Prevalence and correlates of generalized anxiety disorder and perceived stress among Sudanese medical students.

BACKGROUND: Generalized Anxiety Disorder (GAD) causes significant disturbance in an individual's well-being and activity. Whereby, interfering with the dynamic progress in life. Also, anxiety is a product of stress and a major predictor of academic performance. This study aimed to assess the prevalence of Generalized Anxiety Disorder (GAD), measure levels of anxiety and perceived stress, evaluate the academic profile, identify lifestyle characteristics, and explore the relationship between these factors. METHODS: In this cross-sectional study, 340 Sudanese medical students filled out online questionnaires, composed of the sociodemographic and lifestyle characteristics, academic profile, Generalized Anxiety Disorder-2 scale (GAD-2), and Perceived Stress Scale-10 (PSS-10). Descriptive and inferential statistics were applied using Statistical Package for Social Science (SPSS) Version 20.0 for data analysis. RESULTS: Of 340 medical students, 3.8% of them were diagnosed with GAD, while 29.1% scored ≥ 3 in GAD-2, indicating a possible diagnosis. The study found that 9.7% of the participants used addictive substances, with 42% of them having high GAD-2 scores. Moreover, high anxiety levels were associated with high-stress scores (p-value = 0.000). Also, high GAD-2 scores were significantly associated with students who spent less than 10,000 SDG (18 USD) weekly, spent more time on entertainment using smart devices (p-value = 0.004), and had an unhealthy diet (p-value = 0.004). Low anxiety levels were associated with better sleep quality (p-value = 0.00), satisfaction with religious practices (p-value = 0.00), and increased leisure/hobby time (p-value = 0.018). High-stress levels were observed in females (p-value = 0.035), those with lower academic performance satisfaction levels, and increased hours of smart device usage for entertainment (p-value = 0.001). Reduced stress levels were associated with being ≥ 23 years old, increased leisure/hobby time (p-value = 0.002), satisfaction with religious practices [F(3, 166.6) = 10.8, p-value = 0.00)], and having a healthy diet (p-value = 0.006). CONCLUSION: The low prevalence of GAD corresponded with previous literature, but 29.1% of medical students had a high probability of having GAD. The study emphasizes on providing accessible mental health services for medical students and interventions addressing modifiable risk factors.

Sensitive and effective electrochemical determination of butenafine in the presence of itraconazole using titanium nanoparticles-ionic liquid based nanocomposite sensor.

The evaluation of the bioavailability of topically applied medications that act inside or under the skin is a challenging task. Herein, the current study describes a simple, quick, and low-cost electrochemical platform for determining butenafine hydrochloride (BTH) that is mainly prescribed as a treatment of dermatophytosis, applying titanium nanoparticles and an ionic liquid as outstanding mediators. In terms of low detection limits (61.63 nM) and extensive range of 2.21 × 10-7-13.46 × 10-5 M, the established electrochemical technique provided worthy analytical performance for butenafine hydrochloride sensing. The suggested sensor's practical applicability was effectively demonstrated in pharmaceutical preparations, actual stratum corneum samples, and simultaneous detection of butenafine hydrochloride and Itraconazole in pharmaceutical preparation for the first time. All of the experimental factors, like the pH and scan rate, have been investigated and optimized. Diffusion coefficients of butenafine hydrochloride at bare and modified sensors were calculated. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02593-3.

SARS-CoV-2 Antibody Prevalence and Population-Based Death Rates, Greater Omdurman, Sudan.

In a cross-sectional survey in Omdurman, Sudan, during March-April 2021, we estimated that 54.6% of the population had detectable severe acute respiratory syndrome coronavirus 2 antibodies. Overall population death rates among those >50 years of age increased 74% over the first coronavirus disease pandemic year.

Inflammatory Breast Cancer: The Cytokinome of Post-Mastectomy Wound Fluid Augments Proliferation, Invasion, and Stem Cell Markers.

