Multiparametric MRI with diffusion-weighted imaging in predicting response to chemotherapy in cases of osteosarcoma and Ewing’s sarcoma

Objective:To evaluate the multiparametric MRI in predicting chemotherapy response in pathologically proven cases of osteosarcoma and Ewing’s sarcoma. Correlation between the tumor size changes and internal breakdown using RECIST 1.1, modified RECIST, quantitative apparent diffusion coefficient (ADC) and tumor volume as well as dynamic contrast-enhanced MRI (DCE-MRI).Methods:The study included 104 patients pathologically proved osteosarcoma (53) and Ewing`s sarcoma (51) underwent MRI examinations; before and after chemotherapy. All patients were assessed using the RECIST 1.1 criteria, m-RECIST, quantitative ADC, and tumor volume evaluation. 21 patients underwent DCE-MRI curve type with quantitative parameters. Correlation between the different evaluations was carried out. Results were correlated with the post-operative pathology in 42 patients who underwent surgery and for statistical evaluation, Those patients were classified into responders (≥90% necrosis) and non-responders (<90% necrosis).Results:The initial mean ADC of 104 patients of osteosarcoma and Ewing’s sarcoma (0.90 ± 0.29) and (0.71 ± 0.16) respectively, differed significantly from that after treatment (1.62 ± 0.46) and (1.6 ± 0.39) respectively with (p<0.001).ADC variations (ADC%) in the non-progressive group were higher than those of the progressive group (128.3 ± 63.49 vs 36.34 ± 78.7) % with (p<0.001).ADC values and ADC variations were inversely correlated with morphologic changes, regardless of the effectiveness of chemotherapy expressed as changes in tumor size based on (RECIST 1.1, RECIST, and 3D volume). Linear regression analysis revealed a Pearson correlation coefficient of r=-0.427, -0.498 and -0.408, respectively with (p<0.001).An increase in the ADC value was not always associated with a reduction in tumor volume. The disease control rate (defined as the percentage of CR+PR+SD patients) was 89.4% and 93.9% according to RECIST 1.1 and m-RECIST respectively.42 out of the 104 patients had postsurgical histological evaluation as regards the chemotherapeutic response divided into two groups. ADC values showed a statistically significant difference between Group A and Group B being more evident with minimum ADC% (p<0.001).Conclusion:Quantitative diffusion-weighted imaging with ADC mapping and ADC % after chemotherapy allows a detailed analysis of the treatment response in osteosarcoma and Ewing’s sarcoma. The therapeutic response can be underestimated using RECIST 1.1, so the modified RECIST should be also considered.Advances in knowledge:Quantitative ADC especially ADC% provided an accurate non-invasive tool in the assessment of post-therapeutic cases of osteosarcoma and Ewing''s sarcoma     

Improving the Th1 cellular efficacy of the lead Yersinia pestis rF1-V subunit vaccine using SA-4-1BBL as a novel adjuvant

The lead candidate plague subunit vaccine is the recombinant fusion protein rF1-V adjuvanted with alum. While alum generates Th₂ regulated robust humoral responses, immune protection against Yersinia pestis has been shown to also involve Th₁ driven cellular responses. Therefore, the rF1-V-based subunit vaccine may benefit from an adjuvant system that generates a mixed Th₁ and humoral immune response. We herein assessed the efficacy of a novel SA-4-1BBL costimulatory molecule as a Th₁ adjuvant to improve cellular responses generated by the rF1-V vaccine. SA-4-1BBL as a single adjuvant had better efficacy than alum in generating CD4⁺ and CD8⁺ T cells producing TNFα and IFNγ, signature cytokines for Th₁ responses. The combination of SA-4-1BBL with alum further increased this Th₁ response as compared with the individual adjuvants. Analysis of the humoral response revealed that SA-4-1BBL as a single adjuvant did not generate a significant Ab response against rF1-V, and SA-4-1BBL in combination with alum did not improve Ab titers. However, the combined adjuvants significantly increased the ratio of Th₁ regulated IgG_2c in C57BL/6 mice to the Th₂ regulated IgG₁. Finally, a single vaccination with rF1-V adjuvanted with SA-4-1BBL + alum had better protective efficacy than vaccines containing individual adjuvants. Taken together, these results demonstrate that SA-4-1BBL improves the protective efficacy of the alum adjuvanted lead rF1-V subunit vaccine by generating a more balanced Th₁ cellular and humoral immune response. As such, this adjuvant platform may prove efficacious not only for the rF1-V vaccine but also against other infections that require both cellular and humoral immune responses for protection.     

