness value at 950 °C and 1000 °C for 1 hour holding time. The solid solubility of carbon and alloying elements in the matrix increases as the holding time extends, resulting in a large number of carbides redissolved into the matrix, making the hardness of the alloy decrease; the hardness of the alloy at 14 h is less than that at 10 min. Under 1050 °C, the size and density of the secondary carbide increase significantly; extending the holding time will lead to the continuous reduction of the carbide rod that provides strength, thus, the hardness curve shows a downward trend.

2.
Nat Rev Nephrol ; 20(1): 21-36, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37684523

RESUMEN

Mammalian kidneys are specialized to maintain fluid and electrolyte homeostasis. The epithelial transport processes along the renal tubule that match output to input have long been the subject of experimental and theoretical study. However, emerging data have identified a new dimension of investigation: sex. Like most tissues, the structure and function of the kidney is regulated by sex hormones and chromosomes. Available data demonstrate sex differences in the abundance of kidney solute and electrolyte transporters, establishing that renal tubular organization and operation are distinctly different in females and males. Newer studies have provided insights into the physiological consequences of these sex differences. Computational simulations predict that sex differences in transporter abundance are likely driven to optimize reproduction, enabling adaptive responses to the nutritional requirements of serial pregnancies and lactation - normal life-cycle changes that challenge the ability of renal transporters to maintain fluid and electrolyte homeostasis. Later in life, females may also undergo menopause, which is associated with changes in disease risk. Although numerous knowledge gaps remain, ongoing studies will provide further insights into the sex-specific mechanisms of sodium, potassium, acid-base and volume physiology throughout the life cycle, which may lead to therapeutic opportunities.


Asunto(s)
Riñón , Caracteres Sexuales , Animales , Femenino , Humanos , Masculino , Riñón/fisiología , Túbulos Renales , Electrólitos , Sodio , Mamíferos
3.
Dev Cell ; 58(21): 2338-2358.e5, 2023 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-37673062

RESUMEN

Mammalian organs exhibit distinct physiology, disease susceptibility, and injury responses between the sexes. In the mouse kidney, sexually dimorphic gene activity maps predominantly to proximal tubule (PT) segments. Bulk RNA sequencing (RNA-seq) data demonstrated that sex differences were established from 4 and 8 weeks after birth under gonadal control. Hormone injection studies and genetic removal of androgen and estrogen receptors demonstrated androgen receptor (AR)-mediated regulation of gene activity in PT cells as the regulatory mechanism. Interestingly, caloric restriction feminizes the male kidney. Single-nuclear multiomic analysis identified putative cis-regulatory regions and cooperating factors mediating PT responses to AR activity in the mouse kidney. In the human kidney, a limited set of genes showed conserved sex-linked regulation, whereas analysis of the mouse liver underscored organ-specific differences in the regulation of sexually dimorphic gene expression. These findings raise interesting questions on the evolution, physiological significance, disease, and metabolic linkage of sexually dimorphic gene activity.


Asunto(s)
Riñón , Receptores Androgénicos , Animales , Femenino , Humanos , Masculino , Ratones , Expresión Génica , Regulación de la Expresión Génica , Riñón/metabolismo , Mamíferos/metabolismo , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Caracteres Sexuales
4.
J Physiol ; 2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-37622389

