Prosthetic valve endocarditis due to Candida parapsilosis - a rare case report.

Fungal endocarditis is a rare and fatal condition, most frequently caused by species of the genera Candida and Aspergillus. Fever and changing heart murmur are the most common clinical manifestations. The diagnosis of fungal endocarditis is challenging, with prosthetic valve endocarditis being extremely difficult to diagnose. The optimal management of the condition still remains debatable. We present a case of prosthetic valve endocarditis caused by Candida parapsilosis, managed empirically with liposomal amphotericin B, which was later shifted to combination therapy with high-dose echinocandin and fluconazole, but had a fatal outcome because the patient could not undergo timely surgical intervention. Treating C. parapsilosis endocarditis cases is difficult because of their biofilm production on native and prosthetic heart valves. A combined approach consisting of a high index of clinical suspicion, early diagnosis using serological markers followed by culture or PCR and prompt initiation of appropriate antifungals may aid in improving outcomes.

Development of Enzymatic-Resistant and Compliant Decellularized Extracellular Matrixes via Aliphatic Chain Modification for Bladder Tissue Engineering.

Here, we report the design and development of highly stretchable, compliant, and enzymatic-resistant transiently cross-linked decellularized extracellular matrixes (dECMs) (e.g., porcine small intestine submucosa/dSIS, urinary bladder matrix/dUBM, bovine pericardium/dBP, bovine dermis/dBD, and human dermis/dHD). Specifically, these dECMs were modified with long aliphatic chains (C9, C14, and C18). Upon modification, dECMs became significantly resistant to enzymatic degradation for extended periods, showed increased water contact angle (>20%-90%), and stretched >200% than their control counterparts. Modified dECMs are compliant, undergoing 100% elongation at only 0.3-0.5 MPa of applied tensile stress (∼10%-25% of their control counterparts), similar to the control bladder tissue. Furthermore, modified dECMs remain structurally stable at the physiological temperature with increased storage and loss modulus values but decreased tan δ values compared to their control counterparts. Although modification reduces cell adhesion, the gene expressions in polarized macrophages remain unchanged (e.g., TGFß, CD163, and CD86), except for the modified bovine pericardium (dBP) where a significant decrease in TNFα gene expression is observed. When implanted in the rat subcutaneous model, modified dECMs degraded relatively slowly and did not cause significant fibrotic tissue formation. The numbers of pro-regenerative macrophages increased to several folds in a later time point of evaluation. Modified dECM also supported the bladder wall regeneration with formations of the urothelium, lamina propria, blood vessels, and muscle bundles and reduced the occurrence of calculi formation by 50% in a rat bladder augmentation model. We anticipate that the enhanced stretchability, compliance, and physiological stability of dECMs indicate their suitability for urologic tissue regeneration.

Tunable elastomer materials with vascular tissue-like rupture mechanics behavior.

Purpose. Laboratory models of human arterial tissues are advantageous to examine the mechanical response of blood vessels in a simplified and controllable manner. In the present study, we investigated three silicone-based materials for replicating the mechanical properties of human arteries documented in the literature.Methods. We performed uniaxial tensile tests up to rupture on Sylgard184, Sylgard170 and DowsilEE-3200 under different curing conditions and obtained their True (Cauchy) stress-strain behavior and Poisson's ratios by means of digital image correlation (DIC). For each formulation, we derived the constitutive parameters of the 3-term Ogden model and designed numerical simulations of tubular models under a radial pressure of 250 mmHg.Results. Each material exhibits evident non-linear hyperelasticity and dependence on the curing condition. Sylgard184 is the stiffest formulation, with the highest shear moduli and ultimate stresses at relative low strains (µ184 = 0.52-0.88 MPa,σ184 = 15.90-16.54 MPa,ε184 = 0.72-0.96). Conversely, Sylgard170 and DowsilEE-3200 present significantly lower shear moduli and ultimate stresses that are closer to data reported for arterial tissues (µ170 = 0.33-0.7 MPaσ170 = 2.61-3.67 MPa,ε170 = 0.69-0.81;µdow= 0.02-0.09 MPaσdow= 0.83-2.05 MPa,εdow= 0.91-1.05). Under radial pressure, all formulations except DowsilEE-3200 at 1:1 curing ratio undergo circumferential stresses that remain in the elastic region with values ranging from 0.1 to 0.18 MPa.Conclusion. Sylgard170 and DowsilEE-3200 appear to better reproduce the rupture behavior of vascular tissues within their typical ultimate stress and strain range. Numerical models demonstrate that all three materials achieve circumferential stresses similar to human common carotid arteries (Sommeret al2010), making these formulations suited for cylindrical laboratory models under physiological and supraphysiological loading.

