A case of severe dermatitis in a patient with Polycythemia Vera during cytoreductive therapy

Polycythemia Vera (PV) is a Philadelphia-negative chronic myeloproliferative neoplasm (MPN) mainly characterized by erythrocytosis. In this report we describe a case of severe cutaneous toxicity in patients with PV treated with hydroxyurea. A 72-year-old woman diagnosed with PV with V617F mutation of JAK2 performed more than 10 years before and treated with hydroxyurea plus phlebotomies and low-dose ASA for about 7 years addressed our center for the appearance of serious dermatitis at the face symptomatic for severe itch. The patient underwent a dermatology visit with diagnosis of desquamative dermatitis due to iatrogenic cause related to the use of hydroxyurea. HU was stopped for a month with no improvement after a month of wash-out. Ruxolitinib was prescribed at a dose of 20 mg per day, in order to control hypercytosis and considering the severe intolerance to hydroxyurea. Ruxolitinib allowed not only to reduce the haematocrit, reaching the target value of 45%, and control thrombocytosis, but also to switch off the severe itch and to completely resolve skin toxicity

An innovative technique to improve safety of volatile anesthetics suction from the cardiopulmonary bypass circuit

Context: Myocardial injury during cardiac surgery on cardiopulmonary bypass (CPB) is a major determinant of morbidity and mortality. Preclinical and clinical evidence of dose- and time-related cardioprotective effects of volatile anesthetic drugs exist and their use during the whole surgery duration could improve perioperative cardiac protection. Even if administering volatile agents during CPB are relatively easy, technical problems, such as waste gas scavenging, may prevent safe and manageable administration of halogenated vapors during CPB. Aims: The aim of this study is to improve the safe administration of volatile anesthesia during CPB. Settings and Design: Tertiary teaching hospital. Subjects and Methods: We describe an original device that collects and disposes of any volatile anesthetic vapors present in the exit stream of the oxygenator, hence preventing its dispersal into the operating theatre environment and adaptively regulates pressure of oxygenator chamber in the CPB circuit. Results: We have so far applied a prototype of this device in more than 1300 adult cardiac surgery patients who received volatile anesthetics during the CPB phase. Conclusions: Widespread implementation of scavenging system like the one we designed may facilitate the perfusionist and the anesthesiologist in delivering these cardioprotective drugs with beneficial impact on patients' outcome without compromising on safety

Nurses’ behavior regarding pain treatment in an emergency department: A single-center observational study

Purpose: The aim of this prospective study was to assess the behavior of emergency department (ED) nurses with regard to pain and their role in pain management in a real-life clinical setting. Methods: A total of 509 consecutive patients were enrolled during a 6-week period. A case-report form was used to collect data on nurses’ approaches to pain, time to analgesia provision, and patient-perceived quality of analgesia. Results: Triage nurses actively inquired about pain in almost every case, but they did not estimate pain intensity in a third of patients. In the majority of cases, triage nurses did not report pain-related findings to the physician, who was the only professional that could prescribe analgesia to patients. The assignment of the color-coding of triage by nurses appears to be related to the perceived severity of the clinical case and a more comprehensive evaluation of pain. More than half of patients were at least fairly satisfied with analgesia. Conclusion: Pain is increasingly screened during triage, but its comprehensive assessment and management still lack systematic application. We believe that further education and implementation of analgesia protocols may empower nurses to manage ED patients’ pain more effectively and in a more timely manner

Replicated carbon fiber RICH mirror for AMS-02

Presented are results of a fabrication program to produce the Ring Imaging Cherenkov, RICH, mirror for the Alpha Magnetic Spectrometer, AMS-02, which is to be placed on the International Space Station. Composite Mirror Applications, Inc., CMA, in Tucson AZ was contracted by Carlo Gavazzi Space, CGS, to produce a conical mirror 1.3m diameter 0.5m in height, from high modulus carbon fiber, flight qualified composite materials, having an optical surface on the inside of the cone. The flight model mirror was completed to specification, yielding nearly 2m 2 of replicated optical surface area and weighs 8 kg. CMA measured the surface roughness and slope errors and the mirror dimensions were measured using a CMM at The University of Arizona's Instrument Shop. The results show the mirror meets conformance to the required specifications. The RICH mirror is currently undergoing flight testing and integration

Phylogenetic comparison of huntingtin homologues reveals the appearance of a primitive polyQ in sea urchin

