Serum Caspase-3 Levels as a Predictive Molecular Biomarker for Acute Ischemic Stroke.

Caspases are key players in the apoptotic process and have been found to contribute to the pathogenesis of a variety of diseases, including neurological disorders such as ischemic stroke. This study aimed to investigate the serum levels of Caspase-3 in patients with acute ischemic stroke (AIS) and in control patients without ischemic events. Moreover, we explored any potential associations with the clinical outcomes of AIS. We enrolled 69 consecutive patients with clinical signs and symptoms of AIS in the presence of a negative CT scan who presented themselves at the Clinical Neurological Department from the Emergency Clinical Hospital of Galati within the first 24 h of symptom onset. The control group comprised 68 patients without cerebral ischemic pathologies. A comparison of the two groups showed significantly higher levels of caspase-3 at 24 and 48 h after hospital admission. No significant associations between caspase-3 levels and clinical features of AIS were seen. However, in a subgroup analysis conducted on patients with moderate/severe and severe stroke, lower levels of caspase-3 were associated with early mortality. Caspase-3 levels did not directly correlate with AIS severity or prognosis when considering all AIS patients. In patients with moderate to severe National Institute of Health Stroke Scale (NIHSS) scores, caspase-3 might be a prognostic indicator of early death. Further studies are required to confirm these results and further explore the mechanisms behind these findings.

Monte Carlo simulation-guided design for size-tuned tumor spheroid formation in 3D printed microwells.

Tumor spheroid models have garnered significant attention in recent years as they can efficiently mimic in vivo models, and in addition, they offer a more controlled and reproducible environment for evaluating the efficacy of cancer drugs. In this study, we present the design and fabrication of a micromold template to form multicellular spheroids in a high-throughput and controlled-sized fashion. Briefly, polydimethylsiloxane-based micromolds at varying sizes and geometry were fabricated via soft lithography using 3D-printed molds as negative templates. The efficiency of spheroid formation was assessed using GFP-expressing human embryonic kidney 293 cells (HEK-293). After 7 days of culturing, circularity and cell viability of spheroids were >0.8 and 90%, respectively. At 1500 cells/microwell of cell seeding concentration, the spheroids were 454 ± 15 µm, 459 ± 7 µm, and 451 ± 18 µm when cultured in microwells with the diameters of 0.4, 0.6, and 0.8 µm, respectively. Moreover, the distance between each microwell and surfactant treatment before cell seeding notably impacted the uniform spheroid formation. The centrifugation was the key step to collect cells on the bottom of the microwells. Our findings were further verified using a commercial microplate. Furthermore, Monte Carlo simulation confirmed the seeding conditions where the spheroids could be formed. This study showed prominent steps in investigating spheroid formation, thereby leveraging the current know-how on the mechanism of tumor growth.

Madelung's Disease Evolving to Liposarcoma: An Uncommon Encounter.

(1) Background: Madelung's disease-known also as Benign Symmetric Adenolipomatosis (BSA) or Multiple Symmetric Lipomatosis (MSL), is a rare subcutaneous tissue disease characterized by the proliferation of non-encapsulated fat tissue with mature adipocytes. Patients develop symmetrical fatty deposits of varying sizes, (located particularly around the neck, shoulders, upper and middle back, arms, abdomen, and thighs), having clinical, esthetic, and psychiatric repercussions. (2) Methods: We report a case diagnosed with BSA upon admission to the Neurological and Internal Medicine Departments of the Emergency Clinical Hospital of Galati. (3) Results: This patient developed compressive phenomena and liposarcoma with liver metastasis, followed by death shortly after hospital presentation. The histopathology examination confirmed right latero-cervical liposarcoma and round cell hepatic metastasis. The specific metabolic ethiopathogenic mechanism has not been elucidated, but the adipocytes of BSA are different from normal cells in proliferation, hormonal regulation, and mitochondrial activity; a rare mitochondrial gene mutation, together with other interacting genetic or non-genetic factors, have been considered in recent studies. A thorough literature search identified only three cases reporting malignant tumors in BSA patients. (4) Conclusions: The goal of our paper is to present this rare case in the oncogenic synergism of two tumors. In the management of this BSA disorder, possible malignant transformation should be considered, although only scarce evidence was found supporting this.