RESUMEN

Despite widespread and striking examples of physiological oscillations, their functional role is often unclear. Even glycolysis, the paradigm example of oscillatory biochemistry, has seen questions about its oscillatory function. Here, we take a systems approach to argue that oscillations play critical physiological roles, such as enabling systems to avoid desensitization, to avoid chronically high and therefore toxic levels of chemicals, and to become more resistant to noise. Oscillation also enables complex physiological systems to reconcile incompatible conditions such as oxidation and reduction, by cycling between them, and to synchronize the oscillations of many small units into one large effect. In pancreatic ß-cells, glycolytic oscillations synchronize with calcium and mitochondrial oscillations to drive pulsatile insulin release, critical for liver regulation of glucose. In addition, oscillation can keep biological time, essential for embryonic development in promoting cell diversity and pattern formation. The functional importance of oscillatory processes requires a re-thinking of the traditional doctrine of homeostasis, holding that physiological quantities are maintained at constant equilibrium values, a view that has largely failed in the clinic. A more dynamic approach will initiate a paradigm shift in our view of health and disease. A deeper look into the mechanisms that create, sustain and abolish oscillatory processes requires the language of nonlinear dynamics, well beyond the linearization techniques of equilibrium control theory. Nonlinear dynamics enables us to identify oscillatory ('pacemaking') mechanisms at the cellular, tissue and system levels.

5.
Genome Biol ; 24(1): 128, 2023 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-37221612

RESUMEN

BACKGROUND: Therapy resistance in cancer is often driven by a subpopulation of cells that are temporarily arrested in a non-proliferative G0 state, which is difficult to capture and whose mutational drivers remain largely unknown. RESULTS: We develop methodology to robustly identify this state from transcriptomic signals and characterise its prevalence and genomic constraints in solid primary tumours. We show that G0 arrest preferentially emerges in the context of more stable, less mutated genomes which maintain TP53 integrity and lack the hallmarks of DNA damage repair deficiency, while presenting increased APOBEC mutagenesis. We employ machine learning to uncover novel genomic dependencies of this process and validate the role of the centrosomal gene CEP89 as a modulator of proliferation and G0 arrest capacity. Lastly, we demonstrate that G0 arrest underlies unfavourable responses to various therapies exploiting cell cycle, kinase signalling and epigenetic mechanisms in single-cell data. CONCLUSIONS: We propose a G0 arrest transcriptional signature that is linked with therapeutic resistance and can be used to further study and clinically track this state.


Asunto(s)
Genómica , Neoplasias , Humanos , Puntos de Control del Ciclo Celular , Ciclo Celular , Mutagénesis
6.
bioRxiv ; 2023 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-37205355

RESUMEN

Mammalian organs exhibit distinct physiology, disease susceptibility and injury responses between the sexes. In the mouse kidney, sexually dimorphic gene activity maps predominantly to proximal tubule (PT) segments. Bulk RNA-seq data demonstrated sex differences were established from 4 and 8 weeks after birth under gonadal control. Hormone injection studies and genetic removal of androgen and estrogen receptors demonstrated androgen receptor (AR) mediated regulation of gene activity in PT cells as the regulatory mechanism. Interestingly, caloric restriction feminizes the male kidney. Single-nuclear multiomic analysis identified putative cis-regulatory regions and cooperating factors mediating PT responses to AR activity in the mouse kidney. In the human kidney, a limited set of genes showed conserved sex-linked regulation while analysis of the mouse liver underscored organ-specific differences in the regulation of sexually dimorphic gene expression. These findings raise interesting questions on the evolution, physiological significance, and disease and metabolic linkage, of sexually dimorphic gene activity.

7.
bioRxiv ; 2023 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-37131596

RESUMEN

Inference of gene regulatory networks (GRNs) can reveal cell state transitions from single-cell genomics data. However, obstacles to temporal inference from snapshot data are difficult to overcome. Single-nuclei multiomics data offer means to bridge this gap and derive temporal information from snapshot data using joint measurements of gene expression and chromatin accessibility in the same single cells. We developed popInfer to infer networks that characterize lineage-specific dynamic cell state transitions from joint gene expression and chromatin accessibility data. Benchmarking against alternative methods for GRN inference, we showed that popInfer achieves higher accuracy in the GRNs inferred. popInfer was applied to study single-cell multiomics data characterizing hematopoietic stem cells (HSCs) and the transition from HSC to a multipotent progenitor cell state during murine hematopoiesis across age and dietary conditions. From networks predicted by popInfer, we discovered gene interactions controlling entry to/exit from HSC quiescence that are perturbed in response to diet or aging.

