Cognitive decline and depressive symptoms: early non-motor presentations of parkinsonism among Egyptian Gaucher patients

neurogenetics - Evidence about the link between glucocerebrosidase (GCase) and parkinsonism is growing. Parkinsonism was described in adult type 1 Gaucher disease (GD); few case reports described...     

Immunological role of CD4<Superscript>+</Superscript>CD28<Superscript>null</Superscript> T lymphocytes,natural killer cells,and interferon-gamma in pediatric patients with sickle cell disease: relation to disease severity and response to therapy

Sickle cell disease (SCD) is associated with alterations in immune phenotypes. CD4⁺CD28^null T lymphocytes have pro-inflammatory functions and are linked to vascular diseases. To assess the percentage of CD4⁺CD28^null T lymphocytes, natural killer cells (NK), and IFN-gamma levels, we compared 40 children and adolescents with SCD with 40 healthy controls and evaluated their relation to disease severity and response to therapy. Patients with SCD steady state were studied, focusing on history of frequent vaso-occlusive crisis, hydroxyurea therapy, and IFN-gamma levels. Analysis of CD4⁺CD28^null T lymphocytes and NK cells was done by flow cytometry. Liver and cardiac iron overload were assessed. CD4⁺CD28^null T lymphocytes, NK cells, and IFN-gamma levels were significantly higher in patients than controls. Patients with history of frequent vaso-occlusive crisis and those with vascular complications had higher percentage of CD4⁺CD28^null T lymphocytes and IFN-gamma while levels were significantly lower among hydroxyurea-treated patients. CD4⁺CD28^null T lymphocytes were positively correlated to transfusional iron input while these cells and IFN-gamma were negatively correlated to cardiac T2* and duration of hydroxyurea therapy. NK cells were correlated to HbS and indirect bilirubin. Increased expression of CD4⁺CD28^null T lymphocytes highlights their role in immune dysfunction and pathophysiology of SCD complications.     

Caspase-, cathepsin-, and PERK-dependent regulation of MDA-7/IL-24-induced cell killing in primary human glioma cells

Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) is a novel cytokine displaying selective apoptosis-inducing activity in transformed cells without harming normal cells. The present studies focused on defining the mechanism(s) by which a GST-MDA-7 fusion protein inhibits cell survival of primary human glioma cells in vitro. GST-MDA-7 killed glioma cells with diverse genetic characteristics that correlated with inactivation of ERK1/2 and activation of JNK1-3. Activation of JNK1-3 was dependent on protein kinase R-like endoplasmic reticulum kinase (PERK), and GST-MDA-7 lethality was suppressed in PERK-/- cells. JNK1-3 signaling activated BAX, whereas inhibition of JNK1-3, deletion of BAX, or expression of dominant-negative caspase-9 suppressed lethality. GST-MDA-7 also promoted a PERK-, JNK-, and cathepsin B-dependent cleavage of BID; loss of BID function promoted survival. GST-MDA-7 suppressed BAD and BIM phosphorylation and heat shock protein 70 (HSP70) expression. GST-MDA-7 caused PERK-dependent vacuolization of LC3-expressing endosomes whose formation was suppressed by incubation with 3-methyladenine, expression of HSP70 or BiP/GRP78, or knockdown of ATG5 or Beclin-1 expression but not by inhibition of the JNK1-3 pathway. Knockdown of ATG5 or Beclin-1 expression or overexpression of HSP70 reduced GST-MDA-7 lethality. Our data show that GST-MDA-7 induces an endoplasmic reticulum stress response that is causal in the activation of multiple proapoptotic pathways, which converge on the mitochondrion and highlight the complexity of signaling pathways altered by mda-7/IL-24 in glioma cells that ultimately culminate in decreased tumor cell survival.     