Inflammatory breast cancer (IBC) is an aggressive phenotype with a high recurrence and low survival rate. Approximately 90% of local breast cancer recurrences occur adjacent to the same quadrant as the initial cancer, implying that tumor recurrence may be caused by residual cancer cells and/or quiescent cancer stem cells (CSCs) in the tumor. We hypothesized that wound fluid (WF) collected after modified radical mastectomy (MRM) may activate cancer cells and CSCs, promoting epithelial mesenchymal transition (EMT) and invasion. Therefore, we characterized the cytokinome of WF drained from post-MRM cavities of non-IBC and IBC patients. The WF of IBC patients showed a significantly higher expression of various cytokines than in non-IBC patients. In vitro cell culture models of non-IBC and IBC cell lines were grown in media conditioned with and/without WF for 48 h. Afterwards, we assessed cell viability, the expression of CSCs and EMT-specific genes, and tumor invasion. Genes associated with CSCs properties and EMT markers were regulated in cells seeded in media conditioned by WF. IBC-WF exhibited a greater potential for inducing IBC cell invasion than non-IBC cells. The present study demonstrates the role of the post-surgical tumor cavity in IBC recurrence and metastasis.

Role of adipose tissue-derived cytokines in the progression of inflammatory breast cancer in patients with obesity.

BACKGROUND: Inflammatory breast cancer (IBC) represents a deadly aggressive phenotype of breast cancer (BC) with a unique clinicopathological presentation and low survival rate. In fact, obesity represents an important risk factor for BC. Although several studies have identified different cellular-derived and molecular factors involved in IBC progression, the role of adipocytes remains unclear. Cancer-associated adipose tissue (CAAT) expresses a variety of adipokines, which contribute to tumorigenesis and the regulation of cancer stem cell (CSC). This research investigated the potential effect of the secretome of CAAT explants from patients with BC on the progression and metastasis of the disease. METHODS: This study established an ex-vivo culture of CAAT excised from IBC (n = 13) vs. non-IBC (n = 31) patients with obesity and profiled their secretome using a cytokine antibody array. Furthermore, the quantitative PCR (qPCR) methodology was used to validate the levels of predominant cytokines at the transcript level after culture in a medium conditioned by CAAT. Moreover, the impact of the CAAT secretome on the expression of epithelial-mesenchymal transition (EMT) and cells with stem cell (CSC) markers was studied in the non-IBC MDA-MB-231 and the IBC SUM-149 cell lines. The statistical differences between variables were evaluated using the chi-squared test and unpaired a Student's t-test. RESULTS: The results of cytokine array profiling revealed an overall significantly higher level of a panel of 28 cytokines secreted by the CAAT ex-vivo culture from IBC patients with obesity compared to those with non-IBC. Of note, interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemo-attractant protein 1 (MCP-1) were the major adipokines secreted by the CAAT IBC patients with obesity. Moreover, the qPCR results indicated a significant upregulation of the IL-6, IL-8, and MCP-1 mRNAs in CAAT ex-vivo culture of patients with IBC vs. those with non-IBC. Intriguingly, a qPCR data analysis showed that the CAAT secretome secretions from patients with non-IBC downregulated the mRNA levels of the CD24 CSC marker and of the epithelial marker E-cadherin in the non-IBC cell line. By contrast, E-cadherin was upregulated in the SUM-149 cell. CONCLUSIONS: This study identified the overexpression of IL-6, IL-8, and MCP-1 as prognostic markers of CAAT from patients with IBC but not from those with non-IBC ; moreover, their upregulation might be associated with IBC aggressiveness via the regulation of CSC and EMT markers. This study proposed that targeting IL-6, IL-8, and MCP-1 may represent a therapeutic option that should be considered in the treatment of patients with IBC.

Effect of mesenchymal stem cells derived exosomes and green tea polyphenols on acetic acid induced ulcerative colitis in adult male albino rats.

Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD) that result in recurrent inflammation plus ulcers of the colon and rectum. Recently, mesenchymal stem cell-derived exosomes MSC-EXs have shown a lot of promise for the treatment of gut disorders, with cell regeneration and angiogenesis. Green tea polyphenols (GTPs) display specific beneficial effects on health and pathologies. The aim of this study was to explore the possible effect of MSC-EXs and GTPs on acetic acid-induced UC in rats. Sixty adult male rats were divided into five groups: group I, control group; group II, UC; group ΙIΙ, UC treated with GTPs; group ΙV, UC treated with MSC-EXs; and group V, UC treated with combined GTPs and MSC-EXs. Colonic samples were processed for histological and immunohistochemical methods. Expression of CXCR2 and TLR4 levels was measured. Groups ΙI and III showed ulceration, loss of surface columnar epithelium, disturbed crypt architecture with few goblet cells, and many cellular infiltrations with the overexpression of CXCR2 and TLR4. Group IV showed attenuation of some histological changes. Group V showed improvement of the most histological and immunohistochemical changes described previously. MSC-EXs represent future therapeutic hopes for chronic intestinal inflammatory states, keeping the integrity of innate immunity through their regenerative and anti-inflammatory effects. The combination of GTPs and MSC-EXs was more effective and produced an additive effect than using MSC-EXs alone.

