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This opinion paper provides a summary of the current reconstructive surgical techniques for the scapholunate interosseous ligament (SLIL) and critically highlights their benefits and shortcomings. Due to limited success with direct repair of the ligament, current practice focuses on achieving biomechanical stabilization and does not allow for tissue regeneration to occur. In addition, the biomechanical behaviour of the ligament is still poorly described and understood, resulting in a very large variation in published mechanical parameters. Therefore, a thorough understanding of the biomechanics of the joint, via both experimental testing and numerical modelling is necessary for enabling the design of the next generation of implants in order to address mechanical stabilisation and regeneration.

Physician-patient communication is the most basic element and vital skill of physicians in the diagnosis, treatment, and establishing diagnostic protocols. As the risks of contagion and viral infection are higher in physicians and health workers, front line soldiers inpatient care units, so they should establish strict protective measures. However, patients value greatly face to face and close relationships with their doctors, including facial interviews and physical examinations. So social and physical distancing between physician and their patients can be remarked as a bigger toll than the risk of COVID-19 contagious.

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.

Background: Corona virus disease is a highly infectious disease caused by the newly innovated corona virus. An emerging respiratory disease was abbreviated as COVID-19, after it has been first reported in December 2019 in Wuhan city of China. Ethiopia Ministry of health initiated multidisciplinary approach to tackle COVID-19 of which awareness creation is the main. The aim of this study is to assess knowledge, practice and associated factors towards prevention of novel corona virus among clients in Debre Tabor general hospital, Northwest Ethiopia, 2020. Methods: Institution based cross sectional study design was conducted in Debre Tabor General hospital from May 15 to May 30, 2020. A structured questionnaire was used for data collection. The data were entered into epi data version 4.4 and exported to SPSS window version 25 for analysis. Binary and multivariable logistic regression was fitted. Odds Ratios with 95% Confidence interval and p - value ≤ 0.05 were considered to assert significance. Result: A total of 345 clients were analyzed and the response rate was 96.4%. The mean age was 32.95 with S.D ± 13.18 years. Majority of the respondents were male (75.7%). Among the study participants 54.2% with (95% CI: [49.0, 59.2%]) and 49.0% with (95% CI: [43.5, 53.4%]) have good knowledge and god practice on COVID-19 preventions respectively. Sex AOR: 4.33 (2.06, 9.09), family size AOR: 2.49 (1.01, 6.15 and heard from social media AOR: 2.78 (1.21, 6.39) were significantly associated with knowledge of respondents. Knowledge AOR: 3.11 (1.59, 6.10) was significantly associated with practice of clients. Residency and those heard from TV were significant variables for both. Conclusion and recommendation: In this study the overall knowledge and preventive practices of the respondents were found to be low. Sex, family size, residency and sources of information were associated factors for knowledge. In addition to this knowledge was significant factor for practice. Health education programs aimed at mobilizing and improving COVID-19 related knowledge and practice intend to be strengthened.

Purpose: Sacroiliac joints (SIJ) inflammation and pain is particularly common in patients with Spondyloarthritis. Intraarticular SIJs injections represent a valuable therapeutic option in this condition. In the rheumatological outpatient clinics this procedure is usually done by landmark guidance (LG) or ultrasound guidance (USG). Thus we aimed to compare the short term efficacy of USG vs. LG SIJ injections using five outcome measures: 1. Pain; 2. SIJ status (number of positive provocation tests per symptomatic SIJ on physical examination); 3. Disability; 4. Quality of the night sleep; 5. Patients’ satisfaction. Methods: We enrolled 44 consecutive spondyloarthritis patients with pain in the SIJs that did not respond to NSAIDS and that were otherwise on a stable medical treatment. All patients also had ≥ 3 positive pain provocation tests per SIJ on physical examination. Patients were randomly allocated to receive a single SIJ injection with 7 mg Betamethasone (1 ml) and 1% Lidocaine (1.5 ml) either under USG or with LG. Results: Both groups showed significant improvement in all outcome parameters. However, the USG approach performed significantly better than the LG ones in all parameters. In addition, there was a significant correlation between the improvement in all patient reported outcomes (VAS, RMDQ, JSEQ) and the reduction in the number of positive SIJ pain provocation tests per symptomatic joint. Conclusion: Both USG and LG SIJ injections proved to be an efficient treatment for SIJ pain in SpA patients. However, USG of the intervention led to statistically better results in the present study.

