Stem Cell Therapy in Ocular Pathologies in the Past 20 Years

Stem cell therapies are successfully used in various fields of medicine. This new approach of research is also expanding in ophthalmology. Huge investments, resources and important clinical trials have been performed in stem cell research and in potential therapies. In recent years, great strides have been made in genetic research, which permitted and enhanced the differentiation of stem cells. Moreover, the possibility of exploiting stem cells from other districts (such as adipose, dental pulp, bone marrow stem cells, etc.) for the treatment of ophthalmic diseases, renders this topic fascinating. Furthermore, great strides have been made in biomedical engineering, which have proposed new materials and threedimensional structures useful for cell therapy of the eye. The encouraging results obtained on clinical trials conducted on animals have given a significant boost in the creation of study protocols also in humans. Results are limited to date, but clinical trials continue to evolve. Our attention is centered on the literature reported over the past 20 years, considering animal (the most represented in literature) and human clinical trials, which are limiting. The aim of our review is to present a brief overview of the main types of treatments based on stem cells in the field of ophthalmic pathologies

How and when of eyelid reconstruction using autologous transplantation

Reconstructive surgery of the eyelid after tumor excision, trauma or other causes can be challenging, especially due to the complexities of the anatomic structures and to the necessity of both functional and aesthetic successful outcomes. The aim of this minireview was to investigate the use of tissue transplantation in eyelid reconstruction. Surgical procedures are various, based on the use of both flaps, pedicled or free, and grafts, in order to guarantee adequate tissue reconstruction and blood supply, which are necessary for correct healing. Common techniques normally include the use of local tissues, combining non-vascularized grafts with a vascularized flap for the two lamellae repair, to attempt a reconstruction similar to the original anatomy. When defects are too wide, vast, deep, and complex or when no adjacent healthy tissues are available, distant area tissues need to be recruited as free flaps or grafts and paired with mucosal layer reconstruction. With regards to the anterior lamella, full thickness skin grafts are commonly preferred. With regards to the reconstruction of posterior lamella, there are different graft options, which include conjunctival or tarsoconjunctival, mucosal or palatal or cartilaginous grafts usually combined with local flaps. Free flap transplantation, normally reserved for rare select cases, include the use of the radial forearm and anterolateral flaps combined with mucosal grafts, which are surgical options currently reported in the literature

Autologous micrografts and methotrexate in plantar erosive lichen planus: healing and pain control. A case report

Erosive lichen planus is an uncommon variant of lichen planus. We report a case of long-standing and refractory plantar ELPs causing disabling and opiate-resistant pain treated with 'classic' meshed skin graft combined with RigeneraVR micrografts. After approximately 9 months follow-up, no clinical recurrence or pain were observed. Erosive lichen planus (ELP) is an uncommon variant of lichen planus, involving oral cavity and genitalia and, less often plantar areas, where it usually presents with chronic erosions of the soles, along with intense, disabling pain and progressive loss of toenails. An abnormal immune cellular response (CD8+ lymphocytes and macrophages) and the consequent altered production of multiple mediators (interleukin-12, interferon-gamma, tumor necrosis factor-alpha, RANTES and MMP-9), seem to play a crucial role in the pathogenesis, although the etiology remains uncertain. From a histological point of view, ELP shows keratinocyte apoptosis, intense inflammatory response and basal epithelial keratinocytes TNF-alpha overexpression. Several therapies have been proposed, with variable and controversial results. While topical corticosteroids and topical calcineurin inhibitors are the treatments of choice for localized forms, short pulses of systemic glucocorticoids, phototherapy, and systemic immunosuppressants are recommended for generalized cases. Surgery has been reported as a possible therapeutic option in refractory and stable cases with localized lesions, either alone or with cyclosporine. Herein, we report a case of longstanding and refractory plantar ELPS causing disabling and opiate-resistant pain treated with 'classic' meshed skin graft combined with RigeneraVR micrografts

Calcareous Bio-Concretions in the Northern Adriatic Sea: Habitat Types, Environmental Factors that Influence Habitat Distributions, and Predictive Modeling

