Disposable paper electrodes for detection of changes in dopamine concentrations in rat brain homogenates.

Dopamine, the main catecholamine neurotransmitter plays an important role in renal, cardiovascular, central nervous systems, and pathophysiological processes. The abnormal dopamine levels can result in neurological disorders such as Parkinson's, Alzheimer's, schizophrenia, acute anxiety, neuroblastoma and also contribute to cognitive dysfunctions. Given the widespread importance of dopamine concentration levels, it is imperative to develop sensors that are able to monitor dopamine. Herein, we have developed pre-anodized disposable paper electrode modified with 1-pyrenebutyric acid, for the selective and sensitive determination of dopamine. The sensor was characterized with Fourier transform infrared spectroscopy, Energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and electrochemical techniques for addressing the robust formation and electrochemical activity. The modified electrode exhibited excellent electrocatalytic activity towards dopamine without the common interference from ascorbic acid. The calibration plot for the dopamine sensor resulted linear range from 0.003 µM to 0.5 µM with a detection limit of 0.11 nM. The sensor's potential utility was tested by monitoring dopamine concentration changes in rat brain homogenates when subjected to neurotoxicity. The developed sensor was validated with gold-standard UV-Vis spectroscopy studies and computational studies were performed to understand the interaction between 1-pyrenebutyric acid and dopamine.

Assessing the Knowledge and Practices of Burn First Aid in Al-Baha Region, Saudi Arabia.

Background Burns are a prevalent type of injury that can result in substantial morbidity and mortality. Burn first aid knowledge is essential for reducing its complications and improving outcomes. However, evidence of the amount of burn first aid knowledge among the general population in many nations is sparse. Methodology A cross-sectional survey was conducted among 346 persons over the age of 18 from the Al-Baha region of Saudi Arabia. The participants' knowledge of first aid for burns, including the appropriate steps to take in the event of a burn, the types of burns, and the proper application of burn dressings was assessed using a structured questionnaire. Results The majority of participants (73.6%) had inadequate knowledge of first aid for burns, while only 26.4% had adequate knowledge. The most common misconception among participants was the use of toothpaste, honey, or ice for burn treatment, which is not recommended. Additionally, hot water was the main cause of burning in this study. Conclusions This study underscores the necessity for targeted education and awareness-raising activities to improve the general population's knowledge and habits about first aid for burns. Such programs can be tailored to clarify myths and misunderstandings regarding burn treatment and encourage evidence-based strategies for preventing and treating burns.

Epidemiological Differences in Hajj-Acquired Airborne Infections in Pilgrims Arriving from Low and Middle-Income versus High-Income Countries: A Systematised Review.

This systematised review aims to compare the epidemiological patterns of Hajj-acquired airborne infections among pilgrims from low and middle-income countries (LMIC) versus those from high-income countries (HIC). A PubMed search was carried out for all published articles before February 2023, using a combination of MeSH terms and text words. The Newcastle-Ottawa Scale (NOS) was used to assess data quality. From a total of 453 titles identified, 58 studies were included in the review (LMIC = 32, and HIC = 26). In the pooled sample, there were 27,799 pilgrims aged 2 days to 105 years (male: female = 1.3:1) from LMIC and 70,865 pilgrims aged 2 months to 95 years (male: female = 1:1) from HIC. Pilgrims from both HIC and LMIC had viral and bacterial infections, but pilgrims from HIC tended to have higher attack rates of viral infections than their LMIC counterparts. However, the attack rates of bacterial infections were variable: for instance, pilgrims from LMIC seemed to have higher rates of meningococcal infections (0.015-82% in LMIC vs. 0.002-40% in HIC) based on the study population, but not Mycobacterium tuberculosis (0.7-20.3% in LMIC vs. 38% in HIC). Targeted measures are needed to prevent the spread of airborne infections at Hajj.

Hand hygiene knowledge and practices, and rates of respiratory tract infections between Hajj and Umrah pilgrims: a comparative study.

