Investigating Potential Cancer Therapeutics: Insight into Histone Deacetylases (HDACs) Inhibitions.

Histone deacetylases (HDACs) are enzymes that remove acetyl groups from ɛ-amino of histone, and their involvement in the development and progression of cancer disorders makes them an interesting therapeutic target. This study seeks to discover new inhibitors that selectively inhibit HDAC enzymes which are linked to deadly disorders like T-cell lymphoma, childhood neuroblastoma, and colon cancer. MOE was used to dock libraries of ZINC database molecules within the catalytic active pocket of target HDACs. The top three hits were submitted to MD simulations ranked on binding affinities and well-occupied interaction mechanisms determined from molecular docking studies. Inside the catalytic active site of HDACs, the two stable inhibitors LIG1 and LIG2 affect the protein flexibility, as evidenced by RMSD, RMSF, Rg, and PCA. MD simulations of HDACs complexes revealed an alteration from extended to bent motional changes within loop regions. The structural deviation following superimposition shows flexibility via a visual inspection of movable loops at different timeframes. According to PCA, the activity of HDACs inhibitors induces structural dynamics that might potentially be utilized to define the nature of protein inhibition. The findings suggest that this study offers solid proof to investigate LIG1 and LIG2 as potential HDAC inhibitors.

Factors affecting citizen safety of urban transportation service in Bangladesh: The case of Pabna municipality.

Background: With the rapid growth of cities, the extent of road accidents has increased, posing a threat to the safety of citizens. In Bangladesh, like many other countries, urban areas face a high incidence of road accidents, leading to loss of life, injuries, and economic costs. This research aims to investigate the factors affecting citizen safety of urban transportation service in Bangladesh. Methods: This study utilized verbal interviews maintained by questionnaires to gather data on citizen perception regarding factors impacting transportation safety. The questionnaire consisted of two sections, collecting non-parametric data on travel behavior and socioeconomic factors, and parametric data on factors related to transportation safety. The dataset was subsequently analyzed using statistical devices such as descriptive statistics, Principal Component Analysis (PCA), Pearson's Correlation Matrix (PCM), and Cluster Analysis (CA). Results and conclusion: The findings of the study indicate strong significant correlations among several pairs of variables. Notably, traffic rules and enforcement, and driver travel behavior demonstrate a strong positive correlation of 0.784. Similarly, vehicle condition and safety features, and traffic rules and enforcement display a robust positive association of 0.764. PCA demonstrate 23% of the total variance, with a significant positive loading affecting citizen safety, which is influenced by traffic rules enforcement and drivers' travel behavior. The research findings emphasize the implication of traffic rule enforcement and responsible driver behavior in ensuring citizen safety. In Bangladesh, inadequate transportation regulation enforcement has led to high rates of reckless driving and traffic accidents, especially among pedestrians, cyclists, and motorcyclists.

Presence of CRISPR CAS-Like Sequences as a Proposed Mechanism for Horizontal Genetic Exchanges between Trichomonas vaginalis and Its Associated Virus: A Comparative Genomic Analysis with the First Report of a Putative CRISPR CAS Structures in Eukaryotic Cells.

Introduction: Trichomonas vaginalis genome is among the largest genome size and coding capacities. Combinations of gene duplications, transposon, repeated sequences, and lateral gene transfers (LGTs) have contributed to the unexpected large genomic size and diversity. This study is aimed at investigating genomic exchange and seeking for presence of the CRISPR CAS system as one of the possible mechanisms for some level of genetic exchange. Material and Methods. In this comparative analysis, 398 publicly available Trichomonas vaginalis complete genomes were investigated for the presence of CRISPR CAS. Spacer sequences were also analyzed for their origin using BLAST. Results: We identified a CRISPR CAS (Cas3). CRISPR spacers are highly similar to transposable genetic elements such as viruses of protozoan parasites, especially megavirals, some transposons, and, interestingly, papillomavirus and HIV-1 in a few cases. Discussion. There is a striking similarity between the prokaryotes/Archaean CRISPR and what we find as eukaryotic CRISPR. About 5-10% of the 398 T. vaginalis possess a CRISPR structure. Conclusion: According to sequences and their organization, we assume that these repeated sequences and spacer, along with their mentioned features, could be the eukaryotic homolog of prokaryotes and Archaean CRISPR systems and may involve in a process similar to the CRISPR function.

