Asymptomatic infection and transmission of COVID-19 among clusters: systematic review and meta-analysis.

OBJECTIVES: Countries throughout the world are experiencing COVID-19 viral load in their populations, leading to potential transmission and infectivity of asymptomatic COVID-19 cases. The current systematic review and meta-analysis aims to investigate the role of asymptomatic infection and transmission reported in family clusters, adults, children and health care workers, globally. STUDY DESIGN: Systematic review and meta-analysis. METHODS: An online literature search of PubMed, Google Scholar, medRixv and BioRixv was performed using standard Boolean operators and included studies published up to 17 August 2021. For the systematic review, case reports, short communications and retrospective studies were included to ensure sufficient asymptomatic COVID-19 transmission data were reported. For the quantitative synthesis (meta-analysis), participant data from a collection of cohort studies focusing on groups of familial clusters, adults, children and health care workers were included. Inconsistency among studies was assessed using I2 statistics. The data synthesis was computed using the STATA 16.0 software. RESULTS: This study showed asymptomatic transmission among familial clusters, adults, children and health care workers of 15.72%, 29.48%, 24.09% and 0%, respectively. Overall, asymptomatic transmission was 24.51% (95% confidence interval [CI]: 14.38, 36.02) among all studied population groups, with a heterogeneity of I2 = 95.30% (P < 0.001). No heterogeneity was seen in the population subgroups of children and health care workers. The risk of bias in all included studies was assessed using the Newcastle Ottawa Scale. CONCLUSIONS: For minimising the spread of COVID-19 within the community, this study found that following the screening of asymptomatic cases and their close contacts for chest CT scan (for symptomatic patients), even after negative nucleic acid testing, it is essential to perform a rigorous epidemiological history, early isolation, social distancing and an increased quarantine period (a minimum of 14-28 days). This systematic review and meta-analysis supports the notion of asymptomatic COVID-19 infection and person-to-person transmission and suggests that this is dependent on the varying viral incubation period among individuals. Children, especially those of school age (i.e. <18 years), need to be monitored carefully and follow mitigation strategies (e.g. social distancing, hand hygiene, wearing face masks) to prevent asymptomatic community transmission of COVID-19.

Gene expression profiling in rat cerebellum following in utero and lactational exposure to mixtures of methylmercury, polychlorinated biphenyls and organochlorine pesticides.

Although human populations are continuously exposed to complex mixtures of contaminants, the effects of such exposure on the developing brain transcriptome are poorly characterized. Rats were exposed perinatally to the northern contaminant mixture (NCM) which was designed to reflect the blood contaminant profile of Canadian arctic populations, to components of the NCM administered separately (methylmercury (MeHg), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCs)) or to the goitrogen propylthiouracyl. Post-natal day (PND) 14 cerebellum global gene expression resulting from such exposures was investigated using high-density cDNA microarrays. Fifty known genes were identified as differentially expressed between the control group and at least one other treatment group. The microarray data were validated by quantitative PCR (qPCR) on a subset of 10 genes. The differentially expressed genes are involved in a variety of processes, including nerve cell differentiation, migration, myelination and synaptic transmission. The comparison of cerebellum gene expression profiles resulting from exposure to the NCM and its individual components in male and female pups revealed that (i) gender is a crucial biological variable influencing genomic response to environmental contaminants and (ii) contaminant co-exposure significantly masks the effects of individual mixture components on cerebellum gene expression.

Co-amplification of dhfr and a homologue of hmsh3 in a Chinese hamster methotrexate-resistant cell line correlates with resistance to a range of chemotherapeutic drugs.

