Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities?

The severe form of COVID-19 is marked by an abnormal and exacerbated immunological host response favoring to a poor outcome in a significant number of patients, especially those with obesity, diabetes, hypertension, and atherosclerosis. The chronic inflammatory process found in these cardiometabolic comorbidities is marked by the overexpression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumoral necrosis factor-alpha (TNF-α), which are products of the Toll-Like receptors 4 (TLR4) pathway. The SARS-CoV-2 initially infects cells in the upper respiratory tract and, in some patients, spread very quickly, needing respiratory support and systemically, causing collateral damage in tissues. We hypothesize that this happens because the SARS-CoV-2 spike protein interacts strongly with TLR4, causing an intensely exacerbated immune response in the host's lungs, culminating with the cytokine storm, accumulating secretions and hindering blood oxygenation, along with the immune system attacks the body, leading to multiple organ failure.     

Is antiviral therapy in gastroduodenal pathology necessary?

Mucous membrane of the gastroduodenal region of 104 patients with different pathologies (gastritis and erosive ulcerative alterations) was investigated by polymerase chain reaction (PCR). Examination of the biopsy material revealed frequent occurrence of pathogenic strains of Helicobacter pylori (up to 80%) and Herpesviridae (EBV, HHV 6, HHV 7, HHV 8) in various combinations. In such cases it is necessary to use adequate antibacterial and antiviral therapy with individual choice of immunomodulators.     

Analysis of synonymous codon usage in Shigella flexneri 2a strain 301 and other Shigella and Escherichia coli strains

In this study, we analysed synonymous codon usage in Shigella flexneri 2a strain 301 (Sf301) and performed a comparative analysis of synonymous codon usage patterns in Sf301 and other strains of Shigella and Escherichia coli. Although there was a significant variety in codon usage bias among different Sf301 genes, there was a slight but observable codon usage bias that could primarily be attributable to mutational pressure and translational selection. In addition, the relative abundance of dinucleotides in Sf301 was observed to be independent of the overall base composition but was still caused by differential mutational pressure; this also shaped codon usage. By comparing the relative synonymous codon usage values across different Shigella and E. coli strains, we suggested that the synonymous codon usage pattern in the Shigella genomes was strain specific. This study represents a comprehensive analysis of Shigella codon usage patterns and provides a basic understanding of the mechanisms underlying codon usage bias.     

Is there a pathology of prevention? the implications of visualizing the invisible in screening programs

The preventive orientation that has been gaining ground in Sweden is indicative of ways in which our society is organized to sustain values like a healthy life, a healthy body, and a healthy society. Search for health dangers and risks shows how medical technology has been integrated with our thinking about health. Preventive language, like all language of medicine, besides describing a pre-existing biological reality, creates in the process its own objects of analysis. This also has an impact and influences how lay people experience their bodies. The study presented focuses on one form of prevention in an attempt to describe how the ambition to secure a healthy society, through the detection of early disease, may have the opposite effect. Medical health-care ambitions in screening for cholesterolaemia will be related to implications for a group of men in whom cholesterol was found to be elevated. The men feel healthy yet are in some sense diseased. This raises the issue of visualizing the invisible in health care and the implications of such a process for the patients concermed.     

Is Follow-up BRAFV600E Mutation Analysis Helpful in the Differential Diagnosis of Thyroid Nodules with Negative Results on Initial Analysis?

Background

We evaluated the usefulness of follow-up BRAF^V600E mutation analysis using ultrasonography-guided fine-needle aspiration (US-FNA) in diagnosis of thyroid nodules showing negative BRAFV600E mutation on prior analysis.

Methodology/Principal Finding

A total of 49 patients (men: 6, women: 43, mean age: 50.4 years) with 49 thyroid nodules were included. Patients had undergone initial and follow-up US-FNA and subsequent BRAF^V600E mutation analysis from US-FNA aspirates. All patients had negative results on initial BRAF^V600E mutation analysis. Clinicopathologic findings, US assessment, and BRAF^V600E mutation results were analyzed according to the final pathology. Of the 49 nodules, 12 (24.5%) were malignant and 37 (75.5%) were benign. Seven (58.3%) of the 12 malignant nodules were positive for BRAF^V600E mutation on follow-up, all showing suspicious US features. Initial US-FNA cytology of the 7 nodules were non-diagnostic (n = 2), benign (n = 2), or atypia (n = 3), while follow-up were benign (n = 1), indeterminate (n = 1), suspicious for malignancy (n = 4), and malignancy (n = 1).

