Infection Rates of an Intraoral Versus Extraoral Approach to Mandibular Fracture Repairs are Equal: A Systematic Review and Meta-Analysis.

PURPOSE: This study investigates whether the intraoral approach to mandibular open reduction and internal fixation, through exposure to the oral cavity's microbiome, results in higher infection rates compared to the extraoral approach, thus addressing a critical public health concern, potentially offering an opportunity to reduce health-care costs, and aiming to guide effective clinical practice. METHODS: In this systematic review with meta-analyses, a review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A comprehensive literature search was conducted using Embase and PubMed for articles published between 1989 and 2023. Inclusion criteria targeted studies on open reduction and internal fixation mandibular fractures comparing intraoral and extraoral approaches and reporting infection rates. Exclusion criteria eliminated non-English articles, case reports, and studies with insufficient approach-specific data. The primary outcome was the postoperative infection rate, with surgical approach as the predictor. Covariates such as age, sex, diabetes, and smoking status were included when reported. Data were analyzed using R software, employing random-effects models due to anticipated heterogeneity (I2 statistics). RESULTS: From 61 studies, 11 provided direct comparisons involving 1,317 patients-937 intraoral and 380 extraoral. Infection rates were 5.9% for intraoral and 10% for extraoral approaches. Pooled relative risk was 0.94 [95% confidence interval, 0.63, 1.39], suggesting no significant risk difference. Prevalence of infections was estimated at 9% for intraoral and 6.1% for extraoral procedures, with significant heterogeneity (I2 = 84% for intraoral and 56% for extraoral). CONCLUSION: Our meta-analysis found no significant difference in infection rates between the two approaches. There is opportunity to expand on reporting complication rates comparing the various approaches to mandibular fixation. Until these data are presented, surgeon preference may dictate the operative approach to expose the mandible for reduction and fixation.

The impact of amplitude modulation frequency in harmonic motion imaging on inclusion characterization.

OBJECTIVE: Ultrasound elasticity imaging techniques aim to provide a non-invasive characterization of tissue mechanical properties to detect pathological changes and monitor disease progression. Harmonic motion imaging (HMI) is an ultrasound-based elasticity imaging technique that utilizes an oscillatory acoustic radiation force to induce localized displacements and estimate relative tissue stiffness. Previous studies have applied a low amplitude modulation (AM) frequency of 25 or 50 Hz in HMI to assess the mechanical properties of different tissue types. In this study, we investigate the dependence of AM frequency in HMI and whether the frequency can be adjusted based on the size and mechanical properties of the underlying medium for enhanced image contrast and inclusion detection. METHODS: A tissue-mimicking phantom with embedded inclusions at different sizes and stiffnesses was imaged within a range of AM frequencies from 25 to 250 Hz at 25-Hz step size. DISCUSSION: The AM frequency at which the maximum contrast and CNR are achieved depends on the size and stiffness of the inclusions. A general trend shows that contrast and CNR peak at higher frequencies for smaller inclusions. In addition, for some inclusions with the same size but different stiffnesses, the optimized AM frequency increases with the stiffness of the inclusion. Nevertheless, there is a shift between the frequencies at which the contrast peaks and those with maximum CNR. Finally, in agreement with the phantom findings, imaging an ex-vivo human specimen with a 2.7-cm breast tumor at a range of AM frequencies showed that the highest contrast and CNR are achieved at the AM frequency of 50 Hz. CONCLUSION: These findings indicate that the AM frequency can be optimized in different applications of HMI, especially in the clinic, for improved detection and characterization of tumors with different geometries and mechanical properties.

An Efficient and Multi-Focal Focused Ultrasound Technique for Harmonic Motion Imaging.

