The CLIP-domain serine protease homolog SPCLIP1 regulates complement recruitment to microbial surfaces in the malaria mosquito Anopheles gambiae

The complement C3-like protein TEP1 of the mosquito Anopheles gambiae is required for defense against malaria parasites and bacteria. Two forms of TEP1 are present in the mosquito hemolymph, the full-length TEP1-F and the proteolytically processed TEP1(cut) that is part of a complex including the leucine-rich repeat proteins LRIM1 and APL1C. Here we show that the non-catalytic serine protease SPCLIP1 is a key regulator of the complement-like pathway. SPCLIP1 is required for accumulation of TEP1 on microbial surfaces, a reaction that leads to lysis of malaria parasites or triggers activation of a cascade culminating with melanization of malaria parasites and bacteria. We also demonstrate that the two forms of TEP1 have distinct roles in the complement-like pathway and provide the first evidence for a complement convertase-like cascade in insects analogous to that in vertebrates. Our findings establish that core principles of complement activation are conserved throughout the evolution of animals

Impaired Liver Size and Compromised Neurobehavioral Activity are Elicited by Chitosan Nanoparticles in the Zebrafish Embryo Model

The use of chitosan nanoparticles (ChNPs) in various biological and environmental applications is attracting great interest. However, potential side effects related to ChNP toxicity remain the major limitation hampering their wide application. For the first time, we investigate the potential organ-specific (cardiac, hepatic, and neuromuscular) toxicity of ChNPs (size 100–150 nm) using the zebrafish embryo model. Our data highlight the absence of both acute and teratogenic toxic effects of ChNPs (~100% survival rate) even at the higher concentration employed (200 mg/L). Although no single sign of cardiotoxicity was observed upon exposure to 200 mg/L of ChNPs, as judged by heartbeat rate, the corrected QT interval (QTc, which measures the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle), maximum cardiac arrest, and ejection fraction assays, the same dosage elicited the impairment of both liver size (decreased liver size, but without steatosis and lipid yolk retention) and neurobehavioral activity (increased movement under different light conditions). Although the observed toxic effect failed to affect embryo survival, whether a prolonged ChNP treatment may induce other potentially harmful effects remains to be elucidated. By reporting new insights on their organ-specific toxicity, our results add novel and useful information into the available data concerning the in vivo effect of ChNPs.This work was supported by the NPRP grant [#9-254-2-120] from the Qatar National Research Fund, a Member of Qatar Foundation. The study was also partially supported by the grants [GCC-2017-001] given to G.K.N. and [QUCG-CHS-2018n2019-1] given to G.P

The Potential of MET Immunoreactivity for Prediction of Lymph Node Metastasis in Early Oral Tongue Squamous Cell Carcinoma

Objective MET positivity is independently associated with survival in oral squamous cell carcinoma (OSCC). Since MET is a known orchestrator of invasive tumor growth, we investigated its association with LNM in early oral tongue squamous cell carcinoma (OTSCC). As it is recommended by the NCCN to use tumor depth of invasion (DOI) in making decisions on elective neck dissection (END), the results obtained for MET positivity were aligned with those for DOI > 4 mm. The cutoff value used in our institution. Methods Tumor samples from patients who underwent primary tumor resection and neck dissection between 1995 and 2013, were collected from the archives of the Leiden and Erasmus University Medical Center. Immunohistochemistry with D1C2 was performed to identify MET negative (= 10% uniform positivity) cancers. ROC curve analysis and the Chi-squared test were used to investigate the association of MET positivity with LNM (pN+ and occult). Binary logistic regression was used to investigate the association of MET positivity with LNM. Results Forty-five (44.1%) of the 102 cancers were MET positive. Ninety were cN0 of which 20 were pN+ (occult metastasis). The remaining 12 cancers were cN+, of which 10 were proven pN+ and 2 were pN0. MET positivity was associated with LNM with a positive predictive value (PPV) of 44.4% and a negative predictive value (NPV) of 82.5% for pN+. For the occult group, the PPV was 36.8% and the NPV was 88.5%. Regression analysis showed that MET positivity is associated with pN+ and occult LNM (p-value < 0.05). Conclusion MET positivity is significantly associated with LNM in early OTSCC, outperforming DOI. The added value of MET positivity could be in the preoperative setting when END is being considered during the initial surgery. For cases with DO

Repurposing Ivermectin for COVID-19: Molecular Aspects and Therapeutic Possibilities