Muscle Hernias in the Upper Limb: Treatment and Literature Review.

PURPOSE: A muscle hernia is defined as a protrusion of the muscle belly through an acquired or congenital fascial defect. A nontraumatic herniation may occur through congenital fascial defects or be acquired by means of exertion, blunt trauma, or a penetrating injury. In this study, our aim was to review our experience with this rare condition and report the results of surgical treatment of these cases. METHODS: During the period between January 1, 2014, and August 30, 2018, 12 cases of symptomatic muscle hernia in the upper limb were included in our study: 9 cases involving the forearm and 3 cases involving the arm. All patients underwent direct repair of their fascial defect with overlapping of the deep fascia using nonabsorbable sutures. RESULTS: There were improvements in postoperative pain, swelling, appearance, weakness, and paresthesia. There was significant improvement in the Disabilities of the Arm, Shoulder and Hand score from a mean of 51.8 before surgery to 6.9 after surgery. The mean period to return to activities of daily living was 18 days (range, 15-20 days). CONCLUSIONS: Muscle hernia in the upper limb is an uncommon condition that can be successfully treated. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Relationship between resilience and health-related quality of life among patients with a permanent colostomy.

BACKGROUND: The assessment of health-related quality of life (HRQoL) and resilience are important aspects of colorectal cancer care, as well as an indicator of patients' health status. This study was conducted to investigate the relationship between resilience and HRQoL among patients with a permanent colostomy. METHOD: A cross-sectional descriptive correlational design employing the City of Hope Quality of Life Ostomy Questionnaire and the Resilience Scale was adopted. A purposive sample population was recruited. RESULTS: The study enrolled 158 colostomy patients. Half the participants (50.6%) were female and the mean age was 58.20 years [standard deviation (SD)=8.70]. Colostomy patients had a mean HRQoL score of 129.61 (SD)=98 (interquartile range: 109-148), with a spiritual domain that was lower than any other HRQoL domain. The Resilience Scale mean score was 106 (interquartile range: 82-126). CONCLUSION: This study observed a general low score on the HRQoL Questionnaire and this was reflected in the Resilience Scale score of this group of patients with a colostomy.

"Clinical Aspects of Chronic Granulomatous Disease in Upper Egypt".

Chronic granulomatous disease (CGD) is a rare inherited primary immunodeficiency disorder that affects phagocytes and is characterized by a marked increased susceptibility to severe bacterial and fungal infections. We aimed to describe the clinical presentations of pediatric patients with CGD in Upper Egypt and to identify the defective component of NADPH oxidase. Pediatric patients diagnosed with CGD within one year from January 2018 to January 2019 were enrolled in the study. Patient history, clinical and laboratory investigations were carried out, including nitroblue tetrazolium test and flow cytometry DHR analysis. Infectious microorganisms were isolated from infected sites to identify the causative agents and their resistance profile. A total of 15 patients were diagnosed with CGD. Failure to thrive and lymphadenopathy were the most common presentations. The median age of clinical onset was 1.17 years of age. The most common gene mutations were observed in the CYBA gene. All cases showed pulmonary infections followed by abscesses. Staphylococcus aureus and Klebsiella pneumoniae were the most frequently isolated bacterial pathogens, Aspergillus spp and Candida spp were isolated from fungal infections. 4/15 (26.7%) children died due to severe serious infections. We concluded that CGD is common in Upper Egypt, and we recommend raising the awareness and testing for CGD in pediatric patients with recurrent or persistent infections, especially those with a familiar history of similar manifestations to avoid delays in proper diagnosis and deterioration of cases. Abbreviations: CGD: chronic granulomatous disease; XL: X-linked; AR: autosomal recessive.

3E-Net: Entropy-Based Elastic Ensemble of Deep Convolutional Neural Networks for Grading of Invasive Breast Carcinoma Histopathological Microscopic Images.

