IMPROVEMENT OF PHARMACEUTICAL SPECIALISTS DURING THE PERIOD OF REFORMING MEDICINE AND PHARMACY IN UKRAINE

The article describes the need to determine the main directions and priorities of the development of the pharmaceutical industry in Ukraine, which is conditioned by real political and socioeconomic processes. The main element here is the introduction and development of a formular system - a complex of management methods for the application of rational, organizational and cost-effective methods of supplying and using drugs to ensure, in specific conditions, high quality medical care and optimal use of available resources.Key words: pharmaceutical industry, pharmacist, pharmacist, higher education

Enhanced photocatalytic activity of CuWO4 doped TiO2 photocatalyst towards carbamazepine removal under UV irradiation

Abatement of contaminants of emerging concerns (CECs) in water sources has been widely studied employing TiO2 based heterogeneous photocatalysis. However, low quantum energy yield among other limitations of titania has led to its modification with other semiconductor materials for improved photocatalytic activity. In this work, a 0.05 wt.% CuWO4 over TiO2 was prepared as a powder composite. Each component part synthesized via the sol-gel method for TiO2, and CuWO4 by co-precipitation assisted hydrothermal method from precursor salts, underwent gentle mechanical agitation. Homogenization of the nanopowder precursors was performed by zirconia ball milling for 2 h. The final material was obtained after annealing at 500◦C for 3.5 h. Structural and morphological characterization of the synthesized material has been achieved employing X-ray diffraction (XRD), Fourier transform infra-red (FTIR) spectroscopy, Brunauer–Emmett–Teller (BET) N2 adsorption–desorption analysis, Scanning electron microscopy-coupled Energy dispersive X-ray spectroscopy (SEM-EDS), Transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and UV-Vis diffuse reflectance spectroscopy (UV-vis DRS) for optical characterization. The 0250.05 wt.% CuWO4-TiO2 catalyst was investigated for its photocatalytic activity over carbamazepine (CBZ), achieving a degradation of almost 100% after 2 h irradiation. A comparison with pure TiO2 prepared under those same conditions was made. The effect of pH, chemical scavengers, H2O2 as well as contaminant ion effects (anions, cations), and humic acid (HA) was investigated, and their related influences on the photocatalyst efficiency towards CBZ degradation highlighted accordingly

Anatomic and Cellular Niches for Mycobacterium tuberculosis in Latent Tuberculosis Infection.

Latent tuberculosis has been recognized for over a century, but discovery of new niches, where Mycobacterium tuberculosis resides, continues. We evaluated literature on M.tuberculosis locations during latency, highlighting that mesenchymal and hematopoietic stem cells harbor organisms in sensitized asymptomatic individuals.This work was supported by grants from the Medical Research Council (ref. MR/P024548/1; to A. R. M.) and the DELTAS Africa Initiative (ref. DEL-15-011 [to J. M.], via THRiVE-2). The DELTAS Africa Initiative is an independent funding scheme of the AAS’s Alliance for Accelerating Excellence in Science in Africa and supported by the NEPAD Agency with funding from the Wellcome Trust Grant No. 107742/Z/15/Z and the United Kingdom government

