Orthopedic manifestations in patients with mucopolysaccharidosis type II (Hunter syndrome) enrolled in the Hunter Outcome Survey

Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare, inherited disorder caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase. As a result of this deficiency, glycosaminoglycans accumulate in lysosomes in many tissues, leading to progressive multisystemic disease. The cardiopulmonary and neurological problems associated with MPS II have received considerable attention. Orthopedic manifestations are common but not as well characterized. This study aimed to characterize the prevalence and severity of orthopedic manifestations of MPS II and to determine the relationship of these signs and symptoms with cardiovascular, pulmonary and central nervous system involvement

Peripheral Nerve Sheath Tumor in the Upper Eyelid in a Dog

Background: Schwannomas are benign neurogenic tumours of peripheral nerves. They originate from Schwann cells, which form the neural sheath.Peripheral nerve sheath tumors are most commonly found on the head and neck regions of both dogs and people. Schwannomas are rarely observed in ophthalmic areas. When they occur, ocular Schwannomas are usually located in the orbit, uveal tract and conjunctiva. The occurrence of uveal schwannoma, a subset of PNST has been well documented in the veterinary literature. This is the first report of a palpebral PNST in the dog. The lip-to-lid flap is a feasible technique to reconstruct the upper eyelid following wide surgical removal of a tumor in the dog.Case: A 9-year-old, spayed female mixed-breed dog was referred for evaluation of a large mass involving the right upper eyelid for a duration of approximately one month. The inspection revealed sero-sanguinolent discharge and an oval-shaped mass occupying more than 70% of the right upper eyelid. The dog was alert and the ophthalmic and general physical examination did not revealed abnormalities. Ocular ultrasonography did not show significant findings. A fine-needle aspirate of the palpebral tumor was not elucidative, even so, a presumptive diagnosis of eyelid neoplasia was considered most likely. Excision of the entire mass with a 2 cm margin was performed. The third eyelid and dorso-medial bulbar conjunctiva were also removed. Upper eyelid reconstruction was performed based on a similar technique previously described in cats (lip-to-lid flap). As a result, neoplastic spindle cells exhibited immunoreactivity for S100 and intense cytoplasmic staining for vimentin, supporting the diagnosis of schwannoma. Fifteen days later, the margins of the subdermal pattern flap were healed and skin sutures were removed. On the last follow-up, 9 months post-surgery, the dog was visual, and the flap was well incorporated and covered the ocular surface. Ten months later, another large mass arising from the right inferior palpebral conjunctiva was observed. Once ultrasound revealed orbital invasion exenteration combined with orbitectomy were performed, and the defect was covered with an auricular axial pattern flap. Although the second tumor had the same histological and immunohistochemical characteristics of the first mass additional staining for Ki67 was used to investigate the biological behavior of both masses.Discussion: Reported eyelid neoplasms in dogs include adenomas and adenocarcinomas of the meibomian glands, melanomas, fibroma, fibrosarcoma, histiocytoma, mastocytoma, lipomas, papillomas, and squamous cell carcinomas. To the author´s knowledge, however, this is the first case description of a PNST affecting the eyelid in a dog. The histologic distinction between PNSTs and other spindle cell tumors, including myxosarcoma, fibrosarcoma, leiomyosarcoma, hemangiopericytoma, and melanoma can be challenging and requires immunohistochemical stainin. S100 is an acidic protein that identifies various nervous tissue cells, including Schwann cells, and the majority of canine PNSTs diffusely express this molecule. As in the case presented here, neoplastic cells of different ocular and adnexal structures were also positive for S100 and vimentin in all PNSTs previously reported in the veterinary literature. This is the first report of PNST affecting the eyelid in a dog. The lip-to-lid flap is a feasible technique to reconstruct the upper eyelid following wide surgical removal of a tumor in dogs. However, the authors suggest radical surgery combining orbitectomy, exenteration and a miocutaneous flap if PNST is diagnosed in the eyelids of dogs. They also caution once recurrence is possible and can be more aggressive.Keywords: lip-to-lid transposition, S100, vimentin, desmin, Ki67, dog

Severe Corneal Edema in a Dog Naturally Infected by Leishmania spp.