Identification of potential inhibitors of HER2 targeting breast cancer-a structure-based drug design approach.

Breast cancer is one of the most prevalent and malignant cancers in women. Most breast cancer patients show overexpression of the HER2 protein. The current study focused on identifying potent inhibitors of HER2 using a structure-based drug design approach. Prefiltered compounds from the Drugbank and the ZINC database were docked on HER2 protein using the FlexX docking tool of LeadIT. The docking study identified the 12 best molecules that interacted strongly with the active site of HER2 and also fulfilled the ADMET parameters. The complexes of these compounds with HER2 were further subjected to molecular dynamics simulation using GROMACS 2021.4, followed by the end-state MMGBSA binding energy calculations. The RMSD analysis was conducted to study the conformational changes, which revealed stability throughout the 100 ns simulation period. The local flexibility and dynamics of the simulated ligand-protein complexes were studied using RMSF analysis. The values of the radius of gyration were computed to analyze the compactness of HER2. The MMGBSA analysis provided insights into the energetic aspects of the system. The compound DB15187 emerged as the most potent candidate, showing MMGBSA-computed binding energy of -63.60 ± 3.39 kcal/mol. The study could help develop targeted therapies for HER2-positive breast cancer.Communicated by Ramaswamy H. Sarma.

Evaluation of the Role of MAP4K4 in Focal Adhesion Dynamics and Regulation of Cell Migration of Breast Cancer Cell Line MDA-MB-231.

In the migration and metastasis of cancer cells, it is necessary to rotate the focal adhesion (FA). MAP4K4 plays a vital role in the formation of cytoskeletal regeneration, but its role in regulating FA dynamics and cancer cell migration is not well understood. This present aimed to investigate the role of MAP4K4 in regulating FA dynamics and cell migration in the human breast cancer cell line. For this purpose, different variants, including MAP4K4 (wild type), partial active mutation kinase (MAP4K4-T178D), mutant with inactivated or reduced activity kinase (MAP4K4-T178A) and inactive kinase mutation (MAP4K4-K54R) was used in the evaluation. GFP-paxillin was also used as a marker in basal breast cancer cells (MDA-MB-231) in determining FA dynamics. Time-lapse and confocal microscopes were used to record FA dynamics and cell migration. The present study's findings showed that cells expressing MAP4K4-K54R, MAP4K4-T178D and MAP4K4-T178A type slowly down the FA turnover rates and had much larger FAs than those expressing WT MAP4K4 in MDA-MB-231 breast cancer cell line. Furthermore, inhibiting MAP4K4 strongly inhibited FA formation and reduced cell migration speed. In conclusion, MAP4K4 regulates FA dynamics and cancer cell migration, most probably through activating FA proteins and cytoskeleton.

The Role of Akt/Rab5A Signalling in Regulating Cell Migration of MDA-MB-231 Breast Cancer Cell Line.