BACKGROUND: Hajj and Umrah mass gatherings (MGs) in the Kingdom of Saudi Arabia amplify the risk of viral respiratory tract infections (RTIs), but there is a lack of comparative data from these two MGs. This study aims to compare pilgrims' hand hygiene knowledge, practices, and rates of RTIs during the peak periods of Umrah and Hajj in 2021. MATERIALS AND METHODS: The datasets of this comparative study were obtained from two previously conducted studies that used similar study tools and identical syndromic definitions. The binary logistic regression was applied to compare the categorical variables and, a t-test was used to compare the continuous variables. RESULTS: A total of 510 Hajj pilgrims and 507 Umrah pilgrims were recruited. The majority of Hajj pilgrims (68%) were ≥ 40 years old, while most Umrah pilgrims (63%) were < 40 years old. The mean total knowledge scores of hand hygiene between the Hajj and Umrah pilgrims differed significantly (4.1 vs. 3.7, respectively, p < 0.001) so did their compliance with frequent use of alcohol-based hand rubs (53.0% vs. 36.3%, respectively, p < 0.001) and the rates of RTIs (4.7% vs. 2.2%, respectively, p = 0.05). CONCLUSIONS: These differences could be attributable to the distinctive characteristics of Hajj and Umrah pilgrimages, and the unique differences in risks posed by those MGs.

The relationship between hand hygiene and rates of acute respiratory infections among Umrah pilgrims: A pilot randomised controlled trial.

BACKGROUND: There is a lack of randomised controlled trials (RCTs) investigating the role of hand hygiene in preventing and containing acute respiratory infections (ARIs) in mass gatherings. In this pilot RCT, we assessed the feasibility of establishing a large-scale trial to explore the relationship between practising hand hygiene and rates of ARI in Umrah pilgrimage amidst the COVID-19 pandemic. METHODS: A parallel RCT was conducted in hotels in Makkah, Saudi Arabia, between April and July 2021. Domestic adult pilgrims who consented to participate were randomised 1:1 to the intervention group who received alcohol-based hand rub (ABHR) and instructions, or to the control group who did not receive ABHR or instructions but were free to use their own supplies. Pilgrims in both groups were then followed up for seven days for ARI symptoms. The primary outcome was the difference in the proportions of syndromic ARIs among pilgrims between the randomised groups. RESULTS: A total of 507 (control: intervention = 267: 240) participants aged between 18 and 75 (median 34) years were randomised; 61 participants were lost to follow-up or withdrew leaving 446 participants (control: intervention = 237:209) for the primary outcome analysis; of whom 10 (2.2 %) had developed at least one respiratory symptom, three (0.7 %) had 'possible ILI' and two (0.4 %) had 'possible COVID-19'. The analysis of the primary outcome found no evidence of difference in the proportions of ARIs between the randomised groups (odds ratio 1.1 [0.3-4.0] for intervention relative to control). CONCLUSION: This pilot trial suggests that conducting a future definitive RCT to assess the role of hand hygiene in the prevention of ARIs is feasible in Umrah setting amidst such a pandemic; however, outcomes from this trial are inconclusive, and such a study would need to be very large given the low rates of outcomes observed here. TRIAL REGISTRATION: This trial was registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12622001287729), the full protocol can be accessed there.

Observer-based controller for VTOL-UAVs tracking using direct Vision-Aided Inertial Navigation measurements.

This paper proposes a novel observer-based controller for Vertical Take-Off and Landing (VTOL) Unmanned Aerial Vehicle (UAV) designed to directly receive measurements from a Vision-Aided Inertial Navigation System (VA-INS) and produce the required thrust and rotational torque inputs. The VA-INS is composed of a vision unit (monocular or stereo camera) and a typical low-cost 6-axis Inertial Measurement Unit (IMU) equipped with an accelerometer and a gyroscope. A major benefit of this approach is its applicability for environments where the Global Positioning System (GPS) is inaccessible. The proposed VTOL-UAV observer utilizes IMU and feature measurements to accurately estimate attitude (orientation), gyroscope bias, position, and linear velocity. Ability to use VA-INS measurements directly makes the proposed observer design more computationally efficient as it obviates the need for attitude and position reconstruction. Once the motion components are estimated, the observer-based controller is used to control the VTOL-UAV attitude, angular velocity, position, and linear velocity guiding the vehicle along the desired trajectory in six degrees of freedom (6 DoF). The closed-loop estimation and the control errors of the observer-based controller are proven to be exponentially stable starting from almost any initial condition. To achieve global and unique VTOL-UAV representation in 6 DoF, the proposed approach is posed on the Lie Group and the design in unit-quaternion is presented. Although the proposed approach is described in a continuous form, the discrete version is provided and tested.