Background: Visceral leishmaniasis (VL) is an infectious disease caused by the protozoan Leishmania infantum that is transmitted to dogs and humans by sandflies. The incidence of eye injuries in VL is high. They occur in 20 to 81% of infected dogs and include blepharitis, granulomatous conjunctivitis, scleritis, keratitis, anterior uveitis, keratoconjunctivitis sicca, and secondary glaucoma. However, some dogs present only the clinical signs of eye damage. The main objective of this manuscript is to report a case of anterior uveitis with severe corneal edema in a dog with VL that underwent clinical and surgical ophthalmic treatments after miltefosine therapy.Case: An 8-month-old, intact male Labrador Retriever with brown fur presented with pruritus, diffuse desquamation, and conjunctival hyperemia on physical evaluation. On the basis of an ophthalmic examination, nodular conjunctivitis and uveitis were diagnosed in both eyes. Moreover, laboratory examination results showed hyperproteinemia, increased serum alkaline phosphatase activity, and positive reactions to immunochromatographic tests for VL. Clinical treatment was instituted from the moment of diagnosis, when miltefosine and allopurinol were prescribed. At the end of treatment, based on laboratory examination results, only allopurinol was prescribed at a lower dose than initially prescribed for treatment continuation. Topical medications (prednisolone eye drops and sodium hyaluronate) were recommended for the ophthalmic changes. One week after the start of topical treatment, the dog showed an improvement in eye inflammation but still had bilateral corneal edema. A hyperosmotic agent was prescribed to improve edema, and a surgical procedure was recommended if there was no improvement. The physician opted for the surgical procedure in one of the eyes that had not shown significant improvement after the clinical treatment.Discussion: VL is a zoonosis, and the domestic dog is the main reservoir. These animals often have dermatological conditions, and the ophthalmic changes observed can be unilateral or bilateral, with more than one change in the same eye. Lymphoplasmacytic or granulomatous anterior uveitis is the most prevalent change, as the uvea and conjunctiva are important lymphoid areas of the eye; this also explains the high incidence of uveitis and conjunctivitis in dogs with VL. In uveitis, corneal edema is driven by endothelial cell damage induced by prostaglandins, which interfere with the function of the endothelial pump and interrupt the normal dehydrated state of the cornea. Severe corneal edema can result in the formation of fluid-filled multifocal bubbles in the corneal stroma—a condition called bullous keratopathy. These bubbles accumulate under or inside the corneal epithelium, and they can burst spontaneously, leading to corneal erosions or ulcerations. Drug therapy with hyperosmotic agents could, in principle, reduce the formation of bubbles. Surgical options to decrease edema and blistering include a permanent conjunctival graft or thermokeratoplasty. Thermokeratoplasty induces the formation of superficial scars in the corneal stroma, applying multiple cauterization foci to the stroma exposed in the areas of bullous keratopathy and epithelial ulceration. In conclusion, the surgical therapeutic choice results in better visual quality in patients who do not respond well to clinical treatment

