Metabolic predictors of COVID-19 mortality and severity: a survival analysis.

Introduction: The global healthcare burden of COVID-19 pandemic has been unprecedented with a high mortality. Metabolomics, a powerful technique, has been increasingly utilized to study the host response to infections and to understand the progression of multi-system disorders such as COVID-19. Analysis of the host metabolites in response to SARS-CoV-2 infection can provide a snapshot of the endogenous metabolic landscape of the host and its role in shaping the interaction with SARS-CoV-2. Disease severity and consequently the clinical outcomes may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. Hence, the host metabolome can help predict potential clinical risks and outcomes. Methods: In this prospective study, using a targeted metabolomics approach, we studied the metabolic signature in 154 COVID-19 patients (males=138, age range 48-69 yrs) and related it to disease severity and mortality. Blood plasma concentrations of metabolites were quantified through LC-MS using MxP Quant 500 kit, which has a coverage of 630 metabolites from 26 biochemical classes including distinct classes of lipids and small organic molecules. We then employed Kaplan-Meier survival analysis to investigate the correlation between various metabolic markers, disease severity and patient outcomes. Results: A comparison of survival outcomes between individuals with high levels of various metabolites (amino acids, tryptophan, kynurenine, serotonin, creatine, SDMA, ADMA, 1-MH and carnitine palmitoyltransferase 1 and 2 enzymes) and those with low levels revealed statistically significant differences in survival outcomes. We further used four key metabolic markers (tryptophan, kynurenine, asymmetric dimethylarginine, and 1-Methylhistidine) to develop a COVID-19 mortality risk model through the application of multiple machine-learning methods. Conclusions: Metabolomics analysis revealed distinct metabolic signatures among different severity groups, reflecting discernible alterations in amino acid levels and perturbations in tryptophan metabolism. Notably, critical patients exhibited higher levels of short chain acylcarnitines, concomitant with higher concentrations of SDMA, ADMA, and 1-MH in severe cases and non-survivors. Conversely, levels of 3-methylhistidine were lower in this context.

Correction of the Tuberous Breast with Fat Grafting and Implant: Techniques, Evaluation with BREAST-Q, and Preliminary Results.

BACKGROUND: The correction of tuberous breast deformity with fat grafting has gained popularity in recent years, but it remains unclear whether this new technique can produce patient satisfaction levels comparable to those achieved with implant-based correction. METHODS: This study aimed to compare patients' satisfaction and quality of life using the BREAST-Q questionnaire after correction of tuberous breast deformity with fat grafting and implants. Twenty-four patients (36 breasts) were included in our study. Thirteen patients (15 breasts) had a correction with lipofilling (mean 2.67 interventions) and 11 patients (21 breasts) had an implant-based correction (mean 1 intervention). RESULTS: Both fat and implant treatments showed statistically significant improvements in breast satisfaction (p value=0.001, 0.002, respectively), psychosocial (p value=0.003, 0.003, respectively), and sexual satisfaction (p value=0.008, 0.002, respectively) between the pre-treatment and post-treatment stages. However, the only statistically significant differences between the treatments were observed in the physical condition pre-treatment (p value=0.008) and sexual condition post-treatment (p value=0.030). The outcome of both treatments was not statistically different. Furthermore, the outcome exhibited a statistically significant positive linear relationship with breast satisfaction for both treatments. CONCLUSIONS: This study suggests that lipofilling can achieve breast and outcome satisfaction comparable to that of implants, although this parity in results comes at the cost of more interventions. These preliminary results lend support to the notion that, as surgeons have access to two equally effective techniques, it is crucial to provide appropriate guidance to patients to ensure their satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Review on anti-alzheimer drug development: approaches, challenges and perspectives.

Alzheimer is an irreversible progressive neurodegenerative disease that causes failure of cerebral neurons and disability of the affected person to practice normal daily life activities. There is no concrete evidence to identify the exact reason behind the disease, so several relevant hypotheses emerged, highlighting many possible therapeutic targets, such as acetylcholinesterase, cholinergic receptors, N-methyl d-aspartate receptors, phosphodiesterase, amyloid ß protein, protein phosphatase 2A, glycogen synthase kinase-3 beta, ß-secretase, γ-secretase, α-secretase, serotonergic receptors, glutaminyl cyclase, tumor necrosis factor-α, γ-aminobutyric acid receptors, and mitochondria. All of these targets have been involved in the design of new potential drugs. An extensive number of these drugs have been studied in clinical trials. However, only galantamine, donepezil, and rivastigmine (ChEIs), memantine (NMDA antagonist), and aducanumab and lecanemab (selective anti-Aß monoclonal antibodies) have been approved for AD treatment. Many drugs failed in the clinical trials to such an extent that questions have been posed about the significance of some of the aforementioned targets. On the contrary, the data of other drugs were promising and shed light on the significance of their targets for the development of new potent anti-alzheimer drugs.

