The AAA-ATPase p97 plays vital roles in mechanisms of protein homeostasis, including ubiquitin-proteasome system (UPS) mediated protein degradation, endoplasmic reticulum-associated degradation (ERAD), and autophagy. Herein we describe our lead optimization efforts focused on in vitro potency, ADME, and pharmaceutical properties that led to the discovery of a potent, ATP-competitive, D2-selective, and orally bioavailable p97 inhibitor 71, CB-5083. Treatment of tumor cells with 71 leads to significant accumulation of markers associated with inhibition of UPS and ERAD functions, which induces irresolvable proteotoxic stress and cell death. In tumor bearing mice, oral administration of 71 causes rapid accumulation of markers of the unfolded protein response (UPR) and subsequently induces apoptosis leading to sustained antitumor activity in in vivo xenograft models of both solid and hematological tumors. 71 has been taken into phase 1 clinical trials in patients with multiple myeloma and solid tumors.

Babesiosis is an emerging tick-borne disease caused by intraerythrocytic protozoa that are primarily transmitted by hard-bodied (Ixodid) ticks and rarely through blood transfusion, perinatally, and organ transplantation. More than 100 Babesia species infect a wide spectrum of wild and domestic animals worldwide and six have been identified as human pathogens. Babesia microti is the predominant species that infects humans, is found throughout the world, and causes endemic disease in the United States and China. Babesia venatorum and Babesia crassa-like agent also cause endemic disease in China. Babesia divergens is the predominant species in Europe where fulminant cases have been reported sporadically. The number of B. microti infections has been increasing globally in recent decades. In the United States, more than 2000 cases are reported each year, although the actual number is thought to be much higher. In this review of the epidemiology of human babesiosis, we discuss epidemiologic tools used to monitor disease location and frequency; demographics and modes of transmission; the location of human babesiosis; the causative Babesia species in the Americas, Europe, Asia, Africa, and Australia; the primary clinical characteristics associated with each of these infections; and the increasing global health burden of this disease.

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BackgroundPlexiform schwannoma (PS) is a rare, peripheral nerve sheath tumor arranged in a plexiform pattern.Case presentationWe report an unusual case of a 19-year-old woman, who complained of pain in the plantar aspect of the left foot. Magnetic resonance image (MRI) demonstrates three solitary nodules of varying sizes in the deep soft tissue of the plantar aspect of the foot that are homogeneously isointense to skeletal muscle on T1-weighted images and hyperintense on T2-weighted fat-suppressed images, especially the rim of the lesion. Subsequent pathological examination confirmed the diagnosis of PS.ConclusionMRI characteristic plays an important role in detecting this rare lesion. A review of the literature on PS is also presented.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-342) contains supplementary material, which is available to authorized users.

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There were two factual errors in the original publication of our manuscript [...]

Introduction: Tibia is the most commonly fractured bone due to road traffic accidents and other highenergy trauma and surgical management is required for most of these fractures, with either internal or external fixation. Locked intramedullary nailing has been widely accepted as a satisfactory treatment of tibial fracture. The indications of their use have been extended to fractures closer to proximal / distal fragments with introduction of expert tibial nail. It is a new kind of low, multidirectional locking tibial intramedullary nail developed to attain increased angular stability and to enhance the axial and lateral stability of fracture fragments. Aim: To study the functional outcome and duration of union of metaphyseal and diaphyseal fractures of tibia treated with expert tibial interlocking nail. Methodology: Study was done in 30 patients with fresh tibial metaphyseal/diaphyseal fractures treated surgically with expert tibial nail between October 2016-March 2018. Patients were followed up at 6 weeks, 3 months, and 6 months. The intra-operative blood loss, duration of surgery, intra operative complications, post-operative complication, and duration of hospital stay were studied. Functional outcome was assessed based on Johner and Wruh's Criteria. Results: Among the 30 patients treated with expert tibia nail for metaphyseal/diaphyseal tibial fractures, 25 were male and 5 were females. Most of patients were in the age group ranging from 20-30 years with a mean age group of 40.1 years. The mode of injury for 24 patients was road traffic accidents which accounted for about 80 %, 5 were due to fall which accounted for 16.67 % and 1 was due to assault which accounted for 3.33 %.16 cases sustained right side tibia fracture and 14 cases sustained left side tibia fracture. The average period of commencement partial weight bearing was 7 weeks and full weight bearing was 13.43 weeks. Excellent results were seen in 43.33% cases, Good results were seen in 33.33%, Fair results in 16.67 %, poor results in 6.67% according to Johner and Wruh's Criteria. Conclusion:Our results with expert tibial interlocking nailing are encouraging and demonstrate the benefits of new nailing system. Changes in the design of the nail for improved proximal and distal locking enables it to use in metaphyseal/diaphyseal fractures of tibia. A better stabilization of small fragments has been achieved by the availability of locking option in three planes, thus providing a higher stability of the bone implant construct. Complications were comparable to other studies.