Transcriptional Landscape of 3D vs. 2D Ovarian Cancer Cell Models

Data Availability Statement: RNAseq and array data can be found via the following NCBI accession codes: PRJNA472611, PRJNA530150, PRJNA564843, PRJNA564843, PRJNA232817, and PRJNA318768. A full list of samples can be viewed in Supplementary Table S1 available online at https://www.mdpi.com/2072-6694/15/13/3350#app1-cancers-15-03350 .Simple Summary: Ovarian cancer is one of the most lethal female cancers. Numerous investigations into the development and progression of this disease have resulted in the creation of numerous three-dimensional culture models to better reflect the natural microenvironment of these tumours. In this study, we leverage the available transcriptomics and clinical and novel experimental data to evaluate the impact of the growth conditions on various cancer cells and examine whether they better approximate the behaviour of tumour cells compared to the classical two-dimensional models. Our results show that variability in the growth conditions can impact key genes and biological processes that are hallmarks of cancer, highlighting the need for future studies to identify which is the most appropriate in vitro/preclinical model to study tumour microenvironments.Supplementary Materials: The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cancers15133350/s1, Figure S1: Top enriched gene sets for 2D vs. 3D OVCAR8; Table S1: Cell line information and associated accession codes; Figure S2: Growth of SKOV3 cells from Day 2 to Day 9 showing clear spheroid-like structures; Table S2: (A) Top 150 differentially expressed genes in OVCAR8 in all three grown media: grown on agarose, collagen, Matrigel. The differential expression in each of the growth media is with respect to 2D controls of the OVCAR8; (B) Top 150 differentially expressed genes across the cell lines A1847, A2780, C30, C70, OVCAR3, OVCAR4, OVCAR5, OVCAR8, OVCAR10, PEO1, SKOV-3, UPN275 grown on agarose vs. 2D controls; (C) Top 150 differentially expressed genes in the cell lines Kuramochi, OVCAR4, and OVCAR8, grown on collagen vs. 2D controls or the respective cell lines.Copyright © 2023 by the authors. Three-dimensional (3D) cancer models are revolutionising research, allowing for the recapitulation of an in vivo-like response through the use of an in vitro system, which is more complex and physiologically relevant than traditional monolayer cultures. Cancers such as ovarian (OvCa) are prone to developing resistance, are often lethal, and stand to benefit greatly from the enhanced modelling emulated by 3D cultures. However, the current models often fall short of the predicted response, where reproducibility is limited owing to the lack of standardised methodology and established protocols. This meta-analysis aims to assess the current scope of 3D OvCa models and the differences in the genetic profiles presented by a vast array of 3D cultures. An analysis of the literature (Pubmed.gov) spanning 2012–2022 was used to identify studies with paired data of 3D and 2D monolayer counterparts in addition to RNA sequencing and microarray data. From the data, 19 cell lines were found to show differential regulation in their gene expression profiles depending on the bio-scaffold (i.e., agarose, collagen, or Matrigel) compared to 2D cell cultures. The top genes differentially expressed in 2D vs. 3D included C3, CXCL1, 2, and 8, IL1B, SLP1, FN1, IL6, DDIT4, PI3, LAMC2, CCL20, MMP1, IFI27, CFB, and ANGPTL4. The top enriched gene sets for 2D vs. 3D included IFN-α and IFN-γ response, TNF-α signalling, IL-6-JAK-STAT3 signalling, angiogenesis, hedgehog signalling, apoptosis, epithelial–mesenchymal transition, hypoxia, and inflammatory response. Our transversal comparison of numerous scaffolds allowed us to highlight the variability that can be induced by these scaffolds in the transcriptional landscape and identify key genes and biological processes that are hallmarks of cancer cells grown in 3D cultures. Future studies are needed to identify which is the most appropriate in vitro/preclinical model to study tumour microenvironments.Cancer Treatment and Research Trust and the University Hospitals Coventry and Warwickshire NHS Trust (grant no. 12899)