8.
Adv Sci (Weinh) ; 10(16): e2300398, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37068177

RESUMEN

Aqueous Zn metal-based batteries have considerable potential as energy storage system; however, their application is extremely limited by dendrite development and poor reversibility. In this study, to overcome both challenges, F-doped carbon nanoparticles (FCNPs) are uniformly constructed on substrates (Ti, Zn, Cu, and steel) by a plasma-assisted surface modification, which endows reversible and uniform deposition of Zn metal. FCNPs with high surface charge density act as nucleation assistors and form numerous homogenous Zn nucleation sites toward Zn 3D growth, which improves Zn plating kinetic and results in uniform Zn deposition. Furthermore, the ZnF2  solid electrolyte interface generated during cycling contributes to rapid mass transfer and enhances Zn reversibility, but also suppresses the side reaction. Accordingly, the half-cell of P-Ti coupled with Zn exhibits an average Coulombic efficiency of 99.47% with 500 cycles. The symmetric cell of the P-Zn anode presents a lifespan of over 1500 h at the current density of 5 mA cm-2 . Notably, the cell works for 100 h at 50 mA cm-2 . It is believed that this ingenious surface modification broadens revolutionary methods for uniform metallic deposition, as well as the dendrite-free rechargeable batteries system.

9.
J Reconstr Microsurg ; 39(5): 334-342, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35952676

RESUMEN

BACKGROUND: Microsurgery is an indispensable tool of upper extremity reconstruction addressing defect coverage and the restoration of function. Perioperative anticoagulation and antiplatelet therapy are controversially discussed with impact on microsurgical outcome, but without clear evidence. This study aims to evaluate the impact of perioperative anticoagulation and antiplatelet therapy in microsurgical upper extremity reconstruction. METHODS: All eligible patients treated with microsurgical upper extremity reconstruction between January 2000 and July 2014 were included in a comparative analysis to define a superior anticoagulation and antiplatelet regime in a retrospective study. Endpoints were all major complications (e.g., total flap loss, arterial and venous thrombosis) as well as minor complication. RESULTS: A total of 183 eligible free flaps to the upper extremity were transferred in 169 patients. Altogether, 11 arterial (6.0%) and 9 venous (4.9%) thromboses, 11 total flap losses (6.0%), and 16 cases with hematoma (8.7%) were detected. In the subgroup analysis, patients who did not receive any heparin intraoperatively (n = 21; 11.5%) had a higher rate of major complications (p = 0.001), with total flap loss being the most frequent event (p = 0.004). A trend was shown for intraoperative bolus administration of 501 to 1,000 units unfractionated heparin (UFH) intravenously to have the lowest rate of major complications (p = 0.058). Intraoperative administration of acetylsalicylic acid (n = 13; 8.1%) did not have any influence on the rate of major complications. Postoperative anticoagulation with continuous UFH intravenously (n = 68; 37.2%) resulted in more frequent complications (p = 0.012), for example, an increased rate of total flap loss (p = 0.02) and arterial thrombosis (p = 0.02). CONCLUSION: The results of the present study favor administration of 501 to 1,000 units UFH intravenously as an intraoperative bolus (e.g., 750 units UFH intravenously). Postoperative low molecular weight heparin subcutaneous application in a prophylactic dose given once or twice a day was associated with less complications compared with continuous infusion of UFH, although continuously applied UFH may reflect an increased risk profile.