A Cross-Sectional Study on the Role of a Lab Test Screening Program in Defining Cardiovascular Disease Risk Prevalence.

Recent epidemiologic studies carried out in Romania confirmed an ascending trend for cardiovascular disease (CVD) risk factor prevalence such as diabetes mellitus (DM), obesity and dyslipidemia. The aim of this study is to describe the CVD risk factor profile and preventative behavior in a representative sample of the general adult population of an Eastern Romanian urban area. More than 70% of the studied population had a body mass index (BMI) above the normal range for their age, with 36.7% of the subjects residing in obesity and severe obesity clusters. For overweight and obese subjects, the number of comorbidities (CVD, arterial hypertension and DM type 2) was higher than in the population with normal weight (44% vs. 31%, 22% vs. 14% and 18% vs. 10%, respectively). The prevalence of high blood pressure was almost double that reported in previous Romanian studies (69.3% vs. 36.6%) and higher than expected, based on self-reported known CVD diagnoses (37.5%). There was a visible difference between the results obtained for quantifiable CVD risk factors and self-reported lifestyle ones. Routine blood test monitoring may be an easy and inexpensive tool to guide educational and medical interventions to address modifiable CV risk factors in the adult population in order to prevent the fatal consequences of cardiovascular disease.

Thrombomodulin Serum Levels-A Predictable Biomarker for the Acute Onset of Ischemic Stroke.

The early diagnosis of acute ischemic stroke (AIS) can be challenging in cases presenting with a scarcity of clinical signs, normal cerebral imaging in early stages and a lack of specific serum markers. Thrombomodulin has been shown to be associated with cerebrovascular ischemic events and can be considered an important biomarker for the acute onset of ischemic stroke. In our study, we compared the serum levels of thrombomodulin (sTM) between a relevant patient group of 70 AIS patients and a control group of patients without AIS admitted into the neurology department between June 2022 and May 2023. sTM levels were measured at 24 h and 48 h after patients' admissions into the hospital. There was a significant difference between the two groups (AIS: 23.2 ± 9.17 ng/mL vs. controls: 3.64 ± 1.72 ng/mL; p-value < 0.001). sTM values were correlated with the score of neurological deficits, with gender and dyslipidemia. The association of sTM values with the acute onset of AIS as an end point was significant, which allows rapid therapeutic interventions, even in the absence of a well-defined clinical syndrome (AUC = 0.99). Reanalysis of the patients after propensity score matching increased the power of sTM as a biomarker (AUC = 1). sTM represents a potentially useful biomarker to diagnose the onset of an AIS, even in scarce clinical presentations, which makes thrombomodulin a valuable indicator for early treatment initiation.

Natural Bio-Compounds from Ganoderma lucidum and Their Beneficial Biological Actions for Anticancer Application: A Review.

Ganoderma lucidum (G. lucidum) has been known for many centuries in Asian countries under different names, varying depending on the country. The objective of this review is to investigate the scientific research on the natural active bio-compounds in extracts obtained from G. lucidum with significant biological actions in the treatment of cancer. This review presents the classes of bio-compounds existing in G. lucidum that have been reported over time in the main databases and have shown important biological actions in the treatment of cancer. The results highlight the fact that G. lucidum possesses important bioactive compounds such as polysaccharides, triterpenoids, sterols, proteins, nucleotides, fatty acids, vitamins, and minerals, which have been demonstrated to exhibit multiple anticancer effects, namely immunomodulatory, anti-proliferative, cytotoxic, and antioxidant action. The potential health benefits of G. lucidum are systematized based on biological actions. The findings present evidence regarding the lack of certainty about the effects of G. lucidum bio-compounds in treating different forms of cancer, which may be due to the use of different types of Ganoderma formulations, differences in the study populations, or due to drug-disease interactions. In the future, larger clinical trials are needed to clarify the potential benefits of pharmaceutical preparations of G. lucidum, standardized by the known active components in the prevention and treatment of cancer.

