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Zinc induced pediatric preventing respiratory 2019-nCoV is required that supplementation with zinc gluconate 20 mg in Zn deficient children resulted in a nearly twofold reduction of acute lower respiratory infections as well as the time to recovery. Zinc supplementation in children is associated with a reduction in the incidence and prevalence of pneumonia. Preventing 2019-nCoV pneumonia is required that zinc supplementation alone (10 to 20 mg) for more than 3 months significantly reduces in the rate of pneumonia. zinc pediatric intake may be required to be effective range 10～20 mg/d for 2019-CoV prevention, 10～30 mg/d for reduction of COVID-19 bronchitis, and 20～30 mg/d for recovery from COVID-19 pneumonia, in which Zn2+ could bind with viral surface proteins by Zn2+ions-centered tetrahedrally coordination pattern. On the other hand, for aults, the zinc-homeostatic immune concentration may provide a protective role against the COVID-19 pandemic, likely by improving the host’s resistance against viral infection. 50 mg of zinc per day might provide an additional shield against the COVID-19 pandemic, possibly by increasing the host resistance to viral infection to minimize the burden of the disease. In order to prevent that an outbreak of respiratory sickness caused by a novel coronavirus (COVID-19) has become a serious public threat and disrupted many lives,assessing the efficacy of FDA-approved Zn-ejector drugs such as disulfiram combined with interferon to treat COVID-19 infected patients has been proposed. The key strategies for preventing lung damages include avoiding direct lung infection, altering host-virus interactions, promoting immune responses, diluting virus concentrations in lung tissues by promoting viral migration to the rest of the body, maintaining waste removal balance, protecting heart function and renal function, avoiding other infections, reducing allergic reactions and anti-inflammatory. The interactions had been found on the binding specificity by Zn2+ ions-centered tetrahedral geometric coordination of the inhibitors against 3C and 3C-like proteases. In addition, transient zinc chelation TPEN and EPDTC have been noted as preventing virus replication. Zinc-induced ROS production in COVID-19 respiratory ailment and pneumonia occurs both in children and adults. In children. ROS production in zinc (Ⅱ)-immune pediatric patient with COVID-19 bronchitis and pneumonia cannot be elucidated yet. In adults, zinc induced ROS generation in pulmonary COVID-19 infected cells is that alterations of ROS-producing and scavenging pathways that are caused by respiratory viral infections are implicated in inflammation, lung epithelial disruption, and tissue damage, and, in some cases, even pulmonary fibrosis. The involvement of oxidative stress in cell deaths caused during RNA virus infection and ROS production is correlated with host cell death.

Amyloidoma is an exceptional, progressive disorder demonstrating a characteristic accumulation of significant quantities of amyloid within soft tissues. Amyloidoma is additionally nomenclated as tumoural amyloidosis, nodular amyloid or localized amyloidosis. Furthermore, insulin-derived amyloidoma is referred to as insulin ball. Amyloid is a protein polymer configured of identical monomeric protein units wherein pathological variety is articulated from misfolded proteins. In excess > of twenty three subtypes of proteins can configure amyloid fibres in vivo. Extra-cellular or intra-cellular deposition of amyloid can modify normal organ function [1]. Amyloidosis is categorized into systemic and localized subtypes. Localized amyloidosis displays a localized mass effect and demonstrates a superior prognosis. Insulin-derived amyloidosis was initially documented by Storkel, et al. in 1983 who recognized accumulated insulin- amyloid fibrils in diabetic individuals subjected to continuous infusion of porcine insulin over a period of 5 weeks or more [1,2]. Amyloid nodules may be associated with systemic amyloidosis.