Vitamin D receptor gene polymorphism as possible risk factor in rheumatoid arthritis and rheumatoid related osteoporosis

Objective

To study the role of VDR polymorphisms as risk factor for RA and osteoporosis, and whether osteoporosis complicating RA is due to RA or VDR polymorphisms.

Methods

VDR gene polymorphisms ApaI, TaqI, BsmI and FokI were typed by RFLP for 128 RA patients, 30 postmenopausal osteoporotic females and 150 healthy controls.

Results

Significant differences were found between patients and healthy controls in the frequency of BsmI and TaqI (Pc < 0.05) but no significant associations were found for FokI and ApaI polymorphisms except for aa genotype (Pc < 0.001). Titers of RF were higher with aa and bb genotypes. Anti-CCP and CRP levels were higher with aa genotype and more bone loss was associated with Bb genotype. Ff genotype frequency was higher in RA patients with osteoporosis than those without osteoporosis.

Conclusions

The ApaI, BsmI and TaqI polymorphisms may be a susceptibility risk factors for RA and the Ff genotype may be responsible for development of osteoporosis in RA Egyptian patients. However, the present study needs to be replicated in a large number of patients from allover the Egypt and also in multi-ethnic populations.     

Effects of vitamin K in postmenopausal women: Mini review

Possible benefits of vitamin K on bone health, fracture risk, markers of bone formation and resorption, cardiovascular health, and cancer risk in postmenopausal women have been investigated for over three decades; yet there is no clear evidence-based universal recommendation for its use.     

Scientific principles of regenerative medicine and their application in the female reproductive system

The goal of regenerative medicine is to repair, replace, or regenerate diseased tissues/organs in order to restore normal function. In this paper we will first discuss the general principle of regenerative medicine and the various techniques and approaches that have been used to replace or regenerate cells in diseased tissues and organs. Then, we will review different regenerative medicine approaches that have been used to treat specific diseased tissues and organs of the reproductive system in both animal and human experiments. It is clear from this article that regenerative medicine holds significant promise, and we hope that the review will serve as a platform for further development of regenerative medicine technologies for the treatment of inadequacies of the reproductive system.     

EMAS position statement: Individualized breast cancer screening versus population-based mammography screening programmes

Introduction

Breast cancer is the most prevalent cancer in women, with slightly more than ten percent developing the disease in Western countries. Mammography screening is a well established method to detect breast cancer.

Aims

The aim of the position statement is to review critically the advantages and shortcomings of population based mammography screening.

Materials and methods

Literature review and consensus of expert opinion.

Results and conclusion

Mammography screening programmes vary worldwide. Thus there are differences in the age at which screening is started and stopped and in the screening interval. Furthermore differences in screening quality (such as equipment, technique, resolution, single or double reading, recall rates) result in a sensitivity varying from 70% to 94% between studies. Reporting results of screening is subject to different types of bias such as overdiagnosis. Thus because of the limitations of population-based mammography screening programmes an algorithm for individualized screening is proposed.     

Validation of LittlEARS® Early Speech Production Questionnaire in Arabic-speaking children with normal hearing

Objectives:To validate an Arabic version of the LittlEARS^® Early Speech Production Questionnaire (LEESPQ), which assesses the early development of speech and language in infants between 0 and 18 months, in Arabic-speaking children with normal hearing in Saudi Arabia.Methods:This is a cross-sectional study conducted in the city of Riyadh, Saudi Arabia between September and December 2020. Parents completed the LEESPQ regarding their child’s speech production development. To assess the ability of normal hearing children aged 0-18 months in developing speech and language production, a norm curve has been generated based on the standardized values that were calculated from the Arabic normal-hearing data set.Results:A total of 198 questionnaires were analyzed. The total score on the LEESPQ correlated with age, gender, and bilingualism. A norm curve for early speech production in children with normal hearing was created.Conclusion:The Arabic version of LEESPQ appears to be a valid questionnaire that can be used in the assessment of early language and speech development of Arabic-speaking children with normal hearing in the age range of 0-18 months. The Arabic version of the LEESPQ might also be a useful tool to detect developmental delays and hearing disorders in young children.     