Asunto(s)
Colgajos Tisulares Libres , Trombosis , Humanos , Heparina , Heparina de Bajo-Peso-Molecular/efectos adversos , Anticoagulantes , Estudios Retrospectivos , Inhibidores de Agregación Plaquetaria , Reproducibilidad de los Resultados , Complicaciones Posoperatorias , Trombosis/tratamiento farmacológico
10.
J Pers Med ; 12(10)2022 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-36294702

RESUMEN

Background: There is no clear consensus on the optimal surgical strategy for providing safe coverage in salvage free flap surgery after total free flap failure. Methods: A retrospective study was conducted to evaluate patients with total failure of the primary free flap in lower extremity reconstruction between 2000 and 2017. Results: In a cohort of 1.016 patients, we identified 43 cases of total flap failure (4.2%). A total of 30 patients received a salvage free flap with a success rate of 83.3% (25/30). One patient received a secondary salvage free flap. Overall limb salvage after primary free flap loss was 83.7% (36/43). Conclusions: Microsurgical management of free flap loss in the lower extremity is challenging and requires a decisive re-evaluation of risk factors and alternative strategies. This should include reconsidering the flap choice with a tendency towards traditional and safe workhorse flaps, a low-threshold switch to different recipient vessels, including arteriovenous (AV) loops, bypasses (especially in case of venous insufficiency) and back-up procedures, such as negative pressure wound therapy or dermal regeneration templates with skin grafting in cases of lower demand and critically ill patients. We derived one suggestion from our previous practice: replacing perforator flaps with axial pattern flaps ("safe workhorses").

11.
Prog Biophys Mol Biol ; 174: 28-40, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35752348

RESUMEN

The tumor suppressor p53 oscillates in response to DNA double-strand breaks, a behavior that has been suggested to be essential to its anti-cancer function. Nearly all human cancers have genetic alterations in the p53 pathway; a number of these alterations have been shown to be oncogenic by experiment. These alterations include somatic mutations and copy number variations as well as germline polymorphisms. Intriguingly, they exhibit a mixed pattern of interactions in tumors, such as co-occurrence, mutual exclusivity, and paradoxically, mutual antagonism. Using a differential equation model of p53-Mdm2 dynamics, we employ Hopf bifurcation analysis to show that these alterations have a common mode of action, to abolish the oscillatory competence of p53, thereby, we suggest, impairing its tumor suppressive function. In this analysis, diverse genetic alterations, widely associated with human cancers clinically, have a unified mechanistic explanation of their role in oncogenesis.


Asunto(s)
Neoplasias , Proteína p53 Supresora de Tumor , Roturas del ADN de Doble Cadena , Variaciones en el Número de Copia de ADN , Humanos , Mutación , Neoplasias/genética , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
12.
Regen Biomater ; 8(2): rbab003, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33738117

RESUMEN

Associated with persistent oxidative stress, altered inflammatory responses, poor angiogenesis and epithelization, wound healing in diabetic patients is impaired. N-acetylcysteine (NAC) is reported to resist excess reactive oxygen species (ROS) production, prompt angiogenesis and maturation of the epidermis. Studies have revealed that graphene oxide (GO) can regulate cellular behavior and form cross-links with naturally biodegradable polymers such as collagen (COL) to construct composite scaffolds. Here, we reported a COL-based implantable scaffold containing a mixture of GO capable of the sustained delivery of NAC to evaluate the wound healing in diabetic rats. The morphological, physical characteristics, biocompatibility and NAC release profile of the GO-COL-NAC (GCN) scaffold were evaluated in vitro. Wound healing studies were performed on a 20 mm dorsal full-skin defect of streptozotocin (STZ)-induced diabetic rats. The injured skin tissue was removed at the 18th day post-surgery for histological analysis and determination of glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) activity. In diabetic rats, we confirmed that the GCN scaffold presented a beneficial effect in enhancing the wound healing process. Additionally, due to the sustained release of NAC, the scaffold may potentially induce the antioxidant defense system, upregulating the expression levels of the antioxidant enzymes in the wound tissue. The findings revealed that the antioxidant biocompatible composite collagen dressing could not only deliver NAC in situ for ROS inhibition but also promote the wound healing process. This scaffold with valuable therapy potential might enrich the approaches for surgeon in diabetic wound treatment in the future.

