Q fever: a new ocular manifestation

Q Fever is a zoonosis caused by Coxiella burnetii. Ocular manifestations are rare in this infection. We describe the case of a man complaining of an intense retro-orbital headache, fever, arthralgia, and bilateral loss of vision, who showed an anterior uveitis accompanied by exudative bilateral inferior retinal detachment and optic disk edema. At the beginning, a Vogt–Koyanagi–Harada (VKH) syndrome was suspected, but the patient was diagnosed with Q fever and treatment with doxycycline was initiated, with complete resolution after 2 weeks. We wondered if Q fever could unleash VKH syndrome or simulate a VKH syndrome by a similar immunological process

Ethanol-Induced Oxidative Stress Modifies Inflammation and Angiogenesis Biomarkers in Retinal Pigment Epithelial Cells (ARPE-19): Role of CYP2E1 and its Inhibition by Antioxidants

The retinal pigment epithelium (RPE) plays a key role in retinal health, being essential for the protection against reactive oxygen species (ROS). Nevertheless, excessive oxidative stress can induce RPE dysfunction, promoting visual loss. Our aim is to clarify the possible implication of CYP2E1 in ethanol (EtOH)-induced oxidative stress in RPE alterations. Despite the increase in the levels of ROS, measured by fluorescence probes, the RPE cells exposed to the lowest EtOH concentrations were able to maintain cell survival, measured by the Cell Proliferation Kit II (XTT). However, EtOH-induced oxidative stress modified inflammation and angiogenesis biomarkers, analyzed by proteome array, ELISA, qPCR and Western blot. The highest EtOH concentration used stimulated a large increase in ROS levels, upregulating the cytochrome P450-2E1 (CYP2E1) and promoting cell death. The use of antioxidants such as N-acetylcysteine (NAC) and diallyl sulfide (DAS), which is also a CYP2E1 inhibitor, reverted cell death and oxidative stress, modulating also the upstream angiogenesis and inflammation regulators. Because oxidative stress plays a central role in most frequent ocular diseases, the results herein support the proposal that CYP2E1 upregulation could aggravate retinal degeneration, especially in those patients with high baseline oxidative stress levels due to their ocular pathology and should be considered as a risk factor.LVG was recipient of a pre-doctoral fellowship (EDUCV-PRE-2015-006). Financial support by grant #94/2016 from the PROMETEO program from the Generalitat Valenciana, Valencia, Spain, to FJR

The Mitochondria-Targeted Antioxidant MitoQ Modulates Mitochondrial Function and Endoplasmic Reticulum Stress in Pancreatic β Cells Exposed to Hyperglycaemia.

BACKGROUND/AIMS: Mitochondria-targeted antioxidants such as mitoquinone (MitoQ) have demonstrated protective effects against oxidative damage in several diseases. The increase in reactive oxygen species (ROS) production during glucose metabolism in β cells can be exacerbated under hyperglycaemic conditions such as type 2 diabetes (T2D), thus contributing to β cell function impairment. In the present work, we aimed to evaluate the effect of MitoQ on insulin secretion, oxidative stress, endoplasmic reticulum (ER) stress and nuclear factor kappa B (NFκB) signalling in a pancreatic β cell line under normoglycaemic (NG, 11.1 mM glucose), hyperglycaemic (HG, 25 mM glucose) and lipidic (palmitic acid (PA), 0.5mM) conditions. METHODS: We incubated the pancreatic β cell line INS-1E with or without MitoQ (0.5µM) under NG, HG and PA conditions. We then assessed the following parameters: glucose-induced insulin secretion, O₂ consumption (with a Clark-type electrode); mitochondrial function, oxidative stress parameters and calcium levels (by fluorescence microscopy); ER stress markers and NFκB-p65 protein levels (by western blotting). RESULTS: MitoQ increased insulin secretion and prevented the enhancement of ROS production and O₂ consumption and decrease in GSH levels that are characteristic under HG conditions. MitoQ also reduced protein levels of ER stress markers (GRP78 and P-eIF2α) and the proinflammatory nuclear transcription factor NFκB-p65, both of which increased under HG. MitoQ did not significantly alter ER stress markers under lipidic conditions. CONCLUSION: Our findings suggest that treatment with MitoQ modulates mitochondrial function, which in turn ameliorates endoplasmic reticulum stress and NFκB activation, thereby representing potential benefits for pancreatic β cell function

Mutational screening of the USH2A gene in Spanish USH patients reveals 23 novel pathogenic mutations

