39 research outputs found
Crevice Corrosion Behavior of Nickel-Based Alloy 718 in both Aerated and De-Aerated Chloride Environment
In this study, anodic potentiodynamic polarization techniques were used to study the crevice corrosion behaviour of Nickel alloy 718 (with and without a crevice former) in both aerated and de-aerated solution of 3.5wt% sodium chloride solution. Surface observation of the specimens after each experiment was done with the optical microscope. The results showed that crevice corrosion were initiated at potentials as low as 520mVSCE, while the surface observation on the specimen with a crevice former revealed that the crevice corrosion attack was restricted under the crevice gap and at the border areas of the crevice former but did not occur at the surfaces outside the shielded areas. Conversely, the specimen without a crevice former showed evidence of waterline corrosion. These results can be attributed to the development of differential oxygen concentration in the specimen depending on the exposure of the parts to dissolved oxygen. This study has developed a more comprehensive understanding of the crevice corrosion initiation mechanism and behaviour of Nickel-based Alloy 718 under applied crevice torques, chloride environment and exact potentials, thereby leading to better prevention and control of localized corrosion in this alloy
Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy
BRCA1, a key factor in homologous recombination repair may also regulate base excision repair (BER). Targeting BRCA1-BER deficient cells by blockade of ATM and DNA-PKcs could be a promising strategy in breast cancer. We investigated BRCA1, XRCC1 and pol β protein expression in two cohorts (n=1602 sporadic and n=50 germ-line BRCA1 mutated) and mRNA expression in two cohorts (n=1952 and n=249). Artificial neural network analysis for BRCA1-DNA repair interacting genes was conducted in 249 tumours. Pre-clinically, BRCA1 proficient and deficient cells were DNA repair expression profiled and evaluated for synthetic lethality using ATM and DNA-PKcs inhibitors either alone or in combination with cisplatin. In human tumours, BRCA1 negativity was strongly associated with low XRCC1, and low pol β at mRNA and protein levels (p<0.0001). In patients with BRCA1 negative tumours, low XRCC1 or low pol β expression was significantly associated with poor survival in univariate and multivariate analysis compared to high XRCC1 or high pol β expressing BRCA1 negative tumours (ps<0.05). Pre-clinically, BRCA1 negative cancer cells exhibit low mRNA and low protein expression of XRCC1 and pol β. BRCA1-BER deficient cells were sensitive to ATM and DNA-PKcs inhibitor treatment either alone or in combination with cisplatin and synthetic lethality was evidenced by DNA double strand breaks accumulation, cell cycle arrest and apoptosis. We conclude that XRCC1 and pol β expression status in BRCA1 negative tumours may have prognostic significance. BRCA1-BER deficient cells could be targeted by ATM or DNA-PKcs inhibitors for personalized therapy
Clinicopathological Investigations Among Recurrent Camelpox Outbreaks in Omanis’ Arabian Camels (Camelus dromedarius)
Camelpox remains a widespread viral disease in camelids, with socioeconomic relevance. The present study explored the hematological, biochemical, and histopathological alterations in dromedary-racing camels from the North of Oman infected with camelpox virus diagnosed by real-time PCR. Blood and skin samples were collected from camels with clinical signs and skin lesions (n=4) and from healthy camels (n=3) from 10 different camel herds. The results indicated that the infected camels showed clinical signs, including pyrexia, lacrimation, nasal mucus discharge, affixed and swollen eyelids, emaciation, and pimples on the skin of the head, legs, and abdomen. Hemoglobin, hematocrit, and platelets were significantly greater, with a significant reduction in leukocyte and lymphocyte counts in infected camels than in healthy camels. Infected camels had higher CK and creatinine levels and hepatic-related metabolites, including AST, ALP, AST, GGT, and LDH, than the apparently healthy camels. Histopathological examination of skin scab samples revealed ballooning degeneration of epidermal cells in the presence of typical large eosinophilic intracytoplasmic inclusion bodies and suppurative dermatitis following secondary bacterial infection in all examined infected camels. Camelpox viral DNA was detected using real-time PCR in the blood and skin samples of all infected camels. These findings in dromedary-racing camels associated with a molecular diagnosis of camelpox are described for the first time in the Sultanate of Oman. Therefore, further studies are warranted
Overview on Blood Transfusion-Transmitted Diseases
As it is important for the Blood transfusion to be extremely safe, some measures have to be taken long safeguarded the blood supply from the major transfusion transmissible diseases (TTIs). The risk of transfusion-transmitted infection (TTI) rises with the number of donors exposed, and the effects of TTI are frequently more severe in immune compromised people. TTIs (hepatitis B virus [HBV], HIV, and hepatitis C virus [HCV]) are examples of typical transfusion-transmitted infectious agents. As a result of the gradual application of nucleic acid-amplification technology (NAT) screening for HIV, HCV, and HBV, the residual risk of infected window-period donations has been minimized. Nonetheless, infections emerge far more frequently than is commonly acknowledged, needing ongoing surveillance and individual assessment of transfusion-associated risk. Although there is a constant need to monitor present dangers owing to established TTI, the ongoing issues in blood safety are mostly related to surveillance for developing agents, as well as the creation of quick reaction systems when such agents are detected