Introduction: Endothelial progenitor cells (EPC) are involved in vascular repair and proliferation, contributing to the long-term outcomes of apheretic treatment. Aim of this study was to investigate the relationships between endothelial function, assessed by levels of bone marrow-derived progenitor cells and endothelial response to hyperaemia, and clinical and biohumoral parameters in high vascular risk patients before, immediately after, 24-hours and 72 hours after a single lipid apheresis procedure. Material and Methods: We evaluated lipid profile, endothelial function and endothelial progenitor cells before (T0), immediately after (T1), 24h after (T2) and 72h after (T3) a lipoprotein apheresis procedure, in 8 consecutive patients [Sex: 62.5% M; Age; 63.29(12), mean, (range) years] with a personal history of acute coronary syndrome, symptomatic peripheral arterial disease and elevated plasma levels of lipoprotein (a) [Lp(a)]. Patients were on regularly weekly or biweekly lipoprotein apheresis, and they were treated with the FDA-approved Heparin-induced Extracorporeal LDL Precipitation (H.E.L.P.) (Plasmat Futura, B.Braun, Melsungen, Germany) technique. PAT values were expressed as the natural logarithm (Ln-RHI, normal values≥0.4) of the reactive hyperaemia index (RHI), which is the parameter automatically calculated by the device. Results: We found a reduction in the natural logarithm of reactive hyperaemia index (Ln-RHI), assessed immediately after the procedure (0.57±0.21 vs 0.72± 0.29); difference between T2 and T0 was statistically significant (0.43±0.24 vs 0.72±0.29; p=0.006). Reduction in Ln-RHI values was documented in all patients, two subjects showing a Ln-RHI<0.4 at T1, and four at T2. At T3, PAT values were increased significantly (0.91±0.18) in comparison to T1 and T2, showing a median value higher than at T0. Cd34+/Kdr+ and Cd133+/Kdr+ showed a minimum increase in median values at T1, and a higher increase at T2, in comparison to baseline. Differences in Cd34+/133+/Kdr+ values at different times were not statistically significant. A significant reduction in circulating endothelial cells (CEC) count at T2 in comparison to T0 was found (12.00±8.85 vs 23.86±12.39; p=0.024). Discussion: At 24h and 72h after procedures, we found an improvement in endothelial function, expressed by an increase in PAT values and EPC levels, and by a reduction in CEC.

According to recent guidelines, endovascular angioplasty is the standard treatment for TASC A and B primary aorto-iliac occlusive (AIOD) disease, and the first-line approach for TASC C lesions [1,2]. Extended TASC D occlusive disease is usually treated by open surgery yielding excellent patency rates at a cost of a higher mortality (2%-4%) and a severe morbidity (up to 10%) [3]. However, several studies have reported promising results after endovascular treatment of extensive AIOD and full reconstruction of the aortic bifurcation [4,5]. In a recent meta-analysis, Jongkind et al., concluded that endovascular treatment of extensive AIOD can be performed successfully by experienced interventionists in selected patients [6]. Although primary patency rates seem to be lower than those reported for surgical revascularization, reinterventions can often be performed percutaneously yielding a secondary patency comparable to surgical repair.

Since the discovery of the dystrophin gene (DMD gene) thirty years ago, several therapeutic approaches have been investigated to treat Duchenne muscular dystrophy (DMD). This includes cell therapy, exon jumping, exonic knockout, and the CinDel method. In this article, we present the challenges of developping a treatment for DMD and the advances of these various approaches. We included the new CRISPR-Cas9 system, which permits not only major progress in the development of new treatments based on genome editing but also the production of new animal models.

Osteoarthritis is the most common form of arthritis, affecting millions of people worldwide. Aim of our study was to assess the clinical and the cytogenetic characteristics in longlivers with osteoarthritis from Precarpathian region (Ukraine). Methods: Cytogenetic, Clinical Results: All of the subjects were separated into three groups: І group - 146 longlivers patients who had hypertension and osteoarthritis (ОА); II group - 93 longlivers patients only with ОА. The control (third) group included 130 patients aged 90-102 years without osteoarthritis and hypertension in anamnesis. In the age group more than 95 years, men and women of both groups were significant difference (p<0,05) to be compared with control. Cytogenetic characteristics of the long-livers with on osteoarthritis showed that most there is a tendency for a higher frequency of chromosomal aberrations in male long-livers and tere are significant difference among control (p<0,05). The number of chromosomes associated in a single cell was significantly higher (p<0,05) in both groups compared to control. Conclusion: The importance of this study resides, to the best of our knowledge, in the fact that the largest group of patients in Ukraine was analyzed and assessed.