Investigation of the Optical Properties of Indium Tin Oxide Thin Films by Double Integration Sphere Combined with the Numerical IAD Method.

Transparent conductive electrodes have become essential components of numerous optoelectronic devices. However, their optical properties are typically characterized by the direct transmittance achieved by making use of spectrophotometers, avoiding an in-depth knowledge of the processes involved in radiation attenuation. A different procedure based on the Double Integration Sphere combined with the numerical Inverse Adding-Doubling (IAD) method is employed in this work to provide a comprehensive description of the physical processes limiting the light transmittance in commercial indium tin oxide (ITO) deposited on flexible PET samples, highlighting the noticeable contribution of light scattering on the total extinction of radiation. Moreover, harnessing their flexibility, the samples were subjected to different mechanical stresses to assess their impact on the material's optical and electrical properties.

Optical Behavior of Human Skin Substitutes: Absorbance in the 200-400 nm UV Range.

The most recent generation of bioengineered human skin allows for the efficient treatment of patients with severe skin defects. Despite UV sunlight can seriously affect human skin, the optical behavior in the UV range of skin models is still unexplored. In the present study, absorbance and transmittance of the UGRSKIN bioartificial skin substitute generated with human skin cells combined with fibrin-agarose biomaterials were evaluated for: UV-C (200−280 nm), -B (280−315 nm), and -A (315−400 nm) spectral range after 7, 14, 21 and 28 days of ex vivo development. The epidermis of the bioartificial skin substitute was able to mature and differentiate in a time-dependent manner, expressing relevant molecules able to absorb most of the incoming UV radiation. Absorbance spectral behavior of the skin substitutes showed similar patterns to control native skin (VAF > 99.4%), with values 0.85−0.90 times lower than control values at 7 and 14- days and 1.05−1.10 times the control values at 21- and 28-days. UV absorbance increased, and UV transmission decreased with culture time, and comparable results to the control were found at 21 and 28 days. These findings support the use of samples corresponding to 21 or 28 days of development for clinical purposes due to their higher histological similarities with native skin, but also because of their absorbance of UV radiation.

The Production of Biodegradable Polymers-medium-chain-length Polyhydroxyalkanoates (mcl-PHA) in Pseudomonas putida for Biomedical Engineering Applications.

BACKGROUND: Polyhydroxyalkanoates (PHAs) are bacteria-synthesized biopolymers under imbalanced growth conditions. These biopolymers are acknowledged as potential biomaterials for future applications because of their characteristics of biocompatibility and biodegradability, and ability to be produced rapidly, and strong functionality of mechanical resistance. This article aims to perform microbial fermentation using the Pseudomonas putida strain to identify the quantity of biopolymers, particularly of the medium-chain-length (mcl-PHA) polyhydroxyalkanoates, based on the type and quantity of the added precursors (glucose and fatty acids). METHODS: To understand the microbial interaction and the mechanism involved in PHA biosynthesis, several methods were employed and microbial biomass was obtained using the Pseudomonas putida strain capable of producing PHA. The polymer production by acetone extraction was analyzed using the Soxhlet method, while the biopolymer purification was done via the methanol-ethanol treatment, after which the biomass estimation was done through spectrophotometric analysis. This was followed by measuring the dry weight of the cells and quantification of the biopolymer produced using the gas chromatography method (GC). RESULTS: The highest PHA yield was obtained using the octanoic (17 mL in 2000 mL medium) and hexanoic acids (14 mL in 2000 mL medium) as the precursors. As a result, the octanoic acid - octanoic acid, heptanoic acid - nonanoic acid, and octanoic acid - hexanoic acid were identified as the different precursors that supported the quantity of PHA obtained. CONCLUSION: Among the 4 types of structurally related substrates, the Pseudomonas putida ICCF 319 strain showed a preference for the C8 sublayer for the biosynthesis of the elastomeric PHAs composed predominantly of more C8 monomers than the C6 and C10.

Point-of-Care Testing-The Key in the Battle against SARS-CoV-2 Pandemic.

