Efficacy and Safety of Expanded Polytetrafluoroethylene Implantation in the Correction of Long-Term Posttraumatic Enophthalmos.

SUMMARY: Long-term enophthalmos is a common orbital fracture sequela. Various autografts and alloplastic materials have been studied in posttraumatic enophthalmos repair. However, expanded polytetrafluoroethylene (ePTFE) implantation in late enophthalmos repair has rarely been reported. The authors report novel use of ePTFE for late posttraumatic enophthalmos repair. This retrospective study included patients with posttraumatic long-term enophthalmos who underwent hand-carved ePTFE intraorbital implantation for enophthalmos correction. Computed tomography data were collected preoperatively and at follow-up. The volume of ePTFE, the degree of proptosis (DP), and enophthalmos were measured. Postoperative and preoperative DP and enophthalmos were compared using the paired t test. The correlation between ePTFE volume and DP increment was established using linear regression. Complications were identified by chart review. From 2014 to 2021, 32 patients were included, with a mean follow-up of 19.59 months. The mean volume of implanted ePTFE was 2.39 ± 0.89 mL. After surgery, the DP of the affected globe improved significantly, from 12.75 ± 2.12 mm to 15.06 ± 2.50 mm ( P < 0.0001). A significant linear correlation was found between ePTFE volume and DP increment ( P < 0.0001). Enophthalmos was substantially ameliorated from 3.35 ± 1.89 mm to 1.09 ± 2.07 mm ( P < 0.0001). Twenty-five patients (78.23%) had postoperative enophthalmos of less than 2 mm. Infection and implant dislocation were not observed. The authors concluded that ePTFE intraorbital implantation exhibited long-term efficacy and safety for late posttraumatic enophthalmos repair and represents an effective and predictable alternative. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Application of Segmented Template in Three-Dimensionally Guided Mandibular Angle Osteotomy.

BACKGROUND: The procedure of mandibular angle osteotomy (MAO) via an intraoral approach is challenging and experience-dependent due to the limited field of view and inadequate operational space. Uncertainty about the osteotomy line and plane can lead to severe complications. A three-dimensional printed guidance template based on a computer-assisted preoperative simulation is a potential solution to this problem. The current study aims to retrospectively investigate the feasibility and accuracy of using a custom-made segmented template to guide the osteotomy plane during the procedure. METHODS: Sixty patients who had segmented template-guided MAO were included in the study. Preoperative simulation using the custom-designed template and postoperative computed tomography were collected and parameters, including mandibular angle, gonion distance, and the mandibular plane angle were measured. A paired t tests and intraclass correlation coefficients (ICCs) were used to evaluate the efficacy, accuracy, and symmetry of the results. All complications were reviewed. RESULTS: The patients had a significantly larger mandibular angle and narrower gonion distance postoperatively. Preoperative simulations and postoperative outcomes were compared; ICCs were larger than 95% indicating significant agreement. Bilateral postoperative comparisons of the mandible also demonstrated excellent agreement (ICC > 95%). Numbness in the chin area was the most frequent complication but all recovered by 3 months postoperatively. CONCLUSIONS: The custom-made template can guide the osteotomy plane during the MAO procedure and achieve favorable accuracy and symmetry. Direct contact of the saw with the guidance template not only facilitates control of the osteotomy line but also the oblique angle of the osteotomy plane. This methodology may be a feasible and effective tool for mandibular contouring.

A Single-Blinded Prospective Study on Using Botulinum Toxin Type A for Reducing Alar Mobility.

