A rare muscle anomaly: the supraclavicularis proprius muscle

In the Dissection Team of the Second Chair of Anatomy at the School of Medicine of the University of Buenos Aires, Argentina, during the routine dissection of 78 cadavers (corresponding to 156 supraclavicular fossae),10% formalin fixed, we found the supraclavicularis proprius muscle over the lower part of the left supraclavicular fossa in an adult Caucasian male cadaver. We described this rare muscular anomaly, the likelihood of finding this muscle, and its participation in supraclavicular nerve entrapment syndrome

Covalent Immobilization of Aldehyde and Alcohol Dehydrogenases on Ordered Mesoporous Silicas

Purpose This work studies the immobilization of two enzymes, the alcohol dehydrogenase (ADH) and the aldehyde dehydrogenase (AldDH) both from Saccharomyces cerevisiae, which could be used to produce high value-added molecules from carboxylic acids embedded in anaerobic digestate.Methods In particular, three mesoporous siliceous materials, with different specific surface areas and pore sizes, (MSU-H, MSU-F and MCF0.75) were used as supports for covalent immobilization. The support materials were characterized by complementary techniques. Then, after a functionalization, creating a covalent bond between the enzyme and the support was performed. The specific activity and immobilization yield of the biocatalysts were then evaluated.Results The best results were obtained with MSU-H and MSU-F, resulting in an immobilization yield greater than 50% in all cases, a specific activity of 0.13 IU/g(supp) with the AldDH/MSU-H, 0.10 IU/g(supp) with AldDH/MSU-F, 48.6 IU/g(supp) with ADH/MSU-H and 12.6 IU/g(supp) with ADH/MSU-H. These biocatalysts were then characterized by optimal pH and temperature and the stability factor was evaluated. With ADH/MSU-F no decrease in activity was observed after 120 h incubated at 50 degrees C. Finally, the biocatalysts AldDH/MSU-H and ADH/MSU-H were used to perform the reduction reaction and it was seen that after five reaction cycles the residual activity was greater than 20% in both cases.Conclusion The ADH and AldDH enzymes have been successfully immobilized on mesoporous siliceous supports, considerably increasing their thermal stability and being able to reuse them for several reaction cycles. The use of this immobilization and these supports is adaptable to a wide variety of enzymes

Acute promyelocytic Leukemia: Update on the mechanisms of leukemogenesis, resistance and on innovative treatment strategies

This review highlights new findings that have deepened our understanding of the mechanisms of leukemogenesis, therapy and resistance in acute promyelocytic leukemia (APL). Promyelocytic leukemia-retinoic acid receptor alpha (PML-RARa) sets the cellular landscape of acute promyelocytic leukemia (APL) by repressing the transcription of RARa target genes and disrupting PML-NBs. The RAR receptors control the homeostasis of tissue growth, modeling and regeneration, and PML-NBs are involved in self-renewal of normal and cancer stem cells, DNA damage response, senescence and stress response. The additional somatic mutations in APL mainly involve FLT3, WT1, NRAS, KRAS, ARID1B and ARID1A genes. The treatment outcomes in patients with newly diagnosed APL improved dramatically since the advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). ATRA activates the transcription of blocked genes and degrades PML-RAR alpha, while ATO degrades PML-RARa by promoting apoptosis and has a pro-oxidant effect. The resistance to ATRA and ATO may derive from the mutations in the RARa ligand binding domain (LBD) and in the PML-B2 domain of PML-RARa, but such mutations cannot explain the majority of resistances experienced in the clinic, globally accounting for 5-10% of cases. Several studies are ongoing to unravel clonal evolution and resistance, suggesting the therapeutic potential of new retinoid molecules and combinatorial treatments of ATRA or ATO with different drugs acting through alternative mechanisms of action, which may lead to synergistic effects on growth control or the induction of apoptosis in APL cells