In 1992, a patient, born July 10, 1910, aged 82, with major osteoporosis [1-3], was operated on her left hip. The surgeon performs a biomaterial transplant using natural coral [4]. Follow-up is two years. She died in 1994 of acute respiratory failure. Three bone graft osteodensitometry [5] shows a regular increase in mineralization; however, on the opposite side, bone mineralization decreases. The anatomical part is examined using x-rays, scanners, photographs, histology [6]. The article reports the findings of this study. It is noted a partial resorption of the biomaterial essentially at the periphery of the graft as well as the different local connections of the preexisting bone with the newly formed bone from the grafted area. The severity of fractures of the femoral neck is no longer to be demonstrated [7]. Multiple therapeutic trials have demonstrated their effectiveness [8,9]. Twenty two patients were transplanted. There was no failure. All died without fracturing their grafted hips. 

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.

Background: In India, the genetic disease is a disregarded service element in the community health- protection system. This study aims to gauge the accessibility of services for treating genetic disorders and also to evaluate the practices on deterrence and management services in the district health system. Methods: A cross-sectional survey of selected health amenities from 454 medical officers (MO’s), 94 accredited social health activist (ASHAs) workers, 86 multipurpose health assistant-female (MPHA-F), 34 multipurpose health assistant-male (MPHA-M), 14 multipurpose health supervisors-female (MPHS-F), 10 multipurpose health supervisors-male (MPHS-M), 6 multipurpose health extension officer/ community health officer (MPHEO/CHO), 10 public health nurse (PHN), 45 lab technicians (LT’s) working in the government health sector and 254 in the private health sector, 409 nursing staff working in the government health sector and 995 in the private health sector, 15 primary health centers (PHC’s), 4 community health centers (CHC’s), 1 district government hospital (DGH), 3 referral hospitals (RH’s). From the side of private health institutions 25 corporate hospitals (CH’s), 3 medical colleges (MC’s), and 25 diagnostic laboratories (DL’s) were conducted. Results: The findings show that adequate staff was in place at more than 70% of health centers, but none of the staff have obtained any operative training on genetic disease management. The largest part of the DH’s had rudimentary infrastructural and diagnostic facilities. However, the greater part of the CHC’s and PHC’s had inadequate diagnostic facilities related to genetic disease management. Biochemical, molecular, and cytogenetic services were not available at PHC’s and CHC’s. DH’s, RH’s, and all selected medical colleges were found to have offered the basic Biochemical genetics units during the survey. In 24% of CH’s, the basic biochemical units are available and 32% (8 out of 25) of DL’s have the advanced biochemical genetics units by study. Molecular genetics units were found to be available in 28% (7 out of 25) of DL’s during the study. About 6 (24%) diagnostic centers of cytogenetic laboratories were located in the Visakhapatnam district under the private sector. Conclusion: The district health care infrastructure in India has a shortage of basic services to be provided for the genetic disorder. With some policy resolutions and facility strengthening, it is possible to provide advanced services for a genetic disorder in the district health system.

It is with interest and pleasure that I see notices of meetings and symposia, and articles, devoted to the theme Noncommunicable disease. I still live in the economic and geographical ‘South’ but the concern arises from the continued use of terminology that dulls the senses to the urgency of the problems involved. Since I wrote the letter (reference at end) the epidemic of the so called ‘non’ communicable disease has increased greatly; obesity, cardiovascular disease, diabetes, cancers, accidental trauma, road deaths etc, and there is still less research and action about breaking the methods of spread than there is about the illnesses.