BACKGROUND: With widespread utilization of instant social media, people desire a minimally invasive treatment to improve alar dynamic aesthetic, but few practical procedures on reducing alar mobility have been conducted. OBJECTIVES: This study aimed to verify the effects of botulinum toxin on reducing nasal alar mobility and provide a supplemental treatment of rhinoplasty. METHODS: This single-blind prospective study included a cohort of 20 participants with the desire to improve their alar dynamic aesthetic. The experimental group was injected with 3U botulinum toxin type A at dilator naris anterior, dilator naris vestibularis, levator labii superioris alaeque nasi, and dilator naris, and the control group received the equivalent of saline. Standardized facial movement (from rest to maximum smile without revealing teeth) was recorded with a 3-dimensional imaging system. The changes between rest and maximum smile statuses represented alar mobility and were generated by MOBILITY=WIDTHsmile-WIDTHrestWIDTHrest×100 % . Alar mobility and root mean square analysis were employed for postoperative evaluations. RESULTS: In the experimental group, alar flaring mobility decreased from 10.05% ± 6.40% to 4.91% ± 3.48%(P < 0.05), and alar base mobility decreased from 16.83% ± 5.69% to 12.50% ± 4.89% (P < 0.05), whereas no significant changes in alar mobility were found in the control group. In root mean square analysis, changes in the experimental group were significantly higher than in the control group (P < 0.05). CONCLUSIONS: Botulinum toxin type A can effectively restrain alar mobility without any significant adverse events and improve alar dynamic esthetic, which can serve as a minimally invasive method or supplemental treatment for rhinoplasty.

Midfacial Soft Tissue Changes After Reduction Malarplasty: A Computed Tomographic Study.

BACKGROUND: The reduction malarplasty has become one of the most popular esthetic surgeries among Asian women to improve facial contour. However, it is still controversial whether midfacial soft tissue changes after surgery, and more studies are needed. METHODS: This retrospective observational study reviewed 30 patients who underwent L-shaped reduction malarplasty during January 2018 and August 2019. The preoperative and postoperative soft tissue thickness and the angle of nasolabial fold of the midfacial were assessed using photographs, three-dimensional skull computerized tomography images, and the Wrinkle Severity Rating Scale. RESULTS: The postoperative average level of nasolabial fold angle was lower than that observed in preoperative conditions, with the difference being statistically significant (t = -10.262, P < 0.001). The postoperative fifth and sixth layers of soft tissue in the midface were significantly higher than those observed in preoperative tissues. CONCLUSIONS: Although L-shaped reduction malarplasty has evident effects on soft tissue changes of middle face, they are within acceptable ranges and do not affect patient satisfaction.

MEF/KSF-conditioned culture medium: An effective method for in vitro culture of mouse dermal papilla cells with osteogenic differentiation potential.

Hair follicle stem cells are pluripotent and have a self-renewal capacity and multi-differentiation potential in vitro. As hair follicle stem cells can be easily sampled from the skin and hair of clinical patients at a considerable quantity, these cells have potential applications in wound repair and skin tissue engineering. Effective approaches for the in vitro culture and amplification of mouse hair follicle stem cells, as well as the in vitro osteogenic differentiation potential and cell source when obtaining mouse-separated cells were examined. Serial subculture was performed in different culture systems. Cell source was detected based on the relevant surface markers derived from mouse hair follicles at the gene and protein levels, and the differential potential was determined. The proliferative ability of hair follicle-derived stem cells obtained from mouse embryonic fibroblast (MEF)/keratinocyte serum-free medium (KSF)-conditioned medium was the highest among all culture systems. The induced group had a stronger osteogenic differentiation potential compared with the non-induced group, indicating that the cells obtained from MEF/KSF-conditioned medium were cells derived from the hair follicle dermal papilla. Therefore, the strong osteogenic differentiation potential of the hair follicle-derived mesenchymal stem cells was screened with MEF/KSF-conditioned culture medium following amplification, and biological characteristics similar to those of hair follicle dermal papilla cells were observed.

A novel p.Pro871Leu missense mutation in SPECC1L gene causing craniosynostosis in a patient.

INTRODUCTION: Craniosynostosis is one of the most common craniofacial abnormalities. It involves premature closure of one or more cranial sutures. Mutations in many genes have been and continue to be identified in patients. SETTINGS AND SAMPLE POPULATION: Whole blood samples were collected from the patient and family members. MATERIAL AND METHODS: Whole exome sequencing was performed to identify potential mutations in the patient. The results were verified by Sanger sequencing by comparing SPECC1L gene sequence of blood samples from 100 unrelated population-matched controls. RESULTS: The patient presented with craniosynostosis with fusion of the bicoronal and sagittal sutures. A novel missense mutation (c.2612C>T, p.Pro871Leu) in the SPECC1L gene was identified. Gene analysis showed a missense mutation in exon1 of SPECC1L that led to an amino acid substitution in the region between coiled-coil domain 3 and calponin homology domain. CONCLUSION: Our observations expand the molecular spectrum of gene mutations in craniosynostosis and emphasize the importance of gene testing in the diagnosis of craniosynostosis. The observations also reinforce the characteristics of SPECC1L-related cranial disorders.