Rab5A and Akt pathways are reported to be responsible for the invasiveness of cancer cells, indicated by the fact that Rab5A activates the downstream Phosphoinositide-3-kinases (PI3K)/Akt signalling pathway, which results in promoting cancer metastasis. However, little attention has been given to the emerging role of Rab5A and Akt signalling pathways in regulating the direction of MDA-MB-231 cell migration. MDA-MB-231 breast cancer cell line was used as a model in this study because it is highly metastatic and motile. Time-lapse microscopy was used to examine the effect of Akt and Rab5A inhibitors on cell migration, proliferation and wound healing. Later, the cells were transfected with GFP-Akt-PH or GFP-Rab5A (used as a biosensor to detect Akt and Rab5A). Therefore, confocal time-lapse images were used to visualize Akt and Rab5A at the front and rear edges of the cells. The recorded data demonstrated that Akt and Rab5A inhibition reduced cell migration, proliferation and wound healing. The results of the current study also demonstrated that Akt localizes at the trailing edge while Rab5A localize more at the leading edge than the trailing edge of cells. This study suggests that Akt and Rab5A inhibition might regulate the direction of breast cancer migration.

Elucidating novel antibacterial compounds from the NPASS database against the FimH lectin domain for the treatment of urinary tract infections: an in-silico study.

The increase in multidrug-resistant pathogens in urinary tract infections (UTIs) among communities and hospitals threatens our ability to treat these common pathogens. Uropathogenic Escherichia coli (UPEC) strains are the most frequent uropathies linked to the development of UTIs. This work aims to introduce bioactive natural products via virtual screening of small molecules from a public database to prevent biofilm formation by inhibiting FimH, a type 1 fimbriae that plays a crucial role in UPEC pathogenicity. A total of 30926 small molecules from the NPASS database were subjected to screening via molecular docking. Followed by performing in silico ADME studies, seven molecules showed promising docking results ranging from -6.8 to -8.7 kcal/mol. As a result of the docking score findings, 100 ns Molecular dynamics (MD) simulations were performed. Based on MM-PBSA analysis, NPC313334 ligand showed high binding affinity -42 and stability with the binding pocket of FimH protein during molecular dynamic simulations. DFT calculations were also performed on the ligands to calculate the HOMO-LUMO energies of the compounds in order to an idea about their structure and reactivity. This research suggests that NPC313334 may be a possible antibacterial drug candidate that targets FimH to reduce the number of UPEC-related urinary tract infections.Communicated by Ramaswamy H. Sarma.

Regulation of Focal Adhesion Dynamics and Cell Migration by PLC/PI3K-Mediated Metabolism of PtdIns (4,5) P2 in a Breast Cancer Cell Line.

Background: Focal adhesions (FAs) are highly dynamic complex structures that assembled and disassembled on an ongoing basis. The balance between the two processes mediates various aspects of cell behavior, ranging from cell adhesion to cell migration. Assembly and disassembly processes of FAs are regulated by a variety of cellular signaling proteins and adaptors. We previously demonstrated that local levels of Phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) in MDA-MB-231 cells increases during FA assembly and declines during disassembly. In this study we aimed to investigate whether PtdIns(4,5)P2 regulates FA turnover. Methods: MDA-MB-231 cells were co-transfected with a labeling vinculin (or zyxin) and the PLC𝛅1-PH biosensor to visualize FA localization and PtdIns(4,5)P2 in the cell membrane. We also used pharmacological inhibitors to determine the mechanism underlying the changes of PtdIns(4,5)P2 level during FA turnover and cell migration. Immunostaining, immunoprecipitation, and Western blotting were used to examine the localization and interaction between phospholipase C (PLC)/phosphatidylinositol 3-kinase (PI3K) FA proteins. Results: We showed that inhibition of PLC, PI3K significantly reduced the decline of PtdIns(4,5)P2 levels within FA disassembly and the slowdown rate of FA turnover and cell migration. We also showed that the inhibition of enzymes implicated in the downstream pathway of PtdIns(4,5)P2, such as diacylglycerol kinase (DAGK) and protein kinase C (PKC) significantly reduced FA turnover time and the speed of cell migration. Additionally, we demonstrated that PLC but not PI3K interact with FAs. In conclusion. Discussion: This study suggests that dynamical changes of PtdIns(4,5)P2 might regulate FA turnover and facilitate cell migration.

Kinetic Changes of Ptdins (3,4,5) P3 within Fast and Slow Turnover Rates of Focal Adhesion.

