Radiographic features of COVID-19 based on an initial cohort of 96 patients in Singapore

INTRODUCTIONChest radiographs (CXRs) are widely used for the screening and management of COVID-19. This article describes the radiographic features of COVID-19 based on an initial national cohort of patients.METHODSThis is a retrospective review of swab-positive patients with COVID-19 who were admitted to four different hospitals in Singapore between 22 January and 9 March 2020. Initial and follow-up CXRs were reviewed by three experienced radiologists to identify the predominant pattern and distribution of lung parenchymal abnormalities.RESULTSIn total, 347 CXRs of 96 patients were reviewed. Initial CXRs were abnormal in 41 (42.7%) out of 96 patients. The mean time from onset of symptoms to CXR abnormality was 5.3 ± 4.7 days. The predominant pattern of lung abnormality was ground-glass opacity on initial CXRs (51.2%) and consolidation on follow-up CXRs (51.0%). Multifocal bilateral abnormalities in mixed central and peripheral distribution were observed in 63.4% and 59.2% of abnormal initial and follow-up CXRs, respectively. The lower zones were involved in 90.2% of initial CXRs and 93.9% of follow-up CXRs.CONCLUSIONIn a cohort of swab-positive patients, including those identified from contact tracing, we found a lower incidence of CXR abnormalities than was previously reported. The most common pattern was ground-glass opacity or consolidation, but mixed central and peripheral involvement was more common than peripheral involvement alone.     

Bacteria-phagocyte interactions: Fusobacterium-induced secretion of a neutrophil self-regulatory factor

Direct interaction between Fusobacterium nucleatum and human neutrophils resulted in the secretion of a neutrophil self-regulatory factor(s). The secretion of this factor was bacteria specific, and depended on the integrity of the bacteria cell surface. Factor secretion occurred within 15 min of bacteria--neutrophil interaction. Pre-treatment of neutrophils with cytochalasin B but not sodium fluoride inhibited factor secretion. The factor was sensitive to trypsin and heat treatment. Ultrafiltration experiments showed that it has a molecular weight between 10,000 and 30,000 daltons. Its biologic role may be that of a molecular mediator for the recruitment of resting neutrophils so as to amplify the immunological and inflammatory response.     

Nuclear localization of NADPH:cytochrome c (P450) reductase enhances the cytotoxicity of mitomycin C to Chinese hamster ovary cells

Overexpression of endoplasmic reticulum-localized NADPH: cytochrome c (P450) reductase (NPR) in Chinese hamster ovary cells increases the hypoxic/aerobic differential toxicity of the mitomycins. Because considerable evidence indicates that DNA cross-links are the major cytotoxic lesions generated by the mitomycins, we proposed that bioactivation of the mitomycins in the nucleus close to the DNA target would influence the cytotoxicity of these drugs. The simian virus 40 large T antigen nuclear localization signal was fused to the amino-terminal end of a human NPR protein that lacked its membrane anchor sequence. Immunofluorescent imaging of transfected cell lines expressing the fusion protein confirmed the nuclear location of the enzyme. Regardless of the oxygenation state of the cell, mitomycin C (MC) cytotoxicity was enhanced in cells with overexpressed NPR localized to the nuclear compartment compared with cells overexpressing an endoplasmic reticulum localized enzyme. Enhanced cytotoxicity in cells treated under hypoxic conditions correlated with increases in genomic DNA alkylations, with more MC-DNA adducts being formed when the enzyme was expressed closer to its DNA target. No change was observed in the hypoxic/aerobic differential toxicity as a function of enzyme localization. These findings indicate that drug efficacy is increased when the subcellular site of drug activation corresponds to its site of action.     

The sensitivity and specificity of clinical assessment compared with bitewing radiography for detection of occlusal dentin caries.