Nanotechnology is a smart technology in the field of biomedical engineering used for the diagnosis and treatment of diseases. Nanodrugs provide better encapsulation of drug and efficiency at low dosage to kill the targeted tissue/cells. However, the chances of chronic toxicity and high cost of treatment limits its applicability [1]. To overcome these problems still, the experts of the scientific community have been working on it, to design the best one and cost-effective treatment for the human welfare.

The present report highlights our results on synthesis of NaYF4:Yb,Er@SiO2@Ag core–shell nanoparticles (CSNPs) for plasmon-enhanced upconversion luminescence (UCL). Hydrophilic surface UCL nanoparticles (UCLNPs) as cores were obtained by precipitation of Rare Earth Elements (REE) chlorides from water-alcohol solutions. The formation of a hydrophobic surface of α-NaYF4:Yb,Er NPs was achieved by thermolysis method at 280 °C and β-NaYF4:Yb,Er by precipitation method in nonpolar medium at 320 °C. Silica shell was formed by the modified Stöber method on the surfaces of UCLNPs with different polarity and phase composition. A mixture of hexane-cyclohexane-isopropyl alcohol was used as a medium for the formation of mononuclear CSNPs on hydrophobic surfaces of cores with different thicknesses of the silica shell: 5 nm and 14 nm. Formation of a predetermined thickness of silica shell was carried out by introducing a precise quantity of TEOS taking into account the size of core NPs with molar ratio TEOS: H2O equal to 1:6. The morphology and phase composition of cores and CSNPs were examined by transmission electron microscopy and selected area electron diffraction, respectively. The insertion of Ag NPs into the structure of NaYF4:Yb,Er@SiO2 was carried out in parallel at the stage of shell formation, which made this synthesis a one-step process. The control of the size of Ag NPs was implemented through the use of a colloidal solution of NPs of the cluster structure by changing the polarity of the medium. The highest intensity enhancement of 85-fold with 5 nm and 29-fold with 14 nm shell thickness was recorded, respectively. For the first time, tests on bioimaging of neutrophil cells by those CSNPs are demonstrated.

Highly selective and sensitive detection of cardiac troponin I (cTnI) is a powerful complement to clinical diagnosis of acute myocardial infarction (AMI). In this study, a strategy for cTnI detection was developed by constructing a universal biosensing interface composed of zwitterionic peptides and aptamers. The peptides were self-assembled onto gold chips, and some of them were biotinylated. The cTnI-specific binding aptamers were immobilized through the streptavidin-biotin system. Surface plasmon resonance (SPR) measurements revealed the preparation process. The developed aptasensor presents a linear detection with cTnI ranging from 20 ng/ml to 600 ng/ml and a detection limit of 20 ng/ml. The high immobilization of the aptamer enhances the sensitivity of the aptasensor and the calculated KD was 6.75 nM. Due to the outstanding antifouling property of the zwitterionic peptide, the developed aptasensor possesses a high resistance towards protein fouling. Moreover, the aptasensor has excellent selectivity and specificity towards cTnI in complex media. Hence, the proposed peptide-based aptasensor shows great potential for practical application in medium sized Myocardial Infarction (MI).