Conclusions/Significance

Follow-up BRAF^V600E mutation analysis may be helpful in the diagnosis of selected thyroid nodules negative for BRAF^V600E mutation on initial analysis, which are assessed as suspicious malignant on US, diagnosed as non-diagnostic, benign or atypia on follow-up US-FNA.     

Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology

A. Talaat, D. Brinkmann, J. Dhundee, Y. Hana, J. Bevan, R. Irvine, S. Bailey and R. Woolas
Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology Objective: To review the risk of pre‐invasive and invasive gynaecological pathology in women referred with cervical cytology reporting ?glandular neoplasia. Methods: Review of the case notes of all women referred with cervical cytology reported as ?glandular neoplasia between January 1999 and December 2008 at two UK hospitals: Portsmouth Hospitals NHS Trust and Queen Mary’s Hospital Sidcup. The category of ‘borderline nuclear change in endocervical cells’, result code 8 according to the national health service cancer screening programme (NHSCSP), was excluded from the study. Results: A total of 200 women were identified using the hospitals’ pathology computer systems. Invasive carcinoma was found in 48 women (24%): 28 endocervical adenocarcinomas, eight squamous cell carcinomas (SCC), ten endometrial and two ovarian adenocarcinomas. Pre‐invasive neoplasia was found in 115 (57.5%), including 14 cervical glandular intraepithelial neoplasia (CGIN), 31 cervical intraepithelial neoplasia (CIN) grade 2/3 and 70 concomitant CGIN and CIN2/3. CIN1/HPV was found in 25, simple endometrial hyperplasia in three and no histological abnormality in three. Thirty‐four (70.8%) of 48 invasive carcinomas (of which 23 were endocervical adenocarcinomas) were in asymptomatic women investigated for abnormal cytology. Fourteen of 34 (41.4%) of those with ?glandular neoplasia thought to be endometrial were CGIN or CIN2/3. Colposcopic appearances were normal in 47.6% of women with pure cervical glandular neoplasia (adenocarcinoma or CGIN) compared with 12.8% with squamous cell lesions (CIN2/3 or SCC): P = 0.0001. Thus, colposcopy was more sensitive for detecting squamous cell abnormalities than their glandular counterparts. Although cervical adenocarcinomas are less amenable to prevention by screening than cervical SCC, in our study cervical cytology predominantly detected these abnormalities at their early asymptomatic stages. Conclusion: At least CIN2 was found in 81.5% in women referred with cervical cytology reporting ?glandular neoplasia. A thorough evaluation of the whole genital tract is needed if colposcopy is negative.     

Are copper, zinc and selenium in erythrocytes valuable biological indexes of nutrition and pathology?

The real significance of the level of trace elements copper, zinc and selenium in erythrocytes is still a matter of debate. This review is an evaluation of the potential value of copper, zinc and selenium in red blood cells in physiology, nutrition and pathology, taking into account the other commonly used indices and the analytical difficulty encountered for erythrocyte determinations. The main analytical methods and reference values in erythrocytes are also presented. The literature of the last 3 decades was analyzed. On the basis of these papers, the role of erythrocyte copper in various pathologies should be re-investigated, especially when they include inflammatory processes or hormonal changes. The main interest of zinc determination in red blood cells concerns thyroid pathology. In general, the value of selenium in erythrocytes agrees with selenium in serum and its determination is often unnecessary.     

Is the interaction of CNP with tubulin and microtubules required for process extension in oligodendrocytes?

The STOP protein (stable tubule-only polypeptide) is a calmodulin-regulated protein which associates with microtubules and induces cold stabilization. There are different isoforms of this protein that arise from alternative splicing of STOP mRNA. Neurons express two major variants N-STOP (125 kDa) and E-STOP (84 kDa). NIH 3T3 fibroblasts contain a major F-STOP isoform (42 kDa) and two minor STOP variants (48 and 89 kDa). Previously, we demonstrated the presence of N-STOP in the cytoskeleton associated with myelin isolated from animals injected with apotransferrin. Since this protein was only described as a neuronal protein we decided to further investigate the expression of this protein in oligodendrocyte cultures. The analysis of the STOP protein expression in oligodendrocyte shows that STOP protein is expressed in the soma and processes of oligodendrocyte precursors, as well as in immature and mature oligodendroglial cells. In addition, we found that MBP shows a high degree of colocalization with STOP protein. By Western blot analysis, it was found that these cells express a major STOP variant (89 kDa). When the cultures were exposed to cold temperature we found that STOP protein associates with microtubules and induces microtubule cold stabilization. Under these experimental conditions, we found that MBP associates with microtubules too, and maintains its colocalization with STOP protein. At present, we are doing new assays directed to further characterize STOP (89 kDa) protein and to elucidate how this protein participates in the formation of myelin by oligodendrocytes.     