<p>Abstract</p> <p>Background</p> <p>Usher Syndrome type II (USH2) is an autosomal recessive disorder, characterized by moderate to severe hearing impairment and retinitis pigmentosa (RP). Among the three genes implicated, mutations in the <it>USH2A </it>gene account for 74-90% of the USH2 cases.</p> <p>Methods</p> <p>To identify the genetic cause of the disease and determine the frequency of <it>USH2A </it>mutations in a cohort of 88 unrelated USH Spanish patients, we carried out a mutation screening of the 72 coding exons of this gene by direct sequencing. Moreover, we performed functional minigene studies for those changes that were predicted to affect splicing.</p> <p>Results</p> <p>As a result, a total of 144 DNA sequence variants were identified. Based upon previous studies, allele frequencies, segregation analysis, bioinformatics' predictions and <it>in vitro </it>experiments, 37 variants (23 of them novel) were classified as pathogenic mutations.</p> <p>Conclusions</p> <p>This report provide a wide spectrum of <it>USH2A </it>mutations and clinical features, including atypical Usher syndrome phenotypes resembling Usher syndrome type I. Considering only the patients clearly diagnosed with Usher syndrome type II, and results obtained in this and previous studies, we can state that mutations in <it>USH2A </it>are responsible for 76.1% of USH2 disease in patients of Spanish origin.</p

Downregulation of miR-31 in Diabetic Nephropathy and its Relationship with Inflammation

Background/Aims: There is a lack of reliable biological markers for the early diagnosis of diabetic nephropathy (DN) during type 2 diabetes. In this pilot study we aim to assess whether miR-31 levels are modulated by the presence of DN and whether the expression of this miRNA is related to leukocyte-endothelial interactions and inflammation. Methods: Thirty-one T2D patients were enrolled in this pilot study; 18 with no diabetic complications and 13 with diabetic nephropathy. 24 non-diabetic subjects and 13 T2D patients with retinopathy (absent of other complications) were included to test the specificity of miR-31. Following anthropometric and biochemical evaluation, serum miR-31 levels were assessed by Real Time-PCR. Leukocyte-endothelial interactions were evaluated by a parallel flow chamber in vitro model. Serum TNFα, IL-6 and ICAM-1 levels were determined by XMAP-technology in a flow cytometry-based Luminex 200 instrument. Results: Serum miR-31 levels were similar between control and T2D subjects. However, T2D patients with DN displayed reduced levels of miR-31 with respect to patients without complications. This decrease in miR-31 was more pronounced in patients with macroalbuminuria than in those with microalbuminuria and was specific for DN, since patients with retinopathy displayed unaltered miR-31 levels. The presence of DN involved a lower leukocyte rolling velocity and an increased rolling flux and adhesion. miR-31 levels were positively correlated with leukocyte rolling velocity and negatively associated to leukocyte adhesion, TNFα, IL-6 and ICAM-1 levels. Conclusion: Serum miR-31 may be a biomarker for DN in T2D patients. The regulation of this miRNA seems to be related to the recruitment of leukocytes to vascular walls induced by pro-inflammatory and adhesion molecules

Risk factors for pressure sores in adult patients with myelomeningocele – a questionnaire-based study

BACKGROUND: Myelomeningocele (MMC) is a part of a complex neural tube defect and a disorder of the cerebrospinal fluid system. Pressure sores are a frequent complication for patients with MMC. Little is known about the risk factors for pressure sores in adults with MMC. The aim of this study was to investigate an association between the presence of pressure sores and other patient characteristics, in order to develop an improved strategy for the management of sores. METHODS: A structured questionnaire regarding sores, medical condition, function and living factors was designed and sent to the 193 patients with MMC registered in the year 2003 at TRS, a National Centre for Rare Disorders in Norway. RESULTS: Out of 193 total, 87 patients participated and 71 patients (82%) reported sores; 26 (30%) at the time of the interview and 45 (52%) during the last 5 years. Sores were mostly localized on toes and feet and occurred exclusively in regions with reduced or missing sensibility. A significant association was found between sores and memory deficit (p = 0.02), Arnold Chiari malformation (p = 0.02) and a record of previous sores (p = 0.004). Sores were not significantly associated with hydrocephalus, syringomyelia, nutrition, body mass index, smoking, physical activity, employment or living together with other persons. Some patients (18, 21%) reported skin inspection by others and the remainder relied on self-inspection. CONCLUSION: Patients with sensory deficit, memory problems, and Arnold Chiari malformation had a higher risk of having pressure sores. This patient group needs improved skin inspection routines and sore treatment

Smoking and age-related macular degeneration: review and update

Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health

Signatures of mutational processes in human cancer.

All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy

Introducció a les Xarxes Telemàtiques: problemes amb solució

Col·lecció de problemes resolts d'IXT (Introducció a les Xarxes Telemàtiques) amb solució, 1er curs dels graus de l'ETSETB.2022/20232n quadrimestr