INTRODUCTION: In pediatric kidney patients, where clinical presentation is often not fully developed and renal biopsy too risky or inconclusive, it may be difficult to establish the underlying pathology. In cases such as these, genetic diagnosis may be used to guide the treatment, prognosis and counselling. Given the large number of genes involved in kidney disease, introducing next generation sequencing with extended gene panels as part of the diagnostic algorithm presents a viable solution. METHODS: A cohort of 87 consecutive independent cases (83 children and 4 terminated pregnancies) with renal disease were recruited. Exome sequencing with MiSeq or NovaSeq 6 000 (Illumina) platforms and analysis of extended gene panels was used for genetic testing. RESULTS: Depending on the presenting pathology, the cases were grouped as patients with glomerular disease, ciliopathies, congenital anomalies, renal electrolyte imbalances and chronic/acute kidney disease. The overall diagnostic yield was app. 42% (37 out of 87) with most disease-causing mutations found in COL4A3, COL4A4, COL4A5 and PKHD1 genes. A change or clarification of preliminary diagnosis, or adjustment of initial treatment plan based on the results from the genetic testing was made for app. one third of the children with meaningful genetic findings (11 out 37). DISCUSSION: Our results prove the value of targeted exome sequencing as non-invasive, versatile and reliable diagnostic tool for pediatric renal disease patients. Providing genetic diagnosis will help for better understanding of disease etiology and will give basis for optimal clinical management and insightful genetic counseling.
In the current pandemic of coronavirus disease (COVID-19), the identification of the patients admitted with severe infection-who are disposed to a high risk of acute respiratory distress syndrome (ARDS) development, is of a major significance for the determination of the appropriate therapeutic strategy. Laboratory records in admission were retrospectively reviewed from 493 cases of severe COVID-19 divided into two groups: Group 1 with ARDS and Group 2 without ARDS. The platelet distribution width (PDW) difference between Group 1 and Group 2 is significant-15.10 ± 2.08 fl for those who developed ARDS versus 12.94 ± 2.12 fl for those without ARDS. The sensitivity and the specificity of this parameter is lower than that of D-dimer. After grouping of the PDW values into intervals and combining them with the rate of increase in D-dimer (D-PDWf index) to form a forecasting index, a significant increase in the specificity and sensitivity of the two parameters is identified-area under the ROC curve (AUC) is 0.874 for D-PDWf index, with respective AUC for PDW 0.768 and AUC for D-dimer 0.777. Conclusion: PDW is a significant predictive parameter at admission for subsequent development of ARDS in patients, with increased significance in combination with the degree of increase in D-dimer.
Hybrid mobile applications (apps) combine the features of Web applications and "native" mobile apps. Like Web applications, they are implemented in portable, platform-independent languages such as HTML and JavaScript. Like native apps, they have direct access to local device resources-file system, location, camera, contacts, etc. Hybrid apps are typically developed using hybrid application frameworks such as PhoneGap. The purpose of the framework is twofold. First, it provides an embedded Web browser (for example, WebView on Android) that executes the app's Web code. Second, it supplies "bridges" that allow Web code to escape the browser and access local resources on the device. We analyze the software stack created by hybrid frameworks and demonstrate that it does not properly compose the access-control policies governing Web code and local code, respectively. Web code is governed by the same origin policy, whereas local code is governed by the access-control policy of the operating system (for example, user-granted permissions in Android). The bridges added by the framework to the browser have the same local access rights as the entire application, but are not correctly protected by the same origin policy. This opens the door to fracking attacks, which allow foreign-origin Web content included into a hybrid app (e.g., ads confined in iframes) to drill through the layers and directly access device resources. Fracking vulnerabilities are generic: they affect all hybrid frameworks, all embedded Web browsers, all bridge mechanisms, and all platforms on which these frameworks are deployed. We study the prevalence of fracking vulnerabilities in free Android apps based on the PhoneGap framework. Each vulnerability exposes sensitive local resources-the ability to read and write contacts list, local files, etc.-to dozens of potentially malicious Web domains. We also analyze the defenses deployed by hybrid frameworks to prevent resource access by foreign-origin Web content and explain why they are ineffectual. We then present NoFrak, a capability-based defense against fracking attacks. NoFrak is platform-independent, compatible with any framework and embedded browser, requires no changes to the code of the existing hybrid apps, and does not break their advertising-supported business model.