Biometric Identification System as a Potential Source of Nosocomial Infection Among Medical Students.

In the current situation, biometric devices, electronic devices, and medical apparatus usage cannot be restricted in hospitals and offices. These devices will act as a vehicle for the transmission of bacterial agents. Our study observed that a biometric device is acting as a vehicle/source of spreading bacterial agents. It will be more in the hospital environment. The only way to protect from infections is strict adherence to infection control and good hygienic practices. We also observed fewer samples containing yielding of bacteria, indicating that either student is not interacting with biometric devices or is more aware of infection spread and followed the hand hygiene practice with alcohol.

Nonsurgical Orthodontic Treatment of a Severe Open Bite Case Using Miniscrews with Modified Multiloop Edgewise Arch Wire Technique.

Skeletal open bite is one of the most challenging malocclusions to treat and maintain due to the difficulty and instability of correction. Although a combination of orthodontic treatment and orthognathic surgery may be the ideal approach in most cases, the complications, risks, and costs of surgery have sparked an interest in alternative treatment options that use temporary anchorage devices to achieve orthognathic-like effects. Adult patients can be treated without the need for special compliance using temporary anchorage devices such as miniscrews. This case report demonstrates a goal-oriented strategy for nonsurgical treatment of a complex skeletal open bite malocclusion in an adult patient using miniscrews and a modified multiloop edgewise arch wire (MEAW) technique, with the results evaluated clinically and cephalometrically.

Low Prevalence of Syndromic Respiratory Tract Infections among Returning Hajj Pilgrims Amidst the COVID-19 Pandemic: A Post-Hajj Survey.

This study estimates the point prevalence of symptomatic respiratory tract infections (RTIs) among returned Hajj pilgrims and their contacts in 2021. Using the computer-assisted telephone interview (CATI) technique, domestic pilgrims were invited to participate in this cross-sectional survey two weeks after their home return from Hajj. Of 600 pilgrims approached, 79.3% agreed to participate and completed the survey. Syndromic definitions were used to clinically diagnose possible influenza-like illnesses (ILI) and COVID-19. Median with range was applied to summarise the continuous data, and frequencies and proportions were used to present the categorical variables. Simple logistic regression was carried out to assess the correlations of potential factors with the prevalence of RTIs. The majority of pilgrims (88.7%) reported receiving at least two doses of the COVID-19 vaccine before Hajj. Eleven (2.3%) pilgrims reported respiratory symptoms with the estimated prevalence of possible ILI being 0.2%, and of possible COVID-19 being 0.4%. Among those who were symptomatic, five (45.5%) reported that one or more of their close contacts had developed similar RTI symptoms after the pilgrims' home return. The prevalence of RTIs among pilgrims who returned home after attending the Hajj 2021 was lower compared with those reported in the pre-pandemic studies; however, the risk of spread of infection among contacts following Hajj is still a concern.

Adaptive Neural Network Stochastic-Filter-Based Controller for Attitude Tracking With Disturbance Rejection.

This article proposes a real-time neural network (NN) stochastic filter-based controller on the Lie group of the special orthogonal group [Formula: see text] as a novel approach to the attitude tracking problem. The introduced solution consists of two parts: a filter and a controller. First, an adaptive NN-based stochastic filter is proposed, which estimates attitude components and dynamics using measurements supplied by onboard sensors directly. The filter design accounts for measurement uncertainties inherent to the attitude dynamics, namely, unknown bias and noise corrupting angular velocity measurements. The closed-loop signals of the proposed NN-based stochastic filter have been shown to be semiglobally uniformly ultimately bounded (SGUUB). Second, a novel control law on [Formula: see text] coupled with the proposed estimator is presented. The control law addresses unknown disturbances. In addition, the closed-loop signals of the proposed filter-based controller have been shown to be SGUUB. The proposed approach offers robust tracking performance by supplying the required control signal given data extracted from low-cost inertial measurement units. While the filter-based controller is presented in continuous form, the discrete implementation is also presented. In addition, the unit-quaternion form of the proposed approach is given. The effectiveness and robustness of the proposed filter-based controller are demonstrated using its discrete form and considering low sampling rate, high initialization error, high level of measurement uncertainties, and unknown disturbances.

