Mössbauer study of some novel iron-bis-glyoxime and iron-tris-glyoxime complexes

Dioximes as ligands are used as analytical reagents and serve as models for biological systems as well as catalysts in chemical processes. A number of novel mixed complexes of the type [Fe(DioxH)2(amine)2] have been prepared and characterised by FTIR, 57Fe Mössbauer and mass spectroscopy by us. We have found strong Fe–N donor acceptor interactions and iron occurred in low-spin FeII state in all complexes. Later, we have also found that the incorporation of branching alkyl chains (isopropyl) in the complexes alters the Fe–N bond length and results in high-spin iron(II) state [1, 2]. The question arises: can the spin state of iron be manipulated generally by replacing the short alkyl chains with high volume demand ones in Fe-azomethine-amine complexes? To answer the question we have synthetized novel iron-bis-glioxime and iron-tris-gloxime complexes when long chain alkyl or aromatic ligands replaced the short alkyl ones and studied by 57Fe Mössbauer spectroscopy, MS, FTIR, UV-VIS, TG-DTA-DTG and XRD methods. Novel iron-bis-glyoxime and iron-tris-glyoxime type complexes, [Fe(Diethyl-Diox)3(BOH)2], [Fe(Diethyl-Diox)3(BOEt)2] and [Fe(phenyl-Me-Diox)3(BOEt)2], were synthesized similarly as described in [2]. The FTIR, UV-VIS, TG-DTA-DTG and MS measurements indicated that the expected novel complexes could be successfully synthesized

Synthetic Lethality of Chk1 Inhibition Combined with p53 and/or p21 Loss During a DNA Damage Response in Normal and Tumor Cells

Cell cycle checkpoints ensure genome integrity and are frequently compromised in human cancers. A therapeutic strategy being explored takes advantage of checkpoint defects in p53-deficient tumors in order to sensitize them to DNA-damaging agents by eliminating Chk1-mediated checkpoint responses. Using mouse models, we demonstrated that p21 is a key determinant of how cells respond to the combination of DNA damage and Chk1 inhibition (combination therapy) in normal cells as well as in tumors. Loss of p21 sensitized normal cells to the combination therapy much more than did p53 loss and the enhanced lethality was partially blocked by CDK inhibition. In addition, basal pools of p21 (p53 independent) provided p53 null cells with protection from the combination therapy. Our results uncover a novel p53-independent function for p21 in protecting cells from the lethal effects of DNA damage followed by Chk1 inhibition. As p21 levels are low in a significant fraction of colorectal tumors, they are predicted to be particularly sensitive to the combination therapy. Results reported in this study support this prediction

Treatment of chronic anterior shoulder dislocation by open reduction and simultaneous Bankart lesion repair

<p>Abstract</p> <p>Background</p> <p>Untreated chronic shoulder dislocation eventually leads to functional disability and pain. Open reduction with different fixation methods have been introduced for most chronic shoulder dislocation. We hypothesized that open reduction and simultaneous Bankart lesion repair in chronic anterior shoulder dislocation obviates the need for joint fixation and leads to better results than previously reported methods.</p> <p>Methods</p> <p>Eight patients with chronic anterior dislocation of shoulder underwent open reduction and capsulolabral complex repair after an average delay of 10 weeks from injury. Early motion was allowed the day after surgery in the safe position and the clinical and radiographic results were analyzed at an average follow-up of one year.</p> <p>Results</p> <p>The average Rowe and Zarin's score was 86 points. Four out of eight shoulders were graded as excellent, three as good and one as fair (Rowe and Zarins system). All patients were able to perform their daily activities and they had either mild or no pain. Anterior active forward flexion loss averaged 18 degrees, external active rotation loss averaged 17.5 degrees and internal active rotation loss averaged 3 vertebral body levels. Mild degenerative joint changes were noted in one patient.</p> <p>Conclusion</p> <p>The results show that the overall prognosis for this method of operation is more favorable than the previously reported methods and we recommend concomitant open reduction and capsulolabral complex repair for the treatment of old anterior shoulder dislocation.</p> <p>Level of Evidence</p> <p>Therapeutic study, Level IV (case series [no, or historical, control group])</p

The role of serological testing in the SARS-CoV-2 outbreak

Antibody tests for the novel coronavirus, SARS-CoV2, have been developed both as rapid diagnostic assays and for high-throughput formal serology platforms. Although these tests may be a useful adjunct to a diagnostic strategy, they have a number of limitations. Because of the antibody and viral dynamics of the coronavirus, their sensitivity can be variable, especially at early time points after symptom onset. Additional data are required on the performance of the tests in the South African population, especially with regard to development and persistence of antibody responses and whether antibodies are protective against reinfection. These tests may, however, be useful in guiding the public health response, providing data for research (including seroprevalence surveys and vaccine initiatives) and development of therapeutic strategies

Power estimation of tests in log-linear non-uniform association models for ordinal agreement