CCN3, POSTN, and PTHLH as potential key regulators of genomic integrity and cellular survival in iPSCs.

Reprogramming human somatic cells into a pluripotent state, achieved through the activation of well-defined transcriptional factors known as OSKM factors, offers significant potential for regenerative medicine. While OSKM factors are a robust reprogramming method, efficiency remains a challenge, with only a fraction of cells undergoing successful reprogramming. To address this, we explored genes related to genomic integrity and cellular survival, focusing on iPSCs (A53T-PD1) that displayed enhanced colony stability. Our investigation had revealed three candidate genes CCN3, POSTN, and PTHLH that exhibited differential expression levels and potential roles in iPSC stability. Subsequent analyses identified various protein interactions for these candidate genes. POSTN, significantly upregulated in A53T-PD1 iPSC line, showed interactions with extracellular matrix components and potential involvement in Wnt signaling. CCN3, also highly upregulated, demonstrated interactions with TP53, CDKN1A, and factors related to apoptosis and proliferation. PTHLH, while upregulated, exhibited interactions with CDK2 and genes involved in cell cycle regulation. RT-qPCR validation confirmed elevated CCN3 and PTHLH expression in A53T-PD1 iPSCs, aligning with RNA-seq findings. These genes' roles in preserving pluripotency and cellular stability require further exploration. In conclusion, we identified CCN3, POSTN, and PTHLH as potential contributors to genomic integrity and pluripotency maintenance in iPSCs. Their roles in DNA repair, apoptosis evasion, and signaling pathways could offer valuable insights for enhancing reprogramming efficiency and sustaining pluripotency. Further investigations are essential to unravel the mechanisms underlying their actions.

Design, Synthesis, and Biological Evaluation of New Potential Unusual Modified Anticancer Immunomodulators for Possible Non-Teratogenic Quinazoline-Based Thalidomide Analogs.

Sixteen new thalidomide analogs were synthesized. The new candidates showed potent in vitro antiproliferative activities against three human cancer cell lines, namely hepatocellular carcinoma (HepG-2), prostate cancer (PC3), and breast cancer (MCF-7). It was found that compounds XII, XIIIa, XIIIb, XIIIc, XIIId, XIVa, XIVb, and XIVc showed IC50 values ranging from 2.03 to 13.39 µg/mL, exhibiting higher activities than thalidomide against all tested cancer cell lines. Compound XIIIa was the most potent candidate, with an IC50 of 2.03 ± 0.11, 2.51 ± 0.2, and 0.82 ± 0.02 µg/mL compared to 11.26 ± 0.54, 14.58 ± 0.57, and 16.87 ± 0.7 µg/mL for thalidomide against HepG-2, PC3, and MCF-7 cells, respectively. Furthermore, compound XIVc reduced the expression of NFκB P65 levels in HepG-2 cells from 278.1 pg/mL to 63.1 pg/mL compared to 110.5 pg/mL for thalidomide. Moreover, compound XIVc induced an eightfold increase in caspase-8 levels with a simultaneous decrease in TNF-α and VEGF levels in HepG-2 cells. Additionally, compound XIVc induced apoptosis and cell cycle arrest. Our results reveal that the new candidates are potential anticancer candidates, particularly XIIIa and XIVc. Consequently, they should be considered for further evaluation for the development of new anticancer drugs.

The retrospective study of the metabolic patterns of BCG-vaccination in type-2 diabetic individuals in COVID-19 infection.