BMP-2 and VEGF-A modRNAs in collagen scaffold synergistically drive bone repair through osteogenic and angiogenic pathways.

Bone has a remarkable potential for self-healing and repair, yet several injury types are non-healing even after surgical or non-surgical treatment. Regenerative therapies that induce bone repair or improve the rate of recovery are being intensely investigated. Here, we probed the potential of bone marrow stem cells (BMSCs) engineered with chemically modified mRNAs (modRNA) encoding the hBMP-2 and VEGF-A gene to therapeutically heal bone. Induction of osteogenesis from modRNA-treated BMSCs was confirmed by expression profiles of osteogenic related markers and the presence of mineralization deposits. To test for therapeutic efficacy, a collagen scaffold inoculated with modRNA-treated BMSCs was explored in an in vivo skull defect model. We show that hBMP-2 and VEGF-A modRNAs synergistically drive osteogenic and angiogenic programs resulting in superior healing properties. This study exploits chemically modified mRNAs, together with biomaterials, as a potential approach for the clinical treatment of bone injury and defects.

A Study on Tuberculosis Classification in Chest X-ray Using Deep Residual Attention Networks.

The introduction of deep learning techniques for the computer-aided detection scheme has shed a light for real incorporation into the clinical workflow. In this work, we focus on the effect of attention in deep neural networks on the classification of tuberculosis x-ray images. We propose a Convolutional Block Attention Module (CBAM), a simple but effective attention module for feed-forward convolutional neural networks. Given an intermediate feature map, our module infers attention maps and multiplied it to the input feature map for adaptive feature refinement. It achieves high precision and recalls while localizing objects with its attention. We validate the performance of our approach on a standard-compliant data set, including a dataset of 4990 x-ray chest radiographs from three hospitals and show that our performance is better than the models used in previous work.

Postoperative Complications of Box-Shift Osteotomy for Orbital Hypertelorism.

OBJECTIVE: To summarize and analyze the postoperative complications of box-shift osteotomy performed at our center for Chinese orbital hypertelorism patients from 2008 to 2017. METHOD: This retrospective study reviews the records of 78 patients with complete medical records and at least 2 years of postoperative follow-up data. Both radiologic and anthropometric assessments were conducted before, 1 month after and 2 years after surgery to evaluate the bony and soft-tissue alterations. Postoperative complications were recorded during hospitalization and at each follow-up visit and divided into 3 groups: acute complications that occurred within 1 month after surgery; early complications that occurred within 6 months after surgery; and long-term complications that occurred within 2 years after surgery. RESULTS: Both bony and soft-tissue alterations were significant at 1 month after surgery. The acute complications that occurred in our center included infection (12.8%), cerebrospinal fluid leakage (29.5%), epilepsy (2.6%), and nasal tip skin necrosis (1.3%). The early complications included strabismus (11.5%) and nasolacrimal duct obstruction (3.8%). The long-term complications included insufficient correction (55.1%), palpable metal implants (92.3%) and a drooping nasal tip (33.9%). Due to the insufficient correction and the continued growth of rib graft, the difference in the hypertelorism index and nasal length, between one month and 2 years postoperatively were statistically significant (P < 0.01). Other radiographic and anthropometric measurements changed with growth without a significance difference between 1 month and 2 years after surgery. CONCLUSION: In this study, we recorded all postoperative complications of box-shift osteotomy. The challenge of our future work is to identify methods for decreasing the incidence of these complications.

A Novel Method to Enhance Dynamic Rhinoplasty Outcomes: Double "V" Carving for Alloplastic Grafts.

