Nano- and micro-fiber combined scaffolds : a new architecture for bone tissue engineering

One possible interesting way of designing a scaffold for bone tissue engineering is to base it on trying to mimic the biophysical structure of natural extracellular matrix (ECM). This work was developed in order to produce scaffolds for supporting bone cells. Nano and micro fiber combined scaffolds were originally produced from starch based biomaterials by means of a fiber bonding and a electrospinning, two step methodology. The cell culture studies with SaOs-2 human osteoblast-like cell line and rat bone marrow stromal cells demonstrated that presence of nanofibers influenced cell shape and cytoskeletal organization of the cells on the nano/micro combined scaffolds. Moreover, cell viability and Alkaline Phosphatase (ALP) activity for both cell types was found to be higher in nano/micro combined scaffolds than in control scaffolds based on fiber meshes without nanofibers. Consequently, the developed structures are believed have a great potential on the 3D organization and guidance of cells that is provided for engineering of 3-dimensional bone tissues

Perforated Hepatic Hydatid Cyst into the Peritoneum with Mild Symptoms

Rupture into the abdominal cavity is a rare but serious complication of hydatid disease that necessitates emergency surgical intervention. We present herein a case with mild abdominal symptoms due to hydatid cyst rupture into the peritoneum after trauma. A 24-year-old man was admitted to the emergency room with mild abdominal pain. His symptoms had started after a fall four days earlier. Ultrasonography and computed tomography showed cystic lesions in the liver and peritoneum with intraabdominal free fluid. He was treated surgically with partial cystectomy and falciformoplasty. Postoperative albendazole therapy was given for two months. There was not recurrence four months postoperatively at control computed tomography

Design, Development and Temporal Evaluation of an MRI-Compatible In-Vitro Circulation Model Using a Compliant AAA Phantom

Biomechanical characterization of abdominal aortic aneurysms (AAA) has become commonplace in rupture risk assessment studies. However, its translation to the clinic has been greatly limited due to the complexity associated with its tools and their implementation. The unattainability of patient-specific tissue properties leads to the use of generalized population-averaged material models in finite element analyses, which adds a degree of uncertainty to the wall mechanics quantification. In addition, computational fluid dynamics modeling of AAA typically lacks the patient-specific inflow and outflow boundary conditions that should be obtained by non-standard of care clinical imaging. An alternative approach for analyzing AAA flow and sac volume changes is to conduct in vitro experiments in a controlled laboratory environment. We designed, built, and characterized quantitatively a benchtop flow-loop using a deformable AAA silicone phantom representative of a patient-specific geometry. The impedance modules, which are essential components of the flow-loop, were fine-tuned to ensure typical intra-sac pressure conditions. The phantom was imaged with a magnetic resonance imaging (MRI) scanner to acquire time-resolved images of the moving wall and the velocity field inside the sac. Temporal AAA sac volume changes lead to a corresponding variation in compliance throughout the cardiac cycle. The primary outcome of this work was the design optimization of the impedance elements, the quantitative characterization of the resistive and capacitive attributes of a compliant AAA phantom, and the exemplary use of MRI for flow visualization and quantification of the deformed AAA geometry

Evaluation of e148q and concomitant aa amyloidosis in patients with familial mediterranean fever

The aim of the study was to compare the clinical phenotype of patients with familial Mediterranean fever (FMF)-related AA amyloidosis, according to the age of FMF diagnosis and E148Q genotype. Patients with biopsy-confirmed FMF-related AA amyloidosis were included in the study. Tel-Hashomer criteria were applied in the diagnosis of FMF. All patients had detailed baseline assessment of clinical features, renal functions, genetic testing, histopathological diagnosis of amyloidosis, and treatment received. Multiple comparisons were performed according to the age of diagnosis, disease phenotype, mutation, and mortality. Our study included 169 patients with a diagnosis of AA amyloidosis. There were 101 patients diagnosed with FMF \u3c 18 years of age and 68 patients diagnosed who were ≥18 years of age. The three most common clinical manifestations were fever (84.6%), abdominal pain (71.6%), and arthritis (66.9%). The most common allele among FMF patients was M694V (60.6%), followed by E148Q (21.4%), and M680I (10.3%). The most frequent genotypes were M694V/M694V (45.0%), M694V/E148Q (14.8%), and E148Q/E148Q (11.2%) among 169 patients in our cohort. During the follow-up period, 15 patients (10 male, 5 female) died, of whom 14 had M694V homozygous genotype and one was homozygous for E148Q. Clinicians should be aware of patients with homozygous E148Q genotype for close monitoring and further evaluation. The possible relationship between E148Q and AA amyloidosis needs to be confirmed in other ethnicities