Syndromic surveillance of respiratory-tract infections and hand hygiene practice among pilgrims attended Hajj in 2021: a cohort study.

BACKGROUND: The risk of transmission of viral respiratory tract infections (RTIs) is high in mass gatherings including Hajj. This cohort study estimated the incidence of symptomatic RTIs and hand hygiene compliance with its impact among Hajj pilgrims during the COVID-19 pandemic. METHODS: During the week of Hajj rituals in 2021, domestic pilgrims were recruited by phone and asked to complete a baseline questionnaire. Pilgrims were followed up after seven days using a questionnaire about the development of symptoms, and practices of hand hygiene. Syndromic definitions were used to clinically diagnose 'possible' influenza-like illnesses (ILI) and COVID-19 infection. RESULTS: A total of 510 pilgrims aged between 18 and 69 (median of 50) years completed the questionnaire, 280 (54.9%) of whom were female, and all of them (except for one) were vaccinated against COVID-19 with at least one dose. The mean (± SD) of pilgrims' hand hygiene knowledge score (on a scale of 0 to 6) was 4.15 (± 1.22), and a higher level of knowledge was correlated with a higher frequency of handwashing using soap and water. Among those 445 pilgrims who completed the follow-up form, 21 (4.7%) developed one or more respiratory symptoms, of which sore throat and cough were the commonest (respectively 76.2% and 42.8%); 'possible ILI' and 'possible COVID-19' were present in 1.1% and 0.9% of pilgrims. Obesity was found to be a significant factor associated with the risk of developing RTIs (odds ratio = 4.45, 95% confidence interval 1.15-17.13). CONCLUSIONS: Hajj pilgrims are still at risk of respiratory infections. Further larger and controlled investigations are needed to assess the efficacy of hand hygiene during Hajj.

Knowledge and attitude of the general population regarding infant hearing loss in Saudi Arabia.

Background: Ear health and hearing loss (HL) among infants has devastating outcomes. With most HL being deemed preventable, the assessment of one's knowledge and attitude regarding this impairment is important. In Saudi Arabia, the state of the general population's knowledge on infant HL remains unknown. Objectives: To determine and further elucidate the general population's knowledge and attitude with regard to HL in Saudi Arabia. Methods: This is a cross-sectional survey-based study conducted on the general population of Saudi Arabia. A predetermined questionnaire was translated into Arabic. This was distributed among the targeted participants in several provinces of Saudi Arabia (central, northern, eastern, western, and southern) by using an online survey via social media. The data were collected and analyzed via the SPSS program. Results: The knowledge with moderate, poor, and good was determined among 60.9%, 29.6%, and 9.4% of the participants, respectively. The participants with positive and negative attitudes were detected among 92.6% and 7.4% of respondents, respectively. Increasing age was associated with better attitude, while increased knowledge was directly related to higher educational attainment. Those who have a child with HL had nearly twice as poor knowledge as those who do not have a child with HL (P < 0.001). Conclusions: Although most of the respondents possessed a positive attitude toward infant HL, their knowledge about it seems to be lacking. Thus, there is a need to address these knowledge gaps regarding infant HL.

Anticancer Effects of New Ceramides Isolated from the Red Sea Red Algae Hypnea musciformis in a Model of Ehrlich Ascites Carcinoma: LC-HRMS Analysis Profile and Molecular Modeling.