Background: The assembly and disassembly of the focal adhesions (FA) components occurs throughout life cycle of adhesion, with conservation of balance between removal and recruitment rate during temporal stages. Previous studies have demonstrated that phosphotidyilinositols play a role in regulating FA turnover. However, a little attention has been given to quantify the dynamics changes of Phosphatidylinositol 3,4,5-trisphosphate (PtdIns (3,4,5) P3) within and during fast and slow turnover rates of FA. Methods: In this study, we developed a protein purification MDA-MB-231 breast cancer cell line was used as a model in this study due to high metastatic and motile. These cells were co-transfected with GFP- paxillin/vinculin, as FA marker, and the GFP/mCherry-Btk-PH, as a biosensor to visualize PtdIns (3,4,5) P3. Confocal time-lapse images were used to monitor changes or differences in the local generation of PtdIns (3,4,5) P3 within and during assembly and disassembly of FA. Following transfection, immunostaining was used to examine the spatial co-localization between FA and PtdIns (3,4,5) P3. Results: Our data demonstrated that PtdIns (3,4,5) P3 co-localized with FAs and increase during assembly and decline during disassembly of FA which exhibits slow turnover rates and was in a constant level during assembly and disassembly of FA that displays fast turnover rates. Discussion: Our result suggested that the dynamic changes of PtdIns (3,4,5) P3, it may depend on components undergo turnover, such that early, nascent FA displays fast turnover rates and mature FA exhibits slow turnover rates. Thus, the local enrichment of PtdIns (3,4,5) P3 enhances FA assembly and disassembly activation.

Epidemiology of Child Maltreatment during the COVID-19 Pandemic in Saudi Arabia.

Child maltreatment, especially during health crises, is a major public health issue transcending cultural, social, and racial contexts. We assessed the sociodemographic and related risk factors associated with the types and rates of child maltreatment. We also assessed the economic, social, and environmental characteristics of child maltreatment victims and their perpetrators, as they were reported to the Saudi National Family Safety Program (NFSP), with consideration of the COVID-19 pandemic's impact. A secondary data analysis of a retrospective review was conducted to compare types and rates before and during the COVID-19 outbreak, utilizing descriptive and multivariate analyses on anonymized data from the NFSP. According to a predetermined list of relevant risk factors for child maltreatment outlined by the NFSP, these anonymized data were obtained and analyzed with no exclusion criteria (n = 1304). The findings showed that a child's age correlated significantly and positively with their odds of being physically maltreated; as a child's age increased by one year, on average, their corresponding predicted odds of being physically maltreatment tended to rise by a factor equal to 7.6% (p < 0.001). Neglected children, compared to those who had not been previously neglected, were predicted to be almost twice (2.23 times more) as likely to be victims of physical maltreatment on average (p < 0.001). Children were notably more likely to experience sexual abuse during the COVID-19 pandemic than those exposed to abuse during the period before (1.69 times). The COVID-19 pandemic was associated with significantly lower odds of physical child maltreatment (47.7% less). This study found no statistically significant effect of the COVID-19 pandemic on children's odds of being emotionally maltreated (p = 0.169). These findings support the existence of specific risk factors for child maltreatment for both child victims and perpetrators. They also attest to the significant differences between different types of maltreatment. A systematic, proactive system is needed to screen and document child maltreatment with a higher degree of integration with community reporting systems.

A Comparative Study to Visualize PtdIns(4,5) P2 and PtdIns(3,4,5) P3 in MDA-MB-231 Breast Cancer Cell Line.