PURPOSE: This prospective, cross-sectional study examined the sensitivity and specificity of clinical assessment compared to bitewing radiographs in the detection of occlusal dentin caries in permanent molars. METHODS: Subjects were 481 children aged 5-12 years from a school-based dental clinic. Occlusal surfaces of 1929, sealed and unsealed first and second permanent molars were examined clinically and scored using specific criteria. Teeth with any type of restorations or proximal caries, including preventive resin restorations, were excluded from the study. Bitewing radiographs were exposed within 4 weeks of clinical examination and were assessed for dentin radiolucencies beneath the occlusal surface. The results of the clinical examinations were correlated with those of bitewing radiographs. Information provided by the parents on history forms, including systemic fluoride exposure, was also noted. RESULTS: Of the 1833 teeth scored as clinically sound in the study, only 72 (4%) demonstrated a dentin radiolucency on bitewings, and 1761 (96%) were scored as sound. The sensitivity of the clinical examination was determined to be 0.96. In the teeth clinically scored as showing dentin caries, only 56/96 (58%) were found to have dentin radiolucencies on the radiographs. The specificity of the technique was determined to be 0.58. A positive history of a medical condition, or fluoride exposure, in the forms of toothpaste use, or water fluoridation did not affect the examination results. CONCLUSIONS: Clinical examination of cleaned and dried, sealed, and unsealed teeth has a sensitivity of 0.96 and a specificity of 0.58 in the detection of dentin radiolucencies in bitewing radiographs. Dentin radiolucencies beneath clinically sound occlusal surfaces are not significantly associated with gender, medical conditions or fluoride.     

Carbetocin versus oxytocin for prevention of postpartum hemorrhage in infertile women with twin pregnancy undergoing elective cesarean delivery

Objective

To compare the efficacy and safety of carbetocin with those of oxytocin infusion in women with twin pregnancy undergoing elective cesarean delivery.

Length-dependent filament formation assessed from birefringence increases during activation of porcine tracheal muscle

Birefringence and force produced by pig tracheal smooth muscles were recorded every 100 ms during electrically stimulated tetani at muscle lengths that varied 1.5-fold and at the peak of acetylcholine contractures at the same lengths. Isometric force was nearly the same at all lengths. Resting birefringence at the longest length was 30% greater than that at the shortest length. During tetani, birefringence increased with approximately the same time course as force, rising by 20% at the shortest length and 9% at the longest length, and continued to increase by an additional 0.5–1.5% of the resting value for 2–8 s after stimulation ended and force began to fall. This late increase was greatest and more sustained at longer lengths. During contractures, birefringence increased by 25 and 18% at the shortest and longest lengths, respectively. Comparison of these results with our published thick-filament densities suggests that thick-filament density increased by about 80, 72 and 50% during contractures at the short, intermediate and long lengths, and that ∼35% of birefringence in the resting muscle at the longest length was not due to thick filaments. These findings support the hypotheses that tracheal smooth muscle adapts to longer lengths by increasing thick-filament mass and that myosin thick filaments are evanescent, dissociating partially during relaxation and reforming upon activation. The results further suggest that thick-filament formation is sufficiently rapid to account for the velocity slowing and some of the force increase observed during the rise of activation of tracheal smooth muscle.     

Chromosome 11p15.5 regional imprinting: comparative analysis of KIP2 and H19 in human tissues and Wilms' tumors

The imprinted H19 gene is frequently inactivated in Wilms' tumors (WTs) either by chromosome 11p15.5 loss of heterozygosity (LOH) or by hypermethylation of the maternal allele and it is possible that there might be coordinate disruption of imprinting of multiple 11p15.5 genes in these tumors. To test this we have characterized total and allele- specific mRNA expression levels and DNA methylation of the 11p15.5 KIP2 gene in normal human tissues, WTs and embryonal rhabdomyosarcoma (RMS). Both KIP2 alleles are expressed but there is a bias with the maternal allele contributing 70-90% of mRNA. Tumors with LOH show moderate to marked reductions in KIP2 mRNA relative to control tissues and residual mRNA expression is from the imprinted paternal allele. Among WTs without LOH most cases with H19 inactivation also have reduced KIP2 expression and most cases with persistent H19 expression have high levels of KIP2 mRNA. In contrast to the extensive hypermethylation of the imprinted H19 allele, both KIP2 alleles are hypomethylated and WTs with biallelic H19 hypermethylation lack comparable hypermethylation of KIP2 DNA. 5-aza-2'-deoxycytidine (aza-C) increases H19 expression in RD RMS cells but does not activate KIP2 expression. These data indicate coordinately reduced expression of two linked paternally imprinted genes in most WTs and also suggest mechanistic differences in the maintenance of imprinting at these two loci.      