Flow cytometric assessment of circulating platelet and erythrocytes microparticles in young thalassemia major patients: relation to pulmonary hypertension and aortic wall stiffness

Heart disease is the leading cause of mortality and morbidity in β‐thalassemia major (β‐TM). Aggregability of abnormal red cells and membrane‐derived microparticles (MPs) stemming from activated platelets and erythrocytes are responsible for thrombotic risk. We measured platelet and erythrocyte MPs (PMPs and ErMPs) in 60 young β‐TM patients compared with 40 age‐ and sex‐matched healthy controls and assessed their relation to clinicopathological characteristics and aortic elastic properties. Patients were studied stressing on transfusion history, splenectomy, thrombotic events, chelation therapy, hematological and coagulation profiles, flow cytometric measurement of PMPs (CD41b⁺) and ErMPs (glycophorin A⁺) as well as echocardiographic assessment of aortic elastic properties. Aortic stiffness index and pulmonary artery pressure were significantly higher, whereas aortic strain and distensibility were lower in TM patients than controls (P < 0.001). Both PMPs and ErMPs were significantly elevated in TM patients compared with controls, particularly patients with risk of pulmonary hypertension, history of thrombosis, splenectomy or serum ferritin >2500 μg/L (P < 0.001). Compliant patients on chelation therapy had lower MPs levels than non‐compliant patients (P < 0.001). PMPs and ErMPs were positively correlated to markers of hemolysis, serum ferritin, D‐dimer, vWF Ag, and aortic stiffness, whereas negatively correlated to hemoglobin level and aortic distensibility (P < 0.05). We suggest that increased MPs may be implicated in vascular dysfunction, pulmonary hypertension risk, and aortic wall stiffness observed in thalassemia patients. Their quantification could provide utility for early detection of cardiovascular abnormalities and monitoring the biological efficacy of chelation therapy.     

Post-remission retinal microvascular and choroidal thickness changes in eyes with Behḉet’s disease posterior uveitis: an OCTA longitudinal study

International Ophthalmology - To investigate the retinal microvascular and choroidal thickness changes in eyes with active Beh?et’s disease posterior uveitis and post-remission. A...     

Angiotensin II type 1 receptor gene polymorphism and serum angiotensin-converting enzyme level in Egyptian children with systemic lupus erythematosus

Angiotensin II, the major effective molecule of the renin-angiotensin system, plays a vital role in the development of systemic lupus erythematosus (SLE). To study angiotensin II type 1 receptor (AT1R) gene polymorphism at (A1166C) in Egyptian children with SLE and its correlation with serum ACE level and SLE manifestations. AT1R gene polymorphism (A1166C) was done in 123 children with SLE in comparison to 100 healthy controls using polymerase chain reaction-based restriction fragment length polymorphism method (PCR-RFLP) and the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) to confirm the results of the genotyping. Serum ACE level measurement was done using ELISA technique. The frequencies of C-containing genotypes (AC?+?CC) and C-allele of AT1R (A1166C) were significantly higher in SLE patients compared to controls (p?<?0.0001, OR?=?4.9, 95% CI?=?2.7–8.8; p ? 0.0001, OR?=?3.6, 95% CI?=?2.2–5.9, respectively). Lupus nephritis (LN) patients had significantly higher frequency of (AC?+?CC) genotypes and C-allele compared with controls (p ? 0.0001, OR?=?5.1, 95% CI?=?2.7–9.7; p ? 0.0001, OR?=?3.5, 95% CI?=?2.1–6.02, respectively). Mean serum ACE levels were significantly higher in SLE patients compared to controls (p ? 0.0001). There were no associations between AT1R gene polymorphism and serum ACE level and the clinical manifestations of SLE. The AT1R gene polymorphism can be considered a risk factor for the development of SLE in Egyptian children.     

Transconjunctival versus subciliary approach to the infraorbital margin for open reduction of zygomaticomaxillary complex fractures: a randomized feasibility study

Introduction

Although some studies addressed the differences between subciliary and transconjunctival approaches, no previous prospective comparative study on displaced zygomaticomaxillary complex (ZMC) fracture that repaired by three-point internal fixation using also upper gingivolabial incision and upper eye lid incision. So, the effect of these incisions on the comparison was not investigated.

