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Fifty years of Washington’s fixes for healthcare have brought us to the brink: insurance is unaffordable and care is unavailable, certainly not in time. The way to make healthcare work for We the Patients (all Americans) is to take healthcare authority away from third-parties – government and insurance – and restore the direct doctor-patient connection with no bureaucrat in between. The cure for patient Healthcare is StatesCare combined with market-based medicine. Financial models confirm this approach will make care both affordable and accessible in a timely manner. 

Purpose: In an aspect of qualitative treatment, this research gathered lung cancer patients’ actual experiences to understand deeply, such as their expectation for treatment results, their difficulties during treatment, and their various requests to their family and medical teams. Methods: From May to June 2013, semi-structured interviews were conducted with 9 lung cancer patients. Data were collected through a tape-recorded in-depth interview. The analysis of the data was made through the qualitative method. Results: 124 themes regarding the experience were found. From these 35 concepts, 24 subcategories were emerged. The core category was enduring hardship of the treatment with the hope for full recovery. Six categories included ‘Wishing to be cured but concern about recurrence’, ‘Receiving radiation treatment with pleasure and difficult at the same time’. ‘Being sorry for their family’s full support and trying to stand alone‘, ‘Having confidence in their medical team’, ‘regretting for their old days’, and ‘Wanting to live a long life without illness and pain’. Conclusion: The results of this study would help oncology nurses to understand the lung cancer patients receiving concurrent chemo-radiotherapy (CCRT) and to develop a quality of life improvement program for physical, psychosocial, and spiritual aspects of nursing.

Broad-spectrum sunscreens are now widely used worldwide as an adjunct to help prevent sunburn, skin cancers and premature skin aging. In the United States, all persons older than 6 months are recommended to apply sunscreen to all sun-exposed skin from toes to head except eyes and mouth even on cloudy days. Such a recommendation is apparently based on concepts that exposure to sunlight damages the skin, the damage is cumulative and hence any sun exposure should be minimized or prevented. This communication raises several questions suggesting that the above recommendation may need to be reconsidered. For example, numerous previous studies have indicated many potential health benefits from non-burning sun exposure including protection against sunburn, melanoma, colorectal cancer, breast cancer and prostate cancer, increasing vitamin D synthesis, helping sleep, reducing blood pressure, heart attack and stroke. Recent studies suggested that regular lifetime non-burning sun exposure may not result in premature skin aging and the skin aging is mainly caused by the intrinsic factor. Skin aging or whole-body aging has been recently postulated to be mainly attributed to a gradual reduction in cardiac output/index with age and a new anti-aging or age-reversing nutritional theory has been proposed. An apparent lack of long-term cumulative sunray damage was also supported by reported age independence in incidences of sunburn and skin cancers. It is of interest that the current US policy is different from that of World Health Organization and Australia recommending the need of sun protection only when UV Index is 3 or greater. In view of the above, some general guidelines regarding when to best apply sunscreen are proposed.

In today’s busy world, people don’t even have the time to fall ill. Diseases don’t just demand time but also physical efforts, mental peace, loss of work, distress of loved ones and financial loss. According to a report published in Harvard business review, each year in India, 39 million people are pushed into poverty by out-of-pocket payments for healthcare, with households on average devoting 5.8% of their expenditures to medical care [1].

The day before yesterday, it was shameful for some politicians, especially President Trump, to label SARS-CoV2 virus as discriminatory “Chinese Virus”. Politicians should be more professional and graceful, and distance themselves from the independence of the academy if something remains unknown to them. Besides, there were two months for President Trump to prepare the Americans for this Virus [1]; unfortunately, could he have given more attention to his duty of anti-SARS-CoV2 action, despite spending time to defending against the impeachment of his presidency? Besides, in line with this idea, presidential candidate Hillary Clinton wrote: ”The president is turning to racist rhetoric to distract from his failures to take the coronavirus seriously early on, make tests widely available and adequately prepare the country for a period of crisis. Don’t fall for it. Don’t let your friends and family fall for it”.

