Animal Reservoirs and Hosts for Emerging Alphacoronaviruses and Betacoronaviruses

The ongoing global pandemic caused by coronavirus disease has once again demonstrated the role of the family Coronaviridae in causing human disease outbreaks. Because severe acute respiratory syndrome coronavirus 2 was first detected in December 2019, information on its tropism, host range, and clinical manifestations in animals is limited. Given the limited information, data from other coronaviruses might be useful for informing scientific inquiry, risk assessment, and decision-making. We reviewed endemic and emerging infections of alphacoronaviruses and betacoronaviruses in wildlife, livestock, and companion animals and provide information on the receptor use, known hosts, and clinical signs associated with each host for 15 coronaviruses detected in humans and animals. This information can be used to guide implementation of a One Health approach that involves human health, animal health, environmental, and other relevant partners in developing strategies for preparedness, response, and control to current and future coronavirus disease threats.     

Impact of polymorphism in <Emphasis Type="Italic">IL-1RA</Emphasis> gene on the risk of cervical cancer

Introduction Cervical cancer, the second most common malignancy in women worldwide, is almost invariably associated with infection by human papillomavirus (HPV). However, although many women are infected with high-risk types of HPV, only a subset of infected women will ever develop cervical cancer. Therefore, host genetic factor may play a role in cervical carcinogenesis. Several studies suggested that immunological components play a key role in the development of cervical cancer. Polymorphism in the IL-1RA gene was associated with various malignant diseases. Data are lacking for cervical cancer. Materials and methods In a case−control study we analyzed the polymorphism of IL-1RA in 150 women with cervical cancer and 209 healthy controls. Genomic DNA fragments were amplified by PCR. Results There was a strong significantly protective association between heterozygous AB genotype and HPV 18 (OR = 0.11, 95% CI = 0.04–0.30, p = 0.0000000). Similarly this result was demonstrated, in combined AB + BB genotypes of IL-1RA with HPV 18 (OR = 0.12, 95% CI = 0.05–0.30, p = 0.0000000) and HPV type 16 + 18 (OR = 0.18,95% CI = 0.08–0.38, p = 0.000005). We found high protective significant association between heterozygous genotype AB with adenocarcinoma (OR = 0.19, 95% CI = 0.09–0.40, p = 0.0000002) as well. Conclusion These findings therefore suggest that the IL1-RA polymorphism is associated with cervical cancer.     

The clinical advances of fluorine‐2‐D‐deoxyglucose – positron emission tomography/computed tomography in urological cancers

Fluorine‐18 labeled fluorine‐2‐D‐deoxyglucose (FDG) is the most frequently used positron emission tomography (PET) probe but it has certain limitations when used in urological cancers. The introduction of co‐registered PET and computed tomography (PET/CT) represents a major advance in technology and FDG‐PET/CT has now become the new standard. The diagnostic performance of FDG‐PET and PET/CT depends on the metabolic activity of tumor tissue, which is generally low in primary renal cell and prostate cancers and often in their metastatic deposits. In contrast, both seminomatous and nonseminomatous germ cell tumors are characterized by upregulated glucose metabolism with subsequently increased FDG uptake in tumor sites. Generally, the metabolic activity provides accurate information regarding the presence of a viable tumor, except in patients with residual mature teratoma. Although bladder cancer demonstrates sufficiently increased FDG uptake, primary tumors are difficult to identify due to the renal excretion of FDG. The accuracy of FDG‐PET/CT in metabolically active metastases is generally higher compared to conventional CT except for identifying small lung deposits. With disease progression and subsequent de‐differentiation of prostate cancer, castrate resistant disease is more likely to present with lesions that have increased glucose metabolism.     