Augmentation rhinoplasty is one of the most common plastic surgery procedures performed in Asia. Most Asian patients desire not only a natural-looking nose but also a nose with natural feel. Achieving such rhinoplasty outcomes with grafts has been a challenge for surgeons due to rigidity of grafting material. We propose a novel technique to address this limitation. A total of 200 healthy adult patients aged from 18 to 25 years were randomly chosen and classified into 5 groups: A, B, C, D, and control. Each group included 40 patients. The patients assigned to conventional grafting underwent rhinoplasty with L-shaped silicone prosthesis (group A) or expanded polytetrafluoroethylene (e-PTFE; group B), using traditional carving methods. The patients assigned to dynamic rhinoplasty underwent silicone (group C) or e-PTFE grafts (group D) using the modified double "V" method, which involves removing bilateral wedges from the graft to decrease rigidity. Patients in control group do not undergo the surgery. A 3-dimensional raster surface scanner was used to capture the images of the patients accurately and nasal mobility was measured. Subjective evaluations were carried out by a series of questionnaires asked to the patients. The angle α of nasal mobility was significantly lower in conventional grafting (23.09 [5.34] mm for silicone and 17.88 [4.96] mm for e-PTFE) versus the "V" carving (30.53 [3.76] mm for silicone and 23.77 [4.53] mm for e-PTFE; P < .05). The double "V" carving method is a simple, effective, and practical method for improving dynamic nasal outcomes in patient undergoing augmentation rhinoplasty.

Surgical Correction of Proptosis in Craniofacial Benign Bone Lesions Involving the Orbit.

Craniofacial bone lesions involving the orbit are often associated with symptoms, including proptosis, orbital dystopia, and overall facial asymmetry. Fibrous dysplasia and osteoma are the 2 most commonly observed bone tumors in the craniofacial area. Nine patients with either craniofacial fibrous dysplasia or osteoma and an unacceptable aesthetic appearance were treated from January 2015 to July 2016. All patients underwent preoperative craniofacial 3-dimensional computed tomographic (CT) scanning, and standard photographs were obtained. Proptosis measurements were performed on CT images using an annotation ruler provided by the imaging system both pre- and postoperatively. All patients were treated surgically, and a coronal incision was used. Outcomes were assessed by CT scans, and photographs were obtained during routine follow-ups at 1 week, 3 to 6 months, and 1 year after surgery. The Likert scale was used to investigate patients' postoperative satisfaction rate. Favorable outcomes were achieved in all patients. The mean difference between eyeball proptosis was reduced from 3.6 mm before surgery to 1.6, 0.6, and 0.3 mm after the surgery at 1 week, 3 to 6 months, and 1 year, respectively. No complications, such as facial and/or optic nerve injury, recurrence, and malignant degeneration, were noted. This study demonstrated that surgical treatment of craniofacial bone lesions involving the orbit achieved acceptable results shortly after the surgery, and more prominently, starting from 3 to 6 months.

Tetrahydroxystilbene Glucoside Effectively Prevents Apoptosis Induced Hair Loss.

The effect of Polygonum multiflorum against hair loss has been widely recognized. 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) is the main component of Polygonum multiflorum; however, its role in hair regeneration has not been established. To evaluate the hair growth-promoting activity of TSG, depilated C57BL/6J mice were topically treated with normal saline, TSG, Pifithrin-α, Minoxidil for 2 weeks. In this study, we identified that p53, Caspase-3, Active Caspase-3, and Caspase-9 were obviously upregulated in the skin of human and mice with hair loss by western blot analysis. Depilated mice treated with TSG showed markedly hair regrowth. TUNEL+ cells were also reduced in mice with TSG. These changes were accompanied with inhibition of Fas, p53, Bax, Active Caspase-3, and Procaspase-9 activities. These results demonstrated that TSG exerts great hair regrowth effect on hair loss, which was probably mediated by inhibition of p53, Fas, and Bax induced apoptosis.

Recombinant mouse periostin ameliorates coronal sutures fusion in Twist1+/- mice.