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.

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.

Background: Popliteal artery aneurysms (PAAs) are rare, but the diagnosis should not be missed because of the limb and life threatening complications. The purpose of this study was to reach a consensus about the management of PAA based on our own experience and the available literature. Materials and Methods: This is a retrospective analysis of all patients who underwent an open surgical PAA repair at our institution from January 2015 to December 2016. Demographic data, risk factors, clinical presentation, aneurysm characteristics, type of repair and results were reviewed. Results include patency and major complications. Results: Seven patients underwent an open surgical PAA repair (six men). Median age was 72 years. A posterior approach (PA) was chosen four times and a medial approach (MA) was chosen three times. We performed six resections with interposition of a graft and only one ligation with a bypass. Five patients recovered well, did not develop any complication and did not need a second intervention to guarantee patency. These patients underwent a resection of the aneurysm and interposition of a graft (four via a PA and one via a MA). One patient treated by resection and interposition of a Dacron graft via a MA underwent an above-the-knee amputation at postoperative day 14. This patient had a preoperatively dysfunctional leg since several months with no patent outflow vessels. Our patient treated by ligation and bypass via a MA, developed an acute ischemia four months postoperatively because of an extreme flexion of the knee during several hours while watching TV. After unsuccessful trombolysis, he underwent a femorotibial bypass and a partial forefoot amputation. No long-term results are yet available. Conclusions: In our opinion, open surgical repair of PAAs by resection of the aneurysm and interposition of a venous graft has the best results. Depending on the relation to the knee joint and thus the accessibility of the aneurysm, a posterior approach is preferred. We are not convinced of endovascular techniques in the treatment of popliteal artery aneurysms

The administration of a drug substance is an essential step in the management of a patient. It aims either to cure the patient, to prevent a given disease or sometimes to help with the diagnosis. Unfortunately, the action of the drug can go beyond the desired effect, and cause skin-mucous accidents. These accidents, also known as drug-induced attacks, can be isolated or associated with systemic manifestations [1]. Drug eruption is a real public health issue because of the high frequency. In Europe, drug eruption is responsible for about 20% of spontaneous reports of drug accidents. They complicate 2% to 3% of hospital treatments and motivate 1% of consultations, 5% of hospitalizations in dermatology [2]. Some African authors were interested in the subject. Reported prevalence in hospital settings ranges from 0.4% to 1.53% [3,4]. In Mali, there are no national figures. Old statistics from the Department of Dermatology show that about thirty cases occur each year, most of which are represented by severe forms. However, the risk of drug eruption is thought to be very high due to increased local use of drugs without medical advice, the illegal proliferation of drug outlets (‘Street Medicine’). And the lack of enforcement of existing regulations. In addition, some authors believe that the advent of antiretrovirals and the use of antiInfectious infections used to treat opportunistic infections have increased the risk of Drug eruption by 4 to 30 times, particularly in subjects infected with the acquired human immunodeficiency virus (HIV) [2]. This same risk can be observed in leprosy patients on combination chimotherapy. Clinically, the diagnosis of drug eruption is not as easy as one might think because of clinical polymorphism. The responsibility of a drug for the onset of a reaction is also not easy to establish, as in most cases several drugs are administered simultaneously before the onset of the rash. Because of illiteracy, patients find it difficult to make a complete list of the molecules consumed. To this must be added the high frequency of counterfeit medicines circulating both on the street and in private pharmacies. Given the scarcity of African studies and due to local specificities, it seemed interesting to us to undertake a study on Drug eruption in the dermatology department of the Dermatology teaching hospital of Bamako whose purpose is to study epidemiological aspects, clinical, etiological and to identify the molecules responsible in these patients.

58-year-old male patient who came to the dermatology service for a clinical picture consisting of generalized erythematous scaly and pruritic lesions of 2 years of evolution. The clinical judgments provided were: pityriasis versicolor, drop psoriasis, pityriasis rubra pilaris and secondary syphilis (without serology confirming this last hypothesis then). A biopsy of a lesion located on the right costal side was performed. The serology was negative in a second time.