Background: The cross-protective nature of Bacillus Calmette-Guerin (BCG) vaccine against SARS-CoV-2 virus was previously suggested, however its effect in COVID-19 patients with type 2 diabetes (T2D) and the underlying metabolic pathways has not been addressed. This study aims to investigate the difference in the metabolomic patterns of type 2 diabetic patients with BCG vaccination showing different severity levels of COVID-19 infection. Methods: Sixty-seven COVID-19 patients were categorized into diabetic and non-diabetic individuals who had been previously vaccinated or not with BCG vaccination. Targeted metabolomics were performed from serum samples from all patients using tandem mass spectrometry. Statistical analysis included multivariate and univariate models. Results: Data suggested that while BCG vaccination may provide protection for individuals who do not have diabetes, it appears to be linked to more severe COVID-19 symptoms in T2D patients (p = 0.02). Comparing the metabolic signature of BCG vaccinated T2D individuals to non-vaccinated counterparts revealed that amino acid (sarcosine), cholesterol esters (CE 20:0, 20:1, 22:2), carboxylic acid (Aconitic acid) were enriched in BCG vaccinated T2D patients, whereas spermidine, glycosylceramides (Hex3Cer(d18:1_22:0), Hex2Cer(d18:1/22:0), HexCer(d18:1/26:1), Hex2Cer(d18:1/24:0), HexCer(d18:1/22:0) were higher in BCG vaccinated non- T2D patients. Furthermore, data indicated a decrease in sarcosine synthesis from glycine and choline and increase in spermidine synthesis in the BCG vaccinated cohort in T2D and non-T2D groups, respectively. Conclusion: This pilot study suggests increased severity of COVID-19 in BCG vaccinated T2D patients, which was marked by decreased sarcosine synthesis, perhaps via lower sarcosine-mediated removal of viral antigens.

Neurological manifestations of mycetoma: a cross-sectional community-based study.

Mycetoma is a chronic specific granulomatous progressive and disfiguring subcutaneous inflammatory disease. It is caused by true fungi (Eumycetoma) or by higher bacteria (actinomycetoma). Mycetoma mainly affects the lower limbs, followed by the upper limbs, back, and rarely the head and neck. Mycetoma is mainly transmitted through trauma with infected sharp objects. Herein, we want to determine the neurological manifestations of mycetoma in Sudanese patients. Methodology: A descriptive cross-sectional community-based study included 160 patients with mycetoma seen in the White Nile state. A team of doctors collected data using standardized questionnaires that included clinical history, neurological examination, investigations including laboratory, neurophysiological studies, and imaging. Results: Almost 160 patients were included in the study; 90% of them were male. Two patients presented with entrapment neuropathy, one presented with proximal neuropathy, one had peripheral neuropathy, one had dorsal spine involvement and presented with spastic paraplegia with sensory level, one had cervical cord compression, and one patient had repeated attacks of convulsion. Conclusion: Although it is rare, clinicians should highly suspect neurological involvement in mycetoma patients.

Design, synthesis, anticancer evaluation, and in silico ADMET analysis of novel thalidomide analogs as promising immunomodulatory agents.

Immunomodulatory medications like thalidomide and its analogs prevent the production of some proinflammatory cytokines linked to cancer. A new series of thalidomide analogs were designed and synthesized in order to develop potential antitumor immunomodulatory agents. The antiproliferative activities of the new candidates against a panel of three human cancer cell lines (HepG-2, PC3 and MCF-7) were assessed in comparison to thalidomide as a positive control. The obtained results showed the relative significant potency of 18f (IC50 = 11.91 ± 0.9, 9.27 ± 0.7, and 18.62 ± 1.5 µM) and 21b (IC50 = 10.48 ± 0.8, 22.56 ± 1.6, and 16.39 ± 1.4 µM) against the mentioned cell lines, respectively. These results were comparable to thalidomide (IC50 = 11.26 ± 0.54, 14.58 ± 0.57, and 16.87 ± 0.7 µM, respectively). To see to what extent the biological properties of the new candidates are relative to those of thalidomide, the effects of 18f and 21b on the expression levels of TNF-α, CASP8, VEGF, and NF-κB P65 were evaluated. Significant reductions in the proinflammatory TNF-α, VEGF, and NF-κB P65 levels in HepG-2 cells were observed after exposure to compounds 18f and 21b. Furthermore, a sharp increase in CASP8 levels was detected. The obtained results revealed that 21b is of greater significance than thalidomide in TNF-α and NF-κB P65 inhibition. The in silico ADMET and toxicity studies showed that most of tested candidates have a good profile of drug-likeness and low toxicity potential.