The global virome: The viruses have a global distribution, phylogenetic diversity and host specificity. They are obligate intracellular parasites with single- or double-stranded DNA or RNA genomes, and afflict bacteria, plants, animals and human population. The viral infection begins when surface proteins bind to receptor proteins on the host cell surface, followed by internalisation, replication and lysis. Further, trans-species interactions of viruses with bacteria, small eukaryotes and host are associated with various zoonotic viral diseases and disease progression. Virome interface and transmission: The cross-species transmission from their natural reservoir, usually mammalian or avian, hosts to infect human-being is a rare probability, but occurs leading to the zoonotic human viral infection. The factors like increased human settlements and encroachments, expanded travel and trade networks, altered wildlife and livestock practices, modernised and mass-farming practices, compromised ecosystems and habitat destruction, and global climate change have impact on the interactions between virome and its hosts and other species and act as drivers of trans-species viral spill-over and human transmission. Zoonotic viral diseases and epidemics: The zoonotic viruses have caused various deadly pandemics in human history. They can be further characterized as either newly emerging or re-emerging infectious diseases, caused by pathogens that historically have infected the same host species, but continue to appear in new locations or in drug-resistant forms, or reappear after apparent control or elimination. The prevalence of zoonoses underlines importance of the animal–human–ecosystem interface in disease transmission. The present COVID-19 infection has certain distinct features which suppress the host immune response and promote the disease potential. Treatment for epidemics like covid-19: It appears that certain nutraceuticals may provide relief in clinical symptoms to patients infected with encapsulated RNA viruses such as influenza and coronavirus. These nutraceuticals appear to reduce the inflammation in the lungs and help to boost type 1 interferon response to these viral infections. The human intestinal microbiota acting in tandem with the host’s defence and immune system, is vital for homeostasis and preservation of health. The integrity and balanced activity of the gut microbes is responsible for the protection from disease states including viral infections. Certain probiotics may help in improving the sensitivity and effectivity of immune system against viral infections. Currently, antiviral therapy is available only for a limited number of zoonotic viral infections. Because viruses are intracellular parasites, antiviral drugs are not able to deactivate or destroy the virus but can reduce the viral load by inhibiting replication and facilitating the host’s innate immune mechanisms to neutralize the virus. Conclusion: Lessons from recent viral epidemics - Considering that certain nutraceuticals have demonstrated antiviral effects in both clinical and animal studies, further studies are required to establish their therapeutic efficacy. The components of nutraceuticals such as luteolin, apigenin, quercetin and chlorogenic acid may be useful for developing a combo-therapy. The use of probiotics to enhance immunity and immune response against viral infections is a novel possibility. The available antiviral therapy is inefficient in deactivating or destroying the infecting viruses, may help in reducing the viral load by inhibiting replication. The novel efficient antiviral agents are being explored.

The broad spectrum of heterozygous versus homozygous JAK2V617F mutated MPN consists ET, ET with early features of PV (prodromal PV), classical PV, masked PV, advanced PV and post-PV myelofibrosis. Combined use of bone marrow histology and increased erythrocyte counts above 5.8x1012/L can replace increased red cell mass at time of presentation as the pathognomonic clue for the correct diagnosis of hetero/homozygous or homozygous mutated PV. Erythrocyte counts are in the normal range below 5.8x1012/L in heterozygous JAK2V617F mutated ET and prodromal PV but above 5.8x1012/L in heterozygous-homozygous or homozygous mutated PV. The bone marrow cellularity and morphology in pre-fibrotic ET, prodromal PV and PV carrying the JAK2V617F mutation are overlapping showing clustered increase of large mature pleomorphic megakaryocytes (M) with no increase of cellularity (<60%) in ET. The bone marrow is hypercellular (60%-80%) due to increased erythropoiesis megakaryopoiesis (EM) in prodromal and classical PV and trilinear hypercellular (80%-100% due increased megakaryopoiesis, erythropoiesis and granulopoiesis (EMG) in advanced PV and masked PV. Bone marrow cellularity ranging from normal (<60%) in ET to increased erythropoiesis (EM) in prodromal PV to hypercellular (80-100%) in advanced PV and masked PV largely depends on increasing JAK2V617F mutation load from low to high on top of other biological MPN variables like constitutional symptoms during long-term follow-up. MPL515 mutated ET is featured by an increase of clustered small and giant megakaryocytes with hyper-lobulated staghorn-like nuclei in a normal cellular bone marrow. The third entity of pronounced JAK2/MPL wild type ET associated with primary megakaryocytic granulocytic myeloproliferation (PMGM) without PV features proved to be caused by calreticulin (CALR) mutation. CALR mutated thrombocythemia is characterized by dual proliferation of megakaryocytic and granulocytic bone marrow proliferation of dense clustered large to giant immature dysmorphic megakaryocytes with bulky (bulbous) hyperchromatic nuclei, which are not seen in MPL515-mutated Thrombocythemia and JAK2V617F-Thrombocythemia, prodromal PV and classical PV. 