In natural convection, the fluid motion occurs by natural means such as buoyancy. Heat transfer by natural convection happens in many physical problems and engineering applications such as geothermal systems, heat exchangers, petroleum reservoirs and nuclear waste repositories. These problems and phenomena are modeled by ordinary or partial differential equations. In most cases, experimental solutions cannot be applied to these problems, so these equations should be solved using special techniques. In this paper, natural convection of a non-Newtonian fluid flow between two vertical flat plates is investigated analytically and numerically. Collocation Method (CM) and fourth-order Runge -Kutta numerical method (NUM) are used to solve the present problem. These methods are powerful and convenient algorithms in finding the solutions for the equations. While these are capable of reducing the size of calculations. In order to compare with exact solution, velocity and temperature profiles are shown graphically. The obtained results are valid with significant accuracy.

State Department had evacuated a number of Americans from the U.S. consulate in Guangzhou, China after they experienced unexplained health issues. A group of U.S. diplomats stationed in China have been brought back to the states after being inflicted by a mystery illness that reportedly resembles the brain injuries previously suffered by staff in Cuba. At the end of the December 2018 we have found a medicine fully treating the damages caused the Frey Effect of Microwave and other types of Sonic Weapons in Human’s internal, endogenous organs. I am proposing to use Naphasoline nitrate, (former) nasal decongestant, to treat Carcinogenesis of the Human’s internal, endogenous organs caused by Sonic Weapons through the release and cleaning of the Lymphatic ways in patients with colorectal, colon, pancreatic, breast, etc., cancer. I have proved this healing effect of the Naphazoline nitrate on myself during treatment in last months of the year 2018.

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 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 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 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.

Advances in metagenomics have facilitated population studies of associations between microbial compositions and host properties, but strategies to minimize biases in these population analyses are needed. However, the effects of storage conditions, including freezing and preservation buffer, on microbial populations in fecal samples have not been studied sufficiently. In this study, we investigated metagenomic differences between fecal samples stored in different conditions. We collected 46 fecal samples from patients with lung cancer. DNA quality and microbial composition within different storage Methods were compared throughout 16S rRNA sequencing and post analysis. DNA quality and sequencing results for two storage conditions (freezing and preservation in buffer) did not differ significantly, whereas microbial information was better preserved in buffer than by freezing. In a metagenomic analysis, we observed that the microbial compositional distance was small within the same storage condition. Taxonomic annotation revealed that many microbes differed in abundance between frozen and buffer-preserved feces. In particular, the abundances of Firmicutes and Bacteroidetes varied depending on storage conditions. Microbes belonging to these phyla differed, resulting in biases in population metagenomic analysis. We suggest that a unified storage Methods is requisite for accurate population metagenomic studies.

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.

Background: This study aims to retrospectively investigate the comorbidity of ADHD multiple symptoms (behavioral) with alcohol addiction in a sample of adult alcohol-dependent patients and to test their current attentional skills (behavioral and cognitive). Methods: Thirty-two adult alcohol-dependent patients were examined for ADHD using a semi-structured interview and the Mini Mental State Examination to evaluate attention and inhibition functions. Brown ADD Scales were used to specifically examine ADHD syndrome. Patients were compared with thirty matched control participants selected from healthy population in few measures of attentional control and working memory. Results: 50% of patients showed evidence of primary ADHD symptoms: specifically, 28.12% showed criteria for ADHD highly probable, 12.50% for ADHD probable but not certain and 9.38% for ADHD possible but not likely. Patients also revealed several deficits in the selective visual attention, interference control and verbal working memory compared to the control group. Conclusions: These results revealed that adult alcohol-dependent patients had retrospectively high comorbidity with ADHD and significant current deficits of the executive functions. These findings suggest the importance of early diagnosis and treatment of ADHD in order to prevent the development of alcohol dependence.

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.