Is traditional contraceptive use in Moldova associated with poverty and isolation?

This study investigates the correlates of traditional contraceptive use in Moldova, a poor country in Europe with one of the highest proportions of traditional contraceptive method users. The high reliance on traditional methods, particularly in the context of sub-replacement level fertility rate, has not been systematically evaluated in demographic research. Using cross-sectional data on a sub-sample of 6039 sexually experienced women from the 2005 Moldovan Demographic and Health Survey, this study hypothesizes that (a) economic and spatial disadvantages increase the likelihood of traditional method use, and (b) high exposure to family planning/reproductive health (FP/RH) programmes increases the propensity to modern method use. Multilevel multinomial models are used to examine the correlates of traditional method use controlling for exposure to sexual activity, socioeconomic and demographic characteristics and data structure. The results show that economic disadvantage increases the probability of traditional method use, but the overall effect is small. Although higher family planning media exposure decreases the reliance on traditional methods among younger women, it has only a marginal effect in increasing modern method use among older women. Family planning programmes designed to encourage women to switch from traditional to modern methods have some success--although the effect is considerably reduced in regions outside of the capital Chisinau. The study concludes that FP/RH efforts directed towards the poorest may have limited impact, but interventions targeted at older women could reduce the burden of unwanted pregnancies and abortions. Addressing differentials in accessing modern methods could improve uptake in rural areas.     

Is the ability of biocontrol fluorescent pseudomonads to produce the antifungal metabolite 2,4-diacetylphloroglucinol really synonymous with higher plant protection?

The antifungal compound 2,4-diacetylphloroglucinol (Phl) contributes to biocontrol in pseudomonads, but whether or not Phl(+) biocontrol pseudomonads display higher plant-protecting activity than Phl(-) biocontrol pseudomonads remains to be demonstrated. This issue was addressed by assessing 230 biocontrol fluorescent pseudomonads selected from a collection of 3132 bacterial isolates obtained from 63 soils worldwide. One-third of the biocontrol pseudomonads were Phl(+) and almost all Phl(+) isolates also produced hydrogen cyanide (HCN). The only Phl(+) HCN(-) strain did harbor hcn genes, but with the deletion of a 134 bp hcnC fragment corresponding to an ADP-binding motif. Statistical analysis of biocontrol isolate distributions indicated that Phl production ability was associated with superior disease suppression activity in the Pythium-cucumber and Fusarium-tomato pathosystems, but this was also the case with HCN production ability. However, HCN significance was not as strong, as indicated both by the comparison of Phl(-) HCN(+) and Phl(-) HCN(-) strains and by correlation analyses. This is the first population-level demonstration of the higher plant-protecting activity of Phl(+) biocontrol pseudomonads in comparison with Phl(-) biocontrol pseudomonads.     

Is Scale-Up Worth It? Challenges in Economic Analysis of Diagnostic Tests for Tuberculosis

David Dowdy and colleagues discuss the complexities of costing new TB diagnostic tests, including GeneXpert, and argue that flexible analytic tools are needed for decision-makers to adapt large-sample cost-effectiveness data to local conditions.     

Is beta-galactosidase staining a marker of senescence in vitro and in vivo?

Cytochemically detectable beta-galactosidase (beta-gal) at pH 6.0 has been reported to increase during the replicative senescence of fibroblast cultures and has been used widely as a marker of cellular senescence in vivo and in vitro. In this study, we have characterized changes in senescence-associated (SA) beta-gal staining in early and late passage cultures, cultures established from donors of different ages, virally immortalized cells, and tissue slices obtained from donors of different ages. The effects of different culture conditions were also examined. While we confirm the previous report that SA beta-gal staining increased in low-density cultures of proliferatively senescent cells, we were unable to demonstrate that it is a specific marker for aging in vitro. Cultures established from donors of different ages stained for SA beta-gal activity as a function of in vitro replicative age, not donor age. We also failed to observe any differences in SA beta-gal staining in skin cells in situ as a marker of aging in vivo. The level of cytochemically detectable SA beta-gal was elevated in confluent nontransformed fibroblast cultures, in immortal fibroblast cultures that had reached a high cell density, and in low-density, young, normal cultures oxidatively challenged by treatment with H2O2. Although we clearly demonstrate that SA beta-gal staining in cells is increased under a variety of different conditions, the interpretation of increased staining remains unclear, as does the question of whether the same mechanisms are responsible for the increased SA beta-gal staining observed in senescent cells and changes observed in cells under other conditions.