Harmonic motion imaging (HMI) is an ultrasound-based elasticity imaging technique that utilizes oscillatory acoustic radiation force to estimate the mechanical properties of tissues, as well as monitor high-intensity focused ultrasound (HIFU) treatment. Conventionally, in HMI, a focused ultrasound (FUS) transducer generates oscillatory tissue displacements, and an imaging transducer acquires channel data for displacement estimation, with each transducer being driven with a separate system. The fixed position of the FUS focal spot requires mechanical translation of the transducers, which can be a time-consuming and challenging procedure. In this study, we developed and characterized a new HMI system with a multi-element FUS transducer with the capability of electronic focal steering of ±5 mm and ±2 mm from the geometric focus in the axial and lateral directions, respectively. A pulse sequence was developed to drive both the FUS and imaging transducers using a single ultrasound data acquisition (DAQ) system. The setup was validated on a tissue-mimicking phantom with embedded inclusions. Integrating beam steering with the mechanical translation of the transducers resulted in a consistent high contrast-to-noise ratio (CNR) for the inclusions with Young's moduli of 22 and 44 kPa within a 5-kPa background while the data acquisition speed is increased by 4.5-5.2-fold compared to the case when only mechanical movements were applied. The feasibility of simultaneous generation of multiple foci and tracking the induced displacements is demonstrated in phantoms for applications where imaging or treatment of a larger region is needed. Moreover, preliminary feasibility is shown in a human subject with a breast tumor, where the mean HMI displacement within the tumor was about 4 times lower than that within perilesional tissues. The proposed HMI system facilitates data acquisition in terms of flexibility and speed and can be potentially used in the clinic for breast cancer imaging and treatment.

Regulation of P-glycoprotein and Breast Cancer Resistance Protein Expression Induced by Focused Ultrasound-Mediated Blood-Brain Barrier Disruption: A Pilot Study.

The blood-brain barrier (BBB) controls brain homeostasis; it is formed by vascular endothelial cells that are physically connected by tight junctions (TJs). The BBB expresses efflux transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), which limit the passage of substrate molecules from blood circulation to the brain. Focused ultrasound (FUS) with microbubbles can create a local and reversible detachment of the TJs. However, very little is known about the effect of FUS on the expression of efflux transporters. We investigated the in vivo effects of moderate acoustic pressures on both P-gp and BCRP expression for up to two weeks after sonication. Magnetic resonance-guided FUS was applied in the striatum of 12 rats. P-gp and BCRP expression were determined by immunohistochemistry at 1, 3, 7, and 14 days postFUS. Our results indicate that FUS-induced BBB opening is capable of (i) decreasing P-gp expression up to 3 days after sonication in both the treated and in the contralateral brain regions and is capable of (ii) overexpressing BCRP up to 7 days after FUS in the sonicated regions only. Our findings may help improve FUS-aided drug delivery strategies by considering both the mechanical effect on the TJs and the regulation of P-gp and BCRP.

Synchronous temperature variation monitoring during ultrasound imaging and/or treatment pulse application: a phantom study.

Ultrasound attenuation through soft tissues can produce an acoustic radiation force (ARF) and heating. The ARF-induced displacements and temperature evaluations can reveal tissue properties and provide insights into focused ultrasound (FUS) bio-effects. In this study, we describe an interleaving pulse sequence tested in a tissue-mimicking phantom that alternates FUS and plane-wave imaging pulses at a 1 kHz frame rate. The FUS is amplitude modulated, enabling the simultaneous evaluation of tissue-mimicking phantom displacement using harmonic motion imaging (HMI) and temperature rise using thermal strain imaging (TSI). The parameters were varied with a spatial peak temporal average acoustic intensity (I spta ) ranging from 1.5 to 311 W.cm-2, mechanical index (MI) from 0.43 to 4.0, and total energy (E) from 0.24 to 83 J.cm-2. The HMI and TSI processing could estimate displacement and temperature independently for temperatures below 1.80°C and displacements up to ~117 µm (I spta <311 W.cm-2, MI<4.0, and E<83 J.cm-2) indicated by a steady-state tissue-mimicking phantom displacement throughout the sonication and a comparable temperature estimation with simulations in the absence of tissue-mimicking phantom motion. The TSI estimations presented a mean error of ±0.03°C versus thermocouple estimations with a mean error of ±0.24°C. The results presented herein indicate that HMI can operate at diagnostic-temperature levels (i.e., <1°C) even when exceeding diagnostic acoustic intensity levels (720 mW.cm-2 < I spta < 207 W.cm-2). In addition, the combined HMI and TSI can potentially be used for simultaneous evaluation of safety during tissue elasticity imaging as well as FUS mechanism involved in novel ultrasound applications such as ultrasound neuromodulation and tumor ablation.

Safety evaluation of a clinical focused ultrasound system for neuronavigation guided blood-brain barrier opening in non-human primates.