Determining the influence of N-acetylation on water sorption in chitosan films

Water absorption in chitosan rapidly increases when the deacetylation degree decreases between 85 and 45%. This seems to contradict the fact that water absorption in chitin is much lower than that of chitosan. The aim of this paper is to understand this feature by measuring the main parameters affecting equilibrium water content. Since swelling capacity depends on the water–polymer interaction, the Flory Huggins interaction parameter was evaluated, finding small or null dependence on the deacetylation degree. Other factor influencing elastic energy is chain stiffness related to the elastic modulus that was measured as a function of deacetylation degree. Besides, crystalline structure was measured by X-ray diffraction patterns as a characteristic of cross-linking density. These observations led us to conclude that the instability of crystals during the swelling process increases with decreasing deacetylation degree, explaining the high equilibrium water content of low deacetylation chitosans.The authors gratefully acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness through the MAT2013-46467-C4-1-R project, including FEDER funds. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with the assistance of the European Regional Development Fund.Gámiz González, MA.; Piskin, AE.; Pandis, C.; Chatzimanolis-Moustakas, C.; Kyritsis, A.; Marí Soucase, B.; Gómez Ribelles, JL.... (2015). Determining the influence of N-acetylation on water sorption in chitosan films. Carbohydrate Polymers. 133:110-116. https://doi.org/10.1016/j.carbpol.2015.07.02011011613

Targeting of human interleukin-12B by small hairpin RNAs in xenografted psoriatic skin

<p>Abstract</p> <p>Background</p> <p>Psoriasis is a chronic inflammatory skin disorder that shows as erythematous and scaly lesions. The pathogenesis of psoriasis is driven by a dysregulation of the immune system which leads to an altered cytokine production. Proinflammatory cytokines that are up-regulated in psoriasis include tumor necrosis factor alpha (TNFα), interleukin-12 (IL-12), and IL-23 for which monoclonal antibodies have already been approved for clinical use. We have previously documented the therapeutic applicability of targeting TNFα mRNA for RNA interference-mediated down-regulation by anti-TNFα small hairpin RNAs (shRNAs) delivered by lentiviral vectors to xenografted psoriatic skin. The present report aims at targeting mRNA encoding the shared p40 subunit (IL-12B) of IL-12 and IL-23 by cellular transduction with lentiviral vectors encoding anti-IL12B shRNAs.</p> <p>Methods</p> <p>Effective anti-IL12B shRNAs are identified among a panel of shRNAs by potency measurements in cultured cells. The efficiency and persistency of lentiviral gene delivery to xenografted human skin are investigated by bioluminescence analysis of skin treated with lentiviral vectors encoding the luciferase gene. shRNA-expressing lentiviral vectors are intradermally injected in xenografted psoriatic skin and the effects of the treatment evaluated by clinical psoriasis scoring, by measurements of epidermal thickness, and IL-12B mRNA levels.</p> <p>Results</p> <p>Potent and persistent transgene expression following a single intradermal injection of lentiviral vectors in xenografted human skin is reported. Stable IL-12B mRNA knockdown and reduced epidermal thickness are achieved three weeks after treatment of xenografted psoriatic skin with lentivirus-encoded anti-IL12B shRNAs. These findings mimick the results obtained with anti-TNFα shRNAs but, in contrast to anti-TNFα treatment, anti-IL12B shRNAs do not ameliorate the psoriatic phenotype as evaluated by semi-quantitative clinical scoring and by immunohistological examination.</p> <p>Conclusions</p> <p>Our studies consolidate the properties of lentiviral vectors as a tool for potent gene delivery and for evaluation of mRNA targets for anti-inflammatory therapy. However, in contrast to local anti-TNFα treatment, the therapeutic potential of targeting IL-12B at the RNA level in psoriasis is questioned.</p