The deleterious effects of the coronavirus disease 2019 (COVID-19) pandemic urged the development of diagnostic tools to manage the spread of disease. Currently, the "gold standard" involves the use of quantitative real-time polymerase chain reaction (qRT-PCR) for SARS-CoV-2 detection. Even though it is sensitive, specific and applicable for large batches of samples, qRT-PCR is labour-intensive, time-consuming, requires trained personnel and is not available in remote settings. This review summarizes and compares the available strategies for COVID-19: serological testing, Point-of-Care Testing, nanotechnology-based approaches and biosensors. Last but not least, we address the advantages and limitations of these methods as well as perspectives in COVID-19 diagnostics. The effort is constantly focused on understanding the quickly changing landscape of available diagnostic testing of COVID-19 at the clinical levels and introducing reliable and rapid screening point of care testing. The last approach is key to aid the clinical decision-making process for infection control, enhancing an appropriate treatment strategy and prompt isolation of asymptomatic/mild cases. As a viable alternative, Point-of-Care Testing (POCT) is typically low-cost and user-friendly, hence harbouring tremendous potential for rapid COVID-19 diagnosis.

Skin endometriosis: A case report and review of the literature.

Skin endometriosis is a rare disease with variable clinical and histopathological characteristics that depend on hormonal stimuli. The skin is not a common location, as most cases of endometriosis involve pelvic sites, such as the ovaries, peritoneum and bowel. However, the most common extrapelvic site affected is the abdominal wall and this location of the disease is frequently associated with obstetric and gynecologic surgery. Here we report a case of skin endometriosis emerged as a painful subcutaneous nodule located near to the left side of an obstetrical surgery procedure scar. The patient affected was a woman in her reproductive age, with a history of right ovary endometriotic cyst laparoscopically removed and histologically confirmed as a primary endometriosis. Dermatologists should be aware of this condition in any woman with a painful lump located in the proximity of a pelvic surgery-induced scar. Its non-specific clinical appearance may confuse the clinician and may delay the diagnosis and management.

Color, lightness, chroma, hue, and translucency adjustment potential of resin composites using CIEDE2000 color difference formula.

OBJECTIVE: To evaluate color, lightness, chroma, hue, and translucency adjustment potential of resin composites using CIEDE2000 color difference formula. METHODS: Three resin composites (Filtek Universal, Harmonize, and Omnichroma) were tested. Two types of specimens were prepared: an outer base shade with an inner hole filled with test shades and single-composite specimens of all shades. Spectrorradiometric reflectances measurements and subsequent CIELAB color coordinates and translucency parameter (TP) were performed. Color (CAP00 ), lightness, chroma, hue, and translucency (TAP00 ) adjustment potential using CIEDE2000 color difference were computed. Color and transparency differences among composite materials and shades were statistically tested (P < 0.05). RESULTS: Positive CAP00 and TAP00 values were found for majority of tested materials. CAP00 values ranged from -0.14 to 0.89, with the highest values found for Omnichroma (>0.75 in all cases). TAP00 values ranged from -0.06 to 0.86 with significant translucency differences among dual and single specimens. Omnichroma exhibited the highest adjustment potential for all color dimensions studied. CONCLUSIONS: Lightness, hue, chroma, and translucency adjustment potential have been introduced using CIEDE2000 color difference formula, and have shown their usefulness to evaluate blending effect in dentistry. Color coordinates and translucency adjustment potential were dependent on dental material. Omnichroma exhibited the most pronounced blending effect. CLINICAL SIGNIFICANCE: Resin composites with increased color and translucency adjustment may simplify shade selection, making this process easier and less time consuming. Furthermore, these materials might facilitate challenging and complex color matching situations.

Long-Term in vivo Evaluation of Orthotypical and Heterotypical Bioengineered Human Corneas.