Background: Phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5) P3) and Phosphatidylinositol 4,5-trisphosphate (PtdIns(4,5) P2] form an insignificant amount of phospholipids but play important roles in controlling membrane-bound signalling. Little attention has been given to visualize and monitor changes or differences in the local generation of PtdIns(4,5) P2 and PtdIns(3,4,5) P3 in the cell membranes of MDA-MB-231 breast cancer cell lines. Methods: PLCδ1-PH-GFP and Btk-PH-GFP were used as biosensors to detected PtdIns(4,5) P2 and PtdIns(3,4,5)P3 respectively. These biosensors and antibodies were transfected, immuostained and then visualized by confocal microscopy on different cell surfaces. Results: Our results showed that PLCδ1-PH-GFP/mCherry was localized at the cell membrane, while Btk-PH-GFP/mCherry was sometimes localized at the cell membrane but there was also a large amount of fluorescence present in the cytosol and nucleus. Our results also showed that the cells that expressed low levels of Btk-PH-GFP the fluorescence was predominantly localised to the cell membrane. While the cells that expressed high levels of Btk-PH-GFP the fluorescence was localization in the cytosol and cell membrane. Our results demonstrated that both anti-PtdIns(4,5)P2 and anti-PtdIns(3,4,5)P3 antibodies were localized everywhere in cell. Conclusion: Our results suggest that PLCδ1-PH-GFP and Btk-PH-GFP/mCherry have more specificity, reliability, suitability and accuracy than antibodies in binding with and detecting PtdIns(4,5)P2 and PtdIns(3,4,5)P3 and in studying the molecular dynamics of phospholipids in live and fixed cells.

Antibacterial Efficacy of Liposomal Formulations Containing Tobramycin and N-Acetylcysteine against Tobramycin-Resistant Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii.

The antibacterial activity and biofilm reduction capability of liposome formulations encapsulating tobramycin (TL), and Tobramycin-N-acetylcysteine (TNL) were tested against tobramycin-resistant strains of E. coli, K. pneumoniae and A. baumannii in the presence of several resistant genes. All antibacterial activity were assessed against tobramycin-resistant bacterial clinical isolate strains, which were fully characterized by whole-genome sequencing (WGS). All isolates acquired one or more of AMEs genes, efflux pump genes, OMP genes, and biofilm formation genes. TL formulation inhibited the growth of EC_089 and KP_002 isolates from 64 mg/L and 1024 mg/L to 8 mg/L. TNL formulation reduced the MIC of the same isolates to 16 mg/L. TNL formulation was the only effective formulation against all A. baumannii strains compared with TL and conventional tobramycin (in the plektonic environment). Biofilm reduction was significantly observed when TL and TNL formulations were used against E. coli and K. pneumoniae strains. TNL formulation reduced biofilm formation at a low concentration of 16 mg/L compared with TL and conventional tobramycin. In conclusion, TL and TNL formulations particularly need to be tested on animal models, where they may pave the way to considering drug delivery for the treatment of serious infectious diseases.

Heterologous prime-boost strategies for COVID-19 vaccines.

BACKGROUND/OBJECTIVE: Heterologous prime-boost doses of COVID-19 vaccines ('mix-and-match' approach) are being studied to test for the effectiveness of Oxford (AZD1222), Pfizer (BNT162b2), Moderna (mRNA-1273) and Novavax (NVX-CoV2373) vaccines for COVID in 'Com-Cov2 trial' in UK, and that of Oxford and Pfizer vaccines in 'CombivacS trial' in Spain. Later, other heterologous combinations of CoronaVac (DB15806), Janssen (JNJ-78436735), CanSino (AD5-nCOV) and other were also being trialled to explore their effectiveness. Previously, such a strategy was deployed for HIV, Ebola virus, malaria, tuberculosis, influenza and hepatitis B to develop the artificial acquired active immunity. The present review explores the science behind such an approach for candidate COVID-19 vaccines developed using 11 different platforms approved by the World Health Organization. METHODS: The candidate vaccines' pharmaceutical parameters (e.g. platforms, number needed to vaccinate and intervals, adjuvanted status, excipients and preservatives added, efficacy and effectiveness, vaccine adverse events, and boosters), and clinical aspects must be analysed for the mix-and-match approach. Results prime-boost trials showed safety, effectiveness, higher systemic reactogenicity, well tolerability with improved immunogenicity, and flexibility profiles for future vaccinations, especially during acute and global shortages, compared to the homologous counterparts. CONCLUSION: Still, large controlled trials are warranted to address challenging variants of concerns including Omicron and other, and to generalize the effectiveness of the approach in regular as well as emergency use during vaccine scarcity.