An emerging approach with potential in improving the treatment of neurodegenerative diseases and brain tumors is the use of focused ultrasound (FUS) to bypass the blood-brain barrier (BBB) in a non-invasive and localized manner. A large body of pre-clinical work has paved the way for the gradual clinical implementation of FUS-induced BBB opening. Even though the safety profile of FUS treatments in rodents has been extensively studied, the histological and behavioral effects of clinically relevant BBB opening in large animals are relatively understudied. Here, we examine the histological and behavioral safety profile following localized BBB opening in non-human primates (NHPs), using a neuronavigation-guided clinical system prototype. We show that FUS treatment triggers a short-lived immune response within the targeted region without exacerbating the touch accuracy or reaction time in visual-motor cognitive tasks. Our experiments were designed using a multiple-case-study approach, in order to maximize the acquired data and support translation of the FUS system into human studies. Four NHPs underwent a single session of FUS-mediated BBB opening in the prefrontal cortex. Two NHPs were treated bilaterally at different pressures, sacrificed on day 2 and 18 post-FUS, respectively, and their brains were histologically processed. In separate experiments, two NHPs that were earlier trained in a behavioral task were exposed to FUS unilaterally, and their performance was tracked for at least 3 weeks after BBB opening. An increased microglia density around blood vessels was detected on day 2, but was resolved by day 18. We also detected signs of enhanced immature neuron presence within areas that underwent BBB opening, compared to regions with an intact BBB, confirming previous rodent studies. Logistic regression analysis showed that the NHP cognitive performance did not deteriorate following BBB opening. These preliminary results demonstrate that neuronavigation-guided FUS with a single-element transducer is a non-invasive method capable of reversibly opening the BBB, without substantial histological or behavioral impact in an animal model closely resembling humans. Future work should confirm the observations of this multiple-case-study work across animals, species and tasks.

Harmonic motion imaging of human breast masses: an in vivo clinical feasibility.

Non-invasive diagnosis of breast cancer is still challenging due to the low specificity of the imaging modalities that calls for unnecessary biopsies. The diagnostic accuracy can be improved by assessing the breast tissue mechanical properties associated with pathological changes. Harmonic motion imaging (HMI) is an elasticity imaging technique that uses acoustic radiation force to evaluate the localized mechanical properties of the underlying tissue. Herein, we studied the in vivo feasibility of a clinical HMI system to differentiate breast tumors based on their relative HMI displacements, in human subjects. We performed HMI scans in 10 female subjects with breast masses: five benign and five malignant masses. Results revealed that both benign and malignant masses were stiffer than the surrounding tissues. However, malignant tumors underwent lower mean HMI displacement (1.1 ± 0.5 µm) compared to benign tumors (3.6 ± 1.5 µm) and the adjacent non-cancerous tissue (6.4 ± 2.5 µm), which allowed to differentiate between tumor types. Additionally, the excised breast specimens of the same patients (n = 5) were imaged post-surgically, where there was an excellent agreement between the in vivo and ex vivo findings, confirmed with histology. Higher displacement contrast between cancerous and non-cancerous tissue was found ex vivo, potentially due to the lower nonlinearity in the elastic properties of ex vivo tissue. This preliminary study lays the foundation for the potential complementary application of HMI in clinical practice in conjunction with the B-mode to classify suspicious breast masses.

Displacement Imaging for Focused Ultrasound Peripheral Nerve Neuromodulation.

Focused ultrasound (FUS) is an emerging technique for neuromodulation due to its noninvasive application and high depth penetration. Recent studies have reported success in modulation of brain circuits, peripheral nerves, ion channels, and organ structures. In particular, neuromodulation of peripheral nerves and the underlying mechanisms remain comparatively unexplored in vivo. Lack of methodologies for FUS targeting and monitoring impede further research in in vivo studies. Thus, we developed a method that non-invasively measures nerve engagement, via tissue displacement, during FUS neuromodulation of in vivo nerves using simultaneous high frame-rate ultrasound imaging. Using this system, we can validate, in real-time, FUS targeting of the nerve and characterize subsequent compound muscle action potentials (CMAPs) elicited from sciatic nerve activation in mice using 0.5 to 5 ms pulse durations and 22 - 28 MPa peak positive stimulus pressures at 4 MHz. Interestingly, successful motor excitation from FUS neuromodulation required a minimum interframe nerve displacement of 18 µm without any displacement incurred at the skin or muscle levels. Moreover, CMAPs detected in mice monotonically increased with interframe nerve displacements within the range of 18 to 300 µm . Thus, correlation between nerve displacement and motor activation constitutes strong evidence FUS neuromodulation is driven by a mechanical effect given that tissue deflection is a result of highly focused acoustic radiation force.