Delivering health care is a complex task that marginalized a portion of the population intentionally or unintentionally. Discrepancy in health care providing to the intended patients is sometimes accompanied by unintended collateral damage to the bystanders who desperately needing our help and assistance.

This work aims to evaluate cortical porosity through a high-resolution peripheral quantitative micro-tomography in a group of 47 patients. All patients, in vivo, were subjected to the medical care protocol of the University Hospital Clementino Fraga, 020-213. Patients were women aged from 37 to 82 years old, who did not present fractures in their lower and upper limbs, all of them showing good health. During screening, they were required to have normal BMD (as determined by DXA; T-score ≥ 1.0) and no low-trauma fractures history. The exclusion criteria for all the individuals enrolled in this control study include, for example, alcoholism, chronic drug use, and chronic gastrointestinal disease. Male patients ranging from 42 to 79 years old presented the same health issues as women group. Results showed an increase in the amount of pores on the cortical bone of the evaluated patients over time; however, this increase was also observed in pore diameter, as well as a decrease in the border between the cortical and trabecular bone, indicating a deterioration in cortical bone quality over the years.

Introduction: Suicidal behavior in teenagers constitutes a health problem that, given the necessary measures of social isolation taken by the global emergency of the COVID-19 pandemic, must generate timely actions for its prevention and control from the public health services. Objective: To propose an action plan for the prevention of suicide in teenagers of the Remedios municipality, subjected to voluntary home confinement during the COVID-19 pandemic. Methods: an observational, descriptive, cross-sectional study was carried out in the “XXX Anniversary” Teaching Community Polyclinic of the municipality Remedios. We worked with the population of 25 teenagers between 12 and 19 years old who made suicide attempts in the period 2019-2021. The empirical methods used were: bibliographic and documentary review, participant observation, focus group, semi-structured interview and questionnaire. Results: The suicide attempt was common in female teenagers aged 17 to 19 years not identified as risk, the lack of motivation due to the study activity and the previous suicide attempts by ingesting psychotropic drugs without serious intention of dying predominated. The most frequent psychological disorders were emotional disorders, stress, depression, irritability, apathy and insomnia. Actions are presented for the prevention of suicide and promote behaviors that contribute to mental health in the context of COVID-19. Conclusion: The prevention of suicidal behavior in teenagers in conditions of social isolation due to COVID-19, must include actions that facilitate the coping with stress, intra-family communication and resilience.

Increased exposure to electromagnetic fields such as radio frequencies used by Wifi technology raise questions and concerns about their impact on health. For answer these questions, several scientific studies have carried out followed by results publication in prestigious scientific revues. Literature conducted on the effects of non-ionizing radiation and Wifi waves is vast and sometimes controversial. Epidemiological studies and the results of in vitro and in vivo experimental studies have showed the biological effects of electromagnetic field in different frequencies range. These effects caused disorders at the molecular and behavioral level. However, these studies were insufficient to confirm the directly related effects to the cause. Therefore, further research must be done to raise the controversy about the safety of wireless waves.

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.