Detection of Management-Frames-Based Denial-of-Service Attack in Wireless LAN Network Using Artificial Neural Network.

Wireless Local Area Networks (WLANs) have become an increasingly popular mode of communication and networking, with a wide range of applications in various fields. However, the increasing popularity of WLANs has also led to an increase in security threats, including denial of service (DoS) attacks. In this study, management-frames-based DoS attacks, in which the attacker floods the network with management frames, are particularly concerning as they can cause widespread disruptions in the network. Attacks known as denial of service (DoS) can target wireless LANs. None of the wireless security mechanisms in use today contemplate defence against them. At the MAC layer, there are multiple vulnerabilities that can be exploited to launch DoS attacks. This paper focuses on designing and developing an artificial neural network (NN) scheme for detecting management-frames-based DoS attacks. The proposed scheme aims to effectively detect fake de-authentication/disassociation frames and improve network performance by avoiding communication interruption caused by such attacks. The proposed NN scheme leverages machine learning techniques to analyse patterns and features in the management frames exchanged between wireless devices. By training the NN, the system can learn to accurately detect potential DoS attacks. This approach offers a more sophisticated and effective solution to the problem of DoS attacks in wireless LANs and has the potential to significantly enhance the security and reliability of these networks. According to the experimental results, the proposed technique exhibits higher effectiveness in detection compared to existing methods, as evidenced by a significantly increased true positive rate and a decreased false positive rate.

Design, synthesis, and biological evaluation of novel bioactive thalidomide analogs as anticancer immunomodulatory agents.

Cancer is still a dangerous disease with a high mortality rate all over the world. In our attempt to develop potential anticancer candidates, new quinazoline and phthalazine based compounds were designed and synthesized. The new derivatives were built in line with the pharmacophoric features of thalidomide. The new derivatives as well as thalidomide were examined against three cancer cell lines, namely: hepatocellular carcinoma (HepG-2), breast cancer (MCF-7) and prostate cancer (PC3). Then the effects on the expression levels of caspase-8, VEGF, NF-κB P65, and TNF-α in HepG-2 cells were evaluated. The biological data revealed the high importance of phthalazine based compounds (24a-c), which were far better than thalidomide with regard to the antiproliferative activity. 24b showed IC50 of 2.51, 5.80 and 4.11 µg mL-1 compared to 11.26, 14.58, and 16.87 µg mL-1 for thalidomide against the three cell lines respectively. 24b raised caspase-8 level by about 7 folds, compared to 8 folds reported for thalidomide. Also, VEGF level in HepG-2 cells treated with 24b was 185.3 pg mL-1, compared to 432.5 pg mL-1 in control cells. Furthermore, the immunomodulatory properties were proven to 24b, which reduced TNF-α level by approximately half. At the same time, NF-κB P65 level in HepG-2 cells treated with 24b was 76.5 pg mL-1 compared to 278.1 and 110.5 pg mL-1 measured for control cells and thalidomide treated HepG-2 cells respectively. Moreover, an in vitro viability study against Vero non-cancerous cell line was investigated and the results reflected a high safety profile of all tested compounds. This work suggests 24b as a promising lead compound for development of new immunomodulatory anticancer agents.

Extensive myocardial infarction complicated with stroke as the first presentation of HIV in A young sudanese male: A case report.

Introduction: As it is a disseminated disease, HIV infection can be associated with significant cardiovascular and neurological complications; however, this commonly occurs late. Here, we highlight the unusual initial presentation of HIV infection, which is myocardial infarction complicated by stroke. Case presentation: A 30 years old male with a clear medical background presented with severe chest pain with evidence of ischemia on ECG and positive serum troponin. he received anti-ischemic drugs, and was prepared for coronary angiography with routine investigations tested positive for HIV; however, his condition was later complicated by stroke. Discussion: Antiretroviral medication, HIV disease characteristics, female gender, and HCV co-infection are risk factors for coronary artery disease (CAD) in HIV patients. Patients living with HIV are also at risk of developing stroke, which can be caused by atherosclerosis of the major arteries, small artery disease, cardiac embolism, CNS infections, coagulation issues, and non-atherosclerotic vasculopathy. Conclusion: The presentation of an acute coronary syndrome in a young patient should raise suspicion of uncommon causes and needs a prompt evaluation from digging up in history, detailed examination, and investigations with close follow-up to prevent the complications that may occur. on the other hand, known HIV Patients should be screened periodically with an electrocardiogram.