Biaxial testing system for characterization of mechanical and rupture properties of small samples.

The study of damage and rupture of soft tissues using a tensile testing system is essential to understand the limits of mechanical behavior and loss of function in diseased tissues. However, commercial material testing systems are often expensive and may not be fully suitable for rupture tests of small samples. While several research laboratories have developed custom, less expensive, uniaxial or biaxial devices, there is a need for an open source, inexpensive, accurate and easy to customize biaxial material testing system to perform rupture tests in small soft samples. We designed a testing system (BiMaTS) that (a) was shown able to perform uniaxial and biaxial tests, (b) offers a large travel range for rupture tests of small samples, (c) maintains a centered field of view for effective strain mapping using digital image correlation, (d) provides a controlled temperature environment, (e) utilize many off-the-shelve components for easy manufacture and customization, and it is cost effective (∼$15 K). The instrument performance was characterized using 80%-scaled down, ASTM D412-C shaped PDMS samples. Our results demonstrate the ability of this open source, customizable, low-cost, biaxial materials testing system to successfully characterize the mechanical and rupture properties of small samples with high repeatability and accuracy.

Clinical features, diagnosis and treatment outcome of fungal endocarditis: A systematic review of reported cases.

The landscape of fungal endocarditis (FE) has constantly been evolving in the last few decades. Despite the advancement in diagnostic methods and the introduction of newer antifungals, mortality remains high in FE. This systematic review aimed to evaluate the epidemiology, clinical features, diagnostic and therapeutic interventions in patients with FE. We also aim to examine the aforementioned factors as a determinant of mortality in FE. A literature search was performed in PubMed, Google Scholar and Scopus, and all patients ≥18 years with proven fungal endocarditis were included. A total of 220 articles (250 patients) were included in the final analysis. Candida was the commonest aetiology (49.6%), followed by Aspergillus (30%) and Scedosporium species (3.2%). The proportion of prosthetic valve endocarditis (PVE) and intravenous drug users was 35.2% and 16%, respectively. The overall mortality rate was 40%. On multivariate analysis, Aspergillus endocarditis (HR 3.7, 95% CI 1.4-9.7; p = .009) and immunocompromised state (HR 2.8, 95% CI 1.24-6.3; p = .013) were independently associated with mortality. Patients treated with surgery along antifungals had better survival (HR 0.20, 95% CI 0.09-0.42; p < .001) compared to those treated with antifungals alone. Recurrence of FE was reported in 10.4% of patients. In conclusion, FE carries significant mortality, particularly in immunodeficient and Aspergillus endocarditis. We advocate the use of surgery combined with antifungals to improve clinical outcomes.

The Specific Molecular Composition and Structural Arrangement of Eleutherodactylus Coqui Gular Skin Tissue Provide Its High Mechanical Compliance.

A male Eleutherodactylus Coqui (EC, a frog) expands and contracts its gular skin to a great extent during mating calls, displaying its extraordinarily compliant organ. There are striking similarities between frog gular skin and the human bladder as both organs expand and contract significantly. While the high extensibility of the urinary bladder is attributed to the unique helical ultrastructure of collagen type III, the mechanism behind the gular skin of EC is unknown. We therefore aim to understand the structure-property relationship of gular skin tissues of EC. Our findings demonstrate that the male EC gular tissue can elongate up to 400%, with an ultimate tensile strength (UTS) of 1.7 MPa. Species without vocal sacs, Xenopus Laevis (XL) and Xenopus Muelleri (XM), elongate only up to 80% and 350% with UTS~6.3 MPa and ~4.5 MPa, respectively. Transmission electron microscopy (TEM) and histological staining further show that EC tissues' collagen fibers exhibit a layer-by-layer arrangement with an uninterrupted, knot-free, and continuous structure. The collagen bundles alternate between a circular and longitudinal shape, suggesting an out-of-plane zig-zag structure, which likely provides the tissue with greater extensibility. In contrast, control species contain a nearly linear collagen structure interrupted by thicker muscle bundles and mucous glands. Meanwhile, in the rat bladder, the collagen is arranged in a helical structure. The bladder-like high extensibility of EC gular skin tissue arises despite it having eight-fold lesser elastin and five times more collagen than the rat bladder. To our knowledge, this is the first study to report the structural and molecular mechanisms behind the high compliance of EC gular skin. We believe that these findings can lead us to develop more compliant biomaterials for applications in regenerative medicine.