Automated grading systems using deep convolution neural networks (DCNNs) have proven their capability and potential to distinguish between different breast cancer grades using digitized histopathological images. In digital breast pathology, it is vital to measure how confident a DCNN is in grading using a machine-confidence metric, especially with the presence of major computer vision challenging problems such as the high visual variability of the images. Such a quantitative metric can be employed not only to improve the robustness of automated systems, but also to assist medical professionals in identifying complex cases. In this paper, we propose Entropy-based Elastic Ensemble of DCNN models (3E-Net) for grading invasive breast carcinoma microscopy images which provides an initial stage of explainability (using an uncertainty-aware mechanism adopting entropy). Our proposed model has been designed in a way to (1) exclude images that are less sensitive and highly uncertain to our ensemble model and (2) dynamically grade the non-excluded images using the certain models in the ensemble architecture. We evaluated two variations of 3E-Net on an invasive breast carcinoma dataset and we achieved grading accuracy of 96.15% and 99.50%.

Continuous Opioid Monitoring along with Nerve Agents on a Wearable Microneedle Sensor Array.

There are urgent needs for sensing devices capable of distinguishing between episodes of opioid overdose and nerve agent poisoning. This work presents a wearable microneedle sensor array for minimally invasive continuous electrochemical detection of opioid (OPi) and organophosphate (OP) nerve agents on a single patch platform. The new multimodal microneedle sensor array relies on unmodified and organophosphorus hydrolase (OPH) enzyme-modified carbon paste (CP) microneedle electrodes for square wave voltammetric (SWV) detection of the fentanyl and nerve agent targets, respectively. Such real-time simultaneous sensing provides distinct unique information, along with attractive analytical performance, including high sensitivity, selectivity, and stability, for real-time on-body OPi-OP analysis. The patch represents the first sensing device capable of continuously monitoring fentanyl down to the nanomolar level through a nanomaterial-based multilayered surface architecture. Applicability of the sensor array toward opioids screening is demonstrated for morphine and norfentanyl. Successful OPi-OP detection conducted in a skin-mimicking phantom gel demonstrates the suitability of the device for rapid on-body sensing. Such progress toward continuous minimally invasive transdermal analysis of drugs of abuse and nerve agents holds promise for rapid countermeasures for protecting soldiers, civilians, and healthcare personnel.

Beta-amyloid (Aß) uptake by PET imaging in older HIV+ and HIV- individuals.

The causes of cognitive impairment among older HIV+ individuals may overlap with causes among elderly HIV seronegative (HIV-) individuals. The objective of this study was to determine if beta-amyloid (Aß) deposition measured by [18F] AV-45 (florbetapir) positron emission tomography (PET) is increased in older HIV+ individuals compared to HIV- individuals. Forty-eight HIV+ and 25 HIV- individuals underwent [18F] AV-45 PET imaging. [18F] AV-45 binding to Aß was measured by standardized uptake value ratios (SUVR) relative to the cerebellum in 16 cortical and subcortical regions of interest. Global and regional cortical SUVRs were compared by (1) serostatus, (2) HAND stage, and (3) age decade, comparing individuals in their 50s and > 60s. There were no differences in median global cortical SUVR stratified by HIV serostatus or HAND stage. The proportion of HIV+ participants in their 50s with elevated global amyloid uptake (SUVR > 1.40) was significantly higher than the proportion in HIV- participants (67% versus 25%, p = 0.04), and selected regional SUVR values were also higher (p < 0.05) in HIV+ compared to HIV- participants in their 50s. However, these group differences were not seen in participants in their 60s. In conclusion, PET imaging found no differences in overall global Aß deposition stratified by HIV serostatus or HAND stage. Although there was some evidence of increased Aß deposition in HIV+ individuals in their 50s compared to HIV- individuals which might indicate premature aging, the most parsimonious explanation for this is the relatively small sample size in this cross-sectional cohort study.

IL-8 and MCP-1/CCL2 regulate proteolytic activity in triple negative inflammatory breast cancer a mechanism that might be modulated by Src and Erk1/2.

