A Different Presentation of Mal De Meleda: New Skin Lesions in a Residual Limb after Traumatic Amputation

Mal de Meleda is a rare autosomal recessive skin disease which is known as keratoderma palmoplantaris transgradiens. Here we report a case of Mal de Meleda who had skin lesions in the residual limb and pseudoainhum in the thigh after traumatic lower leg amputation. A 71-year-old female was admitted to our tertiary hospital for prosthetic rehabilitation. On the physical examination, thickening of the skin on palms, left sole and residual limb was present. The patient reported that she had these skin lesions since infancy and she realized new skin lesions after amputation in the residual limb. We requested dermatology consultation and she was diagnosed as Mal de Meleda. To our knowledge, this is the first Mal de Meleda case in the literature with new lesions at the residual limb.  Although exact pathophysiological mechanisms are not well known in Mal de Meleda, prosthesis use might have accelerated disease process in our patient. </p

Drivers behind the public perception of artificial intelligence: insights from major Australian cities

Artificial intelligence (AI) is not only disrupting industries and businesses, particularly the ones have fallen behind the adoption, but also significantly impacting public life as well. This calls for government authorities pay attention to public opinions and sentiments towards AI. Nonetheless, there is limited knowledge on what the drivers behind the public perception of AI are. Bridging this gap is the rationale of this paper. As the methodological approach, the study conducts an online public perception survey with the residents of Sydney, Melbourne, and Brisbane, and explores the collected survey data through statistical analysis. The analysis reveals that: (a) the public is concerned of AI invading their privacy, but not much concerned of AI becoming more intelligent than humans; (b) the public trusts AI in their lifestyle, but the trust is lower for companies and government deploying AI; (c) the public appreciates the benefits of AI in urban services and disaster management; (d) depending on the local context, public perceptions vary; and (e) the drivers behind the public perception include gender, age, AI knowledge, and AI experience. The findings inform authorities in developing policies to minimise public concerns and maximise AI awareness. </p

A newborn with diabetic ketoacidosis and thalassemia major: A rare case

Diabetic ketoacidosis is a systemic situation caused byabsolute insulin deficiency and characterized by hyperglycemia,ketonemia, acidemia, glycosuria and ketonuria.Thalassemia Major is a very serious hereditary blooddisorder due to low levels or absence of “beta globulin”chain, characterized by requiring a blood transfusion from3-4. month of life due to the relatively short life of red cells.We, herein presented a rare case of 20 day-old newbornwith anemia, hyperglycemia, vomiting, acidosis being diagnosedas thalassemia major that required blood transfusionin the early period of life and diabetic ketoacidosiswithout ketonuria who born from 24 year old father carrierof thalassemia and 23-year-old mother with carrier of thalassemiaand gestational diabetes.The case was presented in order to emphasize that diabeticketoacidosis can occur in newborns without ketonuriaand thalassemia major may cause anemia in the earlyperiod of life due to hyperglycemia and acidosis

The effects of functional electrical stimulation cycling on gait parameters in diplegic cerebral palsy: a single-blind randomized controlled trial

PurposeTo investigate the effects of functional electrical stimulation cycling (FES-C) training in addition to conventional physical therapy on gait, muscle strength, gross motor function, and energy expenditure in ambulatory children with spastic diplegic cerebral palsy.Materials and methodsTwenty children with diplegic cerebral palsy were randomly assigned to FES-C group (n = 10) or control group (n = 10). Subjects trained 3 days/week for 8 weeks. Control group received conventional physical therapy. The FES-C group additionally received FES-C training. The functional muscle test was used for muscle strength assessment. Vicon-3D system was used for gait analysis. Gross Motor Function Measure (GMFM-88) was used for motor function assessment and calorimeter was used for energy expenditure. Measurements were performed at the baseline, at the eight week and at the sixteenth week.ResultsFunctional muscle strength, gross motor function, and energy expenditure improved more in the FES-C group after training and follow up (p 0.05). Pelvic tilt while walking decreased after training in the FES-C group (p < 0.05).ConclusionsFES-C applied in addition to conventional physical therapy in children with diplegic cerebral palsy is more effective than conventional physical therapy for increasing functional muscle strength, improving gross motor function functions, and reducing energy expenditure

Toward a Decision Support System for Mitigating Urban Heat

With the continuous rise of global urbanization, city planners and policymakers are increasingly concerned with urban heat islands (UHI), which are metropolitan areas that are significantly warmer than their surrounding rural areas. We address the United Nation’s Sustainable Development Goal 11 “Sustainable Cities and Communities,” and we design and develop a decision support system (DSS), which will help city planners and policymakers to overcome economic barriers to reach environmental sustainability goals

CBL Is Frequently Altered in Lung Cancers: Its Relationship to Mutations in MET and EGFR Tyrosine Kinases

