Jan Jacques Michiels*, Yonggoo Kim, Myungshin Kim, Francisca Valster, Vincent Potters, Zwi Berneman, Alain Gadisseur, Wilfried Schroyens and Hendrik De Raeve
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.
Ailment repairing regiments has turn out to be arduous, despite a plenty of understanding and knowledge acquired in the past relating to the molecular underpinnings of Alzheimer’s disease (AD. Umpteen clinical experiments targeting the fabrication and accumulation have been turned fruitless to fit potency standards. The tests aiming beta-amyloid hypothesis also turned futile making it exigent for further handling tactics. The new emanation of a comparably candid, economical, and punctilious system known as gene editing have showed light in path of cure for AD by CRISPR/Cas9 gene editing. Being a straight approach this procedure has already shown assurance in other neurological disorders too such as Huntington’s disease. This review standpoint the immanent service of CRISPR/Cas9 as a remedial option for AD by aiming on specific genes inclusive of those that induce early-onset AD, as well as those that are substantial risk components for late-onset AD such as the apolipoprotein E4 (APOE4) gene.
Yvonne A Efebera*, Amy S Ruppert, Apollinaire Ngankeu, Sabrina Garman, Prasanthi Kumchala, Alan Howard, Steven M Devine, Parvathi Ranganathan and Ramiro Garzon
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.
In this work is analyzed scientific literature involved in human evolution to be used as an archeological Pathway to link different sciences in an overall new discipline.
A rational classification of single evidence make possible to better understand under new light some Physiological process.
The archeological instrument to be applied in other field like biology or other sciences.
Jan Jacques Michiels*, King H Lam, Fibo Ten Kate, Dong-Wook Kim, Myungshin Kim, Vasily Shuvaev, Francisca Valster, Vincent Potters, Wilfried Schroyens, Mihaela Andreescu, Adrian Trifa, Achille Pich and Hendrik De Raeve
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).
Mauro Luisetto*, Naseer Almukhtar, Ahmed Yesvi Rafa, Behzad Nili Ahmadabadi, Ghulam Rasool Mashori, Farhan Ahmad Khan, Ram Kumar Sahu, Gamal Abdul Hamid and Khaled Edbey
Aim of this work is to verify the effect of some neurotoxins, physical factors and geography in presentation of some Relevant Neurological disorder like some form of ASL, PD, AD.
The geographic diffusion of the ASL/PD in west pacific (GUAM foci), and mutation of SOD 1 and other mutations are interesting facts to verify the recent literature about the neurotoxic process.
Related to the references presented a global conclusion about the pathogenetic progression of some neurological disease will be produced as instrument for new hypothesis and for the introduction of new innovative therapeutic strategies.
Aim:The work was to perform a comparative study of the neuroprotective and nootropic activities of two pharmaceutical substances, the HLDF-6 peptide and its amide form (HLDF-6-NH2).
Materials and Methods: We used in the study healthy adult male Wistar rats aged 180–200 days weighing 280–300 g. We modelled ischemic stroke in rats by chronical occlusion of carotid arteries. Solutions of the HLDF-6-NH2 and HLDF-6 peptides were administered intranasally. Cognitive functions we assessed with Novel object recognition test and Morris maze.
Results: The amide form of HLDF-6 peptide is more efficient: the neuroprotective activity of HLDF-6-NH2, evaluated by improvement of cognitive functions in animals, surpassed that of the native HLDF-6 peptide. A dose of 250 µg/kg of HLDF-6-NH2 peptide resulted in practically complete restoration of the disturbed functions. In the model of ischemic stroke, the amide form of the peptide significantly excelled the reference substance mexidol both in the effective dose and biological activity.
Conclusion: The results of study of the agent allow hoping for its success in further clinical investigation. In view of high demand for the agent and in case of successful clinical trials, it will surely become widely used in clinical practice in treatment of IS.
Aim of this work is to produce a general theory related an new depurative strategy to be devalued for reduce or delay some spinal cord and brain degenerative and inflammatory chronic disease or acute traumatic condition. It is used and informatics approach in order to set correct the problem and the process. Scope of this project is to submit to the researcher a new therapeutic strategy (under a depurative- toxicological-pharmacological) in this complex kind of disease. A Turing machine theory say us a method to TRASLATE the need of a strategy in a practical hypotesys of work. A global conceptual map can help in this field.