Primary myelofibrosis (PMF) is a distinct clinicopathological myeloproliferatve disease (MPD) not preceded by any other MPD ET, PV, CML,... Combined use of bone marrow histology and increased erythrocyte counts above 5.8x1012/L can replace increased red cell mass at time of presentation as the pathognomonic clue for the correct diagnosis of hetero/homozygous or homozygous mutated PV. Erythrocyte counts are in the normal range below 5.8x1012/L in heterozygous JAK2V617F mutated ET and prodromal PV but above 5.8x1012/L in heterozygous-homozygous or homozygous mutated PV. The bone marrow cellularity and morphology in pre-fibrotic ET, prodromal PV and PV carrying the JAK2V617F mutation are overlapping showing clustered increase of large mature pleomorphic megakaryocytes (M) with no increase of cellularity (<60%) in ET. The bone marrow is hypercellular (60%-80%) due to increased erythropoiesis megakaryopoiesis (EM) in prodromal and classical PV and trilinear hypercellular (80%-100% due increased megakaryopoiesis, erythropoiesis and granulopoiesis (EMG) in advanced PV and masked PV. Bone marrow cellularity ranging from normal (<60%) in ET to increased erythropoiesis (EM) in prodromal PV to hypercellular (80-100%) in advanced PV and masked PV largely depends on increasing JAK2V617F mutation load from low to high on top of other biological MPN variables like constitutional symptoms during long-term follow-up. MPL515 mutated ET is featured by an increase of clustered small and giant megakaryocytes with hyper-lobulated staghorn-like nuclei in a normal cellular bone marrow. The third entity of pronounced JAK2/MPL wild type ET associated with primary megakaryocytic granulocytic myeloproliferation (PMGM) without PV features proved to be caused by calreticulin (CALR) mutation. CALR mutated thrombocythemia is characterized by dual proliferation of megakaryocytic and granulocytic bone marrow proliferation of dense clustered large to giant immature dysmorphic megakaryocytes with bulky (bulbous) hyperchromatic nuclei, which are not seen in MPL515-mutated Thrombocythemia and JAK2V617F-Thrombocythemia, prodromal PV and classical PV. 

The present article extends the PVSG-WHO criteria into a simplified set of Rotterdam and European Clinical, Molecular and Pathological (RCP/ECMP) criteria to diagnose and classify the myeloproliferative neoplasms (MPNs). The crude WHO criteria still miss the masked and early stages of ET and PV. Bone marrow histology has a near to 100% sensitivity and specificity to distinguish thrombocythemia in BCR/ABL positive CML and ET, and the myelodysplastic syndromes in RARS-T and 5q-minus syndrome from BCR/ABL negative thrombocythemias in myeloproliferative disorders (MPD). The presence of JAK2V617F mutation with increased erythrocytes above 6x1012/L and hematocrit (>0.51 males and >0.48 females) is diagnostic for PV obviating the need of red cell mass measurement. About half of WHO defined ET and PMF and 95% of PV patients are JAK2V617F positive. The combination of molecular marker screening JAK2V617F, JAK2 exon 12, MPL515 and CALR mutations and bone marrow pathology is 100% sensitive and specific for the diagnosis of latent, early and classical ECMP defined MPNs. The translation of WHO defined ET, PV and PMF into ECMP criteria have include the platelet count above 350 x109/l, mutation screening and bone marrow histology as inclusion criteria for thrombocythemia in various MPNs. According to ECMP criteria, ET comprises three distinct phenotypes of true ET, ET with features of early (“forme fruste” PV), and ET with a hypercellular erythrocythemic, megakaryocytic granulocytic myeloproliferation (EMGM or masked PV). The ECMP criteria clearly differentiate early erythrocythemic, prodromal and classical PV from congenital polycythemia and idiopathic or secondary erythrocytosis. The burden of JAK2V617F mutation in heterozygous ET and in homozygous PV is of major clinical and prognostic significance. JAK2 wild type MPL515 mutated normocellular ET and MF lack PV features in blood and bone marrow. JAK2/MPL wild type hypercellular ET associated with primary megakaryocytic granulocytic myeloproliferation (PMGM) is the third distinct CALR mutated MPN. The translation of WHO into ECMP criteria for the classification of MPNs have a major impact on prognosis assessment and best choice for first line non-leukemogenic approach to postpone potential leukemogenic myelopsuppressive agents as long as possible in ET, PV and PMGM patients.