The cGAS-STING Pathway Affects Vertebral Bone but Does Not Promote Intervertebral Disc Cell Senescence or Degeneration

The DNA-sensing cGAS-STING pathway promotes the senescence-associated secretory phenotype (SASP) and mediates type-I interferon inflammatory responses to foreign viral and bacterial DNA as well as self-DNA. Studies of the intervertebral disc in humans and mice demonstrate associations between aging, increased cell senescence, and disc degeneration. Herein we assessed the role of STING in SASP promotion in STING gain- (N153S) and loss-of-function mouse models. N153S mice evidenced elevated circulating levels of proinflammatory markers including IL-1β, IL-6, and TNF-α, showed elevated monocyte and macrophage abundance in the vertebral marrow, and exhibited a mild trabecular and cortical bone phenotype in caudal vertebrae. Interestingly, despite systemic inflammation, the structural integrity of the disc and knee articular joint remained intact, and cells did not show a loss of their phenotype or elevated SASP. Transcriptomic analysis of N153S tissues demonstrated an upregulated immune response by disc cells, which did not closely resemble inflammatory changes in human tissues. Interestingly, STING-/- mice also showed a mild vertebral bone phenotype, but the absence of STING did not reduce the abundance of SASP markers or improve the age-associated disc phenotype. Overall, the analyses of N153S and STING-/- mice suggest that the cGAS-STING pathway is not a major contributor to SASP induction and consequent disc aging and degeneration but may play a minor role in the maintenance of trabecular bone in the vertebrae. This work contributes to a growing body of work demonstrating that systemic inflammation is not a key driver of disc degeneration

The prognostic role of baseline CEA and CA 19-9 values and their time-dependent variations in advanced colorectal cancer patients submitted to first-line therapy.

Serum marker evaluation is an easily available prognostic indicator that may help clinicians to discriminate patients with an aggressive disease; there are few and small-sized studies exploring the prognostic role of baseline carcinoembryonic antigen (CEA) values and their variations during first-line therapy, and even fewer data are available for carbohydrate antigen 19-9 (CA 19-9). Our aim was to analyze the role of those prognostic markers to exploit them in daily clinical practice. Data of 892 patients with marker determination before and 3 and/or 6 months during therapy were extracted from two institutional databases. Patients were grouped according to single marker variation as always negative (G0), decreasing (G1), stable (G2), or increasing (G3). We evaluated the progression-free survival (PFS) and the overall survival (OS) of all the patents and correlated them with CEA and CA 19-9 values. A concordance between response to therapy and marker decrease was evident in 50.2% and in 34.4% of the patients for CEA and CA 19-9. Patients with low CEA or CA 19-9 baseline values had a longer PFS (15.1 vs. 10.5; 13.6 vs. 10.2 months) and OS (32.0 vs. 22.3; 30.5 vs. 20.1 months). The same results of PFS and OS were obtained by analyzing the data of the four different groups. Multivariate analyses confirmed the independent prognostic role of CEA and CA 19-9. Baseline CEA and CA 19-9 levels and their kinetics demonstrated to be independent prognostic factors. CA 19-9 dosage is not recommended; a possible role of CA 19-9 in patients with negative CEA could be worth further evaluation

the effects of the film thickness and roughness in the anodization process of very thin aluminum films

Introduction The anodization of aluminum foils having micrometer thickness is a common process and results in hexagonally self-ordered alumina membranes. However, anodic aluminum oxide (AAO) membranes fabricated from nanometer-thin films present new challenges to the anodization process, since aluminum films adheres poorly on supporting substrates and the smoothness of the film is highly related to the kind of substrate. In the current work we studied the effect of the aluminum thickness and roughness, using films ranging from 100 to 800 nm in thickness and from 2 to 15 nm in root means square roughness (on a scan area of 100 μm2), on the final alumina morphology. We deposited Al thin films by sputtering method on transparent conductive glass substrates. A strong dependence between the Al film roughness and the final alumina pore organization was observed. It was also determined that by reducing the Al film thickness, smaller Al grains were generated, leading to a homogenous pore formation. It was found that, for thicknesses below 300 nm, the electrolyte used to perform anodization becomes a critical parameter due to the competitive effect of aluminum delamination with respect to the anodization reaction. Phosphoric acid showed less delamination problems than oxalic acid