Peripheral nerve sheath tumor in the upper eyelid in a dog

Background: Peripheral nerve sheath tumors are most commonly found on the head and neck regions of both dogs and people. Schwannomas are rarely observed in ophthalmic areas. When they occur, ocular Schwannomas are usually located in the orbit, uveal tract and conjunctiva. The occurrence of uveal schwannoma, a subset of PNST has been well documented in the veterinary literature. PNST has never been observed in the eyelids of dogs. Therefore, the present report aimed to describe the surgical treatment and outcome of a PNST located in the upper eyelid of a dog. Case: A 9-year-old, spayed female mixed-breed dog was referred for evaluation of a large mass involving the right upper eyelid for a duration of approximately one month. The inspection revealed sero-sanguinolent discharge and an oval-shaped mass occupying more than 70% of the right upper eyelid. A presumptive diagnosis of eyelid neoplasia was considered most likely. Excision of the entire mass with a 2 cm margin was performed. The third eyelid and dorso-medial bulbar conjunctiva were also removed. Upper eyelid reconstruction was performed based on a similar technique previously described in cats (lip-to-lid flap). As a result, neoplastic spindle cells exhibited immunoreactivity for S100 and intense cytoplasmic staining for vimentin, supporting the diagnosis of schwannoma. Fifteen days later, the margins of the subdermal pattern flap were healed and skin sutures were removed. On the last follow-up, 9 months post-surgery, the dog was visual, and the flap was well incorporated and covered the ocular surface. Ten months later, another large mass arising from the right inferior palpebral conjunctiva was observed. Once ultrasound revealed orbital invasion exenteration combined with orbitectomy were performed, and the defect was covered with an auricular axial pattern flap. The second tumor had the same histological and immunohistochemical characteristics of the first mass. Both tumors expressed Ki67; however, the PI in the second mass was higher (7.9%) than the first (3.4%). Discussion: Reported eyelid neoplasms in dogs include adenomas and adenocarcinomas of the meibomian glands, melanomas, fibroma, fibrosarcoma, histiocytoma, mastocytoma, lipomas, papillomas, and squamous cell carcinomas. To the author’s knowledge, however, this is the first case description of a PNST affecting the eyelid in a dog. The histologic distinction between PNSTs and other spindle cell tumors, including myxosarcoma, fibrosarcoma, leiomyosarcoma, hemangiopericytoma, and melanoma can be challenging and requires immunohistochemical stainin. S100 is an acidic protein that identifies various nervous tissue cells, including Schwann cells, and the majority of canine PNSTs diffusely express this molecule. As in the case presented here, neoplastic cells of different ocular and adnexal structures were also positive for S100 and vimentin in all PNSTs previously reported in the veterinary literature. This is the first report of PNST affecting the eyelid in a dog. The lip-to-lid flap is a feasible technique to reconstruct the upper eyelid following wide surgical removal of a tumor in dogs. However, the authors suggest radical surgery combining orbitectomy, exenteration and a miocutaneous flap if PNST is diagnosed in the eyelids of dogs. They also caution once recurrence is possible and can be more aggressive