Inflammatory breast cancer (IBC) is a highly metastatic and lethal breast cancer. As many as 25-30% of IBCs are triple negative (TN) and associated with low survival rates and poor prognosis. We found that the microenvironment of IBC is characterized by high infiltration of tumor associated macrophages (TAMs) and by over-expression of the cysteine protease cathepsin B (CTSB). TAMs in IBC secrete high levels of the cytokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1/CCL2) compared to non-IBC patients. Herein, we tested the roles of IL-8 and MCP-1/CCL2 in modulating proteolytic activity and invasiveness of TN-non-IBC as compared to TN-IBC and addressed the underlying molecular mechanism(s) for both cytokines. Quantitative real time PCR results showed that IL-8 and MCP-1/CCL2 were significantly overexpressed in tissues of TN-IBCs. IL-8 and MCP-1/CCL2 induced CTSB expression and activity of the p-Src and p-Erk1/2 signaling pathways relevant for invasion and metastasis in TN-non-IBC, HCC70 cells and TN-IBC, SUM149 cells. Dasatinib, an inhibitor of p-Src, and U0126, an inhibitor of p-Erk1/2, down-regulated invasion and expression of CTSB by HCC70 and SUM149 cells, a mechanism that is reversed by IL-8 and MCP-1/CCL2. Our study shows that targeting the cytokines IL-8 and MCP-1/CCL2 and associated signaling molecules may represent a promising therapeutic strategy in TN-IBC patients.

Carotid plaques in adult rheumatoid arthritis patients; association with paroxonase 1 enzymatic activity and Q192R paroxonase 1 gene polymorphism.

Paroxonase 1 (PON 1) enzymatic activity and Q192R PON polymorphism has been implicated with greater cardiovascular risk in general population. Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized with increased inflammatory markers leading to increased cardiovascular morbidity. The aim of the work was to study association between PON1 enzymatic activity & gene polymorphism with carotid plaques in RA patients. This case-control study was carried out at Zagazig University Hospitals on 99 subjects divided randomly into two groups; 48 RA patients and 51 controls. RA patients fulfilled the revised 2010 EULAR/ACR classification criteria of RA. All patients were subjected to history taking, clinical evaluation, laboratory investigations & plain X-rays. Carotid intima-media thickness (CIMT) and PON1 enzyme assay & genotyping were done for both groups. PON1 enzyme levels were significantly higher in patients than controls. Also, there was a significant negative correlation of PON1 enzyme activity with increased CIMT & plaques. The cut-off value of PON1 enzyme level that had the highest CVD prediction was 4.2 U/ml. Although PON1 genotyping was insignificantly different between patients and controls, patients with QQ genotype had the lowest PON1 activity then patients with QR genotype then RR genotype. In RA patients, decreased serum PON1 enzymatic activity and QQ genotyping of Q192R PON polymorphism was associated with increased CIMT & plaques. Serum PON1 could be a good marker for atherosclerosis prediction in RA patients at cutoff 4.2 U/ml.

New imidazolone derivatives comprising a benzoate or sulfonamide moiety as anti-inflammatory and antibacterial inhibitors: Design, synthesis, selective COX-2, DHFR and molecular-modeling study.

New imidazol-5-one derivatives 12a,b and 12e, f, 14a,b and 16a,b were synthesized and screened for their in vivo anti-inflammatory activity using a standard acute carrageenan-induced rat paw oedema method. All the tested compounds exhibited good anti-inflammatory activity; especially compound 12f which produced the maximum effect of 49.0% compared to the standard drug, celecoxib, (43.1%). The most active anti-inflammatory agents 12a, 12e, and 12f were studied for their interactions with enzyme COX-2 compared to celecoxib. The study showed that, compound 12e exhibited a high selectivity towards COX-2 inhibition with IC50 = 0.087 µM. Moreover, the antibacterial screening indicated that some synthesized compounds showed good antibacterial activity toward the Gram-negative bacteria Escherichia coli. Additionally, compounds 7, 12a, 12f, and 12 showed a good binding affinity with enzyme dihydrofolate reductase (DHFR) whereas compound 12f has a higher inhibitory effect on DHFR than the tested compounds 7, 12a and 12 h. On the other hand, the combination between these tested compounds and sulfadiazine as a reference drug (10 µM compound + 1 µM reference), showed that compound 12 h has higher potency (0.078 ±â€¯0.002) than sulfadiazine (0.135 ±â€¯0.004). In addition, docking analysis was performed and it confirmed the presented results.

Green biosynthesis of silver nanoparticles by Aspergillus niger and its antiamoebic effect against Allovahlkampfia spelaea trophozoite and cyst.

