EMC10 homozygous variant identified in a family with global developmental delay,mild intellectual disability,and speech delay

In recent years, several genes have been implicated in the variable disease presentation of global developmental delay (GDD) and intellectual disability (ID). The endoplasmic reticulum membrane protein complex (EMC) family is known to be involved in GDD and ID. Homozygous variants of EMC1 are associated with GDD, scoliosis, and cerebellar atrophy, indicating the relevance of this pathway for neurogenetic disorders. EMC10 is a bone marrow-derived angiogenic growth factor that plays an important role in infarct vascularization and promoting tissue repair. However, this gene has not been previously associated with human disease. Herein, we describe a Saudi family with two individuals segregating a recessive neurodevelopmental disorder. Both of the affected individuals showed mild ID, speech delay, and GDD. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify candidate genes. Further, to elucidate the functional effects of the variant, quantitative real-time PCR (RT-qPCR)-based expression analysis was performed. WES revealed a homozygous splice acceptor site variant (c.679-1G>A) in EMC10 (chromosome 19q13.33) that segregated perfectly within the family. RT-qPCR showed a substantial decrease in the relative EMC10 gene expression in the patients, indicating the pathogenicity of the identified variant. For the first time in the literature, the EMC10 gene variant was associated with mild ID, speech delay, and GDD. Thus, this gene plays a key role in developmental milestones, with the potential to cause neurodevelopmental disorders in humans.     

Efficient Diagnosis and Treatment Follow-Up of Human Brucellosis by a Novel Quantitative TaqMan Real-Time PCR Assay: a Human Clinical Survey

Rapid and effective diagnosis of brucellosis is a challenge for clinicians. Even when diagnosis is on time and therapy is initiated, meticulous follow-up appointments are crucial for ensuring the efficacy of the treatment. Due to shortcomings of serological methods, molecular diagnosis, especially real-time PCR, is becoming a main approach in laboratory diagnostics. Thus, the development of efficient procedures and standardization of the PCR tests will have a great impact on the precise detection and quantification of bacterial DNA loads, which is valuable for the medical management of brucellosis patients. We developed a new TaqMan real-time PCR directed to bcsp31, a shared gene of the brucellae. The bcsp31 gene fragment was cloned into pJET1.2. Recombinant pJET1.2-bcsp31 was linearized by HindIII digestion, and the product was used for the preparation of a standard curve. A panel of Brucella spp. and non-Brucella pathogens was tested. No bacterial genomes other than those of the brucellae were detected. According to the results, specificity of the method was 100%. In a clinical assessment, the positive-control group comprised 37 patients with microbiologically confirmed brucellosis, and 25 healthy individuals served as the negative-control group. By the end of the treatment period, there was a significant decrease in the DNA load of the 37 brucellosis patients, which persisted for the 4 weeks of monitoring after treatment, suggesting that our proposed method is an efficient monitoring tool. Serum samples prior to any treatment were collected from the 25 serologically suspicious patients and assessed by our method; 72% of these patients tested positive for brucellosis.     

The effect of regular exercise on antioxidant enzyme activities and lipid peroxidation levels in both hippocampi after occluding one carotid in rat

Regular exercise has beneficial effects on cerebrovascular diseases; however, its biochemical mechanisms are not fully known. The purpose of this study was to determine antioxidant enzyme activities and lipid peroxidation of both hippocampi after applying exercise followed by occluding one common carotid. Wistar rats were divided into four groups of control, exercise, hypoperfusion and exercise–hypoperfusion (exe-hypo). In the exercise and exe-hypo groups, the rats were forced to run on a treadmill for 1 h a day for 2 months. The right common carotid of the animals in the (exe-hypo) group was occluded after the cessation of exercise. Surgery without occlusion of the carotid was applied on the control (without exercise) and exercise groups. All animals were sacrificed 1 and 24 h after surgery. The levels of malondialdehyde (MDA) and antioxidant enzyme activities in the hippocampi were measured. A significant interaction was observed between the exercise and hypoperfusion in both hippocampi (p < 0.05). In comparison with the control group, there was significant elevation of catalase activity in the right and left hippocampus of the hypo group at 24 h (p < 0.0001). Regarding the differences between the hemispheres, there was a significant increase in MDA and decrease in catalase activity in the left hippocampus in hypoperfusion group, but the exercise in the exe-hypo group succeeded in abolishing these alterations which were caused by hypoperfusion, This study shows that exercise pre-conditioning prevents some alterations in brain oxidant–antioxidant status which are induced by cerebral hypoperfusion. Further studies are needed in order to clarify the mechanism of exercise.     

