Articles

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.

Sleep disorders in human are common and detrimental to general health of all age groups. While the neurobiological mechanisms of sleep disorders are not yet fully understood, recent advances in research on the sleep-wake regulation mechanism, genetic and epigenetic factors, cognitive, emotional and physiological changes related to sleep have shed light on the mechanistic basis of sleep disorders. Over the past two decades, studies in Drosophila have yielded new insights into basic questions regarding sleep function and regulation. More recently, powerful genetic approaches in the fly have been applied toward studying primary human sleep disorders and other disorders associated with dysregulated sleep. In this review, we discussed recent advances in neurobiology of sleep-wave cycle and common sleep disorders. Understanding these mechanisms are important in the diagnosis, treatment and prevention of these common disorders.

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.

Herpes simplex virus (HSV)-1 encephalitis is the most common infectious cause of sporadic encephalitis. Despite treatment with acyclovir, HSV encephalitis is still associated with severe morbidity characterized by persistent neurological deficits. HSV encephalitis usually follows a monophasic course, however, some patients might develop relapsing symptoms caused by the formation of auto-antibodies directed against the N-methyl-D-aspartate receptor (NMDAR). Here we present an 82-year-old male patient with HSV encephalitis who developed shortly after his hospital discharge a Post-HSV NMDAR encephalitis, characterized by recurrent epileptic seizures and deterioration of his residual aphasia. First-line immunotherapy with intravenous immunoglobulins (IgIV) was administered and the patient returned almost to his baseline residual deficits of HSV encephalitis. Subsequently, he presented with recurrent relapses of NMDAR encephalitis. Since periodic treatment with IgIV has been started the patient is seizure-free and his neuropsychiatric condition is stable. In conclusion, the recognition of Post-HSV NMDAR encephalitis is very important because neurological manifestations can markedly improve with immunotherapy. Interestingly, in some patients cerebral HSV infection seems to trigger a chronic inflammatory disorder with persistent autoimmune activation which requires chronic treatment.

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

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 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.

Starting from observation of pathogenesis of KURU disease we try to investigate the immunologic role played by central nervous systems. A deeply knowledge in the transmission model of this pathology can be an imaging/diagnostic tool to Verify the progression of this prion molecule from gastro intestinal systems to the brain. (After cannibalistic behavior). The prions can be considered a sort of trace ant in KURU to monitoring this process and immune- brain relationship. Interesting information can be obtained useful to produce new pharmacological strategies in some other degenerative brain disease involving innate immune system activation.

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. 

Spinal muscular atrophy (SMA) is a genetic and gravely disease, portrayed by motor neuron (MN) death, thereby leading to progressive and accelerating muscle fragility, respiratory collapse, and, in the most severe cases, it even pave the way to death. At the neuromuscular junction (NMJ), abnormally have been reported in SMA, including neurofilament (NF) aggregation at presynaptic terminals, immature and smaller endplates, lowered transmitter release, and, eventually, muscle denervation. In this review the role of Agrin in SMA is studied. This review highlights the antagonizing role of Agrin in SMA