Background: Drosophila models of amyotrophic lateral sclerosis (ALS) have been widely used in understanding molecular mechanisms of ALS pathogenesis as well as discovering potential targets for therapeutic drugs. Mutations in the copper/zinc superoxide dismutase (SOD1) cause ALS by gain of toxic functions and induce toxicity in fly motor neurons.
Results: In this study, we have determined that human carbonic anhydrase I (CA1) can alleviate mutant SOD1-induced motor neuron toxicity in the transgenic fly model of ALS. Interestingly, we found that motor neuron expression of CA1 could independently induce locomotion defect as well as decreasing the survival rate. In addition, CA1-induced toxicity in motor neurons is anhydrase activity-dependent. Mechanistically, we identified that both SOD1- and CA1-induced toxicity involve the activation of eIF2α in the ER stress response pathway. Downstream activation of the JNK pathway has also been implicated in the induced toxicity.
Conclusion: Our results have confirmed that SOD1-induced toxicity in fly motor neuron also involves endoplasmic reticulum (ER) stress pathway. More importantly, we have discovered a new cellular role that CA1 plays by antagonizing mutant SOD1-induced toxicity in motor neurons involving the ER stress pathway. Such information can be potentially useful for further understanding disease mechanisms and developing therapeutic targets for ALS.
The biological changes caused by oxidative stress (OS) are known to be involved in the etiology of neurodegenerative disorders, including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. The brain is particularly vulnerable to OS due to its high lipid content and extensive consumption of oxygen. OS processes, particularly the excessive production of reactive oxygen species (ROS), play a critical role in how neurodegenerative disorders develop. This is evidenced by in vivo studies investigating various biomolecules related to OS, such as products of lipid and DNA oxidation. Accordingly, ROS can also cause oxidative-related damage in neurodegenerative disorders, including dopamine auto-oxidation, mitochondrial dysfunction, glial cell activation, α-synuclein aggregation, excessive free iron, and changes in calcium signaling. Furthermore, excessive levels of cellular oxidants reduce antioxidant defenses, which in turn propagate the cycle of OS. As such, it is increasingly important to determine the linkage between a high intake of antioxidants through dietary interventions and a lower risk of developing neurodegenerative diseases. Indeed, in addition to modulating the immune system, optimal nutritional status is capable of changing various processes of neuroinflammation known to be involved in the pathogenesis of neurodegeneration. Accordingly, a better understanding of the role ROS plays in the etiology of neurodegeneration is needed, along with the identification of dietary interventions that may lead to improved therapeutic strategies for both the treatment and prevention of neurodegenerative disorders. Therefore, this review presents a comprehensive summary of the role of ROS in the pathogenesis of neurodegenerative disorders. In addition, nutrients believed to be useful for mitigating and counteracting ROS are discussed.
Background: Gliomas represent the most frequent primary tumors of central nervous system (CNS), contributing to more than half of the incidence of brain tumors. Cancer stem cell markers (CSC) identify a group of patients at high risk for progression. Nestin is an intermediate filament (IF) protein was first described as a neural stem cell/progenitor cell marker. Nestin-positive neuroepithelial stem cells are detected in the subventricular zone of the human adult brain and they remain mitotically active throughout adulthood. The expression of Nestin in gliomas has been suggested to be related to dedifferentiation, improved cell motility, invasive potential and increased malignancy. This study aims to investigate Nestin immunohistochemical expression in different types of glioma and its correlation with different clinicopathological parameters.
Materials and Methods: Nestin immunostaining was studied in 60 specimens of glioma using avidin-biotin peroxidase method.
Results: Nestin was strongly expressed in 11/60 (18.33%), moderately expressed in 29/60 (48.33%) and weekly expressed in 15/60 (25%) of studied gliomas. A significant positive correlation was found between Nestin expression and histologic type (p < 0.001) and increasing grade of gliomas (p < 0.001).
Conclusion: Increased Nestin expression is correlated with tumor progression, increasing grade and poor prognostic parameter of glioma. Nestin is a useful marker for detection of CSC in high-grade glioma which is responsible for resistance to chemo-radiotherapy and may serve as a predictor for patient outcomes.
Background: The acaricidal action of Ozonized sunflower oil (OSO) has demonstrated in different clinical cases of different animal species, such as psoroptic rabbits and pig sarcoptic scabies and recently in demodesic goat.