Prevalence and risk factors of functional seizures among adult Sudanese patients with epilepsy, a cross-sectional clinic-based study.

Background: Epilepsy can be associated with functional seizures. Our main aim is to assess functional seizures' prevalence and risk factors among adult Sudanese patients with epilepsy. Methods: This cross-sectional clinic-based study was conducted from January to February 2021 at Daoud Charity Clinic in Omdurman city, Sudan. Ninety-nine adult Sudanese patients with epilepsy were included. Data were collected using a validated interview-based semi-structured questionnaire. A senior consultant neurologist and a consultant psychiatrist diagnosed the functional seizures based on full clinical history and investigations. The diagnosis was performed according to International League against epilepsy (ILAE) classification. Results: This study included 99 patients with epilepsy, 57% were females, 79% reside in Khartoum state, and 32% reached secondary school. The main types of epilepsy were generalized tonic-clonic (68%), followed by focal seizures with impaired awareness (11%). The majority of the patients have been diagnosed with epilepsy for over three years (65%). Comorbid epilepsy and functional seizures were found in 29% of the patients, with a significantly higher prevalence in patients with social problems and depression (p = 0.005 and p < 0.01, respectively). Patients with depression had a 14 times higher risk of functional seizures than those without depression, 95% CI [3.8, 52.3]. Conclusion: A remarkably high prevalence of functional seizures was found among adult patients with epilepsy. Patients suffering from social problems and/or depression and poor economic status had a higher tendency to develop functional seizures, especially after two to three years of treatment and above.

Identification of Prognostic Metabolomic Biomarkers at the Interface of Mortality and Morbidity in Pre-Existing TB Cases Infected With SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection currently remains one of the biggest global challenges that can lead to acute respiratory distress syndrome (CARDS) in severe cases. In line with this, prior pulmonary tuberculosis (TB) is a risk factor for long-term respiratory impairment. Post-TB lung dysfunction often goes unrecognized, despite its relatively high prevalence and its association with reduced quality of life. In this study, we used a metabolomics analysis to identify potential biomarkers that aid in the prognosis of COVID-19 morbidity and mortality in post-TB infected patients. This analysis involved blood samples from 155 SARS-CoV-2 infected adults, of which 23 had a previous diagnosis of TB (post-TB), while 132 did not have a prior or current TB infection. Our analysis indicated that the vast majority (~92%) of post-TB individuals showed severe SARS-CoV-2 infection, required intensive oxygen support with a significantly high mortality rate (52.2%). Amongst individuals with severe COVID-19 symptoms, we report a significant decline in the levels of amino acids, notably the branched chains amino acids (BCAAs), more so in the post-TB cohort (FDR <= 0.05) in comparison to mild and asymptomatic cases. Indeed, we identified betaine and BCAAs as potential prognostic metabolic biomarkers of severity and mortality, respectively, in COVID-19 patients who have been exposed to TB. Moreover, we identified serum alanine as an important metabolite at the interface of severity and mortality. Hence, our data associated COVID-19 mortality and morbidity with a long-term metabolically driven consequence of TB infection. In summary, our study provides evidence for a higher mortality rate among COVID-19 infection patients who have history of prior TB infection diagnosis, which mandates validation in larger population cohorts.

Modified Benzoxazole-Based VEGFR-2 Inhibitors and Apoptosis Inducers: Design, Synthesis, and Anti-Proliferative Evaluation.

This work is one of our efforts to discover potent anticancer agents. We modified the most promising derivative of our previous work concerned with the development of VEGFR-2 inhibitor candidates. Thirteen new compounds based on benzoxazole moiety were synthesized and evaluated against three human cancer cell lines, namely, breast cancer (MCF-7), colorectal carcinoma (HCT116), and hepatocellular carcinoma (HepG2). The synthesized compounds were also evaluated against VEGFR-2 kinase activity. The biological testing fallouts showed that compound 8d was more potent than standard sorafenib. Such compound showed IC50 values of 3.43, 2.79, and 2.43 µM against the aforementioned cancer cell lines, respectively, compared to IC50 values of 4.21, 5.30, and 3.40 µM reported for sorafenib. Compound 8d also was found to exert exceptional VEGFR-2 inhibition activity with an IC50 value of 0.0554 µM compared to sorafenib (0.0782 µM). In addition, compound 8h revealed excellent cytotoxic effects with IC50 values of 3.53, 2.94, and 2.76 µM against experienced cell lines, respectively. Furthermore, compounds 8a and 8e were found to inhibit VEGFR-2 kinase activity with IC50 values of 0.0579 and 0.0741 µM, exceeding that of sorafenib. Compound 8d showed a significant apoptotic effect and arrested the HepG2 cells at the pre-G1 phase. In addition, it exerted a significant inhibition for TNF-α (90.54%) and of IL-6 (92.19%) compared to dexamethasone (93.15%). The molecular docking studies showed that the binding pattern of the new compounds to VEGFR-2 kinase was similar to that of sorafenib.