Habitat classifications provide guidelines for mapping and comparing marine resources across geographic regions. Calcareous bio-concretions and their associated biota have not been exhaustively categorized. Furthermore, for management and conservation purposes, species and habitat mapping is critical. Recently, several developments have occurred in the field of predictive habitat modeling, and multiple methods are available. In this study, we defined the habitats constituting northern Adriatic biogenic reefs and created a predictive habitat distribution model. We used an updated dataset of the epibenthic assemblages to define the habitats, which we verified using the fuzzy k-means (FKM) clustering method. Redundancy analysis was employed to model the relationships between the environmental descriptors and the FKM membership grades. Predictive modelling was carried out to map habitats across the basin. Habitat A (opportunistic macroalgae, encrusting Porifera, bioeroders) characterizes reefs closest to the coastline, which are affected by coastal currents and river inputs. Habitat B is distinguished by massive Porifera, erect Tunicata, and noncalcareous encrusting algae (Peyssonnelia spp.). Habitat C (non-articulated coralline, Polycitor adriaticus) is predicted in deeper areas. The onshore-offshore gradient explains the variability of the assemblages because of the influence of coastal freshwater, which is the main driver of nutrient dynamics. This model supports the interpretation of Habitat A and C as the extremes of a gradient that characterizes the epibenthic assemblages, while Habitat B demonstrates intermediate characteristics. Areas of transition are a natural feature of the marine environment and may include a mixture of habitats and species. The habitats proposed are easy to identify in the field, are related to different environmental features, and may be suitable for application in studies focused on other geographic areas. The habitat model outputs provide insight into the environmental drivers that control the distribution of the habitat and can be used to guide future research efforts and cost-effective management and conservation plans

Estabelecimento de normas DRIS para o cupuaçueiro na região amazônica.

A avaliação do estado nutricional de um pomar ou lavoura depende da definição de valores de referência que sejam adequados para refletir as condições de crescimento das plantas. Neste sentido, o objetivo deste trabalho foi determinar normas DRIS para cupuaçueiro cultivado na Amazônia, testando em populações com diferentes idades. Amostras foliares de cupuaçu foram coletadas de pomares comerciais, cuja idade das plantas variou de 5 a 18 anos, cultivadas sob monocultivo ou sistemas agroflorestais (SAF's), obtendo-se para cada relação nutricional entre os nutrientes N, P, K, Ca, Mg, Zn, Fe, Mn e Cu as normas DRIS, as quais foram obtidas para o conjunto da população monitorada e para subpopulações específicas. Os diferentes grupos de normas não diferem entre si, possibilitando a obtenção de normas DRIS que possam representar um grande número de condições de produção

Transient Analysis and Modeling of Automotive PEM Fuel Cell System Accounting for Water Transport Dynamics

ABSTRAC

Genetic deletion of osteopontin in TRAMP mice skews prostate carcinogenesis from adenocarcinoma to aggressive human-like neuroendocrine cancers

Osteopontin (OPN) is a secreted glycoprotein, that belongs to the non-structural extracellular matrix (ECM), and its over expression in human prostate cancer has been associated with disease progression, androgen independence and metastatic ability. Nevertheless, the pathophysiology of OPN in prostate tumorigenesis has never been studied. We crossed TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice with OPN deficient (OPN-/-) mice and followed tumor onset and progression in these double mutants. Ultrasound examination detected the early onset of a rapidly growing, homogeneous and spherical tumor in about 60% of OPN-/- TRAMP mice. Such neoplasms seldom occurred in parental TRAMP mice otherwise prone to adenocarcinomas and were characterized for being androgen receptor negative, highly proliferative and endowed with neuroendocrine (NE) features. Gene expression profiling showed up-regulation of genes involved in tumor progression, cell cycle and neuronal differentiation in OPN-deficient versus wild type TRAMP tumors. Downregulated genes included key genes of TGFa pathway, including SMAD3 and Filamin, which were confirmed at the protein level. Furthermore, NE genes and particularly those characterizing early prostatic lesions of OPN-deficient mice were found to correlate with those of human prostate NE tumours. These data underscore a novel role of OPN in the early stages of prostate cancer growth, protecting against the development of aggressive NE tumors