MDX‐1097 induces antibody‐dependent cellular cytotoxicity against kappa multiple myeloma cells and its activity is augmented by lenalidomide

MDX‐1097 is an antibody specific for a unique B cell antigen called kappa myeloma antigen (KMA) that consists of cell membrane‐associated free kappa light chain (κFLC). KMA was detected on kappa human multiple myeloma cell lines (κHMCLs), on plasma cells (PCs) from kappa multiple myeloma (κMM) patients and on κPC dyscrasia tissue cryosections. In primary κMM samples, KMA was present on CD38+ cells that were CD138 and CD45 positive and/or negative. MDX‐1097 exhibited a higher affinity for KMA compared to κFLC and the latter did not abrogate binding to KMA. MDX‐1097‐mediated antibody‐dependent cellular cytotoxicity (ADCC) and in vitro exposure of target cells to the immunomodulatory drug lenalidomide resulted in increased KMA expression and ADCC. Also, in vitro exposure of peripheral blood mononuclear cells (PBMCs) to lenalidomide enhanced MDX‐1097‐mediated ADCC. PBMCs obtained from myeloma patients after lenalidomide therapy elicited significantly higher levels of MDX‐1097‐mediated ADCC than cells obtained prior to lenalidomide treatment. These data establish KMA as a relevant cell surface antigen on MM cells that can be targeted by MDX‐1097. The ADCC‐inducing capacity of MDX‐1097 and its potentiation by lenalidomide provide a powerful rationale for clinical evaluation of MDX‐1097 alone and in combination with lenalidomide.     

High Frequency of Acquired ADAMTS13 Deficiency After Hemolysis in Hemiscorpius Lepturus (Scorpion) Stung Children

Objective

To estimate the frequency of acquired ADAMTS13 deficiency in severe cases of Hemiscorpius lepturus stung patients and the frequency of acute kidney injury (AKI) in these patients.

Methods

Sixty scorpion stung children who were referred with severe hemolysis and hemoglobinuria were studied. None of them had received blood products and no one had a past medical history of renal failure.

Results

Plasma levels of ADAMTS13 and ADAMTS13 antibody (IgG) were measured using ELISA. ADAMTS13 was decreased in 91.7 % of patients and the anti-ADAMTS13 antibody (Ab) was increased in 98.3 %. ADAMTS13 decreased in all of the patients with acute kidney injury and none of those with normal levels of ADAMTS13 developed renal failure; all patients with AKI had also increased levels of ADAMTS13Ab. Acute kidney injury was found in 23.3 % and had significant association with severe anemia, thrombocytopenia, pyuria, hematuria and considerable proteinuria (p?<?0.001). Disseminated intravascular coagulation (DIC) and Hemolytic uremic syndrome (HUS) developed in 6.7 % and 10 % respectively.

Conclusions

The index findings demonstrate that Hemiscorpius lepturus sting is usually associated with ADAMTS13 deficiency, and increased ADAMTS13 autoantibody. These combined mechanisms may contribute to scorpion sting-induced coagulopathies and may predispose patients to develop DIC and HUS.     

Rational design of yolk–shell nanostructures for drug delivery

Yolk–shell nanoparticles (YSNPs) are a new class of hollow nanostructures, and their unique properties can be utilized in drug delivery systems. The recent progress in YSNPs-based carriers is highlighted in drug delivery systems. Doxorubicin hydrochloride, ceftriaxone sodium, and methotrexate are three of the most common drugs that are used in this field. According to the reported studies, the materials used most often as yolk–shells are magnetic nanoparticles and polymers. The used methods for synthesizing a diverse array of YSNPs are classified based on their core structures. Various properties of YSNPs include their high drug-loading capacity, and their ability to decrease drug toxicity and satisfactorily and efficiently release drugs.

The recent progress in yolk–shell nanoparticles (YSNPs) as a new class of hollow nanostructures applied for drug delivery.     