Aliphatic Chain Modification of Collagen Type I: Development of Elastomeric, Compliant, and Suturable Scaffolds.

Collagen type I is one of the most suitable natural biomaterials for constructing tissue-engineering scaffolds. Despite their biocompositional similarities to physiological tissues, these scaffolds lack host specific and matching mechanical properties. While it is possible to enhance their stiffness by cross-linking, it often compromises their abilities to expand or strain under minimal stress, that is, compliance (inverse of stiffness). Here, we report a simple, inexpensive, cross-linking- and elastin-free collagen-based material composition for developing elastomeric scaffolds that are highly compliant, soft yet strong, and suturable, therefore, clinically attractive. Our strategy utilizes room-temperature modification of collagen type I scaffolds with linear aliphatic chains of various lengths (C7-C18). In particular, dodecenylsuccinic anhydride (size: C12, DDSA) modified scaffolds elongated up to 400% of its initial length compared to only ∼20% for collagen-control within the applied tensile stress of 0.2 MPa without breaking. Furthermore, the suture retention strength value increased to 60 g-force from 30 g-force for collagen control. We confirmed that the C12-modified material remained structurally stable at the physiological temperature (37 °C) with a tan δ value of ∼0.3, similar to collagen control; however, tan δ increased sharply for C12-modified collagen above 42 °C, compared to 59 °C for collagen control. To understand the mechanism of hyperextensibility, we studied the morphology of the resultant material by transmission electron microscopy (TEM), which showed an altered microstructure of C12-modified collagen scaffolds. While the partially C12-modified sample had a mixture of typical collagen type I triple helix and diffused gelatinized random coil-like configuration, the fully modified samples showed thick wrinkled and entangled ribbon-like microstructures, which was different than that of thermally denatured gelatin. We further confirmed that the resultant material allowed cell growth in vitro and in vivo in a subcutaneous mouse model.

Investigating the link between benign prostatic hypertrophy, BMI and type 2 diabetes mellitus.

AIMS: To investigate the link between benign prostatic hypertrophy, BMI and type 2 diabetes mellitus. MATERIALS AND METHODS: This was the retrospective study conducted at the urology clinic of NCRHA and SWRHA, in Trinidad. Data was obtained from 85 patients with high PSA values (>4.0ng/mL). The data collected were age, ethnicity, weight, height, lifestyle and their most recent blood sugar levels were recorded. Ultrasound reports of patients diagnosed with BPH were also analyzed to gather data on whether their hyperplasia was benign or malignant. RESULTS: The majority of the sample population was of Afro-Trinidadian descent (41) followed by East Indian descent (26) and then of mixed ethnicity (18). Individuals in the sample population with a normal BMI had a mean PSA value of 23.66ng/mL, while those with a BMI in the overweight range had a mean PSA value of 28.1ng/mL, and those with a BMI in the obese range had a mean PSA value of 18.5ng/mL. There were no statistically significant differences in the mean values of PSA levels between diabetics and non-diabetics, between the 3 major ethnic groups in our sample population and between the 3 different groupings based on BMI ranges. However it was found that the average mean age of patients of East Indian descent (62.96±2.23) was significantly lower than that of patients of African descent (70.15±2.02). CONCLUSIONS: This study did not show any significant differences in the mean values of PSA levels between diabetics and non-diabetics, between the 3 different groupings based on BMI ranges.