DNA-Binding Interaction Studies of Microwave Assisted Synthesized Sulfonamide Substituted 8-Hydroxyquinoline Derivatives

Sulfonamide substituted 8-hydroxyquinoline derivatives were prepared using a microwave synthesizer. The interaction of sulfonamide substituted 8-hydroxyquinoline derivatives and their transition metal complexes with Plasmid (pUC 19) DNA and Calf Thymus DNA were investigated by UV spectroscopic studies and gel electrophoresis measurements. The interaction between ligand/metal complexes and DNA was carried out by increasing the concentration of DNA from 0 to 12 μl in UV spectroscopic study, while the concentration of DNA in gel electrophoresis remained constant at 10 μl. These studies supported the fact that, the complex binds to DNA by intercalation via ligand into the base pairs of DNA. The relative binding efficacy of the complexes to DNA was much higher than the binding efficacy of ligands, especially the complex of Cu-AHQMBSH had the highest binding ability to DNA. The mobility of the bands decreased as the concentration of the complex was increased, indicating that there was increase in the interaction between the metal ion and DNA. Complexes of AHQMBSH were excellent for DNA binding as compared to HQMABS.     

Brainstem auditory evoked responses in term small for gestational age newborn infants born to undernourished mothers.

Our aim was to assess the effect of intrauterine growth retardation on neurosensory development by evaluating brainstem auditory evoked responses (BAER) in term small for gestational age (SGA) newborn infants born to undernourished mothers. This prospective clinical study included 25 singleton healthy SGA newborn infants born between 38 and 41 weeks to undernourished mothers (weight <45kg, height <145cm, haemoglobin <8g/dl, and serum albumin <2.5g/dl). An equal number of age- and sex-matched appropriate for gestational age newborn infants born to healthy mothers served as controls. Mothers with other risk factors and newborns with complications during delivery or immediate newborn period were excluded. BAER was recorded within first 3 days of life. Interpeak latency (IPL), absolute peak latency (APL) and amplitudes of various waveforms were determined and compared between the groups.No statistically significant differences were observed for the mean interpeak and absolute latencies between term SGA and AGA infants (p>0.05). The absolute peak latency (wave V) and central conduction time (I-V interval) were borderline prolonged in the study group compared with controls (p=0.051 and 0.088 respectively). Using multiple regression analysis, maternal haemoglobin was identified to be the only parameter having a negative correlation with both IPL (waves I-V) (F[1,46]=4.12, p=0.048) and APL (wave V) (F[1,46]=5.80, p=0.02). Maternal undernourishment may have a minor effect on intrauterine development of the auditory brainstem. Maternal haemoglobin is the only factor significantly associated with these changes.     

CGS 21680C, an A2 selective adenosine receptor agonist with preferential hypotensive activity

CGS 21680C (2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethyl-carboxamido adenosine) a 2-substituted analog of the riboside uronamide, 5'-N-ethylcarboxamido adenosine and the related analog CGS 21577 (2-phenethylamino-5'-N-ethylcarboxamido adenosine), have high in vitro affinity for brain striatal adenosine A2 receptors (IC50 values = 22 and 13 nM, respectively). Both compounds were considerably less active at A1 receptors with CGS 21577 and CGS 21680C having respective IC50 values of 0.76 and 3.1 microM. The former compound was thus 59-fold selective for A2 receptors whereas CGS 21680C was 140-fold selective. In contrast, the reference A2 selective ligand, CV 1808 (2-phenylaminoadenosine), showed only 8-fold selectivity as an A2 ligand, having an IC50 of 115 nM in the [3H]-5'N-ethylcarboxamide adenosine assay and an IC50 of 910 nM at the N6-[3H] cyclohexyladenosine site. Further examination of CGS 21680C showed that the compound was without effect on binding to 17 other putative neurotransmitter/neuromodulator sites indicating its selectivity as an adenosine receptor ligand. In an isolated perfused working rat heart model, CGS 21680C effectively increased coronary flow with an ED25 value of 1.8 nM. The corresponding value for CGS 21577 was 3 nM whereas that for CV 1808 was 110 nM. The EC25 for eliciting bradycardia for all three compounds was greater than 1000 nM. The effects of all three compounds could be reversed by treatment with the xanthine adenosine antagonist, xanthine amine congener.(ABSTRACT TRUNCATED AT 250 WORDS)