Objectives: This study evaluated the effectiveness of OSO as treatment for generalized demodicosis mange in dogs.
Animals: Twenty dogs of different breeds, between six months and one year of age with generalized demodicosic mange that attended to Veterinary Clinic “José Luis Callejas” Havana, Cuba, during the year 2015, were included in the study.
Methods: The demodicosis diagnostic was based on its clinical history, the mite’s presence by deep scraping and clinical signs. All cases had a history of receiving before conventional treatments without solution. OSO treatment was topically applied daily, every 12 hours, after shaving all affected areas. Monitoring of clinical signs, mite counting on scaling, pruritus and capillary regrowth (7, 14, 28, 56 and 84 days) were performed.
Results: The results showed a significant reduction of mite counts, clinical signs and pruritus since the 7th day of application. The animals recovered the fur on more than 90% of the body surface. All the animals (100%) recovered from generalized demodesic mange in 84 days of treatment.
Conclusion: The effectiveness and safety of OSO as election treatment of generalized demodicosis mange in dogs was demonstrated.
Observing the epidemiology of some neurodegenerative disease is interesting to verify some similarity and also related advanced or non-advanced countries and related diet habits. There are relationship between this conditions and diet habits? Some neurological condition related neuro-degeneration can be related to a complex dynamic system like the glymphatic system and the brain vascular clearance. Failure in this system seem related to aggravates of some condition like PD or vascular or diabetic dementia. (Animal model). But what happen if this dynamic system is saturated? A deep investigation related the specific role in CNS make possible to search new innovative strategies. The social economic cost for the neurodegenerative disease is the right tool to new research.
Sleep is considered as a complex process in human beings and is least understood mechanism. Role of sleep in synaptic plasticity remains a debatable topic till date. Sleep is influenced by genetic background of the individual. EEG done in human sleep showed strong influence of genetic factors. A handful of familial analyses involving specific gene loci and twin studies has been done in this regard. In this review article focused discussion on genetic contribution to sleep phenotypes, twin and familial linkage studies and effect of genetic variation on sleep will be covered
Introduction: Neurocysticercosis (NCC) is a common helminthic infection of the nervous system that occurs when humans become intermediate hosts in the life cycle of the pig tapeworm (Taenia solium) after ingesting its eggs. The objective of this study was to analyze socio-demographic, clinical and paraclinical features of patients with NCC in Lubumbashi, DRC.
Methods: This is a cross-sectional study conducted over a period of 2 years within the Neuropsychiatric Center of Lubumbashi. Socio-demographic, clinical, paraclinical and therapeutic features were studied.
Results: A total of 18 patients with NCC were listed. Epilepsy was found in 72.2% (13/18) of the cases. The mean age of the patients was 30.2 ± 13.5 years; males accounted for 61.2% of the cases. 84.6% were consumers of pork. Generalized epilepsy was found in 84.6% of the cases and hypereosinophilia in 38% of the cases. On the neuroimaging, the parietal location of lesions represented 92.3%; calcifications were the type of lesion in 53.8% of the cases and 69.2% of the cases presented lesions in the 4th evolutionary stage. Electroencephalogram was normal in 84.4% of the cases. Phenobarbital was the antiepileptic drug used in 69.3%; albendazole and prednisone were used in 53.9% of the cases.
Conclusion: This study shows that NCC is one of the causes of epilepsy in Lubumbashi. Generalized tonic-clonic seizures are the most common form of presentation and calcified parenchymal lesions are the most common radiological feature of NCC. So, any patient with acute onset of afebrile seizure should be screened for NCC provided other common causes been ruled out.
Catheter-associated urinary tract infection (CAUTI) is among the most common nosocomial infections especially in acute care settings. Its economic and unanticipated health implications make it burdensome for the healthcare providers and patients. The paper examined the perceived causes and mode of preventing urinary tract infections in patients with spinal cord injury. Qualitative research approach was utilized; the study site was a Tertiary Hospital in Nigeria. Eight (8) in-depth interviews (IDI) were conducted with healthcare providers managing patients with spinal cord injured in the hospital. The major risk factors causing urinary tract infection identified include financial problems, organization of care, human error, hospital environment and patient-related factors. To prevent urinary tract infections among patients in the hospital, a number of suggestions were made by the participants such as training of caregivers and educating patients and relations. The authors concluded that the incidence of CAUTI could be reduced in the hospital if the opinions of stakeholders are fairly considered.