BACKGROUND: Saethre-Chotzen syndrome is an autosomal dominantly inherited disorder caused by mutations in the twist family basic helix-loop-helix transcription factor 1 (TWIST1) gene. Surgical procedures are frequently required to reduce morphological and functional defects in patients with Saethre-Chotzen syndrome. Therefore, the development of noninvasive procedures to treat Saethre-Chotzen syndrome is critical. We identified that periostin, which is an extracellular matrix protein that plays an important role in both bone and connective tissues, is downregulated in craniosynostosis patients. METHODS: We aimed to verify the effects of different concentrations (0, 50, 100, and 200 µg/l) of recombinant mouse periostin in Twist1+/- mice (a mouse model of Saethre-Chotzen syndrome) coronal suture cells in vitro and in vivo. Cell proliferation, migration, and osteogenic differentiation were observed and detected. Twist1+/- mice were also injected with recombinant mouse periostin to verify the treatment effects. RESULTS: Cell Counting Kit-8 results showed that recombinant mouse periostin inhibited the proliferation of suture-derived cells in a time- and concentration-dependent manner. Cell migration was also suppressed when treated with recombinant mouse periostin. Real-time quantitative PCR and Western blotting results suggested that messenger ribonucleic acid and protein expression of alkaline phosphatase, bone sialoprotein, collagen type I, and osteocalcin were all downregulated after treatment with recombinant mouse periostin. However, the expression of Wnt-3a, Wnt-1, and ß-catenin were upregulated. The in vivo results demonstrated that periostin-treated Twist1+/- mice showed patent coronal sutures in comparison with non-treated Twist1+/- mice which have coronal craniosynostosis. CONCLUSION: Our results suggest that recombinant mouse periostin can inhibit coronal suture cell proliferation and migration and suppress osteogenic differentiation of suture-derived cells via Wnt canonical signaling, as well as ameliorate coronal suture fusion in Twist1+/- mice.

Effect of inhomogeneity of the electrospun fibrous scaffolds of gelatin/polycaprolactone hybrid on cell proliferation.

In this article, gelatin (GT) and polycaprolactone (PCL) blended with a weight ratio of 50:50 were dissolved in the trifluoroethanol (TFE) or the acetic acid-doped TFE solvent system (0.2% relative to TFE) to prepare fibrous scaffolds of GT/PCL with different compositional and morphological homogeneities (denoted as the group 1 and the group 2 scaffolds) by electrospinning. The morphology and composition of the two groups of fibrous scaffolds were examined by scanning electron microscopy and Fourier transform infrared spectroscopy, respectively. Then, using green fluorescence protein-labeled mouse fibroblasts and HaCaT cells (a human keratinocyte cell line) as the model cells, cell adhesion, morphology, and proliferation were assessed by laser scanning confocal microscopy, scanning electron microscopy, and cell counting kit-8 assay, respectively. The results showed that the morphological and compositional inhomogeneity of the group 1 scaffolds had a remarkable influence on cell adhesion and proliferation. In contrast, there was no significant difference among the group 2 scaffolds because of their good consistency in fiber morphology and composition. Phase separation resultant GT content variance in the group 1 scaffolds is suggested as one of the major causes. This study highlighted the importance of producing morphologically uniform and compositionally homogeneous composite nanofibers while electrospinning natural and synthetic polymer blends.

The influence of Gelatin/PCL ratio and 3-D construct shape of electrospun membranes on cartilage regeneration.

Scaffolds play an important role in directing three-dimensional (3-D) cartilage regeneration. Our recent study reported the potential advantages of electrospun gelatin/polycaprolactone (GT/PCL) membranes in regenerating 3-D cartilage. However, it is still unknown whether the changes of GT/PCL ratio have significant influence on 3-D cartilage regeneration. To address this issue, the current study prepared three kinds of electrospun membranes with different GT/PCL ratios (70:30, 50:50, 30:70). Adhesion and proliferation of chondrocytes on the membranes were examined to evaluate biocompatibility of the membranes. Cartilage with different 3-D shapes was engineered to further evaluate the influences of GT/PCL ratio on cartilage regeneration. The current results demonstrated that all the membranes with different GT/PCL ratios presented good biocompatibility with chondrocytes. Nevertheless, the high PCL content in the membranes significantly hampered early 3-D cartilage formation at 3 weeks in vivo. Unexpectedly, at 12 weeks, all the cylinder-shaped constructs formed mature cartilage-like tissue with no statistical differences among groups. To our surprise, ear-shaped cartilage regeneration obtained quite different results again: the high PCL content completely disrupted cartilage regeneration even at 12 weeks, and only the least PCL content group formed homogeneous and continuous cartilage with a satisfactory shape and elasticity similar to human ear. All these results indicated that the high PCL content was unfavorable for 3-D cartilage regeneration, especially for the cartilage with a complicated shape, and that GT/PCL 70:30 might be a relatively suitable ratio for ear-shaped cartilage regeneration. The research models established in the current study provide detailed information for cartilage and other tissue regeneration based on electrospun GT/PCL membranes.