Re-infection with a different SARS-CoV-2 clade and prolonged viral shedding in a hematopoietic stem cell transplantation patient
Immunocompromised patients who have a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection pose many clinical and public health challenges. We describe the case of a hematopoietic stem cell transplantation patient with lymphoma who had a protracted illness requiring three consecutive hospital admissions. Whole genome sequencing confirmed two different SARS-CoV-2 clades. Clinical management issues and the unanswered questions arising from this case are discussed
Patterns of Human Respiratory Viruses and Lack of MERS-Coronavirus in Patients with Acute Upper Respiratory Tract Infections in Southwestern Province of Saudi Arabia
We undertook enhanced surveillance of those presenting with respiratory symptoms at five healthcare centers by testing all symptomatic outpatients between November 2013 and January 2014 (winter time). Nasal swabs were collected from 182 patients and screened for MERS-CoV as well as other respiratory viruses using RT-PCR and multiplex microarray. A total of 75 (41.2%) of these patients had positive viral infection. MERS-CoV was not detected in any of the samples. Human rhinovirus (hRV) was the most detected pathogen (40.9%) followed by non-MERS-CoV human coronaviruses (19.3%), influenza (Flu) viruses (15.9%), and human respiratory syncytial virus (hRSV) (13.6%). Viruses differed markedly depending on age in which hRV, Flu A, and hCoV-OC43 were more prevalent in adults and RSV, hCoV-HKU1, and hCoV-NL63 were mostly restricted to children under the age of 15. Moreover, coinfection was not uncommon in this study, in which 17.3% of the infected patients had dual infections due to several combinations of viruses. Dual infections decreased with age and completely disappeared in people older than 45 years. Our study confirms that MERS-CoV is not common in the southwestern region of Saudi Arabia and shows high diversity and prevalence of other common respiratory viruses. This study also highlights the importance and contribution of enhanced surveillance systems for better infection control
Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy
Summary
Human C2orf69 is an evolutionarily conserved gene whose function is unknown. Here, we report eight unrelated families from which 20 children presented with a fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. C2ORF69 bears homology to esterase enzymes, and orthologs can be found in most eukaryotic genomes, including that of unicellular phytoplankton. We found that endogenous C2ORF69 (1) is loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. We show that CRISPR-Cas9-mediated inactivation of zebrafish C2orf69 results in lethality by 8 months of age due to spontaneous epileptic seizures, which is preceded by persistent brain inflammation. Collectively, our results delineate an autoinflammatory Mendelian disorder of C2orf69 deficiency that disrupts the development/homeostasis of the immune and central nervous systems
Checkpoint kinase1 (CHK1) is an important biomarker in breast cancer having a role in chemotherapy response
Background:Checkpoint kinase1 (CHK1), which is a key component of DNA-damage-activated checkpoint signalling response, may have a role in breast cancer (BC) pathogenesis and influence response to chemotherapy. This study investigated the clinicopathological significance of phosphorylated CHK1 (pCHK1) protein in BC.Method:pCHK1 protein expression was assessed using immunohistochemistry in a large, well-characterized annotated series of early-stage primary operable invasive BC prepared as tissue microarray (n=1200).Result:pCHK1 showed nuclear and/or cytoplasmic expression. Tumours with nuclear expression showed positive associations with favourable prognostic features such as lower grade, lower mitotic activity, expression of hormone receptor and lack of expression of KI67 and PI3K (
Luom, a novel high incidence antigen in the Lutheran blood group system:Luom, a novel high incidence antigen in the Lutheran blood group system
Background: The Lutheran blood group system comprises 27 antigens carried on type I membrane glycoproteins with five immunoglobulin-like extracellular domains, encoded by a single gene BCAM located on chromosome 19. Alternative splicing of BCAM results in two glycopro- tein isoforms, 85 kD Lu glycoprotein and 75 kD basal cell adhesion molecule (B-CAM). Both isoforms carry Lutheran antigens, of which there are currently four pairs of antithetical and 19 high incidence antigens
Exonic deletions in the MAL gene, encoding Myelin and Lymphocyte protein, define the rare inherited AnWj-negative phenotype:Exonic deletions in the MAL gene, encoding Myelin and Lymphocyte protein, define the rare inherited AnWj-negative phenotype
Background: AnWj (ISBT 901009) is a high prevalence blood group antigen present on red cells and epithelial tissues of more than 99.9% of individuals but absent on cord cells. Antibodies directed to AnWj antigen are rare and are usually associated with transient suppression of AnWj expression, although a small number of individuals have a persistent, autosomal recessive inherited AnWj-negative phenotype. Anti-AnWj may be clinically significant and has been associated with acute hemolytic transfusion reactions.The carrier molecule for the AnWj antigen has remained elusive; although CD44 and Smyd1 histone methyltransferase have both been reported to be associated with AnWj expression, the mechanism for this has not been elucidated.Myelin and lymphocyte protein (Mal), encoded by the MAL gene on chromosome 2, is an integral 17KDa multi-pass membrane proteolipid, expressed on T-lymphocytes, myelin-forming cells and polarised epithelial cells. It has also been identified as the receptor for Clostridium perfringens epsilon toxin on erythrocyte membranes