Unraveling Spatial-Spectral Dynamics of Speech Categorization Speed Using Convolutional Neural Networks.

The process of categorizing sounds into distinct phonetic categories is known as categorical perception (CP). Response times (RTs) provide a measure of perceptual difficulty during labeling decisions (i.e., categorization). The RT is quasi-stochastic in nature due to individuality and variations in perceptual tasks. To identify the source of RT variation in CP, we have built models to decode the brain regions and frequency bands driving fast, medium and slow response decision speeds. In particular, we implemented a parameter optimized convolutional neural network (CNN) to classify listeners' behavioral RTs from their neural EEG data. We adopted visual interpretation of model response using Guided-GradCAM to identify spatial-spectral correlates of RT. Our framework includes (but is not limited to): (i) a data augmentation technique designed to reduce noise and control the overall variance of EEG dataset; (ii) bandpower topomaps to learn the spatial-spectral representation using CNN; (iii) large-scale Bayesian hyper-parameter optimization to find best performing CNN model; (iv) ANOVA and posthoc analysis on Guided-GradCAM activation values to measure the effect of neural regions and frequency bands on behavioral responses. Using this framework, we observe that α-ß (10-20 Hz) activity over left frontal, right prefrontal/frontal, and right cerebellar regions are correlated with RT variation. Our results indicate that attention, template matching, temporal prediction of acoustics, motor control, and decision uncertainty are the most probable factors in RT variation.

Predictors of Mortality in COVID-19-Positive Patients On and Off CPAP: A Review From a Tertiary Care Setting in the NHS.

Introduction Since the first description of a coronavirus-related pneumonia outbreak in December 2019, the virus SARS-CoV-2 that causes the infection/disease coronavirus disease 2019 (COVID-19) has evolved into a pandemic, and as of today, millions have been affected. Objectives Our aim was to identify the predictors of mortality in COVID-19-positive patients on or off continuous positive airway pressure (CPAP). Methodology This was an observational study. Data were collected from February 2020 to April 2020 with patients admitted to the COVID-19 ward at The James Cook University Hospital, Middlesbrough, England. The inclusion criteria were COVID-19-positive patients confirmed through PCR tests on or off CPAP. Patients who had negative RT-PCR for COVID-19 and those who were intubated were excluded. Results A total of 56 patients diagnosed with COVID-19 (through RT-PCR) were included in the final analysis, among which 27 were on CPAP, while 29 did not require CPAP (NCPAP). The overall mean age of the patients was 66 ± 14 (range: 26-94) years. The mean age of CPAP and NCPAP patients was 63 ± 15 (range: 26-85) years and 68 ± 13 (range: 40-94) years, respectively. The ethnicity of 54 (96.4%) patients was White-Caucasian, while 2 (3.6%) were British-Asian. In the study sample, 16 (28.6%) patients expired, of which 11 (40.7%) were on CPAP, while 5 (16.7%) did not require CPAP during the disease course. Correlation analysis showed that overall higher age, Medical Research Council Dyspnoea (MRCD) score, performance status (PS), and consolidation affecting more than one quadrant of the lungs were significantly correlated with increased mortality. Among patients receiving CPAP, higher age, MRCD score, and PS were significant predictors of mortality. Among the NCPAP group, advancing age, respiratory rate, MRCD score, PS, increased creatinine levels, and consolidation affecting more than one quadrant of the lungs were the predictors of mortality. Conclusion Even with a small sample size, we can see that there are definitive predictors that are directly proportional to increased mortality in COVID-19 patients on CPAP, such as higher age, performance status, MRCD score, and increased lung involvement of consolidation in more than one quadrant, which can help us rationalize management.