Broad medleys of research have recognized the microglial activation in perilous psychiatric maladies such as schizophrenia, bipolar disorder, and major depressive disorder. There is a scenario of enlivening of peripheral monocytic cells along with the microglial interactions within the body while considering the Pathogenesis of psychiatric disorders. this review, epitomize and discuss the activation of microglia and monocytic cells in psychiatric disorders, thereby showcasing the potential association between these cell types and the Pathogenisis of the ailment , and proffer perspectives for future research on these processes.

The research concerning a preventive treatment of an osteoporitic femoral neck fracture started in 1990 because the surgical procedure of unstable femoral neck fractures is difficult. After effects are frequent and their number will increase in the next decade. The goal is to reinforce the femur with a biomaterial acting as a bone graft. Natural coral is bioresorbable and biocompatible. It acts as an autofocus bone graft for reconstruction of either cortex or cancellous bone and increases their mechanical resistance. This work shows evidence of new bone formation in an osteoporotic unbroken femoral neck femur. Consequently, the preventive surgical treatment of osteoporosis should be taken in consideration [1]. The purpose of this work is to show the results on the mineralization of the cancellous bone of an upper femoral metaphyses when a natural biomaterial is set in an unbroken osteoporotic femoral neck. Summary: Mrs. L is an 84 years old lady. Her osteoporotic unbroken right hip was grafted preventively with a biomaterial in order to prevent the high risk of break in case of fall. The biomaterial used is beads of natural coral. The reasons of this preventive treatment is discussed, as well as the choice of the biomaterial. The results are shown including a two years follow up. Brief History: Before going further, few words of history. Three centuries BC, an Aristote’s follower, Théophraste thinks that Natural coral is a petrified plant. For Ovide natural coral is a soft alga air-hardening. Al Biruni classes it among animals, because that respond to touch. At the beginning of the XVIIth century, Marsigli thinks that they are flowers which open out there in aquarium. The French Jean-André Peyssonnel, a young naturalist, says as Biruni, that in fact, corals are animals. At last, Buffon claims: These marine plants, were classified first in the rank of minerals, then in those of plants, and finally in that of animals. Natural coral is obviously an animal. After the Second World War, coral samples were analyzed by American scientists. Among 800 corail species, 3 where specially analyzed: Acropora, Porites and Libophylia. Mrs Nane Guillemin did in France her PHD on natural coral and with her team made a complete fundamental analysis (physical, chemical and biological properties) of the material, while the American scientists worked on the chemical bone’s properties. In France, Pr Ohayoun and his team worked on the surgical application in the dental field, Dr. Yves Cirotteau in the orthopedic surgery, specifically for osteoporotic disease and for the traumatologic field