Purpose

The purpose of this study was to compare transconjunctival and subciliary approaches for open reduction and internal rigid fixation (OR/IF) of ZMC fractures.

Methods

This prospective study was carried out on 40 patients had displaced ZMC fractures repaired by OR/IF. Patients were randomly assigned into two equal groups (20 patients for each); subciliary group subjected to subciliary approach and transconjunctival group subjected to transconjunctival approach for inferior orbital rim repair. In both groups, frontozygomatic and zygomaticomaxillary buttresses were also approached by lateral eye brow and superior gingivolabial incision, respectively. Primary outcome measures include accessibility (need for lateral canthotomy), the exposure duration, postoperative pain, early postoperative edema, and operative complications. Secondary outcome measures include dental occlusion, average intrinsic vertical mouth opening, post subciliary scar assessment, late postoperative complication, and opthalmological assessment concerning ectropion, entropion, scleral show, and eye globe affection (enophthalmos or diplopia).

Results

The mean duration from incisions to fracture exposure was 13.7 ± 2.17 min in subciliary approach and 14.6 ± 2.31 min in transconjunctival approach with nonsignificant difference (p = 0.1284). Lateral canthotomy was required for proper exposure of the fracture and OR/IF using transconjunctival approach while not needed with subciliary approach. Ectropion and scleral show occurred in 10 and 15% respectively in subciliary group and were not encountered in transconjunctival group. Although postoperative periorbital edema was significantly more sever in transconjunctival group within the first postoperative week (p = 0.028), no persistent periorbital edema was reported. Infection, hematoma, and globe complication were not detected in any patient. All authors characterized all scars of the subciliary group as unnoticeable.

Conclusion

Transconjunctival approach mostly needs lateral canthotomy that was not needed with subciliary approach. Transient postoperative edema is more in transconjunctival approach while postoperative ectropion and sclera show was detected only with subciliary approach. So, building up of experience in transconjunctival approach will be beneficial for maxillofacial surgeons and more measures to avoid ectropion are needed with subciliary approach.

     

Hytrosaviridae: a proposal for classification and nomenclature of a new insect virus family

Salivary gland hypertrophy viruses (SGHVs) have been identified from different dipteran species, such as the tsetse fly Glossina pallidipes (GpSGHV), the housefly Musca domestica (MdSGHV) and the narcissus bulbfly Merodon equestris (MeSGHV). These viruses share the following characteristics: (i) they produce non-occluded, enveloped, rod-shaped virions that measure 500–1,000 nm in length and 50–100 nm in diameter; (ii) they possess a large circular double-stranded DNA (dsDNA) genome ranging in size from 120 to 190 kbp and having G + C ratios ranging from 28 to 44%; (iii) they cause overt salivary gland hypertrophy (SGH) symptoms in dipteran adults and partial to complete sterility. The available information on the complete genome sequence of GpSGHV and MdSGHV indicates significant co-linearity between the two viral genomes, whereas no co-linearity was observed with baculoviruses, ascoviruses, entomopoxviruses, iridoviruses and nudiviruses, other large invertebrate DNA viruses. The DNA polymerases encoded by the SGHVs are of the type B and closely related, but they are phylogenetically distant from DNA polymerases encoded by other large dsDNA viruses. The great majority of SGHV ORFs could not be assigned by sequence comparison. Phylogenetic analysis of conserved genes clustered both SGHVs, but distantly from the nudiviruses and baculoviruses. On the basis of the available morphological, (patho)biological, genomic and phylogenetic data, we propose that the two viruses are members of a new virus family named Hytrosaviridae. This proposed family currently comprises two unassigned species, G. pallidipes salivary gland hypertrophy virus and M. domestica salivary gland hypertrophy virus, and a tentative unassigned species, M. equestris salivary gland hypertrophy virus. Here, we present the characteristics and the justification for establishing this new virus family.