Research on cancer diagnosis in Malaysia: current status

Cancer is a major morbidity and mortality concern in Malaysia. Based on National Cancer Registry data, the Malaysian population is estimated to bear a cancer burden of about 40,000 new cases per year, and a cumulative lifetime risk of about 1:4. Cancer research in Malaysia has to consider needs relevant to our population, and resources constraints. Hence, funding bodies prioritise cancers of high prevalence, unique to our community and posing specific clinical problems. Cancer diagnosis is crucial to cancer management. While cancer diagnosis research largely aims at improvements in diagnostic information towards more appropriate therapy, it also impacts upon policy development and other areas of cancer management. The scope of cancer diagnosis upon which this paper is based, and their possible impact on other R&D areas, has been broadly categorized into: (1) identification of aetiological agents and their linkages to the development of precancer and cancer (impact on policy development, cancer prevention and treatment), (2) cancer biology and pathogenesis (impact on cancer prevention, treatment strategies and product development), (3) improvements in accuracy, sensitivity and specificity in cancer detection, monitoring and classification (impact on technology development) and (4) prognostic and predictive parameters (impact on treatment strategies). This paper is based on data collected by the Working Group on Cancer Diagnosis Research for the First National Conference on Cancer Research Coordination in April 2004. Data was collated from the databases of Institutions/Universities where the authors are employed, the Ministry of Science, Technology and Innovation (MOSTI) and targeted survey feedback from key cancer researchers. Under the 7th Malaysia Plan, 76 cancer projects were funded through the Intensified Research in Priority Areas (IRPA) scheme of MOSTI, amounting to almost RM15 million of grant money. 47(61.8%) of these projects were substantially in cancer diagnosis, accounting for 65.6% (RM 9.7 million) of cancer project funds. The 8th Malaysia Plan saw a change in research strategy. The IRPA agency fielded several top-down projects which encouraged a multicentre and multidisciplinary approach. This resulted in larger funding per project i.e. RM32 million for 49 projects. There was also a surge of interest in drug development and natural products. Because of this shift in direction, cancer diagnosis projects constituted only 51% of IRPA-funded cancer projects. Nonetheless funding for cancer diagnosis research has exceeded that of the 7th Malaysia Plan, being RM12.5 million by March 2004. The majority of such research is carried out at the Universities, engaging a large number of young scientists and postgraduate students (51 MSc and 21 PhD). A lot of research findings presented at scientific meetings have not yet been published and there is a glaring shortage of patents and commercialization of research findings (such as creation of test kits). Because diagnosis is very much a part of clinical practice, many researchers felt satisfied and confident that their work will be translated into practice and will significantly improve diagnostic services in Malaysia. National guidelines and consensus development on at least three malignancies i.e. breast cancer, oral cancer and lymphoma, have substantial basis in local R&D work. Problems encountered in research included (1) insufficient funding to realize research objectives, (2) lack of local expertise (most research assistants are inexperienced BSc graduates with no or minimal research experience), (3) inadequate technical support from vendors during equipment failure, (4) inexperienced Institutional development units to assist in product development, (5) lack of venture capital for commercialization of findings, and (6) inadequate incentives to undertake research. Researchers pointed out that plans to promote research should include the establishment of (1) regional and national cancer tissue banks, (2) a National Cancer Research Institute, (3) a dedicated cancer research fund, (4) a registry of cancer researchers, (5) national research coordinators, (6) improved coverage by the National Cancer Registry, (7) more international collaboration, (8) a better career structure for researchers, (9) improved Institutional support for product realization, and (10) better recognition for cancer researchers.