Protocolo de adquisición de imágenes diagnósticas por termografía infrarroja / Acquisition protocol of diagnostic imaging by infrared thermography

Introducción: en aplicaciones biomédicas, la termografía infrarroja ha permitido visualizar el patrón de distribución de temperatura de la piel y el tejido subyacente, permitiendo diagnosticar problemas vasculares o nerviosos y, particularmente, trastornos en la termorregulación como el fenómeno de Raynaud y la intolerancia al frío. Sin embargo, las publicaciones no detallan el protocolo de adquisiciónde imágenes ni validan el mismo; factores determinantes para la calidad y relevancia de la informacióndiagnóstica obtenida. Objetivo: diseñar y validar un protocolo de adquisición de imágenes por termografía infrarroja para analizar la termorregulación en la mano. Materiales y métodos: Se diseñó un nuevo protocolo de adquisición de imágenes por termografía infrarroja utilizando un estímulofrío en la mano. Se analizaron estadísticamente regiones de interés de imágenes termográficas de 18 mediciones intrasujeto en un único sujeto y mediciones intersujeto en 17 individuos sanos. Resultados: En las mediciones intrasujeto e intersujeto se encontró que 10 minutos después del estímulo frío el porcentaje de recuperación de la temperatura fue cercano al 100%, excepto en un individuo en el cual, a pesar de no reportar enfermedades o lesiones previas, la punta de los dedos después del estímulo alcanzó apenas los 28 ºC. La prueba de fatiga en uno de los sujetos sanos mostró alteraciones en el proceso de termorregulación de la mano cuando el protocolo se repite en corto tiempo.

Introduction: in biomedical applications, infrared thermography has allowed to visualize the temperaturedistribution patterns of skin and underlying tissue, allowing the diagnosis of vascular or nervous disorders, particularly disturbances in the thermoregulation process as Raynaud’s phenomenon and cold intolerance. However, most papers not detailed the images acquisition protocol or its validation, being these two determining factors to the quality and relevance of the obtained diagnostic information.Objective: To design and validate an acquisition protocol of diagnostic imaging by infrared thermographyto analyze the thermoregulation process in hand. Material and methods: It was designed a new acquisition protocol of diagnostic imaging by infrared thermography using a cold stimulus in hand. It was statistically analyzed the regions of interest of thermographic images of 18 intrasubject measurements (in one individual) and intersubject measurements in 17 healthy individuals. Results: In the intrasubject and intersubject measurements, it found that 10 minutes after the cold stimulus the temperature measured was close to 100% of initial temperature, except for one of healthy subjects who, despite not report diseases or previous injuries, the temperature of the fingertips after stimulus barely reached 28 °C. The fatigue test in one healthy subject presents alterations in the thermoregulation process in hand when the protocol was repeated in a short time.

Vibroacoustography for the assessment of total hip arthroplasty

OBJECTIVES: This paper proposes imaging with 3-dimensional vibroacoustography for postoperatively assessing the uncovered cup area after total hip arthroplasty as a quantitative criterion to evaluate implant fixation. METHODS: A phantom with a bone-like structure covered by a tissue-mimicking material was used to simulate a total hip arthroplasty case. Vibroacoustography images of the uncovered cup region were generated using a two-element confocal ultrasound transducer and a hydrophone inside a water tank. Topological correction based on the geometry of the implant was performed to generate a 3-dimensional representation of the vibroacoustography image and to accurately evaluate the surface. The 3-dimensional area obtained by the vibroacoustography approach was compared to the area evaluated by a 3-dimensional motion capture system. RESULTS: The vibroacoustography technique provided high-resolution, high-contrast, and speckle-free images with less sensitivity to the beam incidence. Using a 3-dimensional-topology correction of the image, we accurately estimated the uncovered area of the implant with a relative error of 8.1% in comparison with the motion capture system measurements. CONCLUSION: Measurement of the cup coverage after total hip arthroplasty has not been well established; however, the covered surface area of the acetabular component is one of the most important prognostic factors. The preliminary results of this study show that vibroacoustography is a 3-dimensional approach that can be used to postoperatively evaluate total hip arthroplasty. The favorable results also provide an impetus for exploring vibroacoustography in other bone or implant surface imaging applications. .