A Meta-analysis of 2D vs. 3D Ovarian Cancer Cellular Models

bioRxiv preprint doi: https://doi.org/10.1101/2022.12.05.519144; this version posted December 8, 2022. The copyright holder for this preprint (which was not certified by peer review, see: https://www.biorxiv.org/about/FAQ#unrefereed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license.Data Availability Statement: RNAseq and Array data can be found via the following NCBI accession codes: PRJNA472611, PRJNA530150, PRJNA564843, PRJNA564843, PRJNA232817, PRJNA318768. A full list of samples can be viewed in Supplementary table 1.Acknowledgments: The authors acknowledge the Biocenter Finland (BF) and Tampere Imaging Facility (TIF) for the service.Supplementary Materials are available online at https://www.biorxiv.org/content/10.1101/2022.12.05.519144v1.full#F11Copyright © author/funder 2022. Three-dimensional (3D) cancer models are revolutionizing research, allowing for the recapitulation of in vivo like response through the use of an in vitro system, more complex and physiologically relevant than traditional mono-layer culture. Cancers such as ovarian (OvCa), are prone to developing resistance and are often lethal, and stand to benefit greatly from the enhanced modelling emulated by 3D culture. However current models often fall short of predicted response where reproducibility is limited owing to the lack of standardized methodology and established protocols. This meta-analysis aims to assess the current scope of 3D OvCa models and the differences in genetic profile presented by a vast array of 3D cultures. A meta-analysis of the literature (Pubmed.gov) spanning 2012 – 2022, was used to identify studies with comparable monolayer (2D) counterparts in addition to RNA sequencing and microarray data. From the data 19 cell lines were found to show differential regulation in their gene expression profiles depending on the bio-scaffold (i.e. agarose, collagen or Matrigel) compared to 2D cell cultures. Top genes differentially expressed 2D vs. 3D include C3, CXCL1, 2 and 8, IL1B, SLP1, FN1, IL6, DDIT4, PI3, LAMC2, CCL20, MMP1, IFI27, CFB, and ANGPTL4. Top Enriched Gene sets for 2D vs. 3D include IFN-α and IFN-γ Response, TNF-α signalling, IL-6-JAK-STAT3 signalling, angiogenesis, hedgehog signalling, apoptosis, epithelial mesenchymal transition, hypoxia, and inflammatory response. Our transversal comparison of numerous scaffolds allowed us to highlight the variability that can be induced by these scaffolds in the transcriptional landscape as well as identifying key genes and biological processes that are hallmarks of cancer cells grown in 3D cultures. Future studies are needed to identify which is the most appropriate in vitro/preclinical model to study tumour microenvironment.Cancer Treatment & Research Trust and University Hospitals Coventry and Warwickshire NHS Trust (grant no. 12899)

Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity

Morbid Obesity as a Risk Factor for Hospitalization and Death Due to 2009 Pandemic Influenza A(H1N1) Disease

BACKGROUND: Severe illness due to 2009 pandemic A(H1N1) infection has been reported among persons who are obese or morbidly obese. We assessed whether obesity is a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1), independent of chronic medical conditions considered by the Advisory Committee on Immunization Practices (ACIP) to increase the risk of influenza-related complications. METHODOLOGY/PRINCIPAL FINDINGS: We used a case-cohort design to compare cases of hospitalizations and deaths from 2009 pandemic A(H1N1) influenza occurring between April-July, 2009, with a cohort of the U.S. population estimated from the 2003-2006 National Health and Nutrition Examination Survey (NHANES); pregnant women and children <2 years old were excluded. For hospitalizations, we defined categories of relative weight by body mass index (BMI, kg/m(2)); for deaths, obesity or morbid obesity was recorded on medical charts, and death certificates. Odds ratio (OR) of being in each BMI category was determined; normal weight was the reference category. Overall, 361 hospitalizations and 233 deaths included information to determine BMI category and presence of ACIP-recognized medical conditions. Among >or=20 year olds, hospitalization was associated with being morbidly obese (BMI>or=40) for individuals with ACIP-recognized chronic conditions (OR = 4.9, 95% CI 2.4-9.9) and without ACIP-recognized chronic conditions (OR = 4.7, 95%CI 1.3-17.2). Among 2-19 year olds, hospitalization was associated with being underweight (BMI<or=5(th) percentile) among those with (OR = 12.5, 95%CI 3.4-45.5) and without (OR = 5.5, 95%CI 1.3-22.5) ACIP-recognized chronic conditions. Death was not associated with BMI category among individuals 2-19 years old. Among individuals aged >or=20 years without ACIP-recognized chronic medical conditions death was associated with obesity (OR = 3.1, 95%CI: 1.5-6.6) and morbid obesity (OR = 7.6, 95%CI 2.1-27.9). CONCLUSIONS/SIGNIFICANCE: Our findings support observations that morbid obesity may be associated with hospitalization and possibly death due to 2009 pandemic H1N1 infection. These complications could be prevented by early antiviral therapy and vaccination