The Policy of Co–First Authorship and Co–Senior Authorship in Radiology Journals

ObjectiveIncreasingly, medical journals are recognizing “equally credited authors” (ECA) in the primary and senior authorship of articles. The aim of this study was to assess the policies of co–first authorship, co–senior authorship, and designation of a corresponding author in the radiology literature.MethodsWe identified 29 radiology journals based on impact factor ranking. Journal offices were contacted by phone and e-mail to ascertain their practices on first and senior authorship ECA designations. We surveyed the March, June, and December 2018 issues of each journal (when available) to assess the utilization of the co-designations in articles.ResultsTwenty-five of 29 journals responded to our survey (response rate: 86.2%). Of 25 journals, 20 (80%) allowed co–first authorship. Among these, 4 of 25 journals (16%) allowed more than two co–first authors. Among the 25 responses, 14 journals (56%) allowed co–senior authorship. Among the 24 journals who responded to this specific question, 23 (96%) approved designation of a corresponding author, different from the first or senior author. The review of March, June, December 2018 editions found co–first authorship and co–senior authorship ECA rates of 8.6% (range 0.0%-22.7%) and 1.8% (range 0.0%-13.3%), respectively. A corresponding author other than first or senior author was noted in 13.3% (range 0.0%-34.7%).DiscussionThere has been widespread acceptance of the concept of ECA in the policies of the top cited imaging journals particularly for first authors (80%). However, the utilization of these designations is uncommon for first authorship (8.6%) and rare (1.8%) for senior authorship based on our 2018 sampling.     

Healthcare Services During the Transitions to Adulthood Among Individuals with ASD Aged 15–25 Years Old: Stakeholders’ Perspectives

Journal of Autism and Developmental Disorders - Although previous research has shown that the transition to adulthood may be challenging, there exists a lack of research regarding perspectives of...     

Photobiomodulation therapy reduces apoptotic factors and increases glutathione levels in a neuropathic pain model

Neuropathic pain (NP) is caused by damage to the nervous system due to reactive oxygen spices (ROS) increase, antioxidants reduction, ATP production imbalance, and induction of apoptosis. In this investigation, we applied low-level laser 660 nm (photobiomodulation therapy) as a new strategy to modulate pain. In order to study the effects of photobiomodulation therapy (660 nm) on NP, chronic constriction injury (CCI) model was selected. Low-level laser of 660 nm was used for 2 weeks. Thermal and mechanical hyperalgesia were measured before and after surgery on days 7 and 14, respectively. Paw withdrawal thresholds were also evaluated. Expression of p2x3, Bax, and bcl2 protein was measured by western blotting. The amount of glutathione (GSH) was measured in the spinal cord by continuous spectrophotometric rate determination method. The results are presented as mean?±?SD. Statistical analysis of data was carried out using SPSS 21. CCI decreased the pain threshold, 2-week photobiomodulation therapy significantly increased mechanical and thermal threshold, decreased P2X3 expression (p?<?0.001), and increased bcl2 expression (p?<?0.01), but it was not effective on the Bax expression. We speculated that although photobiomodulation therapy increased ROS generation, it increased antioxidants such as GSH. Increase in bcl2 is another mitochondrial protection mechanism for cell survival and that pain relief and decrease in P2X3 expression confirm it.     

The role of MSX1 in tooth agenesis in Iranians

INTRODUCTION: MSX1 gene has a critical role in craniofacial development, the aim of this case-control study is to test the hypothesis that MSX1 mutation contributes to congenital tooth agenesis in Iranians. MATERIALS AND METHODS: The study group consisted of 20 affected individuals with tooth agenesis of lower second premolars or upper lateral incisors with mean age of 24.6. The control group consisted of 20 unaffected individuals. DNA was extracted from all 40 individuals; the polymerase chain reaction (PCR) for MSX1 was carried out with Phenol: Chloroform: Isoamylalchol (PCI) extraction method. Ban II restriction digest and agarose gel electrophoresis of the 20 affected individuals verified the presence of mutation in all 20 affected individuals. The unaffected controls did not show any mutation. Statistical analysis performed by the chi-squared method. RESULTS: Ban II did not digest PCR product (DNA) in the control group (195 bp band on electrophoresis gel) but digested the affected allele (106 bp and 89 bp bands). There is a statistically significant correlation between tooth agenesis and MSX1 mutation (P < 0.001). CONCLUSION: The results indicated that MSX1 gene mutation contributes to tooth agenesis in Iranian individuals. As the timing of tooth calcification can vary, radiographic finding of congenital tooth agenesis can be confirmed by this molecular method during different dental ages to achieve certainty.