PURPOSE: Human cornea substitutes generated by tissue engineering currently require limbal stem cells for the generation of orthotypical epithelial cell cultures. We recently reported that bioengineered corneas can be fabricated in vitro from a heterotypical source obtained from Wharton's jelly in the human umbilical cord (HWJSC). METHODS: Here, we generated a partial thickness cornea model based on plastic compression nanostructured fibrin-agarose biomaterials with cornea epithelial cells on top, as an orthotypical model (HOC), or with HWJSC, as a heterotypical model (HHC), and determined their potential in vivo usefulness by implantation in an animal model. RESULTS: No major side effects were seen 3 and 12 months after implantation of either bioengineered partial cornea model in rabbit corneas. Clinical results determined by slit lamp and optical coherence tomography were positive after 12 months. Histological and immunohistochemical findings demonstrated that in vitro HOC and HHC had moderate levels of stromal and epithelial cell marker expression, whereas in vivo grafted corneas were more similar to control corneas. CONCLUSION: These results suggest that both models are potentially useful to treat diseases requiring anterior cornea replacement, and that HHC may be an efficient alternative to the use of HOC which circumvents the need to generate cornea epithelial cell cultures.

Evaluation of the optical and biomechanical properties of bioengineered human skin generated with fibrin-agarose biomaterials.

SIGNIFICANCE: Recent generation of bioengineered human skin allowed the efficient treatment of patients with severe skin defects. However, the optical and biomechanical properties of these models are not known. AIM: Three models of bioengineered human skin based on fibrin-agarose biomaterials (acellular, dermal skin substitutes, and complete dermoepidermal skin substitutes) were generated and analyzed. APPROACH: Optical and biomechanical properties of these artificial human skin substitutes were investigated using the inverse adding-doubling method and tensile tests, respectively. RESULTS: The analysis of the optical properties revealed that the model that most resembled the optical behavior of the native human skin in terms of absorption and scattering properties was the dermoepidermal human skin substitutes after 7 to 14 days in culture. The time-course evaluation of the biomechanical parameters showed that the dermoepidermal substitutes displayed significant higher values than acellular and dermal skin substitutes for all parameters analyzed and did not differ from the control skin for traction deformation, stress, and strain at fracture break. CONCLUSIONS: We demonstrate the crucial role of the cells from a physical point of view, confirming that a bioengineered dermoepidermal human skin substitute based on fibrin-agarose biomaterials is able to fulfill the minimal requirements for skin transplants for future clinical use at early stages of in vitro development.

In vivo Diagnosis of Primary Cutaneous Amyloidosis -the Role of Reflectance Confocal Microscopy.

Primary cutaneous amyloidosis (PCA) is a form of localized amyloidosis. It is characterized by the deposition of a fibrillar material in the superficial dermis, without affecting other systems or organs. The diagnosis can be made clinically, but usually a skin biopsy is performed in order to exclude other skin diseases with similar appearance. Reflectance confocal microscopy (RCM) is a novel imaging tool that enables in vivo characterization of various skin changes with a high, quasi-microscopic resolution. This technique might have an important role in the differential diagnosis of cutaneous amyloidosis, by the in vivo assessment of epidermal changes and dermal amyloid deposition. Moreover, it is completely non-invasive and can be safely repeated on the same skin area. However, to date, there is only one published paper presenting the confocal features of primary cutaneous amyloidosis. Hereby, we describe the in vivo RCM features of PCA lesions from a patient with diabetes and correlate them with histologic findings. This strengthens the clinical usefulness of in vivo RCM examination for the non-invasive diagnosis of cutaneous amyloidosis, especially in patients that might associate diseases with impaired wound healing.

Outcomes of transoral laser microsurgery for oropharyngeal squamous cell carcinoma in Ireland and review of the literature on transoral approaches.