[Extrapulmonary small-cell lung cancer]. / Metastasiertes kleinzelliges Bronchialkarzinom ohne nachweisbaren Primärtumor.

We report on a 61-year-old male patient who was admitted due to dysphagia, hoarseness and stridor. CT showed extensive metastasis to the thyroid and left adrenal gland. Histology revealed small-cell lung cancer. A primary tumour could not be detected in the lungs and mediastinum. Good symptom control could be achieved by administration of platinum-based chemotherapy.

[Non-small-cell carcinoma of the lung with invasive Aspergillus infection after chemotherapy]. / Sepsis und Aspergillose bei einer Patientin mit nicht-kleinzelligem Lungenkarzinom.

HISTORY: A 56-year-old woman had two years previously undergone a neck dissection and subsequent adjuvant radiotherapy for an adenocarcinoma at the base of the tongue (pT2NOMOG2) when a percutaneous endoscopic gastrostomy (PEG) catheter had been placed. She was now admitted for chemotherapy, recent onset of severe pain in the left hip and knee having been caused by metastasis of a non-small-cell lung carcinoma (NSCLC). She was cachectic and in a reduced general condition (Karnofsky index 80), but had recently only occasionally used the PEG catheter. There were no inflammatory changes of the skin at the site of the PEG. TREATMENT, COURSE AND OUTCOME: The first chemotherapy cycle was initially without complication, but after a week the patient's general condition deteriorated and she developed nausea, fever and pain around the markedly inflamed site of the PEG catheter insertion. Laboratory tests indicated severe neutropenia. Intensive antibiotic and antimycotic treatment at first brought about some improvement, but she died 11 days after admission. Necropsy revealed invasive aspergillosis, with the PEG as the portal of entry and spreading to the stomach and intestines, where numerous hyphae were identified. There had also been a disseminated intravascular coagulopathy. CONCLUSION: Bacterial infections (and occasionally, but difficult to diagnose, fungal infection) are quite common as a result of neutropenia during chemotherapy of solid tumors. Various risk factors, including reduced general condition and weight loss, must be individually assessed in the prevention or treatment of associated infectious complications in such cases.

[Analysis of treatment outcomes in two patient cohorts (2004-2005 and 2007-2008) with limited and extensive disease small-cell lung cancer]. / Vergleich von Behandlungsergebnissen in zwei Patientengruppen (2004-2005 und 2007-2008) mit einem kleinzelligen Bronchialkarzinom im begrenzten und metastasierten Krankheitsstadium.

PURPOSE: The aim of this retrospective study was to compare patient characteristics, treatment patterns and treatment results in two groups of patients with limited disease (LD) and extensive disease (ED) small-cell lung cancer (SCLC) in 2004 - 2005 vs. 2007 - 2008. PATIENTS AND METHODS: We included all patients with LD or ED SCLC in this retrospective analysis who were diagnosed in our department in the periods 2004 - 2005 and 2007 - 2008. We collected data on patient characteristics, chemotherapy, radiotherapy, treatment response and median survival. Statistical analyses were separately performed for patients in LD and ED SCLC. RESULTS: 109 patients had LD SCLC. The response rate on first-line therapy was 74 %. More than half of the cases had recurrent disease. Second-line treatment was given to about two thirds of these patients. Third-line therapy was administered in around 15 % of all cases. Prophylactic cranial irradiation was performed more frequently from 2007 - 2008. The median survival was 17 months. There were no statistically significant differences regarding patient characteristics and treatment results. ED SCLC was present in 188 patients. The response rate was around 68 %. All patients relapsed, second-line therapy was administered in half of these cases; third-line therapy in 10 % of all cases. No statistically significant differences were detected between the two time frames. Median survival was 10 months. CONCLUSION: Overall, no statistically significant differences were present for patients with LD and ED SCLC in 2004 - 2005 vs. 2007 - 2008. Prophylactic cranial irradiation was employed more frequently in LD SCLC from 2007.