The clinical phenotypes in 268 JAK2V617F mutated MPN patients in the Seoul study were PV in 101, ET in 95 and MF in 78 and 56 CALR mutated MPN consisted of PV in none, ET in 40 and MF in 16 cases. CALR mutated MPN patients were younger than JAK2V617F mutated MPN patients (mean ages 57.5 and 66 years), had lower values for values for leukocytes (8.6 vs 11.9x109/L) and higher values for platelets (898 vs 643x109/L respectively). Bone marrow histopathology in 268 JAK2V617F mutated MPN patients in the Seoul study was featured by an increased erythropoiesis and megakaryopoiesis (EM) in 13.5%, an increased erythropoiesis, megakaryopoiesis and granulopoiesis (EMG) in 31.3%, a normocellular megakaryocytic (M) proliferation in 29,1%, a megakaryocytic and granulocytic (MG) proliferation with a relative reduction of erythropoiesis in post-ET and Post-PV myelofibrosis in 26.2%. The bone marrow histology in 56 cases of CALR mutated MPN show a predominantly increased megakaryopoiesis (M) in two thirds and an increased megakaryopoiesis and granulopoiesis (MG) with a decreased erythropoiesis in one third. Thirteen consecutive CALR MPN patients in the Belgian & Dutch cross sectional study presented with thrombocythemia associated with a typical PMGM bone marrow histology in 11 and myelofibrosis in 2 cases. All 11 thrombocythemia and 2 myelofibrosis CALR mutated MPN patients did not have constitutional symptoms and did not suffer from microvascular erythromelalgic disturbances, major thrombosis at platelet counts between 400 and 1000x109/L. There was an occurrence of hemorrhages at platelet counts above 1000x109/L in two CALR thrombocythemia cases. Bone marrow histology of CALR mutated thrombocythemia in the Seoul and Belgian/Dutch study showed loose clusters of large megakaryocytes (M) with bulky, cloud-like nuclei with a normal or a minor reduction of erythropoiesis and no increase in reticulin fibers grade 0 or 1 (RF 0 or 1). CALR thrombocythemia patients show various degrees of increased bone marrow cellularity due to dual megakaryocytic and granulocytic (MG) proliferation featured by large megakaryocytes with roundish bulky nuclear forms and cloud-like clumsy nuclei, which are almost never seen in JAK2V617F ET and PV. Assessment of allele burden is an independent and most important factor for all molecular variants MPN disease burden. Overt myelofibrosis with advanced post PV and or ET myelofibrosis at the bone marrow level occurred in one third (30%) of 208 evaluable JAK2 MPN patients and in 8 (14%) of 56 CALR MPN patients in the Seoul study.

Allogeneic hematopoietic stem cell transplant (alloHSCT) is a curative treatment for many hematologic malignancies. Unfortunately, about 30-50% of all recipients undergoing alloHSCT develop acute graft-versus-host-disease (aGVHD), which is associated with high morbidity and mortality [1,2]. Treatment of aGVHD involves the use of immune suppressive drugs such as high dose of steroids that leads to further immunosuppression and risk for opportunistic infections. Often patients are refractory to steroids therapy making the prognosis dismal. Thus, it is critical to identify robust biomarkers to detect aGVHD before onset of clinical symptoms so that therapeutic strategies can be implemented that may result in better treatment responses and less toxicity. 

Summary: Myelodysplastic Syndrome (MDS) is a heterogeneous group of clonal hematopoietic malignancies characterized by progressive cytopenias, ineffective hematopoiesis, bone marrow hypercellularity and transformation to acute myeloid leukemia (AML). Objectives: Identify plasma proteins from MDS patients and from two healthy controls groups (young and elderly) by SDS-Page. Methods: Plasma from 08 healthy young, 08 healthy elderly and 08 MDS patients were used for this study. Proteins were fractionated, precipitated, used for SDS-PAGE gel analysis, stained with comassie brilliant blue, scanned and bands were analyzed. Results: It was possible to identify in both, 20% fraction and supernatant, proteins that were differentially expressed in each group. The ones that have showed some clinical relevance. Fibronectin was highly expressed only in the young control group. α2-Macroglobulin was also expressed in both control groups, but it was not expressed in the MDS group. Haptoglobin was highly expressed only in the elderly control and SMD groups. Conclusion: Protein expression in plasma can be a biomarker for MDS, and may play a key role in the process of aging and hematologic malignancies development.