Background: Non-small cell lung cancer (NSCLC) is a heterogeneous group of disorders with a number of genetic and proteomic alterations. c-CBL is an E3 ubiquitin ligase and adaptor molecule important in normal homeostasis and cancer. We determined the genetic variations of c-CBL, relationship to receptor tyrosine kinases (EGFR and MET), and functionality in NSCLC. Methods and Findings: Using archival formalin-fixed paraffin embedded (FFPE) extracted genomic DNA, we show that c-CBL mutations occur in somatic fashion for lung cancers. c-CBL mutations were not mutually exclusive of MET or EGFR mutations; however they were independent of p53 and KRAS mutations. In normal/tumor pairwise analysis, there was significant loss of heterozygosity (LOH) for the c-CBL locus (22%, n = 8/37) and none of these samples revealed any mutation in the remaining copy of c-CBL. The c-CBL LOH also positively correlated with EGFR and MET mutations observed in the same samples. Using select c-CBL somatic mutations such as S80N/H94Y, Q249E and W802* (obtained from Caucasian, Taiwanese and African-American samples, respectively) transfected in NSCLC cell lines, there was increased cell viability and cell motility. Conclusions: Taking the overall mutation rate of c-CBL to be a combination as somatic missense mutation and LOH, it is clear that c-CBL is highly mutated in lung cancers and may play an essential role in lung tumorigenesis and metastasis

Analysis of the interaction with the hepatitis C virus mRNA reveals an alternative mode of RNA recognition by the human La protein

Human La protein is an essential factor in the biology of both coding and non-coding RNAs. In the nucleus, La binds primarily to 3′ oligoU containing RNAs, while in the cytoplasm La interacts with an array of different mRNAs lacking a 3′ UUUOH trailer. An example of the latter is the binding of La to the IRES domain IV of the hepatitis C virus (HCV) RNA, which is associated with viral translation stimulation. By systematic biophysical investigations, we have found that La binds to domain IV using an RNA recognition that is quite distinct from its mode of binding to RNAs with a 3′ UUUOH trailer: although the La motif and first RNA recognition motif (RRM1) are sufficient for high-affinity binding to 3′ oligoU, recognition of HCV domain IV requires the La motif and RRM1 to work in concert with the atypical RRM2 which has not previously been shown to have a significant role in RNA binding. This new mode of binding does not appear sequence specific, but recognizes structural features of the RNA, in particular a double-stranded stem flanked by single-stranded extensions. These findings pave the way for a better understanding of the role of La in viral translation initiation

APOMAB®, a La-Specific Monoclonal Antibody, Detects the Apoptotic Tumor Response to Life-Prolonging and DNA-Damaging Chemotherapy

Background: Antineoplastic therapy may impair the survival of malignant cells to produce cell death. Consequently, direct measurement of tumor cell death in vivo is a highly desirable component of therapy response monitoring. We have previously shown that APOMAB® representing the DAB4 clone of a La/SSB-specific murine monoclonal autoantibody is a malignant cell-death ligand, which accumulates preferentially in tumors in an antigen-specific and dose-dependent manner after DNA-damaging chemotherapy. Here, we aim to image tumor uptake of APOMAB® (DAB4) and to define its biological correlates. Methodology/Principal Findings: Brisk tumor cell apoptosis is induced in the syngeneic EL4 lymphoma model after treatment of tumor-bearing mice with DNA-damaging cyclophosphamide/etoposide chemotherapy. Tumor and normal organ accumulation of Indium 111 (111In)-labeled La-specific DAB4 mAb as whole IgG or IgG fragments was quantified by whole-body static imaging and organ assay in tumor-bearing mice. Immunohistochemical measurements of tumor caspase-3 activation and PARP-1 cleavage, which are indicators of early and late apoptosis, respectively, were correlated with tumor accumulation of DAB4. Increased tumor accumulation of DAB4 was associated directly with both the extent of chemotherapy-induced tumor cell death and DAB4 binding per dead tumor cell. Tumor DAB4 accumulation correlated with cumulative caspase-3 activation and PARP-1 cleavage as tumor biomarkers of apoptosis and was directly related to the extended median survival time of tumor-bearing mice. Conclusions/Significance: Radiolabeled La-specific monoclonal antibody, DAB4, detected dead tumor cells after chemotherapy, rather than chemosensitive normal tissues of gut and bone marrow. DAB4 identified late apoptotic tumor cells in vivo. Hence, radiolabeled DAB4 may usefully image responses to human carcinoma therapy because DAB4 would capture the protracted cell death of carcinoma. We believe that the ability of radiolabeled DAB4 to rapidly assess the apoptotic tumor response and, consequently, to potentially predict extended survival justifies its future clinical development as a radioimmunoscintigraphic agent. This article is part I of a two-part series providing proof-of-concept for the the diagnostic and therapeutic use of a La-specific monoclonal antibody, the DAB4 clone of which is represented by the registered trademark, APOMAB®.Fares Al-Ejeh, Jocelyn M. Darby, Chris Tsopelas, Douglas Smyth, Jim Manavis and Michael P. Brow

Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

<p>Abstract</p> <p>Background</p> <p>Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC) - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy.</p> <p>Methods</p> <p>To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC.</p> <p>Results</p> <p>The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression.</p> <p>Conclusion</p> <p>This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that thymosin-β4 may have a role in chondrosarcoma metastasis.</p