The morphological evolution kinetics and instabilities of alpha helical peptide 3.613, which involves large amount of stored torsional elastic deformation energy (3-40 eV/molecule), is formulated by the variational method based on the connection between the rates of internal entropy production and the changes in the global Gibbs free energy, assuming that one has isobaric irreversible processes under the isothermal conditions. The present mesoscopic nonequilibrium thermodynamic approach relies on the fact that the global Gibbs free energy of helical conformation involves not only the bulk Gibbs free energy of the amino-acid back bone structure but also the interfacial Gibbs free energy of the enclosing cylindrical shell or the cage associated with the side-wall molecular branches, and their interactions with the immediate surroundings. The proposed variational analysis applied directly on the proposed macro-model has furnished a nonlinear integral equation in terms of the normalized and scaled internal and external variables. This allows us to track down the motion of the total pitch height of the alpha polypeptide along the well-defined trajectories in the displacement-time space, dictated not only by the initial configuration of the helix but also through the gradients of the global Gibbs free energy of the strained helical conformation as the main driving force. In the negative manifold, there is a well-defined region below the dynamic instability regime, in which the helical conformation can evolve towards the nonequilibrium stationary states by expanding, or contracting, depending upon whether the interfacial free energy and/or the applied stress system are below or above the well-defined thresholds level dictated by the initial pitch height. The highest life time may be realized along that trajectory, which follows up the threshold level of the interfacial specific Gibbs free energy, which is gs = -315 erg/cm2. In the upper region of the negative manifold, the helical conformations are driven by the very large applied uniaxial tension or the negative pressure induced by the thermal expansion, in the range of p > 1GPa and/or the strong negative interfacial free energies [3-4 pH] or their combinations, they show strong kinematic instabilities, which can cause not only the accelerated unfolding phenomenon but also cause large extensions that end up with the catastrophic decimations by ruptures and fragmentations. In the positive manifold, the aging behavior of the polypeptide follows up a S-shape path having rather speedy aging behavior compared to the negative manifold, which is separated from by a well-defined boundary, which represents the isochoric path having longest relaxation times, which can be achieved with great stability. Finally, one could attempt to estimate the upper limit of the relaxation time of aging for the modern hominin, from samples of exceptional preservations, relying on the present nonequilibrium theory as well as on the very limited knowledge on the post-mortem DNA and the present pitch heights of the modern hominin, which is found to be about 25,840 yrs, with a life expectation of 451,800 yrs. These figures are very close to those calculated for Neanderthals (SH), which are found to be 31,820 yrs and 499,100 yrs, respectively.

The Human three-dimensional (3D) musculoskeletal model is based on motion analysis methods and can be obtained by particular motion capture systems that export 3D data with coordinate 3D (C3D) format. Unique cameras and specific software are essential for analyzing the data. This equipment is quite expensive, and using them is time-consuming. This research intends to use ordinary video cameras and open source systems to get 3D data and create a C3D format due to these problems. By capturing movements with two video cameras, marker coordination is obtainable using Skill-Spector. To create C3D data from 3D coordinates of the body points, MATLAB functions were used. The subject was captured simultaneously with both the Cortex system and two video cameras during each validation test. The mean correlation coefficient of datasets is 0.7. This method can be used as an alternative method for motion analysis due to a more detailed comparison. The C3D data collection, which we presented in this research, is more accessible and cost-efficient than other systems. In this method, only two cameras have been used.

Due to the urgent need for water in all parts of industrial or developing societies, water supply, and transmission facilities are suitable targets for biological risks. Given that even a short interruption in water supply and water supply operations has a great impact on daily activities in the community, the deliberate contamination of urban water resources has irreparable consequences in the field of public health, and the economy of society will follow. Unfortunately, most officials in the public health control departments in our country have received limited training in detecting accidental or intentional contamination of water resources and dealing with the spread of waterborne diseases both naturally and intentionally. For this reason, there is low preparedness in the responsible agencies to deal with waterborne diseases during biological risks. In the first step of this research, a review study has been conducted on water biological risks and operational strategies to deal with them. In the following, it has studied how Escherichia coli (E. coli) bacteria spread in aqueous media. In this regard, the kinetic model of the studied microorganism was analyzed based on the implementation of (Fick Law) in polar coordinates and the combination of (Dirac Distribution) with (Legendre polynomial) distribution. Finally, after studying the factors affecting the microbial pollutant emission coefficient, the effects of all three factors of linear velocity, linear motion time period, and angle of motion on the pollutant emission flux and biofilm diffusion time in the water supply network environment were investigated. Studies have shown that the linear velocity parameter of Escherichia coli with a nonlinear relationship has the greatest effects on the release of microbial contaminants.

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.