BACKGROUND: The optimal treatment for oropharyngeal squamous cell carcinoma (OPSCC) is controversial. There is increasing evidence that, in selected cases, minimally invasive transoral surgery can offer improved functional outcomes, with equivalent oncologic outcomes, compared to chemoradiotherapy. AIMS: We report the outcomes of transoral laser microsurgery (TLM) for treatment of OPSCC at our institution. METHODS: Patients with OPSCC undergoing TLM at the South Infirmary Victoria University Hospital, Cork, between 2010 and 2016, were identified from an institutional database. Human papillomavirus (HPV) status was determined by p16 immunohistochemistry. Survival outcomes were analysed using the Kaplan-Meier method. Complications following surgery and gastrostomy tube dependence were evaluated. RESULTS: The study cohort consisted of 26 patients, with mean age of 56 years (range 29-71). Primary tumours were located in the tonsil (18), base of tongue (4) and other subsites (4). Seventeen cases were p16-positive. Complications included haemorrhage necessitating return to theatre (1) and aspiration pneumonia (1). Four patients underwent tracheostomy, all of whom were successfully decannulated. One patient underwent gastrostomy tube insertion during postoperative radiotherapy. No patient was gastrostomy dependent at latest follow-up. Twenty-two patients received adjuvant treatment, with radiation alone (21) or chemoradiotherapy (2). Mean follow-up was 27 months. Five-year locoregional control was 92% and disease-specific survival was 81%. CONCLUSIONS: In selected patients with OPSCC, TLM offers excellent functional and survival outcomes, and as such offers an alternative approach to chemoradiotherapy as primary treatment. We compare TLM to other transoral approaches and discuss its potential use in the Irish healthcare system.

Bedaquiline- versus injectable-containing drug-resistant tuberculosis regimens: a cost-effectiveness analysis.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) continues to be a major public health challenge with suboptimal treatment outcomes including well-documented treatment-related toxicities. We compared the cost-effectiveness of bedaquiline (BDQ) containing regimens with injectable containing regimens (short-course regimen [SCR] and long-course regiman [LCR]) in India, Russia, and South Africa. METHODS: The analysis evaluated the direct costs of DR-TB treatment which included drugs, hospitalization, injectable-related adverse event costs, and other costs. Scenarios altered regimen costs, SCR/LCR ratio, and substitution rate between regimens (whether BDQ or injectable containing). RESULTS: BDQ containing regimens are more cost effective based on cost per treatment success compared with injectable containing regimens, reducing these in SCR by 18-20% and in LCR by 49-54%. Average cost effectiveness ratios (ACERs) of BDQ containing regimens are lower. The incremental cost effectiveness ratio (ICER) is negative. Exclusive use of BDQ containing regimens results in approximately 61,000 more patients treated successfully over 5 years. CONCLUSIONS: Across all countries, BDQ containing regimens are dominant compared to injectable containing regimens, entailing lower treatment costs to achieve better clinical outcomes. This analysis can provide insight and support to local and global decision-makers and public health organizations to allocate efficiently resources improving patient and public health outcomes.

Gingival shade guides: Colorimetric and spectral modeling.

OBJECTIVE: To design colorimetric and spectral models of gingival shade guides that adequately represent the color of human gingiva. MATERIALS AND METHODS: A previously compiled database on the spectral reflectance of healthy keratinized gingiva was used for optimization. Coverage Error (CE) and Maximal Error (ME) were optimized using CIELAB and CIEDE2000 color difference formulas. A two-phase process included an FCM algorithm and a nonlinear optimization. A t test was used to compare the performance of the different numbers of clusters/tabs in gingival shade guide models (α = .05). RESULTS: CIELAB CE and ME for shade guide models with 3 to 6 clusters ranged from 3.1 to 3.9 (P = .028 for 3 vs. 4; and P = .033 for 5 vs. 6 cluster/tab comparison), while the corresponding CIEDE2000 range was from 2.1 to 2.8 (P < .001 for 3 vs. 4 tabs; P < .025 for 4 vs. 5; and P = 0.029 for 5 vs. 6 tab comparisons). The percentage of data points exhibiting a CIELAB color difference lower than the acceptability threshold ranged from 48.7% to 71.4%, and from 52.9% to 82.4%. for CIEDE2000. CONCLUSIONS: An increase in the number of clusters in the gingival shade guide models was associated with a decrease in coverage error (better match) to human gingiva. Gingival shade guide models with only 4 tabs provided a CIELAB and CIEDE2000 coverage error lower than the acceptability threshold for gingival color. Spectral clustering of human gingiva was determined to be valid. CIEDE2000 color difference formula outperformed the CIELAB formula in the optimization process. CLINICAL SIGNIFICANCE: Providing a shade guide model with a small number of tabs and a coverage error lower than the 50:50% acceptability threshold would be an optimal solution for shade matching in dentistry. However, no actual gingival or tooth shade guide complies with this. The clustering method, with optimization of both Coverage Error and Maximal Error and spectral clustering that enables more reliable color formulation of cluster representatives of shade guide models, represents an advance when it comes to computer modeling in dentistry.