Different classes of phytochemicals were previously isolated from the Red Sea algae Hypnea musciformis as sterols, ketosteroids, fatty acids, and terpenoids. Herein, we report the isolation of three fatty acids-docosanoic acid 4, hexadecenoic acid 5, and alpha hydroxy octadecanoic acid 6-as well as three ceramides-A (1), B (2), and C (3)-with 9-methyl-sphinga-4,8-dienes and phytosphingosine bases. Additionally, different phytochemicals were determined using the liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (LC-ESI-HRMS) technique. Ceramides A (1) and B (2) exhibited promising in vitro cytotoxic activity against the human breast adenocarcinoma (MCF-7) cell line when compared with doxorubicin as a positive control. Further in vivo study and biochemical estimation in a mouse model of Ehrlich ascites carcinoma (EAC) revealed that both ceramides A (1) and B (2) at doses of 1 and 2 mg/kg, respectively, significantly decreased the tumor size in mice inoculated with EAC cells. The higher dose (2 mg/kg) of ceramide B (2) particularly expressed the most pronounced decrease in serum levels of vascular endothelial growth factor -B (VEGF-B) and tumor necrosis factor-α (TNF-α) markers, as well as the expression levels of the growth factor midkine in tumor tissue relative to the EAC control group. The highest expression of apoptotic factors, p53, Bax, and caspase 3 was observed in the same group that received 2 mg/kg of ceramide B (2). Molecular docking simulations suggested that ceramides A (1) and B (2) could bind in the deep grove between the H2 helix and the Ser240-P250 loop of p53, preventing its interaction with MDM2 and leading to its accumulation. In conclusion, this study reports the cytotoxic, apoptotic, and antiangiogenic effects of ceramides isolated from the Red Sea algae Hypnea musciformis in an experimental model of EAC.

Public Awareness of Colorectal Cancer Screening in the Al-Baha Region, Saudi Arabia, 2022.

BACKGROUND: According to the WHO, cancer is ranked as the second leading cause of death, accounting for an estimated 9.6 million deaths in 2018. This study aimed to assess public awareness about colorectal cancer (CRC) screening and the barriers that prevent Saudi individuals from undergoing CRC screening.  Materials and methods: A cross-sectional study was conducted in the Prince Mishari Bin Saud General Baljurashi Hospital, and a supervised self-administered questionnaire was utilized. Sociodemographic data, knowledge about colorectal cancer, and attitude toward screening were included in the survey. Data were analyzed using IBM SPSS Version 23 (SPSS Inc., Chicago, IL, USA) and Pearson's chi-square test. A P<0.05 was considered statistically significant. RESULTS: A total of 396 eligible participants completed the survey. About 209 (52%) were female, and 124 (31.3%) belonged to the age group of 18-29 years. Nearly (49.7%) knew that detecting colorectal cancer before symptoms appear is possible. About 64% of the participants cited colonoscopy as the screening method for CRC. More than half of the participants (58.1%) expressed their willingness to be screened for colorectal cancer, while only 2.8% reported that they had undergone screening before. Participants with higher educational status demonstrated better knowledge regarding CRC than others (p<0.05). CONCLUSION:  The overall knowledge of CRC was found to be poor in Al-Baha residents, irrespective of age. Implementing new strategies to increase public awareness about colorectal cancer will aid in the early diagnosis of CRC. We recommend targeted education and screening programs to improve the level of screening awareness and aid in the early diagnosis of colorectal cancer.

Chemical Composition of the Red Sea Green Algae Ulva lactuca: Isolation and In Silico Studies of New Anti-COVID-19 Ceramides.

Coronavirus disease 2019 (COVID-19) is the disease caused by the virus SARS-CoV-2 responsible for the ongoing pandemic which has claimed the lives of millions of people. This has prompted the scientific research community to act to find treatments against the SARS-CoV-2 virus that include safe antiviral medicinal compounds. The edible green algae U. lactuca. is known to exhibit diverse biological activities such as anti-influenza virus, anti-Japanese encephalitis virus, immunomodulatory, anticoagulant, antioxidant and antibacterial activities. Herein, four new ceramides in addition to two known ones were isolated from Ulva lactuca. The isolated ceramides, including Cer-1, Cer-2, Cer-3, Cer-4, Cer-5 and Cer-6 showed promising antiviral activity against SARS-CoV-2 when investigated using in silico approaches by preventing its attachment to human cells and/or inhibiting its viral replication. Cer-4 and Cer-5 were the most effective in inhibiting the human angiotensin converting enzyme (hACE)-spike protein complex which is essential for the virus to enter the human host. In addition to this, Cer-4 also showed an inhibition of the SARS-CoV-2 protease (Mpro) that is responsible for its viral replication and transcription. In this study, we also used liquid chromatography coupled to electrospray ionization high-resolution mass spectroscopy (LC-ESI-HRMS) to identify several metabolites of U. lactuca, including metabolites such as fatty acids, their glyceride derivatives, terpenoids, sterols and oxysterols from the organic extract. Some of these metabolites also possessed promising antiviral activity, as previously reported.