The 2021 EULAR and ACR points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS

Objective: Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of 'points to consider' to improve diagnosis, treatment and long-term monitoring of patients with these rare diseases. Methods: Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates and an allied healthcare professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires and consensus methodology, 'points to consider' to guide patient management were developed. Results: The Task Force devised consensus and evidence-based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment and long-term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI and AGS. Conclusion: These points to consider represent state-of-the-art knowledge to guide diagnostic evaluation, treatment and management of patients with CANDLE/PRAAS, SAVI and AGS and aim to standardise and improve care, quality of life and disease outcomes

The 2021 Eurpean Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type i interferonopathies: CANDLE/PRAAS, SAVI and AGS

Objective: Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of \u27points to consider\u27 to improve diagnosis, treatment and long-term monitoring of patients with these rare diseases. Methods: Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates and an allied healthcare professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires and consensus methodology, \u27points to consider\u27 to guide patient management were developed. Results: The Task Force devised consensus and evidence-based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment and long-term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI and AGS. Conclusion: These points to consider represent state-of-the-art knowledge to guide diagnostic evaluation, treatment and management of patients with CANDLE/PRAAS, SAVI and AGS and aim to standardise and improve care, quality of life and disease outcomes

The 2021 EULAR/American College of Rheumatology Points to Consider for Diagnosis, Management and Monitoring of the Interleukin-1 Mediated Autoinflammatory Diseases: Cryopyrin-Associated Periodic Syndromes, Tumour Necrosis Factor Receptor-Associated Periodic Syndrome, Mevalonate Kinase Deficiency, and Deficiency of the Interleukin-1 Receptor Antagonist

BACKGROUND: The interleukin-1 (IL-1) mediated systemic autoinflammatory diseases, including the cryopyrin- associated periodic syndromes (CAPS), tumour necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD) and deficiency of the IL-1 receptor antagonist (DIRA), belong to a group of rare immunodysregulatory diseases that primarily present in early childhood with variable multiorgan involvement. When untreated, patients with severe clinical phenotypes have a poor prognosis, and diagnosis and management of these patients can be challenging. However, approved treatments targeting the proinflammatory cytokine IL-1 have been life changing and have significantly improved patient outcomes. OBJECTIVE: To establish evidence-based recommendations for diagnosis, treatment and monitoring of patients with IL-1 mediated autoinflammatory diseases to standardise their management. METHODS: A multinational, multidisciplinary task force consisting of physician experts, including rheumatologists, patients or caregivers and allied healthcare professionals, was established. Evidence synthesis, including systematic literature review and expert consensus (Delphi) via surveys, was conducted. Consensus methodology was used to formulate and vote on statements to guide optimal patient care. RESULTS: The task force devised five overarching principles, 14 statements related to diagnosis, 10 on therapy, and nine focused on long-term monitoring that were evidence and/or consensus-based for patients with IL-1 mediated diseases. An outline was developed for disease-specific monitoring of inflammation-induced organ damage progression and reported treatments of CAPS, TRAPS, MKD and DIRA. CONCLUSION: The 2021 EULAR/American College of Rheumatology points to consider represent state-of-the-art knowledge based on published data and expert opinion to guide diagnostic evaluation, treatment and monitoring of patients with CAPS, TRAPS, MKD and DIRA, and to standardise and improve care, quality of life and disease outcomes

The 2021 EULAR and ACR points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS

Objective: Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of 'points to consider' to improve diagnosis, treatment and long-term monitoring of patients with these rare diseases. Methods: Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates and an allied healthcare professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires and consensus methodology, 'points to consider' to guide patient management were developed. Results: The Task Force devised consensus and evidence-based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment and long-term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI and AGS. Conclusion: These points to consider represent state-of-the-art knowledge to guide diagnostic evaluation, treatment and management of patients with CANDLE/PRAAS, SAVI and AGS and aim to standardise and improve care, quality of life and disease outcomes