BACKGROUND: Fungi represent an interesting candidate for the synthesis of nanoparticles. The biosynthesis of silver nanoparticles (AgNPs) has many industrial and biomedical indications. We aimed in this work to biologically synthesize silver nanoparticles using Aspergillus niger and to evaluate its effect against the newly identified Allovahlkampfia spelaea that causes resistant human keratitis. MATERIAL AND METHODS: Aspergillus niger (soil isolate) was treated with silver nitrate to produce silver nanoparticles. AgNPs were characterized by Ultraviolet-Visible Spectroscopy, Transmission Electron Microscopy, and Fourier Transform Infrared Spectroscopy. The effect of the synthesized nanoparticles against Allovahlkampfia spelaea growth, encystation, excystation, and toxicity in host cells was evaluated. RESULTS: AgNPs exhibited significant inhibition of Allovahlkampfia spelaea viability and growth of both trophozoites and cysts, with a reduction of amoebic cytotoxic activity in host cells. CONCLUSION: AgNPs may give a promising future to the treatment of Allovahlkampfia spelaea infections in humans.

Designing Open Metal Sites in Metal-Organic Frameworks for Paraffin/Olefin Separations.

Incorporating open metal sites (OMS) into metal-organic frameworks allows design of well-defined binding sites for selective molecular adsorption, which has a profound impact on catalysis and separations. We demonstrate that Cu(I) sites incorporated into MFU-4l preferentially adsorb olefins over paraffins. Density functional theory (DFT) calculations show that the OMS are independent, with no dependence of binding energy on olefin loading up to one olefin per Cu(I). Experimentally, increasing Cu(I) loading increased olefin uptake without affecting the binding energy, as predicted by DFT and confirmed by temperature-programmed desorption. The potential of this material for olefin/paraffin separation under ambient conditions was investigated by gas adsorption and column breakthrough experiments for an equimolar ratio of olefin/paraffin. High-grade propylene and ethylene (>99.999%) can be generated using temperature-concentration swing recycling from a Cu(I)-MFU-4l packed column with no measurable paraffin breakthrough.

Tumor microenvironmental plasmacytoid dendritic cells contribute to breast cancer lymph node metastasis via CXCR4/SDF-1 axis.

PURPOSE: Plasmacytoid dendritic cells (PDCs) infiltration into breast cancer tissues is associated with poor prognosis. Also, CXCR4 shows compelling evidences to be exploited by cancer cells to migrate to distant sites. The present study investigated lymph node metastasis in the light of PDCs infiltration and the potential cross talk with CXCR4/SDF-1 chemokine axis. METHODS: We assessed circulating PDCs proportions drained from the axillary tributaries, and the in situ expression of both CD303 and CXCR4 in breast cancer patients with positive lymph nodes (pLN) and negative lymph nodes (nLN) using immunohistochemistry and flow cytometry. We also analyzed the expression of SDF-1 in lymph nodes of pLN and nLN patients. We studied the effect of the secretome of PDCs of pLN and nLN patients on the expression of CXCR4 and activation of NF-κB in human breast cancer cell lines SKBR3 and MCF-7. TNF-α mRNA expression level in PDCs from both groups was determined by qPCR. RESULTS: Our findings indicate increased infiltration of PDCs in breast cancer tissues of pLN patients than nLN patients, which correlates with CXCR4+ cells percentage. Interestingly, SDF-1 is highly immunostained in lymph nodes of pLN patients compared to nLN patients. Our in vitro experiments demonstrate an upregulation of NF-κB expression and CXCR4 cells upon stimulation with PDCs secretome of pLN patients than those of nLN patients. Also, PDCs isolated from pLN patients exhibited a higher TNF-α mRNA expression than nLN patients. Treatment of MCF-7 cell lines with TNF-α significantly upregulates CXCR4 expression. CONCLUSIONS: Our findings suggest a potential role for microenvironmental PDCs in breast cancer lymph node metastasis via CXCR4/SDF-1 axis.

Suppression of macrophages- Induced inflammation via targeting RAS and PAR-4 signaling in breast cancer cell lines.