Application of [68Ga]PSMA PET/CT in Diagnosis and Management of Prostate Cancer Patients

Molecular Imaging and Biology - The early and accurate diagnosis of locoregional recurrence or metastasis in prostate cancer (PC) has a significant impact on treatment options. Prostatic-specific...     

Recent advances in metal-free heteroatom-doped carbon heterogonous catalysts

The development of cost-effective, efficient, and novel catalytic systems is always an important topic for heterogeneous catalysis from academia and industrial points of view. Heteroatom-doped carbon materials have gained more and more attention as effective heterogeneous catalysts to replace metal-based catalysts, because of their excellent physicochemical properties, outstanding structure characteristics, environmental compatibility, low cost, inexhaustible resources, and low energy consumption. Doping of heteroatoms can tailor the properties of carbons for different utilizations of interest. In comparison to pure carbon catalysts, these catalysts demonstrate superior catalytic activity in many organic reactions. This review highlights the most recent progress in synthetic strategies to fabricate metal-free heteroatom-doped carbon catalysts including single and multiple heteroatom-doped carbons and the catalytic applications of these fascinating materials in various organic transformations such as oxidation, hydrogenation, hydrochlorination, dehydrogenation, etc.

Recent advances in metal-free heteroatom-doped carbon heterogeneous catalysts including the preparation methods and their catalytic applications in various organic reactions have been reported.     

Application of Pauson–Khand reaction in the total synthesis of terpenes

The Pauson–Khand reaction (PKR) is a formal [2 + 2 + 1] cycloaddition involving an alkyne, an alkene and carbon monoxide mediated by a hexacarbonyldicobaltalkyne complex to yield cyclopentenones in a single step. This versatile reaction has become a method of choice for the synthesis of cyclopentenone and its derivatives since its discovery in the early seventies. The aim of this review is to point out the applications of PKR in the total synthesis of terpenes.

The Pauson–Khand reaction (PKR) is a formal [2 + 2 + 1] cycloaddition involving an alkyne, an alkene and carbon monoxide mediated by a hexacarbonyldicobaltalkyne complex to yield cyclopentenones in a single step.     

Findings on intraprocedural non-contrast computed tomographic imaging following hepatic artery embolization are associated with development of contrast-induced nephropathy

BACKGROUNDContrast-induced nephropathy (CIN) is a reversible form of acute kidney injury that occurs within 48-72 h of exposure to intravascular contrast material. CIN is the third leading cause of hospital-acquired acute kidney injury and accounts for 12% of such cases. Risk factors for CIN development can be divided into patient- and procedure-related. The former includes pre-existing chronic renal insufficiency and diabetes mellitus. The latter includes high contrast volume and repeated exposure over 72 h. The incidence of CIN is relatively low (up to 5%) in patients with intact renal function. However, in patients with known chronic renal insufficiency, the incidence can reach up to 27%.AIMTo examine the association between renal enhancement pattern on non-contrast enhanced computed tomographic (CT) images obtained immediately following hepatic artery embolization with development of CIN.METHODSRetrospective review of all patients who underwent hepatic artery embolization between 01/2010 and 01/2011 (n = 162) was performed. Patients without intraprocedural CT imaging (n = 51), combined embolization/ablation (n = 6) and those with chronic kidney disease (n = 21) were excluded. The study group comprised of 84 patients with 106 procedures. CIN was defined as 25% increase above baseline serum creatinine or absolute increase ≥ 0.5 mg/dL within 72 h post-embolization. Post-embolization CT was reviewed for renal enhancement patterns and presence of renal artery calcifications. The association between non-contrast CT findings and CIN development was examined by Fisher’s Exact Test.RESULTSCIN occurred in 11/106 (10.3%) procedures (Group A, n = 10). The renal enhancement pattern in patients who did not experience CIN (Group B, n = 74 with 95/106 procedures) was late excretory in 93/95 (98%) and early excretory (EE) in 2/95 (2%). However, in Group A, there was a significantly higher rate of EE pattern (6/11, 55%) compared to late excretory pattern (5/11) (P < 0.001). A significantly higher percentage of patients that developed CIN had renal artery calcifications (6/11 vs 20/95, 55% vs 21%, P = 0.02).CONCLUSIONA hyperdense renal parenchyma relative to surrounding skeletal muscle (EE pattern) and presence of renal artery calcifications on immediate post-HAE non-contrast CT images in patients with low risk for CIN are independently associated with CIN development.