Loss of Neutrophil Homing to the Periodontal Tissues Modulates the Composition and Disease Potential of the Oral Microbiota.

Periodontal disease is considered to arise from an imbalance in the interplay between the host and its commensal microbiota, characterized by inflammation, destructive periodontal bone loss, and a dysbiotic oral microbial community. The neutrophil is a key component of defense of the periodontium: defects in their number or efficacy of function predisposes individuals to development of periodontal disease. Paradoxically, neutrophil activity, as part of a deregulated inflammatory response, is considered an important element in the destructive disease process. In this investigation, we examined the role the neutrophil plays in the regulation of the oral microbiota by analysis of the microbiome composition in mice lacking the CXCR2 neutrophil receptor required for recruitment to the periodontal tissues. A breeding protocol was employed that ensured that only the oral microbiota of wild-type (CXCR2+/+) mice was transferred to subsequent generations of wild-type, heterozygote, and homozygote littermates. In the absence of neutrophils, the microbiome undergoes a significant shift in total load and composition compared to when normal levels of neutrophil recruitment into the gingival tissues occur, and this is accompanied by a significant increase in periodontal bone pathology. However, transfer of the oral microbiome of CXCR2-/- mice into germfree CXCR2+/+ mice led to restoration of the microbiome to the wild-type CXCR2+/+ composition and the absence of pathology. These data demonstrate that the composition of the oral microbiome is inherently flexible and is governed to a significant extent by the genetics and resultant phenotype of the host organism.

Antibiotics Prescribing in Intensive Care Settings during the COVID-19 Era: A Systematic Review.

The prevalence of patients admitted to intensive care units (ICUs) with SARS-CoV-2 infection who were prescribed antibiotics is undetermined and might contribute to the increased global antibiotic resistance. This systematic review evaluates the prevalence of antibiotic prescribing in patients admitted to ICUs with SARS-CoV-2 infection using PRISMA guidelines. We searched and scrutinized results from PubMed and ScienceDirect databases for published literature restricted to the English language up to 11 May 2021. In addition, we included observational studies of humans with laboratory-confirmed SARS-CoV-2 infection, clinical characteristics, and antibiotics prescribed for ICU patients with SARS-CoV-2 infections. A total of 361 studies were identified, but only 38 were included in the final analysis. Antibiotic prescribing data were available from 2715 patients, of which prevalence of 71% was reported in old age patients with a mean age of 62.7 years. From the reported studies, third generation cephalosporin had the highest frequency amongst reviewed studies (36.8%) followed by azithromycin (34.2%). The estimated bacterial infection in 12 reported studies was 30.8% produced by 15 different bacterial species, and S. aureus recorded the highest bacterial infection (75%). The fundamental outcomes were the prevalence of ICU COVID-19 patients prescribed antibiotics stratified by age, type of antibiotics prescribed, and the presence of co-infections and comorbidities. In conclusion, more than half of ICU patients with SARS-CoV-2 infection received antibiotics, and prescribing is significantly higher than the estimated frequency of identified bacterial co-infection.

VEGFR-Mediated Cytotoxic Activity of Pulicaria undulata Isolated Metabolites: A Biological Evaluation and In Silico Study.

Natural products play a remarkable role not only in the synthesis, design, and discovery of new drugs but also as the most prominent source of drugs and bioactive substances. Adding to the search for new sources of safe innovative antitumor drugs, here we reported a phytochemical study on Pulicaria undulata which revealed promising antiangiogenic agents. Six compounds were isolated and identified as xanthoxyline (1), stigmasterol (2), oleanolic acid (3), salvigenin (4), rhamnetin (5) and dihydroquercetin-4'-methyl ether (6) using nuclear magnetic resonance (NMR) spectroscopic techniques. Compound 3 and 4 are first reported in Pulicaria genus. Both the extract and isolated compounds were evaluated for in vitro antiproliferative activity against breast cancer cell line (MCF-7). In vivo antiproliferative activity against Ehrlich's ascites carcinoma (EAC) were also assessed. The P. undulata extract and isolates showed significant reduction in tumor weight, decreased both serum vascular endothelial growth factor B (VEGF-B) levels and vascular endothelial growth factor receptor 2 (VEGFR-2) expression significantly compared to the control EAC group, suggesting an antiangiogenic activity through the inhibition of VEGF signaling. Besides, they displayed reduction in CD34 expression, confirming their antiangiogenic effect. Moreover, the potential affinity of isolated compounds to human estrogen nuclear receptor-alpha (hER-α), the most recognized modulator of VEGFR-2 expression, was virtually estimated through molecular modeling studies. The most promising activity profiles were assigned to the investigated flavonoids, compounds 4-6, as well as the alkyl-phenylketone, compound 1. Additionally, these four top active compounds showed respective high to intermediate docking scores while possessing preferential binding with hER-α critical pocket residues. Based on the provided data, these isolated compounds illustrated promising inhibitors of VEGF-stimulated angiogenesis, which could be a possible mechanism for their anticancer activity.