13.
Cancer Res ; 81(7): 1667-1680, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33558336

RESUMEN

Insights into oncogenesis derived from cancer susceptibility loci (SNP) hold the potential to facilitate better cancer management and treatment through precision oncology. However, therapeutic insights have thus far been limited by our current lack of understanding regarding both interactions of these loci with somatic cancer driver mutations and their influence on tumorigenesis. For example, although both germline and somatic genetic variation to the p53 tumor suppressor pathway are known to promote tumorigenesis, little is known about the extent to which such variants cooperate to alter pathway activity. Here we hypothesize that cancer risk-associated germline variants interact with somatic TP53 mutational status to modify cancer risk, progression, and response to therapy. Focusing on a cancer risk SNP (rs78378222) with a well-documented ability to directly influence p53 activity as well as integration of germline datasets relating to cancer susceptibility with tumor data capturing somatically-acquired genetic variation provided supportive evidence for this hypothesis. Integration of germline and somatic genetic data enabled identification of a novel entry point for therapeutic manipulation of p53 activities. A cluster of cancer risk SNPs resulted in increased expression of prosurvival p53 target gene KITLG and attenuation of p53-mediated responses to genotoxic therapies, which were reversed by pharmacologic inhibition of the prosurvival c-KIT signal. Together, our results offer evidence of how cancer susceptibility SNPs can interact with cancer driver genes to affect cancer progression and identify novel combinatorial therapies. SIGNIFICANCE: These results offer evidence of how cancer susceptibility SNPs can interact with cancer driver genes to affect cancer progression and present novel therapeutic targets.


Asunto(s)
Resistencia a Antineoplásicos/genética , Neoplasias/genética , Neoplasias/patología , Proteína p53 Supresora de Tumor/genética , Animales , Antineoplásicos/uso terapéutico , Biomarcadores Farmacológicos/metabolismo , Carcinogénesis/genética , Estudios de Casos y Controles , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Mutación de Línea Germinal/fisiología , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Mutación Missense , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Polimorfismo de Nucleótido Simple/fisiología , Pronóstico , Factores de Riesgo , Transducción de Señal/genética , Resultado del Tratamiento
14.
J Reconstr Microsurg ; 37(7): 608-616, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33592633

RESUMEN

BACKGROUND: Many microsurgeons fear high complication rates and free flap loss when vein grafting is necessary to restore blood flow at the recipient site. The aims of this study were to comparatively analyze surgical outcomes of interposition vein grafts (VG) in microsurgical primary lower extremity reconstruction and secondary salvage procedures. METHODS: A retrospective study was conducted on 58 patients undergoing free flap transfers with vein grafting for primary lower extremity reconstruction (cohort 1) and secondary salvage procedures (cohort 2) between 2002 and 2016. A matched-pair analysis of both cohorts and 58 non-VG flaps was performed. Patient data, preoperative conditions, flap and vein graft characteristics, postoperative outcomes such as flap failure, thrombosis, and wound complications were analyzed. RESULTS: A total of 726 free flap transfers were performed. In total, 36 primary reconstructions (5%) utilized 41 interposition VG (cohort 1). Postoperative vascular compromise was observed in 65 free flaps (9%). In total, 22 out of 65 secondary salvage procedures (33.8%) utilized 26 interposition VG (cohort 2). Two total flap losses occurred in each cohort (5.6 vs. 9.1%; p = 0.63). Postoperative complications were observed in 38.9% of free flaps in cohort 1 and 72.7% in cohort 2 (p = 0.01). Takeback for microvascular compromise was comparable in both cohorts (19.4 vs. 22.7%; p = 0.75). Microvascular complications occurred more often in cohort 2 (22.7%) than in cohort 1 (8.3%; p = 0.28). Lower extremity salvage rates were high among both cohorts (94.4 vs. 90.9%; p = 0.63). Matched-pair analysis did not show any relevant differences on takebacks and flap loss (p = 0.32 and p = 1.0). CONCLUSION: In complex lower extremity reconstructions, VG can be performed with acceptable complication rates and outcomes in primary and especially in salvage cases. With careful planning and a consistent surgical protocol, VG can provide reliable success rates in limb salvage.