Tumor associated macrophages (TAMs) have a crucial role in cancer progression, metastasis and drug response. Piroxicam and sulindac sulfide are non-steroidal anti-inflammatory drugs (NSAID) that decrease the incidence and progression of several types of cancer. However, their role in suppressing the interactions between TAMs and cancer cells remain unclear. Herein, we studied the impact of human monocytes conditioned media (CM) on cellular proliferation of ER-dependent MCF-7 and ER-independent MDA-MB-231 cells, and the effects of piroxicam and sulindac sulfide on the expression levels of RAS, COX-2, IL-6, IL-1ß and PAR-4 (qRT-PCR), BCL-2 and BAX (western blot), Caspase-3, VEGF-a and PGE2 (ELISA), MMP-2 and -9 (zymography) in the stimulated cells. Our results showed that CM caused a significant increase in cells survival through significant increase in RAS expression which resulted in upregulation of COX-2, PGE2, BCL-2, IL-6, IL-1ß, VEGF-A and MMP-9 and down regulation of PAR-4. Treatment with one of the NSAIDs used in this study produced a time and concentration dependent growth inhibition of stimulated cells by inhibiting RAS expression. Suppression of RAS was accompanied by downregulation of its downstream signaling of IL-1ß, IL-6, COX-2 and PGE2, activation of apoptotic machinery through upregulation of PAR-4 and caspase-3, as well as, inhibition of BCL-2, VEGF-A, MMP-2 and MMP-9. In conclusion, our data support the role of piroxicam and sulindac sulfide in suppressing inflammation-driven breast cancer progression and identifies promising novel target in RAS and PAR-4 signaling.

Genetic polymorphism of the N-terminal region in circumsporozoite surface protein of Plasmodium falciparum field isolates from Sudan.

BACKGROUND: Malaria caused by Plasmodium falciparum parasite is still known to be one of the most significant public health problems in sub-Saharan Africa. Genetic diversity of the Sudanese P. falciparum based on the diversity in the circumsporozoite surface protein (PfCSP) has not been previously studied. Therefore, this study aimed to investigate the genetic diversity of the N-terminal region of the pfcsp gene. METHODS: A cross-sectional molecular study was conducted; 50 blood samples have been analysed from different regions in Sudan. Patients were recruited from the health facilities of Khartoum, New Halfa, Red Sea, White Nile, Al Qadarif, Gezira, River Nile, and Ad Damazin during malaria transmission seasons between June to October and December to February 2017-2018. Microscopic and nested PCR was performed for detection of P. falciparum. Merozoite surface protein-1 was performed to differentiate single and multiple clonal infections. The N-terminal of the pfcsp gene has been sequenced using PCR-Sanger dideoxy method and analysed to sequences polymorphism including the numbers of haplotypes (H), segregating sites (S), haplotypes diversity (Hd) and the average number of nucleotide differences between two sequences (Pi) were obtained using the software DnaSP v5.10. As well as neutrality testing, Tajima's D test, Fu and Li's D and F statistics. RESULTS: PCR amplification resulted in 1200 bp of the pfcsp gene. Only 21 PCR products were successfully sequenced while 29 were presenting multiple clonal P. falciparum parasite were not sequenced. The analysis of the N-terminal region of the PfCSP amino acids sequence compared to the reference strains showed five different haplotypes. H1 consisted of 3D7, NF54, HB3 and 13 isolates of the Sudanese pfcsp. H2 comprised of 7G8, Dd2, MAD20, RO33, Wellcome strain, and 5 isolates of the Sudanese pfcsp. H3, H4, and H5 were found in 3 distinct isolates. Hd was 0.594 ± 0.065, and S was 12. The most common polymorphic site was A98G; other sites were D82Y, N83H, N83M, K85L, L86F, R87L, R87F, and A98S. Fu and Li's D* test value was - 2.70818, Fu and Li's F* test value was - 2.83907, indicating a role of negative balancing selection in the pfcsp N-terminal region. Analysis with the global pfcsp N-terminal regions showed the presence of 13 haplotypes. Haplotypes frequencies were 79.4%, 17.0%, 1.6% and 1.0% for H1, H2, H3 and H4, respectively. Remaining haplotypes frequency was 0.1% for each. Hd was 0.340 ± 0.017 with a Pi of 0.00485, S was 18 sites, and Pi was 0.00030. Amino acid polymorphisms identified in the N-terminal region of global pfcsp were present at eight positions (D82Y, N83H/M, K85L/T/N, L86F, R87L/F, A98G/V/S, D99G, and G100D). CONCLUSIONS: Sudanese pfcsp N-terminal region was well-conserved with only a few polymorphic sites. Geographical distribution of genetic diversity showed high similarity to the African isolates, and this will help and contribute in the deployment of RTS,S, a PfCSP-based vaccine, in Sudan.