Community-Based Assessment and Treatment of Hepatitis C Virus-Related Liver Disease, Injecting Drug and Alcohol Use Amongst People Who Are Homeless: A Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: We performed a systematic review and meta-analysis addressing community-based assessment and treatment of hepatitis C virus (HCV)-related liver disease, injecting drug use (IDU) and alcohol use amongst people who are homeless (PWAH). METHODS: Using systematic review methodology, databases were searched (MEDLINE/EMBASE/CINAHL) for studies combining PWAH, HCV-related liver disease and community assessment until December 2019. Studies with a sample size ≥ 30, with PWAH constituting at least 30% of the cohort were included and a quality assessment performed. Pooled estimates of key indicators were analysed using meta-analysis. RESULTS: We identified 39 studies (n = 13,918), 37 categorised as poor quality (Newcastle-Ottawa Scale). Prevalence of homelessness ranged between 30%-100% (37 studies). Eight studies provided all of the following: HCV screening, alcohol/substance use/liver fibrosis assessment and HCV treatment. No study provided interventions for alcohol use, with two providing opioid substitution treatment. Alcohol use prevalence (24 studies) was 4%-97%, being 59% (95% CI 20%-92%) in four studies that included only PWAH. Recent IDU prevalence (16 studies) was 7%-73%, being 21% (95% CI 17%-26%) in four studies that included only PWAH. HCV seroprevalence (25 studies) was 2.5% - 58%; in 13 studies that included only PWAH, this was 20% (95% CI 12%-30%). Prevalence of F4 fibrosis (nine studies) was 6%-28%, being 7% and 16% in two studies that included only PWAH. Direct acting antiviral-based intention-to-treat sustained virological response (SVR) rates (five studies) were 82%-92%, being 92% in the one study that included only PWAH. In the only two randomised controlled trials (RCT) identified, community-based interventions (mental health/peer mentor) significantly increased linkage to care (p = 0.04), HCV treatment (p = 0.005) and SVR rates (p = 0.018). CONCLUSION: The burden from alcohol/IDU and HCV, and consequently liver disease in PWAH needs addressing. RCT trials assessing community-based interventions to improve liver health in PWAH are needed.

Holospiniferoside: A New Antitumor Cerebroside from The Red Sea Cucumber Holothuria spinifera: In Vitro and In Silico Studies.

Chemical investigation of the methanolic extract of the Red Sea cucumber Holothuria spinifera led to the isolation of a new cerebroside, holospiniferoside (1), together with thymidine (2), methyl-α-d-glucopyranoside (3), a new triacylglycerol (4), and cholesterol (5). Their chemical structures were established by NMR and mass spectrometric analysis, including gas chromatography-mass spectrometry (GC-MS) and high-resolution mass spectrometry (HRMS). All the isolated compounds are reported in this species for the first time. Moreover, compound 1 exhibited promising in vitro antiproliferative effect on the human breast cancer cell line (MCF-7) with IC50 of 20.6 µM compared to the IC50 of 15.3 µM for the drug cisplatin. To predict the possible mechanism underlying the cytotoxicity of compound 1, a docking study was performed to elucidate its binding interactions with the active site of the protein Mdm2-p53. Compound 1 displayed an apoptotic activity via strong interaction with the active site of the target protein. This study highlights the importance of marine natural products in the design of new anticancer agents.