Zika virus: what we need to know?

Zika virus is one of the emerging viruses and is of significant threat to human health globally. It is a mosquito borne flavivirus similar to dengue, yellow fever, and West Nile viruses. It was reported about 5 decades ago and then it spreads to different parts of the world. Large outbreaks were reported on Yap Islands in 2007. Now it has gained wide attention globally by health communities. Major vector for virus transmission is Aedes aegypti mosquito. ZIKV infection is mostly asymptomatic but it is also responsible to cause mild influenza like illness to serious manifestations. There is no specific anti‐viral treatment is available for ZIKV infection. The virus disseminates very fast due to which it possesses a serious threat especially in those areas where there is lack of specific immunity against virus. Little knowledge is available on its transmission and pathogenicity. Although virus was discovered years ago but its genomic structure is not clearly understood yet. In this review we focus on the current knowledge of epidemiology of ZIKV, its transmission, its structural biology, different aspects of diagnosis and diagnostic challenges as well as highlighted appropriates antiviral drugs and vaccines regarding treatment.     

Time‐dependent changes in bone healing capacity of scaphoid fractures and non‐unions

The scaphoid is the most frequently fractured carpal bone and prone to non‐union due to mechanical and biological factors. Whereas the importance of stability is well documented, the evaluation of biological activity is mostly limited to the assessment of vascularity. The purpose of this study was to select histological and immunocytochemical parameters that could be used to assess healing potential after scaphoid fractures and to correlate these findings with time intervals after fracture for the three parts of the scaphoid (distal, gap and proximal). Samples were taken during operative intervention in 33 patients with delayed or non‐union of the scaphoid. Haematoxylin and Eosin (HE ), Azan, Toluidine, von Kossa and Tartrate‐resistant acid phosphatase (TRAP ) staining were used to characterise the samples histologically. We determined distribution of collagen 1 and 2 by immunocytochemistry, and scanning electron microscopy (SEM ) was used to investigate the ultrastructure. To analyse the samples, parameters for biological healing status were defined and grouped according to healing capacity in parameters with high, partial and little biological activity. These findings allowed scoring of biological healing capacity, and the ensuing results were correlated with different time intervals after fracture. The results showed reduced healing capacity over time, but not all parts of the scaphoid were affected in the same way. For the distal fragment, regression analysis showed a statistically significant correlation between summarised healing activity scores and time from initial fracture (r  = ?0.427, P  = 0.026) and decreasing healing activity for the gap region (r  = ?0.339, P  = 0.090). In contrast, the analyses of the proximal parts for all patients did not show a correlation (r  = 0.008, P  = 0.969) or a decrease in healing capacity, with reduced healing capacity already at early stages. The histological and immunocytochemical characterisation of scaphoid non‐unions (SNU s) and the scoring of healing parameters make it possible to analyse the healing capacity of SNU s at certain time points. This information is important as it can assist the surgeon in the selection of the most appropriate SNU treatment.     

Variants in CIB2 cause DFNB48 and not USH1J

The genetic, mutational and phenotypic spectrum of deafness‐causing genes shows great diversity and pleiotropy. The best examples are the group of genes, which when mutated can either cause non‐syndromic hearing loss (NSHL) or the most common dual sensory impairment, Usher syndrome (USH). Variants in the CIB2 gene have been previously reported to cause hearing loss at the DFNB48 locus and deaf‐blindness at the USH1J locus. In this study, we characterize the phenotypic spectrum in a multiethnic cohort with autosomal recessive non‐syndromic hearing loss (ARNSHL) due to variants in the CIB2 gene. Of the 6 families we ascertained, 3 segregated novel loss‐of‐function (LOF) variants, 2 families segregated missense variants (1 novel) and 1 family segregated a previously reported pathogenic variant in trans with a frameshift variant. This report is the first to show that biallelic LOF variants in CIB2 cause ARNSHL and not USH. In the era of precision medicine, providing the correct diagnosis (NSHL vs USH) is essential for patient care as it impacts potential intervention and prevention options for patients. Here, we provide evidence disqualifying CIB2 as an USH‐causing gene.     

Spatial aspects of oncogenic signalling determine the response to combination therapy in slice explants from Kras‐driven lung tumours

A key question in precision medicine is how functional heterogeneity in solid tumours informs therapeutic sensitivity. We demonstrate that spatial characteristics of oncogenic signalling and therapy response can be modelled in precision‐cut slices from Kras‐driven non‐small‐cell lung cancer with varying histopathologies. Unexpectedly, profiling of in situ tumours demonstrated that signalling stratifies mostly according to histopathology, showing enhanced AKT and SRC activity in adenosquamous carcinoma, and mitogen‐activated protein kinase (MAPK) activity in adenocarcinoma. In addition, high intertumour and intratumour variability was detected, particularly of MAPK and mammalian target of rapamycin (mTOR) complex 1 activity. Using short‐term treatment of slice explants, we showed that cytotoxic responses to combination MAPK and phosphoinositide 3‐kinase–mTOR inhibition correlate with the spatially defined activities of both pathways. Thus, whereas genetic drivers determine histopathology spectra, histopathology‐associated and spatially variable signalling activities determine drug sensitivity. Our study is in support of spatial aspects of signalling heterogeneity being considered in clinical diagnostic settings, particularly to guide the selection of drug combinations. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

A comparison of differential oscillometric device with invasive mean arterial blood pressure monitoring in intensive care patients

Non‐invasive beat‐to‐beat mean arterial pressure (MAP) in finger arteries recorded by the differential oscillometric device was compared with MAP recorded invasively from A. radialis in 22 patients after cardiac surgery. Based on all 132 paired measurements, the MAP values measured at the radial artery were 2.7 ± 4.9 mmHg higher than those measured on fingers. Among 22 patients there were 8 patients receiving inotropic support, their difference being 2.1 ± 5.6 mmHg. The present study revealed that the mean discrepancy between the invasive radial pressure and finger pressure was small; however, patient data sets showed marked variability in average pressure differences when examined individually.