In silico identification of potential SARS COV-2 2′-O-methyltransferase inhibitor: fragment-based screening approach and MM-PBSA calculations

In the present era, there are many efforts trying to face the emerging and successive waves of the COVID-19 pandemic. This has led to considering new and unusual targets for SARS CoV-2. 2′-O-Methyltransferase (nsp16) is a key and attractive target in the SARS CoV-2 life cycle since it is responsible for the viral RNA protection via a cap formation process. In this study, we propose a new potential inhibitor for SARS COV-2 2′-O-methyltransferase (nsp16). A fragment library was screened against the co-crystal structure of the SARS COV-2 2′-O-methyltransferase complexed with Sinefungin (nsp16 – PDB ID: 6WKQ), and consequently the best proposed fragments were linked via a de novo approach to build molecule AP-20. Molecule AP-20 displayed a superior docking score to Sinefungin and reproduced the key interactions in the binding site of 2′-O-methyltransferase. Three molecular dynamic simulations of the 2′-O-methyltransferase apo structure and its complexed forms with AP-20 and Sinefungin were performed for 150 nano-seconds to provide insights on the dynamic nature of such setups and to assess the stability of the proposed AP-20/enzyme complex. AP-20/enzyme complex demonstrated better stability for the ligand–enzyme complex compared to Sinefungin in a respective setup. Furthermore, MM-PBSA binding free energy calculations showed a better profile for AP-20/enzyme complex compared to Sinefungin/enzyme complex emphasizing the potential inhibitory effect of AP-20 on SARS COV-2 2′-O-methyltransferase. We endorse our designed molecule AP-20 to be further explored via experimental evaluations to confront the spread of the emerging COVID-19. Also, in silico ADME profiling has ascribed to AP-20 an excellent safety and metabolic stability profile.

The identification of AP-20 as a potential SARS COV-2 2′-O-methyltransferase inhibitor: fragment-based screening approach and MM-PBSA calculations.     

Selective and sensitive electrochemical sensors based on an ion imprinting polymer and graphene oxide for the detection of ultra-trace Cd(ii) in biological samples

New selective and sensitive electrochemical sensors were designed based on the deposition of a promising ion imprinted polymer (IIP) on the surface of glassy carbon electrode (GCE) for the detection and monitoring of Cd(ii) in different real samples. Herein, a highly selective Cd-imprinted polymer was successfully synthesized using a novel heterocyclic compound based on the benzo[f]chromene scaffold that acted as a complexing agent and a functional monomer in the presence of azobisisobutyronitrile (initiator) and ethylene glycol dimethacrylate (cross-linker). The characterization of the synthesized chelating agent and IIP was performed using FT-IR, SEM, ¹H-NMR, EIMS, and EDX analyses. After that, the voltammetric sensor was manufactured by introducing graphene oxide (GO) on the surface of GCE; then, the IIP was grown by a drop coating technique. The electrochemical characterization of the voltammetric sensor (IIP/GO@GCE) was performed by CV and EIS. For comparison, the potentiometric sensor was also prepared by embedding IIP in plasticized polyvinyl chloride and depositing it as one layer on the GCE surface. Anodic stripping voltammetry was used to construct the calibration graph; the IIP/GO@GCE exhibited a wider detection range (4.2 × 10⁻¹²–5.6 × 10⁻³ mol L⁻¹) and extremely low detection limit (7 × 10⁻¹⁴ mol L⁻¹) for Cd(ii). Meanwhile, the potentiometric sensor showed a linear calibration curve for Cd(ii) over a concentration range from 7.3 × 10⁻⁸ mol L⁻¹ to 2.4 × 10⁻³ mol L⁻¹ with a detection limit of 6.3 × 10⁻¹⁰ mol L⁻¹. Furthermore, both sensors offered outstanding selectivity for Cd(ii) over a wide assortment of other common ions, high reproducibility, and excellent stability.

New selective and sensitive electrochemical sensors were designed based on the deposition of a promising ion imprinted polymer (IIP) on the surface of glassy carbon electrode (GCE) for the detection and monitoring of Cd(ii) in different real samples.