Color difference thresholds for computer-simulated human Gingiva.

OBJECTIVE: To determine 50:50% perceptibility threshold (PT) and 50:50% acceptability threshold (AT) for computer-simulated samples of human gingiva using CIEDE2000 and CIELAB color difference formulas. MATERIALS AND METHODS: Each of the 60 pairs of simulated human gingiva was displayed on a calibrated monitor, together with three pairs of upper central incisors of different lightness. The color of gingiva left and right from the midline was compared. A total of 30 observers (15 dentists, 15 laypersons) participated in the study. CIEDE2000 and CIELAB formulas were used to calculate the thresholds and a Takagi-Sugeno-Kang Fuzzy Approximation model was used as fitting procedure. Paired t-test (α = 0.05) was used in evaluation of statistical significance of differences. RESULTS: The PT and AT for CIEDE2000 and 95% confidence intervals were 1.1 [0.4, 1.7] and 2.8 [1.8, 4.0], respectively. Corresponding CIELAB values were 1.7 [0.2, 2.6] and 3.7 [2.1, 5.7]. Significant differences (P < .01) were recorded between PT and AT, between the corresponding threshold values in CIEDE2000 and CIELAB formulas as well as between dentists and laypersons. CONCLUSIONS: The difference between the perceptibility and acceptability threshold for gingiva was statistically significant in both CIEDE2000 and CIELAB. The same was true for differences between the corresponding thresholds using two color difference formulas, and between dentists and laypersons. Visual thresholds of human gingiva were not dependent upon lightness of adjacent teeth. Overall, CIEDE2000 color difference formula provided better fit than CIELAB formula in the evaluation of color difference thresholds of human gingiva. CLINICAL SIGNIFICANCE: The data on visual thresholds for healthy human gingiva can be used as quality control tool/guide for selection and evaluation of dental materials, interpretation of color-related findings in clinical dentistry and research, and for standardization in dentistry. It is of particular value that this study was designed based on in-vivo color evaluation of healthy keratinized gingiva of subjects of different ethnicities, age groups, and gender.

Controlling the 3D architecture of Self-Lifting Auto-generated Tissue Equivalents (SLATEs) for optimized corneal graft composition and stability.

Ideally, biomaterials designed to play specific physical and physiological roles in vivo should comprise components and microarchitectures analogous to those of the native tissues they intend to replace. For that, implantable biomaterials need to be carefully designed to have the correct structural and compositional properties, which consequently impart their bio-function. In this study, we showed that the control of such properties can be defined from the bottom-up, using smart surface templates to modulate the structure, composition, and bio-mechanics of human transplantable tissues. Using multi-functional peptide amphiphile-coated surfaces with different anisotropies, we were able to control the phenotype of corneal stromal cells and instruct them to fabricate self-lifting tissues that closely emulated the native stromal lamellae of the human cornea. The type and arrangement of the extracellular matrix comprising these corneal stromal Self-Lifting Analogous Tissue Equivalents (SLATEs) were then evaluated in detail, and was shown to correlate with tissue function. Specifically, SLATEs comprising aligned collagen fibrils were shown to be significantly thicker, denser, and more resistant to proteolytic degradation compared to SLATEs formed with randomly-oriented constituents. In addition, SLATEs were highly transparent while providing increased absorption to near-UV radiation. Importantly, corneal stromal SLATEs were capable of constituting tissues with a higher-order complexity, either by creating thicker tissues through stacking or by serving as substrate to support a fully-differentiated, stratified corneal epithelium. SLATEs were also deemed safe as implants in a rabbit corneal model, being capable of integrating with the surrounding host tissue without provoking inflammation, neo-vascularization, or any other signs of rejection after a 9-months follow-up. This work thus paves the way for the de novo bio-fabrication of easy-retrievable, scaffold-free human tissues with controlled structural, compositional, and functional properties to replace corneal, as well as other, tissues.