A 61-year-old Brazilian black woman consulted with a nephrologist due to proteinuria identified on a routine urine test. She has a personal history of thymoma resection five years ago, followed by multiple episodes of pulmonary infections including mycobacteriosis, recurrent mucocutaneous candidiasis, and paraneoplastic pemphigus. Physical examination showed no edema or hypertension and laboratory tests identified proteinuria of 2.43 g/day without hematuria, serum creatinine of 0.69 mg/dl, urea 34 mg/dl, serum albumin of 2.4 g/dl, hemoglobin 10.9 g/dl, platelets 292,000/mm3, leukocytes 4950/mm3, lymphocytes 594/mm3 and neutrophils 3910/mm3. The hemolysis tests were negative and serum iron was low. Analysis of glicemia and serum lipids levels were normal as well as serum complement and imunoglobulins, except for an IgM level of 283 mg/dl (normal values 40 to 230 mg/dl) and undetectable IgE. Serologies for Syphilis, HIV, hepatitis B, C and antibodies for autoimmune diseases were negative.
We investigated the existence of microalbuminuria in children with corticosteroid-sensitive idiopathic nephrotic syndrome in complete remission. In the study of a series of 18 cases, we noted a clearly different evolution depending on the existence or absence of pathological micro albuminuria.
Microalbuminuria appears to be a prognostic discrimination parameter in idiopathic nephrotic syndrome.
Introduction: Anderson-Hynes pyeloplasty remains the gold standard in the treatment of ureteropelvic junction obstruction. The diagnostic criteria for defining the failure of pyeloplasty are not well-defined or even arbitrary. Likewise, the ideal treatment of persistent hydronephrosis after pyeloplasty is not well established. We tested an innovative endourological procedure, which simultaneously allows a diagnostic definition of failure and treatment when necessary.
Materials and methods: The endourological procedure was applied prospectively to 13 cases from 2006 to 2015. The mean hydronephrosis was 3 cm and all the patients showed an obstructive pattern at scintigraphie. Of these, only 2 patients had symptoms. The procedure consisted in the endoscopic calibration of the pyeloureteral junction. In case of confirmed persistent stenosis, the procedure continued with the high pressure dilation of the junction. The calibration/dilation procedure was carried out with a balloon catheter, previously used for high pressure dilation in the obstructive megaureter. In all patients, a ureteral stent was positioned for 6 - 8 weeks.
The patients were then followed up using ultrasound and renoscintigraphie.
Results: According to the endoscopic balloon procedure, anastomosic stenosis was confirmed in 3 cases, treated with high pressure dilation during the same procedure. In 10 cases no stenosis was found and we followed-up these patients with periodic ultrasound and scintigraphie.
Conclusion: The calibration/dilation of the pyeloureteral junction represents in our opinion a useful diagnostic and therapeutic tool that allows to limit the repetition of open surgery only to symptomatic cases and those non-responders to endoscopic treatment.
We described a case of specific (tuberculous) encephalitis in a patient after kidney transplantation. Immunosuppressive therapy, continuously required in post-tranplant period, may cause various complications, such as infections. Specific meningoencephalitis is an infection that is rarely diagnosed and more common in immunocompromised patients.
Case report: A 30-year-old man had kidney transplantation (kidney donor was his father). He previously was two years on chronic hemodialysis treatment because of end-stagerenal disease based on diabetic nephropathy. He has diabetes type 1. The early post-transplant period duly passed with satisfactory clinical and laboratory parameters of renal function. Two months after transplantation, he presented with febrile condition, signs of septicemia and dehydration with significant neurological deficit and expressed meningeal signs. In cerebrospinal fluid we found lymphocytosis, elevated proteins and positive micobacterium tuberculosis antibodies (Hexagon method) and we suspected to specific etiology of meningitis. Performed computed tomography (CT) scan of the brain with contrast confirmed the expected finding.
Due to the poor prognosis of infections of the central nervous system (CNS) in immunocompromised patients, only prompt diagnosis can improve survival in this group of patients. The therapeutic protocol after kidney transplantation include the prophylactic use of antituberculous drug (Isoniazid 300 mg) during the 9 months.
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Department of Neurosurgery, Queen Elizabeth Hospital, Hong Kong
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University of Port Harcourt Teaching Hospital, Nigeria
Dr. Elizabeth A Awoyesuku
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