Asunto(s)
Colgajos Tisulares Libres , Procedimientos de Cirugía Plástica , Humanos , Recuperación del Miembro , Extremidad Inferior/cirugía , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento
15.
J Reconstr Microsurg ; 37(6): 492-502, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33212513

RESUMEN

BACKGROUND: Risk stratification, economic pressure, and a flat learning curve make the realization and development of proper microsurgical skills and competences a challenging task in the daily clinical practice. In previous studies, we were able to show that microsurgical procedures, e.g., free flaps and replantations, are safe training procedures and teachable in daily clinical practice in view of certain issues of risk stratification. The present study aims to evaluate further improvements in terms of safety and complication rates for free flaps as a training procedure after introduction and continuous implementation of a structured in-house training curriculum for microsurgical skills and competences and a 24-hour free accessible microsurgical training facility for the plastic surgery resident. METHODS: This retrospective comparative cohort study was conducted to review whether microsurgical skills for free flaps to the lower extremity can further be improved after implementation of the curriculum and a 24-hour accessible training facility. Therefore, we compared cohort A before (2009-2012) and B after (2014-2017) implementation. Patient demographics, procedural characteristics, and outcome parameters for free tissue transfer of the lower extremity were evaluated. RESULTS: The comparison of both cohorts showed a significantly reduced postoperative complication rate for cohort B (p <0.05). Furthermore, operation time was shorter, and the hospital stay could be significantly decreased (p <0.01). Workhorse flaps for plastic surgical training were the anterior lateral thigh (ALT) flap or the musculus latissimus dorsi (LD) flap. However, even more complex procedures with arteriovenous loops could be safely performed by plastic surgery residents under the supervision of the senior surgeon in exceptional cases. CONCLUSION: The implementation of a regularly held, microsurgical in-house training curriculum with 24-hour accessible training facility improves procedural and outcome parameters for free flaps to the lower extremity for surgical residents and is an elementary part of skills and competency training. However, risk stratification, repeated surgical exposure, expertise, and institutional infrastructures are essential and must be taken into consideration.


Asunto(s)
Colgajos Tisulares Libres , Internado y Residencia , Procedimientos de Cirugía Plástica , Estudios de Cohortes , Curriculum , Humanos , Extremidad Inferior , Estudios Retrospectivos , Resultado del Tratamiento
16.
J Med Genet ; 58(6): 392-399, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-32591342

RESUMEN

BACKGROUND: Height and other anthropometric measures are consistently found to associate with differential cancer risk. However, both genetic and mechanistic insights into these epidemiological associations are notably lacking. Conversely, inherited genetic variants in tumour suppressors and oncogenes increase cancer risk, but little is known about their influence on anthropometric traits. METHODS: By integrating inherited and somatic cancer genetic data from the Genome-Wide Association Study Catalog, expression Quantitative Trait Loci databases and the Cancer Gene Census, we identify SNPs that associate with different cancer types and differential gene expression in at least one tissue type, and explore the potential pleiotropic associations of these SNPs with anthropometric traits through SNP-wise association in a cohort of 500,000 individuals. RESULTS: We identify three regulatory SNPs for three important cancer genes, FANCA, MAP3K1 and TP53 that associate with both anthropometric traits and cancer risk. Of particular interest, we identify a previously unrecognised strong association between the rs78378222[C] SNP in the 3' untranslated region (3'-UTR) of TP53 and both increased risk for developing non-melanomatous skin cancer (OR=1.36 (95% 1.31 to 1.41), adjusted p=7.62E-63), brain malignancy (OR=3.12 (2.22 to 4.37), adjusted p=1.43E-12) and increased standing height (adjusted p=2.18E-24, beta=0.073±0.007), lean body mass (adjusted p=8.34E-37, beta=0.073±0.005) and basal metabolic rate (adjusted p=1.13E-31, beta=0.076±0.006), thus offering a novel genetic link between these anthropometric traits and cancer risk. CONCLUSION: Our results clearly demonstrate that heritable variants in key cancer genes can associate with both differential cancer risk and anthropometric traits in the general population, thereby lending support for a genetic basis for linking these human phenotypes.