Background: With the advancement of cell therapy research, there is an increasing need for healthy volunteers (HV) to donate small volumes (30 ml) of human bone marrow (BM). The BM procedure required to procure small volumes is invasive, although short-lived (25 seconds), is not without risk. To ensure a sustainable supply of BM for research and cell therapy, greater information of the risks and factors that motivate HV to donate small volumes of BM will help optimize the procedure and HV enrolment, ensuring donors are fully informed of the potential risks. Objective: To identify the adverse events (AE) experienced by HV during and after small volume BM procedure and understand the motivating factors that influence HV to donate BM for research. Method: HV (n = 55) who donated BM (30 ml) for scientific research and provided informed consent were administered a questionnaire to identify the type, duration and severity of AE experienced during and post-BM aspiration; and to determine the motivating factors that influenced their willingness to donate BM. Results: Pain was experienced by 89% of participants during the BM procedure with moderate grade reported by 40%. One/more of the following AE were experienced by 73% of the volunteers post-BM procedure: pain, fatigue, site reaction, nausea and transient hypotension. AE resolved within an average of three days. The reported motivational factors ranked in the following order: first, to advance research for the benefit of future patients; compensation for participation; free medical check-up; lastly, the research question was interesting. Conclusion: Young HV, motivated primarily by altruism and financial compensation, risk the occurrence of transient AE following donation of small-volume BM for research.

The Myeloproliferative Neoplasms (MPN) of trilinear polycythemia vera (PV) and megakaryocytic leukemia (ML = primary megakaryocytic granulocytic myeloproliferation: PMGM) and Essential Thrombocythemia (ET) in the studies of Dameshek and Michiels are caused by the MPN driver mutations JAK2V617F, JAK2exon12, CALR and MPL515 discovered by Constantinescu-Vainchenker, Green and Kralovics. The JAK2V617F mutated trilinear myeloproliferative neoplasms (MPN) include a broad spectrum of clinical laboratory and bone marrow features in essential thrombocythemia (ET), prodromal PV and erythrocythemic PV, classical PV and advanced stages of masked PV and PV complicated by splenomegaly and secondary myelofibrosis (MF). Heterozygous JAK2V617F mutated ET is associated with low JAK2 allele and MPN disease burden and normal life expectance. In combined heterozygous and homozygous or homozygous JAK2V617F mutated trilinear PV, the JAK2 mutation load increases from less than 50% in prodromal PV and classical PV to above 50% up to 100% in hypercellular PV, advanced PV and PV with MF. Bone marrow histology show diagnostic features of eryhrocytic, megakaryocytic and granulocytic (EMG) myeloproliferation in JAK2V617F mutated trilinear MPN, which clearly differs from monolinear megakaryocytic (M) myelproliferation in MPL and CALR thrombocythemia and dual megakaryocytic granulocytic (MG) myeloproliferation in CALR mutated thrombocythemia. The morphology of clustered large pleomorphic megakaryocytes with hyperlobulated nuclei are similar in JAK2V617F thrombocythemia, prodromal PV and classical PV patients. Monolinear megakaryocytic (M) myeloproliferation of large to giant megakaryocytes with hyperlobulated staghorn-like nuclei is the hallmark of MPL515 mutated normocellular thrombocythemia. CALR mutated thrombocythemia usually presents with high platelet count around 1000x109/l and normocellular megakaryocytic (M) proliferation of immature megakaryocytes with cloud-like hyperchromatic nuclei followed by dual megakaryocytic granulocytic (MG) myeloproliferation followed by various degrees of bone marrow fibrosis. Natural history and life expectancy of MPN patients are related to the response to treatment and the degree of anemia, splenomegaly, myelofibrosis and constitutional symptoms. The acquisition of epigenetic mutations at increasing age on top of MPN disease burden independently predict unfavorable outcome in JAK2V617F, MPL515 and CALR mutated myeloproliferative neoplasms (MPNs, which mutually exclude each other).