Pharmaceuticals and Medical Device Agency approval summary: Amenamevir for the treatment of herpes zoster

In July 2017, Japan’s Ministry of Health, Labor and Welfare issued a marketing authorization valid throughout Japan for N-(2,6-dimethylphenyl)-N-(2-{[4-(1,2,4-oxadiazol-3-yl)phenyl]amino}-2-oxoethyl)-1,1-dioxothiane-4-carboxamide (amenamevir) for the first time worldwide. The decision was based on the favorable opinion of the Pharmaceuticals and Medical Device Agency (PMDA) recommending a marketing authorization of amenamevir for treatment of herpes zoster (HZ). Amenamevir has a different action mechanism from previously approved synthetic nucleoside compounds for the treatment of HZ including acyclovir, valacyclovir and famciclovir. The usual adult dose is 400 mg amenamevir p.o. once daily for 7 days. The benefit is its ability to cure HZ as well as preventing postherpetic neuralgia. The most common side-effects are increase of urine N-acetyl-β-D-glucosaminidase and α1-microglobulin levels. However, based on the detailed evaluation of the submitted clinical studies, there seems to be no serious safety concerns about amenamevir regarding the kidney of both renally normal and impaired patients. The objective of this article is to summarize the scientific review of the application. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the PMDA website ( www.pmda.go.jp/PmdaSearch/iyakuSearch/ ).     

Anaplastic variant of diffuse large B‐cell lymphoma: Reappraisal as a nodal disease with sinusoidal involvement

Anaplastic variant (av) of diffuse large B‐cell lymphoma (DLBCL) is morphologically defined in the 2017 World Health Organization classification, but still an enigmatic disease in its clinicopathologic distinctiveness, posing the differential diagnostic problem from gray zone lymphoma (GZL) and classic Hodgkin lymphoma (cHL). Thirty‐one cases previously diagnosed as avDLBCL were reassessed. Of these, 27 (87%) and 4 (13%) were node‐based and extranodal diseases, respectively. They were further reclassified into nodal avDLBCL (n = 18), nodal CD30+ DLBCL with T‐cell/histiocyte‐rich large B‐cell lymphoma‐like features (CD30+ DLBCL‐THRLBCL) (n = 6), GZL with features intermediate between DLBCL and cHL (n = 3) and CD30+ extranodal DLBCL, NOS (n = 4). The nodal avDLBCL cases had a sheet‐like proliferation of large cells and/or Hodgkin/Reed‐Sternberg (HRS)‐like cells in 12 (67%) notably with a sinusoidal pattern in 16 (89%). They showed an expression of CD20 and/or CD79a in all and CD30 in 15 of 18. All of them were negative for PD‐L1 on tumor cells, although HRS‐like cells showed negativity or partial loss of other B‐cell markers to varying degrees. The present study highlighted the distinctiveness of the nodal avDLBCL with sinusoidal pattern, but without neoplastic PD‐L1 expression, which provide refined diagnostic criteria for a more precise pathologic and clinical characterization of this disease.     

3D Printing of Tough Gels Having Tunable Elastic Modulus from the Same Pre‐Gel Solution

A gel forming method with sections with different elastic modulus is developed. Gels with hardness distribution are formed from one base gel material by adjusting the crosslinking density of the polymer network using a 3D gel printer. It is confirmed that hardness is arranged as designed by using mixing rules of composite materials. Furthermore, as a prototype of a practical gel application, a gel finger model having a soft‐fleshy part and a hard‐bony part is printed. 3D printing of an organ model that reproduces a realistic feel that takes not only the shape of the organ but also the distribution of hardness into consideration may become possible.     

Unilateral nephrectomy for young infants with congenital nephrotic syndrome of the Finnish type

Clinical and Experimental Nephrology - The management of congenital nephrotic syndrome of the Finnish type (CNF) is challenging. It is difficult to withdraw intravenous albumin infusions, resulting...     

New combined anteversion technique in hybrid THA: cup-first procedure with CT-based navigation

European Journal of Orthopaedic Surgery & Traumatology - Combined anteversion (CA) technique (stem-first procedure) is generally accepted as the optimal technique to attain an appropriate CA...     

SRK2C, a SNF1-related protein kinase 2, improves drought tolerance by controlling stress-responsive gene expression in Arabidopsis thaliana

Protein phosphorylation/dephosphorylation are major signaling events induced by osmotic stress in higher plants. Here, we showed that a SNF1-related protein kinase 2 (SnRK2), SRK2C, is an osmotic-stress-activated protein kinase in Arabidopsis thaliana that can significantly impact drought tolerance of Arabidopsis plants. Knockout mutants of SRK2C exhibited drought hypersensitivity in their roots, suggesting that SRK2C is a positive regulator of drought tolerance in Arabidopsis roots. Additionally, transgenic plants with CaMV35S promoter::SRK2C-GFP displayed higher overall drought tolerance than control plants. Whereas stomatal regulation in 35S::SRK2C-GFP plants was not altered, microarray analysis revealed that their drought tolerance coincided with up-regulation of many stress-responsive genes, for example, RD29A, COR15A, and DREB1A/CBF3. From these results, we concluded that SRK2C is capable of mediating signals initiated during drought stress, resulting in appropriate gene expression. Our present study reveals new insights around signal output from osmotic-stress-activated SnRK2 protein kinase as well as supporting feasibility of manipulating SnRK2 toward improving plant osmotic-stress tolerance.