Asunto(s)
Pesos y Medidas Corporales , Neoplasias/genética , Oncogenes , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Antropometría , Estudios de Cohortes , Femenino , Ligamiento Genético , Pleiotropía Genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Sitios de Carácter Cuantitativo , Carácter Cuantitativo Heredable , Medición de Riesgo
17.
J Plast Reconstr Aesthet Surg ; 73(9): 1675-1682, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32473855

RESUMEN

In cases with difficult scaphoid screw placement due to small, fragile bone fragments, or transplants and insufficient space, the internal Kirschner wire fixation is a fallback option; however, controversy remains regarding its stability, safety, and outcome. Between 2001 and 2011, 95 patients were treated in our center (n = 80 with cannulated compression screws and n = 15 with Kirschner wires), and retrospectively analyzed. The outcome measurements included the analysis of patient data, union rate and analysis of functional measures, and quality of life. Bony reconstructions were performed with Vascularized Bone Grafts (VBG) based on the 1,2-Intercompartmental Supraretinacular Artery (ICSRA) , Medial Femoral Condyle (MFC)-VBG, cancellous bone, and iliac crest grafts. Bony healing and functional outcome showed no significant differences between Kirschner wire fixation and cannulated compression screws, although significantly more 1,2-ICSRA-VBG were treated with Kirschner wires. Although predominantly used as an intraoperative fallback option, our data demonstrate that Kirschner wire internal fixation can be safe and reliable, with comparable bony union rates and excellent functional outcomes.


Asunto(s)
Tornillos Óseos , Hilos Ortopédicos , Fijación Interna de Fracturas/instrumentación , Fracturas no Consolidadas/cirugía , Hueso Escafoides/cirugía , Adulto , Hueso Esponjoso/trasplante , Evaluación de la Discapacidad , Femenino , Curación de Fractura , Fuerza de la Mano , Humanos , Ilion/trasplante , Masculino , Radio (Anatomía)/trasplante , Rango del Movimiento Articular , Estudios Retrospectivos
18.
Ann Transl Med ; 8(7): 475, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32395519

RESUMEN

BACKGROUND: As a permanent soft tissue filler, the use of polyacrylamide hydrogel (PAAG) has been banned due to its myriad complications. However, a large number of symptomatic and asymptomatic patients whose breasts were augmented with the gel injection have continued to seek medical advice. This study aimed to explore standardized clinical management of breast augmentation with PAAG. METHODS: The authors retrospectively collected the data of a total of 325 patients following PAAG injection for breast augmentation from 2003 to 2018. Magnetic resonance imaging (MRI) was performed preoperatively to disclose the general distribution of the gel and its infiltration into the muscle and gland. Debridement surgery, including the PAAG evacuation, pathologic tissue excision, and pocket irrigation via the periareolar incision, was performed. Immediate breast reconstruction (IBR) using silicone prostheses was carried out on 86 patients and delayed breast reconstruction (DBR) was performed on 35 patients. RESULTS: Most of the patients in the group were satisfied with their surgical outcome, their symptoms disappeared after the debridement surgery, and they experienced no relapse or recurrence. Unfortunately, for most of the cases, it was extremely difficult to remove the PAAG completely-however, improved quality of life as seen through the BREAST-Q evaluation. CONCLUSIONS: With the guidance of MRI images, surgery, including PAAG evacuation, pathologic tissue excision, and pocket irrigation via the periareolar incision, was a reliable method to ensure the maximal removal of the PAAG. Immediate or secondary breast reconstruction with sub-glandular placement of silicone prostheses showed a satisfactory mid-term effect.