Engineering of epidermis skin grafts using electrospun nanofibrous gelatin/ polycaprolactone membranes.

Skin engineering provides a new strategy for treating a wide variety of skin defects. In particular, electrospun nanofibrous membranes have been used as carriers for epidermis engineering. The aim of this study was to investigate the feasibility of a modified gelatin and polycaprolactone (GT/PCL) electrospun membrane for epidermis engineering. The biocompatibility of the membranes was evaluated by seeding HaCaT cells (human keratinocyte cell line) on the membrane and the mechanical properties of the membranes were determined with and without cells after culture. A cell proliferation assay showing that HaCaT cells attached and proliferated well on the membranes demonstrated that the membranes possess good biocompatibility. Mechanical tests showed that the membranes are strong enough to be handled during transplantation. Further in vivo transplantation studies revealed that epidermises engineered with GT/PCL membranes were able to repair skin defects in the nude mouse. These results demonstrate that GT/PCL electrospun membranes could be suitable scaffolds for skin engineering.

Participation of CD34-enriched mouse adipose cells in hair morphogenesis.

Adipose-derived stromal vascular fraction (SVF) cells are heterogeneous in nature, containing a number of different cell types. Recent studies indicate that CD34 may be a specific marker for adipose-derived mesenchymal stem cells (ADMSCs). Using their participation in hair morphogenesis as a model, the multi-differentiation potential of adult stem cells was investigated. In addition, adipose tissue or adipogenic lineage cells appear to be associated with the hair follicle cycle. The purpose of this study was to test the potential of CD34+ cells enriched from fat tissue in hair morphogenesis. To investigate this, unsorted SVF, CD34+ and CD34- cells sorted from the SVF of green fluorescence protein (GFP) transgenic mice were mixed with fetal mouse keratinocytes and dermal fibroblasts of gestational day 17.5 (E17.5) and then subcutaneously injected into nude mice. The results showed that in the reconstituted skin tissue, larger tissue blocks with more developed hair follicles were observed in the CD34+ cell group compared with the other two groups. Histological and immunofluorescent staining analyses revealed that only CD34+ cells may participate in hair morphogenesis by their integration into dermal sheath structures. However, no involvement in other skin appendages was observed. In addition, differentiation into endothelial cells and participation in blood vessel formation were also observed in both CD34+ and SVF cells, but not in CD34- cells. As expected, participation in adipogenesis was observed in all groups. Our results suggest that CD34+ cells may represent the ADMSCs which possess stronger multiple differentiation potential during reconstituted skin development.

Purification of Schwann cells from adult rats by differential detachment.

Differential detachment by collagenase treatment is a new and efficient method for Schwann cell (SC) purification. As its effect on adult animals remains unclear, we have investigated the possibility of SC purification from adult rats. To avoid any systematic bias, Schwann cell purity before and after purification were compared by morphology, immunostaining of P75(NTR) and S100 and flow cytometric analysis. The final SC purities reached 99% as confirmed by three independent analyses SC purity and the cell yields were above 10(6) cells after two rounds of purification. The method of differential detachment is also suitable for SC purification in adult rats and could be useful for research and clinical applications.

3D computerized segmentation of lung volume with computed tomography.

Three-dimensional (3D)-based detection and diagnosis has an important role for significantly improving the detection and diagnosis of lung cancer upon computed tomography (CT). This report presents a 3D-based method for segmenting and visualizing lung volume by using CT images. An anisotropic filtering method was developed on CT slices to enhance the signal-to-noise ratio, and a wavelet transform-based interpolation method was used combined with volume rendering to construct the 3D volumetric data based on entire CT slices. Then an adaptive 3D region-growing algorithm was designed to segment lung volume, incorporated by automatic seed-locating methods through fuzzy logic algorithms and 3D morphological closing approaches. In addition, a 3D visualization tool was designed to view volumetric data, projections, or intersections of the lung volume at any view angle. This segmentation method was tested on single-detector CT images by percentage of volume overlap and percentage of volume difference. The experiment results show that the developed 3D-based segmentation method is effective and robust. This study lays the groundwork for 3D-based computerized detection and diagnosis of lung cancer with CT imaging. In addition, this approach can be integrated into a picture archiving and communication system serving as a visualization tool for radiologists' reading and interpretation.