The Anti-Leukemia Effect of Ascorbic Acid: From the Pro-Oxidant Potential to the Epigenetic Role in Acute Myeloid Leukemia

Data derived from high-throughput sequencing technologies have allowed a deeper understanding of the molecular landscape of Acute Myeloid Leukemia (AML), paving the way for the development of novel therapeutic options, with a higher efficacy and a lower toxicity than conventional chemotherapy. In the antileukemia drug development scenario, ascorbic acid, a natural compound also known as Vitamin C, has emerged for its potential anti-proliferative and pro-apoptotic activities on leukemic cells. However, the role of ascorbic acid (vitamin C) in the treatment of AML has been debated for decades. Mechanistic insight into its role in many biological processes and, especially, in epigenetic regulation has provided the rationale for the use of this agent as a novel anti-leukemia therapy in AML. Acting as a co-factor for 2-oxoglutarate-dependent dioxygenases (2-OGDDs), ascorbic acid is involved in the epigenetic regulations through the control of TET (ten-eleven translocation) enzymes, epigenetic master regulators with a critical role in aberrant hematopoiesis and leukemogenesis. In line with this discovery, great interest has been emerging for the clinical testing of this drug targeting leukemia epigenome. Besides its role in epigenetics, ascorbic acid is also a pivotal regulator of many physiological processes in human, particularly in the antioxidant cellular response, being able to scavenge reactive oxygen species (ROS) to prevent DNA damage and other effects involved in cancer transformation. Thus, for this wide spectrum of biological activities, ascorbic acid possesses some pharmacologic properties attractive for anti-leukemia therapy. The present review outlines the evidence and mechanism of ascorbic acid in leukemogenesis and its therapeutic potential in AML. With the growing evidence derived from the literature on situations in which the use of ascorbate may be beneficial in vitro and in vivo, we will finally discuss how these insights could be included into the rational design of future clinical trials

Follow-Up CT Patterns of Residual Lung Abnormalities in Severe COVID-19 Pneumonia Survivors: A Multicenter Retrospective Study

Prior studies variably reported residual chest CT abnormalities after COVID-19. This study evaluates the CT patterns of residual abnormalities in severe COVID-19 pneumonia survivors. All consecutive COVID-19 survivors who received a CT scan 5–7 months after severe pneumonia in two Italian hospitals (Reggio Emilia and Parma) were enrolled. Individual CT findings were retrospectively collected and follow-up CT scans were categorized as: resolution, residual non-fibrotic abnormalities, or residual fibrotic abnormalities according to CT patterns classified following standard definitions and international guidelines. In 225/405 (55.6%) patients, follow-up CT scans were normal or barely normal, whereas in 152/405 (37.5%) and 18/405 (4.4%) patients, non-fibrotic and fibrotic abnormalities were respectively found, and 10/405 (2.5%) had post-ventilatory changes (cicatricial emphysema and bronchiectasis in the anterior regions of upper lobes). Among non-fibrotic changes, either barely visible (n = 110/152) or overt (n = 20/152) ground-glass opacities (GGO), resembling non-fibrotic nonspecific interstitial pneumonia (NSIP) with or without organizing pneumonia features, represented the most common findings. The most frequent fibrotic abnormalities were subpleural reticulation (15/18), traction bronchiectasis (16/18) and GGO (14/18), resembling a fibrotic NSIP pattern. When multiple timepoints were available until 12 months (n = 65), residual abnormalities extension decreased over time. NSIP, more frequently without fibrotic features, represents the most common CT appearance of post-severe COVID-19 pneumonia