Treating Pain and Fat Necrosis after Breast Cancer Surgery with Fat Grafting: Is one Session Enough?

BACKGROUND: Chronic pain after breast cancer surgery is affecting up to 60% of patients, causing significant morbidity to patients. Lately, fat grafting has been applied as a therapy for chronic neuropathic pain. METHODS: We report a series of eighteen patients, who were treated for pain after breast cancer surgery. Twelve patients had a breast conserving therapy, two a mastectomy and four an autologous flap-based reconstruction. While most presented with neuropathic pain, six patients had fat necrosis in their history. Most patients presented with severe pain (77%) and were treated with fat grafting sessions, performed by water-assisted liposuction. RESULTS: All patients responded to the interventions; the median number of fat grafting sessions was 2, the median duration of the interventions was 4 months, and the median follow-up period was 56.5 months. The median pain prior to the fat grafting procedure had an intensity of 8 (range 7-9) numeric rating scale points; after the first intervention, this was reduced to 4 (range 2.3-5.8); and after the second intervention, it was down to 2 (range 0.8-3.3). Patients with pain intensities of 4-5 had a good chance of achieving analgesia after one session. CONCLUSIONS: Fat grafting could be a new treatment modality for symptomatic fat necrosis: complete or partial suction of the necrosis and/or fat grafting around the necrosis to reduce inflammation and pain. Fat grafting proved a valuable tool, reducing pain or even achieving analgesia after breast cancer surgery presenting with a highly favorable risk-benefit ratio. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

AstraZeneca COVID-19 vaccine: A possible risk factor for ischemic stroke and cerebral venous sagittal sinus thrombosis: A case series.

One of the most prevalent neurological impairments is cerebrovascular accident (CVA). Ischemic stroke and CVST have been linked to the AstraZeneca COVID-19 vaccine. Three Sudanese patients developed these diseases after receiving the AstraZeneca COVID-19 vaccine, indicating a relationship between the AstraZeneca COVID-19 vaccine and these conditions.

COVID-19 exit strategy during vaccine implementation: a balance between social distancing and herd immunity.

Currently, health authorities around the world are struggling to limit the spread of COVID-19. Since the beginning of the pandemic, social distancing has been the most important strategy used by most countries to control disease spread by flattening and elongating the epidemic curve. Another strategy, herd immunity, was also applied by some countries through relaxed control measures that allow the free spread of natural infection to build up solid immunity within the population. In 2021, COVID-19 vaccination was introduced with tremendous effort as a promising strategy for limiting the spread of disease. Therefore, in this review, we present the current knowledge about social distancing, herd immunity strategies, and aspects of their implementation to control the COVID-19 pandemic in the presence of the newly developed vaccines. Finally, we suggest a short-term option for controlling the pandemic during vaccine application.

Clinical characteristics, complications, and predictors of outcome of hospitalized adult Sudanese patients with COVID-19 and malaria coinfection in Sudan: A multicenter retrospective cross-sectional study.