Huntingtin is a completely soluble 3,144 amino acid (aa) protein characterized by the presence of an amino-terminal polymorphic polyglutamine (polyQ) tract, whose aberrant expansion causes the progressively neurodegenerative Huntington's disease (HD). Biological evidence indicates that huntingtin (htt) is beneficial to cells (particularly to brain neurons) and that loss of its neuronal function may contribute to HD. The exact protein domains involved in its neuroprotective function are unknown. Evolutionary analyses of htt primary aa have so far been limited to a few species, but its thorough assessment may help to clarify the functions emerging during evolution. We made an extensive comparative analysis of the available htt protein homologues from different organisms along the metazoan phylogenetic tree and defined the presence of 3 different conservative blocks corresponding to human htt aa 1-386 (htt1), 683-1,586 (htt2), and 2,437-3,078 (htt3), in which HEAT (Huntingtin, Elongator factor3, the regulatory A subunit of protein phosphatase 2A, and TOR1) repeats are well conserved. We also describe the cloning and sequencing of sea urchin htt mRNA, the oldest deuterostome homologue so far available. Multiple alignment shows the first appearance of a primitive polyQ in sea urchin, which predates an ancestral polyQ sequence in a nonchordate environment and defines the polyQ characteristic as being typical of the deuterostome branch. The fact that glutamines have conserved positions in deuterostomes and the polyQ size increases during evolution suggests that the protein has a possibly Q-dependent role. Finally, we report an evident relaxing constraint of the N-terminal block in Ciona and drosophilids that correlates with the absence of polyQ and which may indicate that the N-terminal portion of htt has evolved different functions in Ciona and protostome

Aberrant transcriptional and post-transcriptional regulation of SPAG5, a YAP-TAZ-TEAD downstream effector, fuels breast cancer cell proliferation

Sperm-associated antigen 5 (SPAG5) is an important driver of the cell mitotic spindle required for chromosome segregation and progression into anaphase. SPAG5 has been identified as an important proliferation marker and chemotherapy-sensitivity predictor, especially in estrogen receptor-negative breast cancer subtypes. Here, we report that SPAG5 is a direct target of miR-10b-3p, and its aberrantly high expression associates with poor disease-free survival in two large cohorts of breast cancer patients. SPAG5 depletion strongly impaired cancer cell cycle progression, proliferation, and migration. Interestingly, high expression of SPAG5 pairs with a YAP/TAZ-activated signature in breast cancer patients. Reassuringly, the depletion of YAP, TAZ, and TEAD strongly reduced SPAG5 expression and diminished its oncogenic effects. YAP, TAZ coactivators, and TEAD transcription factors are key components of the Hippo signaling pathway involved in tumor initiation, progression, and metastasis. Furthermore, we report that SPAG5 is a direct transcriptional target of TEAD/YAP/TAZ, and pharmacological targeting of YAP and TAZ severely reduces SPAG5 expression. Collectively, our data uncover an oncogenic feedback loop, comprising miR-10b-3p, SPAG5, and YAP/TAZ/TEAD, which fuels the aberrant proliferation of breast cancer

HIV-1 RNA genome dimerizes on the plasma membrane in the presence of Gag protein

Retroviruses package a dimeric genome comprising two copies of the viral RNA. Each RNA contains all of the genetic information for viral replication. Packaging a dimeric genome allows the recovery of genetic information from damaged RNA genomes during DNA synthesis and promotes frequent recombination to increase diversity in the viral population. Therefore, the strategy of packaging dimeric RNA affects viral replication and viral evolution. Although its biological importance is appreciated, very little is known about the genome dimerization process. HIV-1 RNA genomes dimerize before packaging into virions, and RNA interacts with the viral structural protein Gag in the cytoplasm. Thus, it is often hypothesized that RNAs dimerize in the cytoplasm and the RNA-Gag complex is transported to the plasma membrane for virus assembly. In this report, we tagged HIV-1 RNAs with fluorescent proteins, via interactions of RNA-binding proteins and motifs in the RNA genomes, and studied their behavior at the plasma membrane by using total internal reflection fluorescence microscopy. We showed that HIV-1 RNAs dimerize not in the cytoplasm but on the plasma membrane. Dynamic interactions occur among HIV-1 RNAs, and stabilization of the RNA dimer requires Gag protein. Dimerization often occurs at an early stage of the virus assembly process. Furthermore, the dimerization process is probably mediated by the interactions of two RNA-Gag complexes, rather than two RNAs. These findings advance the current understanding of HIV-1 assembly and reveal important insights into viral replication mechanisms