<p>Abstract</p> <p>Background</p> <p>Log-linear association models have been extensively used to investigate the pattern of agreement between ordinal ratings. In 2007, log-linear non-uniform association models were introduced to estimate, from a cross-classification of two independent raters using an ordinal scale, varying degrees of distinguishability between distant and adjacent categories of the scale.</p> <p>Methods</p> <p>In this paper, a simple method based on simulations was proposed to estimate the power of non-uniform association models to detect heterogeneities across distinguishabilities between adjacent categories of an ordinal scale, illustrating some possible scale defects.</p> <p>Results</p> <p>Different scenarios of distinguishability patterns were investigated, as well as different scenarios of marginal heterogeneity within rater. For sample size of N = 50, the probabilities of detecting heterogeneities within the tables are lower than .80, whatever the number of categories. In additition, even for large samples, marginal heterogeneities within raters led to a decrease in power estimates.</p> <p>Conclusion</p> <p>This paper provided some issues about how many objects had to be classified by two independent observers (or by the same observer at two different times) to be able to detect a given scale structure defect. Our results also highlighted the importance of marginal homogeneity within raters, to ensure optimal power when using non-uniform association models.</p

Sisonke phase 3B open-label study : lessons learnt for national and global vaccination scale-up during epidemics

Sisonke is a multicentre, open-label, single-arm phase 3B vaccine implementation study of healthcare workers (HCWs) in South Africa, with prospective surveillance for 2 years. The primary endpoint is the rate of severe COVID‑19, including hospitalisations and deaths. The Sisonke study enrolled and vaccinated participants nationally at potential vaccination roll-out sites between 17 February and 26 May 2021. After May 2021, additional HCWs were vaccinated as part of a sub-study at selected clinical research sites. We discuss 10 lessons learnt to strengthen national and global vaccination strategies:(i) consistently advocate for vaccination to reduce public hesitancy; (ii) an electronic vaccination data system (EVDS) is critical; (iii) facilitate access to a choice of vaccination sites, such as religious and community centres, schools, shopping malls and drive-through centres; (iv) let digitally literate people help elderly and marginalised people to register for vaccination; (v) develop clear ‘how to’ guides for vaccine storage, pharmacy staff and vaccinators; (vi) leverage instant messaging platforms, such as WhatsApp, for quick communication among staff at vaccination centres; (vii) safety is paramount – rapid health assessments are needed at vaccination centres to identify people at high risk of serious adverse events, including anaphylaxis or thrombosis with thrombocytopenia syndrome. Be transparent about adverse events and contextualise vaccination benefits, while acknowledging the small risks; (viii) provide real-time, responsive support to vaccinees post vaccination and implement an accessible national vaccine adverse events surveillance system; (ix) develop efficient systems to monitor and investigate COVID‑19 breakthrough infections; and (x) flexibility and teamwork are essential in vaccination centres across national, provincial and district levels and between public and private sectors.The Sisonke study is funded by the South African Medical Research Council, National Treasury through the South African National Department of Health and by the Solidarity Fund, the ELMA Vaccines and Immunisation Foundation, the Michael and Susan Dell Foundation and the Bill and Melinda Gates Foundation.http://www.samj.org.zadm2022Paediatrics and Child Healt

Infection pre-Ad26.COV2.S-vaccination primes greater class switching and reduced CXCR5 expression by SARS-CoV-2-specific memory B cells

Neutralizing antibodies strongly correlate with protection for COVID-19 vaccines, but the corresponding memory B cells that form to protect against future infection are relatively understudied. Here we examine the effect of prior SARS-CoV-2 infection on the magnitude and phenotype of the memory B cell response to single dose Johnson and Johnson (Ad26.COV2.S) vaccination in South African health care workers. Participants were either naïve to SARS-CoV-2 or had been infected before vaccination. SARS-CoV-2-specific memory B-cells expand in response to Ad26.COV2.S and are maintained for the study duration (84 days) in all individuals. However, prior infection is associated with a greater frequency of these cells, a significant reduction in expression of the germinal center chemokine receptor CXCR5, and increased class switching. These B cell features correlated with neutralization and antibody-dependent cytotoxicity (ADCC) activity, and with the frequency of SARS-CoV-2 specific circulating T follicular helper cells (cTfh). Vaccination-induced effective neutralization of the D614G variant in both infected and naïve participants but boosted neutralizing antibodies against the Beta and Omicron variants only in participants with prior infection. In addition, the SARS-CoV-2 specific CD8+ T cell response correlated with increased memory B cell expression of the lung-homing receptor CXCR3, which was sustained in the previously infected group. Finally, although vaccination achieved equivalent B cell activation regardless of infection history, it was negatively impacted by age. These data show that phenotyping the response to vaccination can provide insight into the impact of prior infection on memory B cell homing, CSM, cTfh, and neutralization activity. These data can provide early signals to inform studies of vaccine boosting, durability, and co-morbidities