Roles of Endocytic Processes and Early Endosomes on Focal Adhesion Dynamics in MDA-MB-231 Cells.

BACKGROUND: Focal adhesion (FA) play a critical role in many biological processes which include cell survival and cell migration. They serve as cellular anchor, allowing cells to stay attached to the extracellular matrix (ECM), and can also regulate cellular transduction. Previously, it has been suggested that vesicles such as endosomes could interact directly with FA or be implicated in their turnover. In this study, we investigated whether there is a relationship between FA and the early endocytic machinery in MDA-MB-231 cells. METHODS: In this study, cell culture, transfection, time laps confocal microscopies, immunocytochemistry, western blotting, Cell fractionation and immunoprecipitation techniques were performed. RESULTS: Cells acutely treated with Dynasore, an inhibitor of dynamin, or with Pitstop 2, an inhibitor of clathryn-dependent endocytosis showed a reduction in the expression of early endosome biomarkers such as Rab5 and EEA1. Additionally, cells treated with these endocytic inhibitors exhibited an increase number and size of FA, as well as an increase FA turnover duration. This data was consistent with the reduction of the speed of cell migration. We demonstrated that Rab5- and EEA1-positive early endosomes were found to be colocalized with internalized FA. CONCLUSION: The present study suggests that there is a link between FA and early endosome markers, which indicates that the early endosomes may be involved in FA dynamics.

Evaluation of the impact of the COVID-19 pandemic on the reporting of maltreatment cases to the National Family Safety Program in Saudi Arabia.

INTRODUCTION: The COVID-19 pandemic represents a global and nationwide public health crisis. Although protective, socially restrictive measures may cause social isolation, which amounts to an increased ecological risk for mental health disturbance in vulnerable populations. Previous reports have suggested a significant association between the occurrence of public health crises and increased rates of multiple risk factors related to child mental health disturbances, domestic violence, and child-maltreatment. METHODOLOGY: We conducted a retrospective data review of reported child maltreatment cases from the National Family Safety Program during the period of September 2019 to September 2020. A descriptive analysis approach was used to compare rates before and during the COVID-19 pandemic. RESULTS: During COVID-19, abuse was significantly more reported by a family member than by the victims themselves or by a healthcare worker. However, before COVID-19, the offender was less often reported to be known to the victim; was both parents or the mother but was more often described as male, older, single, less educated; and currently unemployed with no significant change observed in their health status (p < 0.001). Interestingly, the predicted type of abuse also significantly differed and was more emotional or sexual than other types (p < 0.001). CONCLUSION: The types of abuse and the characteristics of both abused children and offenders saw significant changes during the COVID-19 pandemic. Sexual and emotional abuses were reported more frequently, and the male gender is considered to feature more commonly in reports prior to the pandemic era than during the pandemic.

The possible role of PtdIns(4, 5)P2 and PtdIns(3, 4, 5)P3 at the leading and trailing edges of the breast cancer cell line

Introduction: Phosphoinositides play a key role in the regulation of focal adhesions (FAs) turnover during cell adhesion and migration. However, their potential role in FA turnover at leading and trailing edge of cell are not yet fully understood. In this study, we investigate their spatial co-localisation with paxillin directly at leading and trailing edge of MDA-MB-231 breast cancer cell line. Materials and methods: Cell lines and cell culture experiments were done using MDA-MB-231human adenocarcinoma cells. Co-trnasfection and confocal microscopy were performed to visualise phosphoinositides and FAs by using GFP-C1-PLCdelta-PH/Btk-PH-GFP and 3 µɡ paxillin-RFP as biosensors. Then, ImageJ was used to measure co-localisation point between Phosphatidylinositol 4,5-trisphosphate (PtdIns(4,5)P2) or Phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and paxillin Spearman's rank correlation value was taken between PtdIns(4,5)P2/PtdIns(3,4,5)P3. Results: Our results demonstrate that the spatial co-localistion of PtdIns(4,5)P2 and PtdIns(3,4,5)P3 with FA at leading and trailing age of cell were slightly changed. Conclusions: This suggests that PtdIns(4,5)P2 and PtdIns(3,4,5)P3 play an equal role at the leading and trailing edges of the cancer metastasis through interaction with FA proteins (AU)