[Late recurrence of renal cell carcinoma in a solitary enlarged paratracheal lymph node]. / Spätrezidiv eines Nierenzellkarzinoms in einem singulären vergrößerten paratrachealen Lymphknoten.

We report on a 67-year-old male patient who had undergone treatment for renal cell carcinoma 19 years previously. A CT scan showed a solitary enlarged lymph node in the right upper paratracheal region. A specimen was obtained by endobronchial ultrasound with transbronchial needle aspiration. Cytological analysis revealed lymph node metastasis of the late relapsing renal cell carcinoma.

Vibro-acoustography and B-mode integration for 3D imaging.

Tridimensional representation of vibro-acoustography images based on the topology acquired by B-mode acquisitions is proposed for the evaluation of bone and implant surfaces. A tridimensional evaluation of the implant coverage used in a total hip arthroplasty procedure was performed to show the feasibility of this approach. A vibro-acoustography image of the uncovered area of the implant was acquired and represented in planar representation. However, tridimensional representation of the exposed surface area is necessary for proper evaluation of the stability of the implant. Hence, the topologies of the implant and the bone region around it were determined by acquiring 280 B-mode images. The B-scan images were processed in order to reconstruct the tridimensional surface of the objects. Finally, the vibro-acoustography image and the B-mode-based surface were aligned for the tridimensional visualization. The B-mode tridimensional representation of the bone and implant was improved by the enhancement of contrast and resolution provided by the vibro-acoustography image. The final tridimensional image presented a resolution of 0.25 mm. The topological correction based on B-mode slices allowed an accurate evaluation of the surface area.

A new apparatus for analysis of viscoelastic fluids by ultrasound radiation force.

The acoustic radiation force has been used as the method to examine the physical properties of materials in several areas. Vibro-acoustography is an acoustic radiation force technique that is being used to perform analysis of mechanical properties of materials. In this application a focused acoustic modulated force excites target which vibrates at the frequency of modulation. The emitted sound is characteristic of the medium mechanical impedance and it is measured using a dedicated hydrophone. In this paper, we propose a modification of the vibro-acoustography (VAG) technique and apply a technique called vibro-acustomagnetography (VAMG) by replacing the hydrophone by a magnetic sensor with high sensitivity. In this case, the modulated acoustic radiation will be applied on a magnetized target immersed in the fluid under study. With this procedure, static and dynamic displacement of the magnetic target (ball) will be measured when acoustically excited. In this study, we used a magnetoresistive sensor with resolution of about nT for mounting the transducer to detect displacement of the magnetic target. The vibration of the target was induced by a non-contact force, using an ultrasonic beam modulated by two concentric beams generated by confocal piezoelectric elements with equal area and common focus to 7 cm. The target used was a magnetic sphere of NdFeB with a radius of 2.36 mm. The apparatus was evaluated through of measurements in water and oil. Viscoelastic parameters were estimated fitting the nonlinear response of the magnetic transducer function of frequency modulation.

[Consecutive aspiration]. / Konsekutive Aspiration.

We report on a 40 year-old man who presented with recurrent pneumonia with limited effect of antibiotics. A chest CT-scan revealed a tumor in the right hilar region leading to a partial atelectasis of the middle lobe. We removed a rather uncommon foreign body from the right main stem bronchus.

Characterizing the decay of ancient Chinese silk fabrics by microbeam synchrotron radiation diffraction.

Scanning synchrotron radiation microdiffraction with an approximately 1 x 1 microm(2) beam has been used as a novel method for characterizing the decay of several T'ang dynasty (618-907 AD) silk fabrics. The crystalline fraction could be visualized based on beta-sheet 210 reflection intensities, extracted by recursive peak fits from several thousand diffraction patterns recorded during mesh scans. The azimuthal width of the 210 reflection, which is related to the orientation distribution of the crystalline domains within nanofibrils and the macroscopic orientation of the fibers traversed by the beam, was found to be sensitive to the overall state of decay of the fabric. The fine structure of the histogram of azimuthal width was related to the fiber hierarchical microstructure and the fabric morphology. SAXS/WAXS analysis supports the assumption of an initial loss of the random chain network with decay. At a subsequent state of aging, decay proceeds into the nanofibrils and the silk fibers break up into even smaller fractions.