Effects of 1% Topical Brinzolamide on Intraocular Pressure in Healthy Dogs

Background: Glaucoma is one of the most common causes of blindness in dogs, and is generally characterized by death of the retinal ganglion cells associated with a rapid loss of vision. Increased intraocular pressure (IOP) occurs in patients with primary glaucoma, due to genetic abnormalities in pectinal ligaments and the trabeculae of the iridocorneal angle, producing inadequate drainage of aqueous humor. IOP is the result of the dynamic equilibrium between the production and drainage of aqueous humor. Intraocular surgery, anterior lens luxation, systemic diseases, immune-mediated, neoplastic and infectious diseases lead to the breakdown of the blood-aqueous barrier and increase the amount of protein and cells in aqueous humor, which can block this drainage pathway. Under these conditions, becomes indispensable the pharmacological control of IOP by reducing aqueous humor production. The main objective of the present study was to evaluate the effects of topical 1% brinzolamide on intraocular pressure (IOP) in twelve healthy dogs.Materials, Methods & Results: The age range of affected dogs was 1-5 years, with a mean age of 2.5 years. Twelve dogs were included in this study. All animals were healthy based on clinical, ophthalmic and hematological examinations. Selected animals were kept in a room with 500 lux luminosity, 56.8% relative humidity, 20°C temperature, exposed to 12 h of light/dark cycle, were fed twice daily and water ad libitum. All animals were adaptation to the procedures and examiners and IOP was measured by applanation tonometry at 08:00 a.m., 11:00 a.m., 02:00 p.m., 05:00 p.m., and 08:00 p.m., for 7 days and 2 days of baseline. Subsequently, one eye of each dog was randomly assigned, the eye received one drop of 1% brinzolamide at 08:30 a.m., 02:30 p.m., and 08:30 p.m. during four consecutive days and adelfo eyes received one drop of sterile saline solution and were considered control eyes. During the treatment phase and on the day after the treatment had finished, all parameters were evaluated in a blind fashion at the same pre-established time points. The value for IOP during the baseline of the treated eye were 16.77 ± 0.22 mmHg. The baseline period, values did not differ significantly between treated and control eyes. Comparison between the first day of brinzolamide-treated eyes with the average daily values of the two days of the baseline period showed that IOP decreased significantly 8.88%. IOP after four days of daily instillations of brinzolamide was able to decrease overall IOP by 1.42 mmHg (8.47%) when compared with the baseline period. Overall IOP values in the brinzolamide-treated eyes decreased 1.02 mmHg (6.24%) when compared to the control eyes. There were no statistically significant differences when compared control eye to baseline. Three times daily instillations of 1% brinzolamide in healthy dogs significantly decrease 8.47% IOP. During the post-treatment period, the average daily values of the brinzolamide-treated eyes remained 1.52 mmHg below the average daily values observed at baseline period.Discussion: The present research showed that, the average daily IOP values in the brinzolamide-treated eyes decreased 1.49 mmHg (8.88%) at the end of the first day, 1.69 mmHg (10.07%) at the end of the fourth day, and the cumulative IOP values after four days of treatment, were able to decrease by 1.42 mmHg (8.53%). Three times daily instillations of 1% brinzolamide in healthy dogs significantly decrease IOP, and therefore may be indicated to management of intraocular hypertension and glaucoma

Optimization of zirconia surface textured designs using Nd:Yag laser for biomedical applications

The development of surface textured designs has influence in primary stability of surgically placed implants since a textured surface allows to firmer mechanical link to the surrounding tissue. Laser technology has been investigated to develop new surface designs on green zirconia compacts by cold pressing. Nd:Yag laser were used to produce several strategies and different laser parameters (laser power, speed and laser passages) were tested to evaluate their impact on cavities geometry and depth. The surface texture designs were analysed by Scanning Electron Microscopy (SEM) and regular geometries such as cavities or pillars were observed. The distance between lines have a strong impact on texturing quality and should be combined with optimum power and speed conditions. Regarding the optimized conditions, several surface textured patterns were created in both green and sintered zirconia compacts. This study allowed to conclude that only some texturing strategies are suitable to obtain high quality surface textured patterns. Otherwise, the remaining strategies are potential solutions for obtaining high quality machined structures (laser does not machine cavities but crosses the entire bulk). High strength zirconia scaffolds were machined by laser and CNC machining technologies and the two promising technologies were compared.This work is supported by FCT (Fundação para a Ciência e a Tecnologia) through the grant SFRH/BD/148031/2019, the project UIDB/04436/2020 and UIDP/04436/2020

International randomised controlled trial for the treatment of newly diagnosed EWING sarcoma family of tumours - EURO EWING 2012 Protocol