PURPOSE: To characterize a methotrexate-resistant Chinese hamster cell line, designated as M5, which had previously been shown to be resistant to gamma radiation, at the cellular and molecular levels. METHODS: Sensitivity towards a number of chemotherapeutic drugs was determined by colony-forming ability and compared with that of parental V79 cells. Expression of the hamster homologue of the human mismatch repair gene hmsh3 was also determined by RT-PCR. RESULTS: Induced killing by chemotherapeutic agents cis-diamminedichloroplatinum II (cisplatin). the antimetabolite 6-thioguanine (6-TG), camptothecin, a topoisomerase I inhibitor, and 4-(9-acridinyl-amino)-methanesulfon-m-anisidide (mAMSA), an inhibitor of topoisomerase II, was less in M5 cells than in the parental V79 cells. The IC50 values, defined as the concentration of the drug that reduced the survival to 50% that of the untreated control, in V79 cells for mAMSA and camptothecin treatment were 0.35 +/- 0.02 microg/ml and 84.3 +/- 16.0 ng/ml, respectively. For M5 cells, equivalent values were 0.52 +/- 0.10 microg/ml and 186 +/- 40.8 ng/ml. Treatment with 30 microM cisplatin reduced the survival of V79 cells to 0.09 +/- 0.07, whereas the same treatment reduced the survival of M5 cells to 0.67 +/- 0.16. Treatment of M5 cells with 6-TG did not induce appreciable killing up to the concentrations studied. However, for V79 cells, 6-TG was very toxic. We further observed that the dihydrofolate reductase (dhfr) gene as well as the hamster homologue of the human mismatch repair gene hmsh3 was amplified in the methotrexate-resistant M5 cells. CONCLUSION: Resistance to this group of chemotherapeutic drugs observed in M5 cells could be due to the amplification of the hamster homologue of hMSH3, which in turn possibly sequesters all the hMSH2 making M5 cells functionally deficient in the mismatch repair system.

Inhibition of BMP signaling during zebrafish fin regeneration disrupts fin growth and scleroblasts differentiation and function.

The zebrafish caudal fin provides a simple model to study molecular mechanisms of dermal bone regeneration. We previously showed that misexpression of Bone morphogenetic protein 2b (Bmp2b) induces ectopic bone formation within the regenerate. Here we show that in addition to bmp2b and bmp4 another family member, bmp6, is involved in fin regeneration. We further investigated the function of BMP signaling by ectopically expressing the BMP signaling inhibitor Chordin which caused: (1) inhibition of regenerate outgrowth due to a decrease of blastema cell proliferation and downregulation of msxb and msxC expression and (2) reduced bone matrix deposition resulting from a defect in the maturation and function of bone-secreting cells. We then identified targets of BMP signaling involved in regeneration of the bone of the fin rays. runx2a/b and their target col10a1 were downregulated following BMP signaling inhibition. Unexpectedly, the sox9a/b transcription factors responsible for chondrocyte differentiation were detected in the non-cartilaginous fin rays, sox9a and sox9b were not only differentially expressed but also differentially regulated since sox9a, but not sox9b, was downregulated in the absence of BMP signaling. Finally, this analysis revealed the surprising finding of the expression, in the fin regenerate, of several factors which are normally the signatures of chondrogenic elements during endochondral bone formation although fin rays form through dermal ossification, without a cartilage intermediate.

Characterization of MboI satellites in Cirrhina mrigala and Clarias batrachus (Pisces).

We have cloned and characterized two highly reiterated, tandemly repeated, and A+T rich MboI DNA fragments, one in Cirrhina mrigala (Cyprinidae), with a monomer size of 266 bp, and one in Clarias batrachus (Clariidae), with a monomer size of 227 bp. The MboI fragment in C. mrigala is species-specific and absent in other carps, such as Catla catla and Labeo rohita. The MboI fragment in C. batrachus was also present in two other catfishes tested, namely Clarias gariepinus and Heteropneustes fossilis. In C, mrigala x C. catla and C. mrigala x L. rohita hybrids, the C. mrigala specific MboI fragment is inherited uniparentally. In the reciprocal hybrids of C. batrachus x H. fossilis, the satellite ladder contains the bands of both parental species. The MboI satellite of carp may be useful in genetic introgression analysis and that of catfish in distinguishing between gynogenetic progeny and true hybrids.