19.
J Plast Reconstr Aesthet Surg ; 73(7): 1318-1325, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32430265

RESUMEN

BACKGROUND: Application of distant skin flaps in facial defect reconstruction has limitations such as leaving a patch like appearance and being restricted by the length of the vascular pedicles. Leveraging the abundance of blood supply from superficial muscular aponeurotic system (SMAS), a local skin flap pedicled by SMAS can be used to avoid the aforementioned problems. Herein, we report the clinical application as well as the anatomical study of SMAS-pedicled skin flaps. METHODS: This study enrolled patients who underwent facial defect reconstruction surgery between 2013 and 2018 using SMAS-pedicled skin flaps. The flaps were designed according to the size and location of the defect. A follow-up was performed to evaluate the treatment outcomes and incidence of adverse events. In addition, six cadaveric heads were used to perform an anatomical study on the distribution and blood supply of SMAS. RESULTS: Twenty-three cases underwent the defect reconstruction surgery in the frontal regions (three cases), temporal region (four cases), periocular region (four cases), nasal region (seven cases), and other regions (five cases). All the flaps survived well. During the follow-up period up to 12 months, the flaps showed a satisfactory appearance, blood supply, and elasticity. The distribution and blood supply of SMAS at different anatomical regions have been successfully observed. Abundant vascular networks could be found in the SMAS layer. CONCLUSION: Based on the broad distribution of SMAS and the abundant blood supply, an SMAS-pedicled skin flap could be flexibly designed and versatilely used to reconstruct post-traumatic or post-excisional facial defects.


Asunto(s)
Aponeurosis/anatomía & histología , Cara/cirugía , Procedimientos de Cirugía Plástica/métodos , Colgajos Quirúrgicos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aponeurosis/irrigación sanguínea , Aponeurosis/trasplante , Cadáver , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
20.
J Reconstr Microsurg ; 36(2): 127-135, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31546263

RESUMEN

BACKGROUND: In elderly patients, complex soft tissue defects are increasingly observed due to the prolonged life expectancy and accompanying comorbidities. The aim of this study is to evaluate whether free tissue transfer is safe in very old patients without additional risk and complications. METHODS: All patients older than 65 years undergoing free tissue transfer between November 2007 and September 2016 were reviewed in a retrospective study. Two cohorts were compared regarding perioperative morbidity and postoperative outcome (cohort 1 [old patients, ages 65-79]; cohort 2 [very old patients, ages ≥ 80]). RESULTS: In total, 256 patients were included in the study (cohort 1 [n = 217]; cohort 2 [n = 39]). Overall, 262 free flaps were performed due to a second microsurgical reconstruction in six cases. No statistically significant differences between cohorts were observed regarding surgical complications, total flap losses, and mortality. Detailed evaluation of cohort 2 revealed a significant learning curve during the observation period regarding the perioperative management and procedure of soft tissue reconstruction: operation length as well as postoperative intensive care unit stay decreased significantly over time (p < 0.05) and also surgical complications showed a positive trend (p = 0.07). We ascertained a shift toward a "more reliable" flap selection from predominantly anterolateral thigh flap) to axial flaps such as rectus abdominis and latissimus dorsi flaps. CONCLUSION: Our study showed that age is not associated with an increased risk of postoperative complications. Reliable muscle free flaps, two-stage procedures, and safe vascular supply are important strategic aspects to achieve microvascular tissue transfer with high success rates in geriatric patients.


Asunto(s)
Colgajos Tisulares Libres , Mamoplastia , Procedimientos de Cirugía Plástica , Anciano , Humanos , Complicaciones Posoperatorias/epidemiología , Recto del Abdomen , Estudios Retrospectivos , Resultado del Tratamiento
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