Evidence of Anti-tumoral Efficacy in an Immune Competent Setting with an iRGD-Modified Hyaluronidase-Armed Oncolytic Adenovirus

To enhance adenovirus-mediated oncolysis, different approaches that tackle the selectivity, tumor penetration, and spreading potential of oncolytic adenoviruses have been reported. We have previously demonstrated that insertion of the internalizing Arginine-Glycine-Aspartic (iRGD) tumor-penetrating peptide at the C terminus of the fiber or transgenic expression of a secreted hyaluronidase can improve virus tumor targeting and spreading. Here we report a new oncolytic adenovirus ICOVIR17K-iRGD in which both modifications have been incorporated. In xenografted A549 tumors in nude mice, ICOVIR17K-iRGD shows higher efficacy than the non-iRGD counterpart. To gain insights into the role of the immune system in oncolysis, we have studied ICOVIR17K-iRGD in the tumor isograft mouse model CMT64.6, partially permissive to human adenovirus 5 replication, in immunodeficient or immunocompetent mice. Whereas no efficacy was observed in the immunodeficient setting due to insufficient viral replication, partial efficacy and a polymorphonuclear and CD8+ T cell infiltrate were observed in the immunocompetent mice. The results indicate that the elicitation of a virus-induced anti-tumoral immune response is responsible for the observed partial antitumoral effect

Enhanced antitumor efficacy of oncolytic adenovirus-loaded menstrual blood-derived mesenchymal stem cells in combination with peripheral blood mononuclear cells

Several studies have evaluated the efficacy of using human oncolytic adenovirus-loaded mesenchymal stem cells for cancer treatment. For example, we have described the antitumor efficacy of CELYVIR, autologous bone marrow mesenchymal stem cells infected with the oncolytic adenovirus ICOVIR-5, for treatment of neuroblastoma patients. Results from this clinical trial point out the role of the immune system in the clinical outcome. In this context, a better understanding of the immunophenotypic changes of human mesenchymal stem cells upon adenoviral infection and how these changes affect human autologous or allogeneic peripheral blood mononuclear cells (PBMCs) could guide strategies to improve the antitumor efficacy of infected Mesenchymal Stem Cells (MSCs). In this work, we show how infection by an oncolytic adenovirus (OAdv) induces Toll-like receptor 9 overexpression and activation of the NF-κB pathway in menstrual blood-derived mesenchymal stem cells (MenSCs), leading to a specific cytokine secretion profile. Moreover, a pro-inflammatory environment, mainly mediated by monocyte activation that leads to the activation of both T-cells and natural killer cells (NK cells), is generated when OAdv-loaded MenSCs are co-cultured with allogeneic PBMCs. This combination of allogeneic PBMCs and OAdv-loaded MenSCs enhances antitumor efficacy both in vitro and in vivo, an effect partially mediated monocytes and NK cells. Altogether our results demonstrate not only the importance of the immune system for the oncolytic adenovirus-loaded MSCs antitumor efficacy, but in particular the benefits of using allogeneic MSCs for this therapy

Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study

Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Efficacy of different treatment protocols for endometritis in Camelus dromedarius

Endometritis is considered a significant cause of infertility problems in dromedary camels. This study aimed to compare the efficacy of different treatment protocols for endometritis in dromedary camels under Abu Dhabi Emirates' conditions. A total of 112 dromedary she-camels with uterine infection were subjected to uterine swabbing for bacterial culture and received one of the following treatments: (i) uterine douching with lotagen every other day for three doses, (ii) single parenteral oxytetracycline injection, (iii) subcutaneous injection with ceftiofur for 5 days, or (vi) combined oxytetracycline-ceftiofur injection. The results showed that Escherichia coli was the most isolated bacteria, followed by Streptococcus species. Treatment efficacy was (P &lt; 0.05) higher in ceftiofur and oxytetracycline-ceftiofur protocols compared with lotagen and oxytetracycline protocols. The fertility indexes, services per conception and pregnancy rate, were improved in ceftiofur and mixed oxytetracycline plus ceftiofur protocols as the pregnancy rate was (P &lt; 0.05) higher in those protocols compared with lotagen and oxytetracycline protocols (71.4 and 67.9% vs. 39.3 and 42.9%, respectively). On the other hand, the number of services per conception was significantly lower in ceftiofur and oxytetracycline-ceftiofur protocols (1.2 for each protocol) than in lotagen and oxytetracycline protocols (1.8 and 1.7, respectively). In conclusion, subcutaneous injection of 1 ml ceftiofur per 50 kg body mass for 5 days can be used as an efficient treatment for uterine infection in female dromedary camels caused by E. coli and Streptococcus species for improving their fertility indexes

Data_Sheet_1_Efficacy of different treatment protocols for endometritis in Camelus dromedarius.docx

