MODIFIED DOUBLE-DISC SYNERGY TEST (MDDST) FOR DETECTION OF EXTENDED-SPECTRUM BETA-LACTAMASES IN AmpC BETA-LACTAMASE-PRODUCING KLEBSIELLA CLINICAL ISOLATES

The detection of ESBL(S) in gram-negative bacteria that produce AmpC beta-lactamases is problematic. In the present study, the performance of MDDST that employs a combination of cefepime and piperacillin-tazobactam for the detection of ESBL(S) Klebsiella producing AmpC beta-lactamases was evaluated and compared with DDST. E-test phenotypic confirmatory and MTDT tests were adopted for more data confidence. A total of 100 clinical isolates of Klebsiella, which met the CLSI (2012) screening criteria as having broth microdilution (BMD) MIC of > or =2 mg/mL for at least one extended spectrum cephalosporin [ceftazidime (CAZ), cefotaxime (CTX) and cefpodoxime], were accurately-selected for the study. MDDST detected ESBLs in 62 out of the100 studied isolates with 100% sensitivity and specificity, whereas DDST detected ESBLs in only 52 isolates with 92.9% sensitivity and 100% specificity. E-test could detect ESBLs in 62 isolates, while as many as 34/62 ESBL positive isolates were confirmed to be AmpC beta-lactamase positive by the MTDT. MDDST and E-Test could detect ESBLs in all the 34 AmpC positive isolates, whereas DDST detect ESBLs in only 26 isolates.The study recommended MDDST as superior to DDST for the detection of ESBLs in AmpC beta-lactamase-producing Klebsiella spp. and this was confirmed by MTDT and E-Tests

Using Lamin B1 mRNA for the early diagnosis of hepatocellular carcinoma: a cross-sectional diagnostic accuracy study [version 1; referees: 2 approved]

Background:  Hepatocellular carcinoma (HCC) is vital medical issue in Egypt. It accounts for 70.48% of all liver tumors among Egyptians. The aim of this study was to determine the diagnostic role of plasma levels of mRNA of lamin B1 by RT-qPCR as an early marker of HCC. Methods: This study was conducted at the Clinical Pathology Department in collaboration with the Department of Tropical Medicine and Infectious Diseases at Ain Shams University Hospitals. It included 30 patients with primary HCC and viral cirrhosis (all were hepatitis C virus-positive) (Group I), in addition to 10 patients with chronic liver diseases (Group II) and 10 healthy age- and sex-matched subjects (Group III). Group I was further classified according to the Barcelona-Clinic Liver Cancer Staging System. Serum α-fetoprotein (AFP) chemiluminescent-immunoassays and RT-qPCR analysis of plasma lamin B1 mRNA levels were performed for all participants. Results: AFP and lamin B1 significantly elevated in patients with HCC compared to those in the other studied groups. AFP and lamin B1 status could discriminate group I from group II and III. A significant increase was found among the three Barcelona stages with regards to AFP and lamin B1 levels. A significant decrease was found between group II and stage 0, A and B with regards to AFP and lamin B1. Lamin B1 and AFP could both differentiate HCC patients with one tumor nodule (T1) from those with two or more tumor nodules (T2&Tm), as well as between those with tumor sizes >3 cm and ≤3 cm. Conclusion: Measurement of lamin B1 mRNA is recommended in patients with chronic liver disease with normal serum AFP, especially in known cirrhotic patients that deteriorate rapidly without any apparent etiology

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Acute and chronic metabolic effects of carvedilol in high-fructose, high fat diet-fed mice: Implication of β-arrestin2 pathway

We aimed to investigate the acute and chronic effects of carvedilol on insulin resistance in high-fructose, high-fat diet (HFrHFD)-fed mice and the implication of β-arrestin2 pathway. The acute effect of carvedilol (10 mg/kg, i.p.) on glucose tolerance and hepatic lipid signaling in normal and insulin resistant mice was investigated. Then, the chronic effect of carvedilol on insulin resistance and dyslipidemia in HFrHFD-fed mice was examined. Changes in β-arrestin2 and its down-stream signals in liver, skeletal muscle, and adipose tissue were measured. This involved measuring phosphatidylinositol 4,5-bisphosphate (PIP2) and diacylglycerol (DAG) levels and protein kinase B (Akt)-activity. Carvedilol acutely reduced fasting blood glucose levels in both normal and insulin resistant mice without significantly affecting the glucose tolerance. These acute effects were associated with increased hepatic PIP2 but decreased hepatic DAG levels. Chronic administration of carvedilol significantly ameliorated insulin resistance and dyslipidemia in HFrHFD-fed mice. These chronic effects were associated with increased β-arrestin2, PIP2 and Akt activity levels but decreased DAG levels in the classical insulin target tissues. In conclusion, carvedilol acutely maintains glucose homeostasis and chronically ameliorates insulin resistance and dyslipidemia in HFrHFD-fed mice. The insulin sensitizing effects of carvedilol are highly correlated with the upregulation of β-arrestin2 pathway.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Recent advances in the use of TiO\u3csub\u3e2\u3c/sub\u3e nanotube powder in biological, environmental, and energy applications

The use of titanium dioxide nanotubes in the powder form (TNTP) has been a hot topic for the past few decades in many applications. The high quality of the fabricated TNTP by various synthetic routes may meet the required threshold of performance in a plethora of fields such as drug delivery, sensors, supercapacitors, and photocatalytic applications. This review briefly discusses the synthesis techniques of TNTP, their use in various applications, and future perspectives to expand their use in more applications

Non‐classical monocytes frequency and serum vitamin D3 levels are linked to diabetic foot ulcer associated with peripheral artery disease

Abstract Aims/Introduction Peripheral artery disease (PAD) serves as a risk factor for diabetic foot ulcers (DFUs). PAD pathology involves atherosclerosis and impaired immunity. Non‐classical monocytes are believed to have an anti‐inflammatory role. 1,25‐Dihydroxy vitamin D (vitamin D3) is claimed to have immune‐modulating and lipid‐regulating roles. Vitamin D receptor is expressed on monocytes. We aimed to investigate if circulating non‐classical monocytes and vitamin D3 were implicated in DFUs associated with PAD. Materials and Methods There were two groups of DFU patients: group 1 (n = 40) included patients with first‐degree DFUs not associated with PAD, and group 2 (n = 50) included patients with DFU with PAD. The monocyte phenotypes were detected using flow cytometry. Vitamin D3 was assessed by enzyme‐linked immunosorbent assay. Results DFU patients with PAD showed a significant reduction in the frequency of non‐classical monocytes and vitamin D3 levels, when compared with DFU patients without PAD. The percentage of non‐classical monocytes positively correlated with vitamin D3 level (r = 0.4, P < 0.01) and high‐density lipoprotein (r = 0.5, P < 0.001), whereas it was negatively correlated with cholesterol (r = −0.5, P < 0.001). Vitamin D3 was negatively correlated with triglyceride/high‐density lipoprotein (r = −0.4, P < 0.01). Regression analysis showed that a high vitamin D3 serum level was a protective factor against PAD occurrence. Conclusions Non‐classical monocytes frequency and vitamin D3 levels were significantly reduced in DFU patients with PAD. Non‐classical monocytes frequency was associated with vitamin D3 in DFUs patients, and both parameters were linked to lipid profile. Vitamin D3 upregulation was a risk‐reducing factor for PAD occurrence

COVID-19 Host Genetics Initiative. A first update on mapping the human genetic architecture of COVID-19

The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity.</p