Malaria and coronavirus disease 2019 (COVID-19) share several characteristics that could lead to cross-infection, particularly in malaria-endemic areas. Early COVID-19 symptoms might be misdiagnosed for malaria in clinical settings. Also, both diseases can cause fatal complications. So, laboratory testing for both diseases was recommended by the World Health Organization. To study the clinical characteristics and outcomes of Adult Sudanese patients with COVID-19 and malaria coinfection. This retrospective cross-sectional study was conducted from January 2021 to October 2021 in Wad Medani. Total coverage of all Sudanese patients above 18 years old with a confirmed diagnosis of coinfection with COVID-19 and malaria was included, and data were collected using a data collection sheet. Data were analyzed using R software version 4.0.2. Data were described and presented as mean, standard deviation, and number (percentage). To find associated factors with in-hospital outcome, χ2 test, fisher exact test, and independent t test or Wilcoxon rank-sum test were used. In this study, 156 participants were diagnosed with COVID-19 and malaria coinfection. Most of them were between 60 and 70 years (30.8%), the majority were males (59%). Shortness of breath (76.3%) and acute respiratory distress syndrome (35.3%) were the most common symptom and complications among coinfected patients, respectively. Ground glass opacity (n = 47/49, 95.9%) is the most common result for computed tomography scan. Atrial fibrillation was the most common abnormal electrocardiogram finding (n = 6/62, 9.7%). Overall mortality among all participants was (63/156, 40.4%). High mortality rate was found among the coinfected patients. More attention is needed towards fighting COVID-19 and malaria coinfection. There may be a link between malaria and COVID-19.

Synthesis, and docking studies of novel heterocycles incorporating the indazolylthiazole moiety as antimicrobial and anticancer agents.

The current study was directed toward developing a new series of fused heterocycles incorporating indazolylthiazole moiety. The newly synthesized compounds were characterized through elemental analysis and spectral data (IR, 1H-NMR, 13C-NMR, and Mass Spectrometry). The cytotoxic effect of the newly synthesized compounds was evaluated against normal human cells (HFB-4) and cancer cell lines (HepG-2 and Caco-2). Among the synthesized compounds, derivatives 4, and 6 revealed a significant selective antitumor activity, in a dose-dependent manner, against both HepG-2 and Caco-2 cell lines, with lower risk toward HFB-4 cells (normal cells). Derivative 8 revealed the maximum antitumor activity toward both tumor cell lines, with an SI value of about 26 and IC50 value of about 5.9 µg/mL. The effect of these derivatives (8, 4, and 6) upon the expression of 5 tumor regulating genes was studied through quantitative real-time PCR, where its interaction with these genes was simulated through the molecular docking study. Furthermore, the antimicrobial activity results revealed that compounds 2, 7, 8, and 9 have a potential antimicrobial activity, with maximum broad-spectrum activity through compound 3 against the three tested pathogens: Streptococcus mutans, Pseudomonas aeruginosa, and Candida albicans. The newly prepared compounds also revealed anti-biofilm formation activity with maximum activity against Streptococcus mutans, Pseudomonas aeruginosa, and Candida albicans, respectively.

New Series of VEGFR-2 Inhibitors and Apoptosis Enhancers: Design, Synthesis and Biological Evaluation.

Background: Cancer is still a major world health threat, causing a high rate of mortality. VEGFR-2 inhibitor anticancer agents are of great significance. However, they showed some serious side effects. Purpose: To discover new effective and safer anticancer agents, a new series of piperazinylquinoxaline-based derivatives was designed and synthesized on the basis of the pharmacophoric features of VEGFR-2 inhibitor drugs. Methods: The new candidates were evaluated against A549 lung cancer cells, HepG-2 hepatoma cells, Caco-2 colon cancer cells, MDA breast cancer cells, and VEGFR-2 kinase. Moreover, cell cycle kinetics and apoptosis rates were studied in HepG-2 cells treated with compound 11, which was the most promising candidate. Results: The new derivatives revealed better antitumor results (IC50 from 6.48 to 38.58 µM) against the aforementioned cancer cell lines than sorafenib. Also, the new candidates showed VEGFR-2 inhibition with IC50 values ranging from 0.19 to 0.60 µM compared to 0.08 µM for sorafenib. Compound 11, meanwhile, showed IC50 values equal to 10.61, 9.52, 12.45, 11.52, and 0.19 µM against the cancer cell lines and VEGFR-2, respectively. Moreover, compound 11 raised the apoptosis rate in HepG-2 cells from 5% to 44% and caused 4, 2.3, and 3-fold increases in BAX/Bcl-2 ratio, caspase-3 level, and P53 expression, respectively, compared to control untreated cells. Finally, the new derivatives displayed the correct binding mode into VEGFR-2 kinase pocket, giving interactions with the essential residues. Conclusion: This work suggests that compound 11 is a very significant anticancer candidate, and piperazinylquinoxaline is an important scaffold in the development of new potential effective and safer VEGFR-2 inhibitor agents.