Endometritis is considered a significant cause of infertility problems in dromedary camels. This study aimed to compare the efficacy of different treatment protocols for endometritis in dromedary camels under Abu Dhabi Emirates' conditions. A total of 112 dromedary she-camels with uterine infection were subjected to uterine swabbing for bacterial culture and received one of the following treatments: (i) uterine douching with lotagen every other day for three doses, (ii) single parenteral oxytetracycline injection, (iii) subcutaneous injection with ceftiofur for 5 days, or (vi) combined oxytetracycline-ceftiofur injection. The results showed that Escherichia coli was the most isolated bacteria, followed by Streptococcus species. Treatment efficacy was (P < 0.05) higher in ceftiofur and oxytetracycline-ceftiofur protocols compared with lotagen and oxytetracycline protocols. The fertility indexes, services per conception and pregnancy rate, were improved in ceftiofur and mixed oxytetracycline plus ceftiofur protocols as the pregnancy rate was (P < 0.05) higher in those protocols compared with lotagen and oxytetracycline protocols (71.4 and 67.9% vs. 39.3 and 42.9%, respectively). On the other hand, the number of services per conception was significantly lower in ceftiofur and oxytetracycline-ceftiofur protocols (1.2 for each protocol) than in lotagen and oxytetracycline protocols (1.8 and 1.7, respectively). In conclusion, subcutaneous injection of 1 ml ceftiofur per 50 kg body mass for 5 days can be used as an efficient treatment for uterine infection in female dromedary camels caused by E. coli and Streptococcus species for improving their fertility indexes.</p

SEROPREVALENCE OF THE VIRAL MARKERS OF HEPATITIS B, HEPATITIS C, AND HIV AMONG MEDICAL WASTE HANDLERS IN SOME HOSPITALS IN SANA'A CITY- YEMEN

Background and Objective: Hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are highly contagious pathogens that threaten medical waste handlers who are highly exposed to these viruses due to the nature of their work. To date, little data is available on the prevalence of viral markers (HBV, HCV, and HIV) among medical waste handlers in Sana'a city, Yemen. Hence, this work was conducted to enhance knowledge of the prevalence of viral markers among medical waste handlers working in some hospitals in the capital, Sana'a. Methods: A cross-sectional prospective study was conducted on 120 randomly selected medical waste handlers from January to June 2022. A pretested and designed questionnaire was used to collect the required data. Total 5mL of venous blood was collected. Then blood was tested for hepatitis B surface antigen and anti-HCV, as well as HIV antibody, were detected using a qualitative by rapid test cassette and positive results were confirmed by ELIZA technique. Results: The overall positive rates for HBsAg, anti-HCV, and HIV were 9.17%, 5.0%, and 0.0%, respectively, based on the rapid test. No significant differences were detected between socio-demographic characteristics and hepatitis B and HCV infection. High rates of hepatitis B and C infection were found in the age group ≥41 years (9.17%) and 21-30 years (8.77%), respectively. These two viruses have also been detected among married people with a history of acute infection between 7-9 times. There was a significant correlation between HBsAg positivity and history of blood transfusion as well as between HBsAg and anti-HCV positivity and history of hepatitis B vaccination. ELISA confirmed that the rate of HBsAg was 4.17% and anti-HCV was 2.5%. Conclusion: Appropriate training, immunization against HBV, and regular motivation of medical waste handlers on the practices of universal standard precautions are recommended to reduce transmission of hepatitis B virus, hepatitis C virus, and HIV among medical waste handlers. &nbsp; &nbsp; &nbsp; &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Peer Review History: Received: 4 May 2022; Revised: 14 June; Accepted: 27 June, Available online: 15 July 2022 Academic Editor: Dr. Muhammad Zahid Iqbal, AIMST University, Malaysia, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency.&nbsp; Received file:&nbsp;&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;Reviewer's Comments: Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.5/10 Reviewers: Rusmir Baljic, Clinic for infectious diseases, Clinical center University of Sarajevo, Bosnia and Herzegovina. [email protected] Dr. Bilge Ahsen KARA, Ankara Gazi Mustafa Kemal Hospital, Turkey,&nbsp;[email protected] Prof. Dr. Hassan A.H. Al-Shamahy, Sana'a University, Yemen, [email protected] Dr. Jucimary Vieira dos Santos, Hemonorte Dalton Barbosa Cunha, Brazil, [email protected]&nbsp; Dr. Bilge Ahsen KARA, Ankara Gazi Mustafa Kemal Hospital, Turkey,&nbsp;[email protected] Similar Articles:&nbsp;&nbsp; PREVALENCE OF HEPATITIS A VIRUS, HEPATITIS B VIRUS, AND HEPATITIS C VIRUS, AMONG PATIENTS WITH HEPATIC JAUNDICE IN SANA’A CITY, YEMEN: A HOSPITAL BASED STUDY SERO-EPIDEMIOLOGICAL STUDY OF HEPATITIS B, C, HIV AND TREPONEMA PALLIDUM AMONG BLOOD DONORS IN HODEIDA CITY- YEMEN EXPLOSION OF HEPATITIS B AND C VIRUSES AMONG HEMODIALYSIS PATIENTS AS A RESULT OF HEMODIALYSIS CRISIS IN YEME