[Background] Although there have been multiple randomised trials in newly diagnosed Ewing sarcoma family of tumours (ESFT) and these have been conducted over many years and involved many international cooperative groups, the outcomes for all stages of disease have plateaued. Internationally, the standard treatment of ESFT is not defined, and there is a need to add new agents other than conventional chemotherapy to improve outcomes. This trial will compare two different induction/consolidation chemotherapy regimens: (1) vincristine, ifosfamide, doxorubicin and etoposide (VIDE) induction and vincristine, actinomycin D, ifosfamide or cyclophosphamide, or busulfan and mephalan (VAI/VAC/BuMel) consolidation and (2) vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide (VDC/IE) induction and ifosfamide and etoposide, vincristine and cyclophosphamide, vincristine, actinomycin D and ifosfamide, or busulfan and mephalan (IE/VC/VAI/BuMel) consolidation (randomisation 1, or R1). A second randomisation (R2) will determine whether the addition of zoledronic acid to consolidation chemotherapy, as assigned at R1, is associated with improved clinical outcome.[Methods] EURO EWING 2012 is an international, multicentre, phase III, open-label randomised controlled trial. There are two randomisations: R1 and R2. Patients are randomly assigned at two different time points: at entry to the trial (R1) and following local control therapy (R2). The primary outcome measure is event-free survival. The secondary outcome measures include overall survival, adverse events and toxicity, histological response of the primary tumour, response of the primary tumour, regional lymph nodes or metastases (or both), and achievement of local control at the end of treatment.[Discussion] This study will establish which is the “standard regimen” of chemotherapy, taking into account both clinical outcomes and toxicity. This will form the chemotherapy backbone for future interventional studies where we may want to add new targeted agents. It will also determine the role of zoledronic acid in conjunction with the separate EE2008 trial. Any trial in ESFT needs to take into account the rarity of the tumour and consider that international cooperation is needed to provide answers in a timely manner.[Trial registration] Registered with EudraCT number 2012-002107-17 on 26 February 2012. Registered with ISRCTN number 92192408 on 4 November 2013.This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement n°602856. The NCC in France, CLB, receives additional funding from SFCE and Ligue contre le cancer. The coordinating sponsor (the University of Birmingham, Birmingham, UK) is funded by Cancer Research UK (grant award reference C5952/A14745)

Co-occurrence of microcystin and microginin congeners in Brazilian strains of Microcystis sp.

Species of Microcystis are the most common bloom-forming cyanobacteria in several countries. Despite extensive studies regarding the production of bioactive cyanopeptides in this genus, there are limited data on isolated strains from Brazil. Three Microcystis sp. strains were isolated from the Salto Grande Reservoir (LTPNA01, 08 and 09) and investigated for the presence of mcy genes, microcystins and other cyanopeptides. Microcystin and microginin production was confirmed in two isolates using high-resolution tandem mass spectrometry after electrospray ionization (ESI-Q-TOF), and the structures of two new microginin congeners were proposed (MG756 Ahda-Val-Leu-Hty-Tyr and MG770 MeAhda-Val-Leu-Hty-Tyr). The biosynthesis profile of the identified cyanopeptides was evaluated at different growth phases via a newly developed HPLC-UV method. Results demonstrated no substantial differences in the production of microcystins and microginins after data normalization to cell quota, suggesting a constitutive biosynthesis. This study represents the first confirmed co-production of microginins and microcystins in Brazilian strains of Microcystis sp. and highlights the potential of Brazilian cyanobacteria as a source of natural compounds with pharmaceutical interest.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) [2010/15651-9, 2010/15696-2]CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)CONICYT (Programa de Cooperacion Cientifica Internacional)CONICYT (Programa de Cooperacion Cientifica Internacional)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico

Developing an acoustic-phonetic characterization of dysarthric speech in French

- ISBN: 2-9517408-6-7 - Domaines: Phonetic Databases, Phonology, Person IdentificationInternational audienceThis paper presents the rationale, objectives and advances of an on-going project (the DesPho-APaDy project funded by the French National Agency of Research) which aims to provide a systematic and quantified description of French dysarthric speech, over a large population of patients and three dysarthria types (related to the parkinson's disease, the Amyotrophic Lateral Sclerosis disease, and a pure cerebellar alteration). The two French corpora of dysarthric patients, from which the speech data have been selected for analysis purposes, are firstly described. Secondly, this paper discusses and outlines the requirement of a structured and organized computerized platform in order to store, organize and make accessible (for selected and protected usage) dysarthric speech corpora and associated patients' clinical information (mostly disseminated in different locations: labs, hospitals, ...). The design of both a computer database and a multi-field query interface is proposed for the clinical context. Finally, advances of the project related to the selection of the population used for the dysarthria analysis, the preprocessing of the speech files, their orthographic transcription and their automatic alignment are also presented