The Cytokines Responses against Parvovirus B19 in Miscarriage Women and the Susceptibility of their RhD Blood Type to Contract Parvovirus B19 in South of Iraq.

BACKGROUND: Parvovirus B19 (B19) infection is linked with various diseases. Cytokines play critical roles in cellular response to viral infection. It has also been reported that's susceptibility of the ABO blood type people to several viral infection. In this study, we evaluated interleukin 6 (IL-6), interleukin 8(IL-8), and interferon gamma (IFN-γ) levels in aborted women infected with parvovirus B19 (B19+/Abr+) and uninfected with B19(B19-/Abr+) in comparison with healthy women (B12-/Abr-) and susceptibility of their RhD blood type to contract B19. METHODS: B19+/Abr+ were diagnosed using IgM and IgG antibodies against B19, and the concentrations of IL-6, IL-8, and IFN-γ were determined using enzyme-linked immunosorbent assay (ELISA) test in both B19+/Abr+, B19-/Abr+, and B19-/Abr-. Here, we also collected blood groups, number of abortion, and gestational ages from 200 B19+/Abr+ along with the same number ofB19-/Abr+ and B19-/Abr-. RESULTS: The levels of IFN-γ were higher in serum of B19-/Abr+andB19+/Abr+ group in comparison to B19-/Abr-, while the serum levels of IL-6, IL-8were increased in B19+/Abr+ group in comparisontoB19-/Abr+ and B19-/Abr-. Our analyzed data also showed that aborted women with RhD+ are more susceptible to contract s B19 than people with RhD- blood type. CONCLUSION: B19 infection may differently modulate the amount of cytokines in the plasma of aborted women. So, it can be suggested that IL-6, IL-8, and IFN-γ potentially useful as markers for inflammation intrauterine. The susceptibility/protection of aborted women against B19 might be determined based on RhD blood type.

Enhancing azithromycin antibacterial activity by encapsulation in liposomes/liposomal-N-acetylcysteine formulations against resistant clinical strains of Escherichia coli.

E. coli is an Enterobacteriaceae that could develop resistance to various antibiotics and become a multi-drug resistant (MDR) bacterium. Options for treating MDR E. coli are limited and the pipeline is somewhat dry when it comes to antibiotics for MDR bacteria, so we aimed to explore more options to help in treating MDR E. coli. The purpose of this study is to examine the synergistic effect of a liposomal formulations of co-encapsulated azithromycin and N-acetylcysteine against E. coli. Liposomal azithromycin (LA) and liposomal azithromycin/N-acetylcysteine (LAN) were compared to free azithromycin. A broth dilution was used to measure the MIC and MBC of both formulations. The biofilm reduction activity, thermal stability measurements, stability studies, and cell toxicity analysis were performed. LA and LAN effectively reduced the MIC of E. coli SA10 strain, to 3 µg/ml and 2.5 µg/ml respectively. LAN at 1 × MIC recorded a 93.22% effectiveness in reducing an E. coli SA10 biofilm. The LA and LAN formulations were also structurally stable to 212 ± 2 °C and 198 ± 3 °C, respectively. In biological conditions, the formulations were largely stable in PBS conditions; however, they illustrated limited stability in sputum and plasma. We conclude that the formulation presented could be a promising therapy for E. coli resistance circumstances, providing the stability conditions have been enhanced.