Evidence of Anti-tumoral Efficacy in an Immune Competent Setting with an iRGD-Modified Hyaluronidase-Armed Oncolytic Adenovirus

To enhance adenovirus-mediated oncolysis, different approaches that tackle the selectivity, tumor penetration, and spreading potential of oncolytic adenoviruses have been reported. We have previously demonstrated that insertion of the internalizing Arginine-Glycine-Aspartic (iRGD) tumor-penetrating peptide at the C terminus of the fiber or transgenic expression of a secreted hyaluronidase can improve virus tumor targeting and spreading. Here we report a new oncolytic adenovirus ICOVIR17K-iRGD in which both modifications have been incorporated. In xenografted A549 tumors in nude mice, ICOVIR17K-iRGD shows higher efficacy than the non-iRGD counterpart. To gain insights into the role of the immune system in oncolysis, we have studied ICOVIR17K-iRGD in the tumor isograft mouse model CMT64.6, partially permissive to human adenovirus 5 replication, in immunodeficient or immunocompetent mice. Whereas no efficacy was observed in the immunodeficient setting due to insufficient viral replication, partial efficacy and a polymorphonuclear and CD8+ T cell infiltrate were observed in the immunocompetent mice. The results indicate that the elicitation of a virus-induced anti-tumoral immune response is responsible for the observed partial anti-tumoral effect. Keywords: oncolytic adenovirus, iRGD tumor-penetrating peptide, immune respons

Study of Comparative Morphology of Eight Cultivated Genotypes of <i>Olea europaea</i> L

The current study was designed to assess the comparative morphology of eight olive cultivars with different geographical origins and diverse genetic backgrounds, introduced to a new climatic zone. The morphological parameters of eight (five exotic and three domestic) olive cultivars (Bari Zaitoon-1, Bari Zaitoon-2, Favolosa (FS-17), Koroneiki, Balkasar, Ottobratica, Leccino, and Arbequina) were compared at the experimental area of the Department of Botany, The Islamia University of Bahawalpur, Pakistan (29°24′0″ North, 71°41′0″ East, 401–421 feet above sea level). Plant height, number of leaves/15 cm shoot, leaf size characteristics (leaf length, leaf width, leaf area, and length/width ratio), leaf shape characteristics (margin, leaf axil, base, and apex angles), leaf pigments (Chlorophyll a, Chlorophyll b, total chlorophyll contents, and carotenoids), phyllotaxy, and leaf color and venation were recorded. The highest plant height (28 cm) was obtained by Bari Zaitoon-2 followed by Bari Zaitoon-1 (24 cm), both of which are domestic cultivar of Pakistan, while the shortest height (5 cm) was obtained by Koroneiki. Leccino displayed the highest average number of leaves (17.8) on main shoot, followed by BARI-2 (16.4) and the lowest score was from Balkasar (10.4). Leaf area ranged from 5.66 cm2 (Bari Zaitoon-1) to 3.08 cm2 (Koroneiki). The longest leaf length (5.74 cm) was found in Bari Zaitoon-1 and the shortest (4.04 cm) in Koroneiki, while the broadest leaves were found in Leccino (1.54 cm) and the narrowest (1.12 cm) in Koroneiki. Bari Zaitoon-2 led in leaf length to width ratio (4.058) followed by Bari Zaitoon-1 (3.772) with small lanceolate leaves hardly reaching the value of 4, with the lowest value illustrated by Leccino. The total chloroplast pigments were highest in FS-17 followed by Bari Zaitoon-1 and Bari Zaitoon-2, while the lowest was in Arbequina. Chlorophyll a was highest in Bari Zaitoon-1 followed by FS-17 and Balkasar, with the lowest rate in Arbequina. Chlorophyll b content of FS-17 was the highest whereas the Chlorophyll b and total chlorophyll contents in Arbequina were the lowest of all the cultivars. The highest value of total carotenoids was found in Balkasar followed by FS-17 with the lowest value in Arbequina. The phyllotaxy was categorized into three types, i.e., alternate, opposite, and whorled. The combination of two or more types was usually observed on the same branch. The whorl of four leaves was also present in rare cases. Leaf venation was both pinnate and reticulate. The leaf base of most (four) of the olive cultivars, i.e., Arbequina, Balkasar, Leccino and FS-17, were cuneate having acute, rounded, apiculate, and cuspidate leaf tips, respectively. The findings revealed remarkable variations in olive morphology, especially in the leaves and a successful record of the preliminary data of olive cultivars from the study area was made. The present research demonstrated that local olive cultivars have unique characteristics that differentiate them from imported cultivars. Thus, local cultivars provide novel genetic resources that should be conserved