As of January 2021, SARS-CoV-2 has killed over 2 million individuals across the world. As such, there is an urgent need for vaccines and therapeutics to reduce the burden of COVID-19. Several vaccines, including mRNA, vector-based vaccines, and inactivated vaccines, have been approved for emergency use in various countries. However, the slow roll-out of vaccines and insufficient global supply remains a challenge to turn the tide of the pandemic. Moreover, vaccines are important tools for preventing the disease but therapeutic tools to treat patients are also needed. As such, since the beginning of the pandemic, repurposed FDA-approved drugs have been sought as potential therapeutic options for COVID-19 due to their known safety profiles and potential anti-viral effects. One of these drugs is ivermectin (IVM), an antiparasitic drug created in the 1970s. IVM later exerted antiviral activity against various viruses including SARS-CoV-2. In this review, we delineate the story of how this antiparasitic drug was eventually identified as a potential treatment option for COVID-19. We review SARS-CoV-2 lifecycle, the role of the nucleocapsid protein, the turning points in past research that provided initial 'hints' for IVM's antiviral activity and its molecular mechanism of action- and finally, we culminate with the current clinical findings

Organ-specific toxicity evaluation of stearamidopropyl dimethylamine (SAPDMA) surfactant using zebrafish embryos

Surfactants are widely used in the industry of detergents, household products, and cosmetics. SAPDMA is a cationic surfactant that is used mostly in cosmetics, conditioning agents and has recently gained attention as a corrosion inhibitor in the sea pipelines industry. In this regard, literature concerning the ecotoxicological classification of SAPDMA on aquatic animals is lacking. This study aims to evaluate the potential ecotoxicity of SAPDMA using the aquatic zebrafish embryo model. The potential toxic effects of SAPDMA were assessed by different assays. This includes (i) mortality/survival assay to assess the median lethal concentration (LC50); (ii) teratogenicity assay to assess the no observed effect concentration (NOEC); (iii) organ-specific toxicity assays including cardiotoxicity, neurotoxicity (using locomotion assay), hematopoietic toxicity (hemoglobin synthesis using o-dianisidine staining), hepatotoxicity (liver steatosis and yolk retention using Oil Red O (ORO) stain); (iv) cellular cytotoxicity (mitochondrial membrane potential) by measuring the accumulation of JC-1 dye into mitochondria. Exposure of embryos to SAPDMA caused mortality in a dose-dependent manner with a calculated LC50 of 2.3 mg/L. Thus, based on the LC50 value and according to the Fish and Wildlife Service (FWS) Acute Toxicity Rating Scale, SAPDMA is classified as “moderately toxic”. The No Observed Effect Concentration (NOEC) concerning a set of parameters including scoliosis, changes in body length, yolk, and eye sizes was 0.1 mg/L. At the same NOEC concentration (0.1 mg/L), no organ-specific toxicity was detected in fish treated with SAPDMA, except hepatomegaly with no associated liver dysfunctions. However, higher SAPDMA concentrations (0.8 mg/L) have dramatic effects on zebrafish organ development (eye, heart, and liver development). Our data recommend a re-evaluation of the SAPDMA employment in the industry setting and its strictly monitoring by environmental and public health agencies

Improving influenza vaccination rate among primary healthcareworkers in Qatar

The purpose of this study was to improve influenza vaccination, and determine factors influencing vaccine declination among health care workers (HCW) in Qatar. We launched an influenza vaccination campaign to vaccinate around 4700 HCW in 22 Primary Health Care Corporation (PHCC) centers in Qatar between 1st and 15th of November, 2015. Our target was to vaccinate 60% of all HCW. Vaccine was offered free of charge at all centers, and information about the campaign and the importance of influenza vaccination was provided to employees through direct communication, emails, and social media networks. Staff were reported as vaccinated or non-vaccinated using a declination form that included their occupation, place of work and reasons for declining the vaccine. Survey responses were summarized as proportional outcomes. We exceeded our goal, and vaccinated 77% of the target population. Only 9% declined to take the vaccine, and the remaining 14% were either on leave or had already been vaccinated. Vaccine uptake was highest among aides (98.1%), followed by technicians (95.2%), and was lowest amongst pharmacists (73.2%), preceded by physicians (84%). Of those that declined the vaccine, 34% provided no reason, 18% declined it due to behavioral issues, and 21% declined it due to medical reasons. Uptake of influenza vaccine significantly increased during the 2015 immunization campaign. This is attributed to good planning, preparation, a high level of communication, and providing awareness and training to HCW with proper supervision and monitoring. 1 2017 by the authors. Licensee MDPI, Basel, Switzerland.Acknowledgments: We would like to thank all staff for participation in the 2015 influenza vaccination campaign at the PHCC. Members of the Health protection at MoPH and PHCC communicable disease control team are highly acknowledged for assistance with implementation. This Study was funded by the Ministry of Public Health.Scopu

Associations of Vaccination and of Prior Infection with Positive PCR Test Results for SARS-CoV-2 in Airline Passengers Arriving in Qatar

The SARS-CoV-2 pandemic has severely affected international travel. With efficacious COVID-19 vaccines available, Qatar implemented a pilot program between February 18 and April 26, 2021, to ease travel restrictions by waiving the quarantine requirement for vaccinated residents who received their second vaccine dose at least 14 days before arrival. The program still required a polymerase chain reaction (PCR) test to be performed on each passenger on arrival at Hamad International Airport, Qatar’s international travel gate. We investigated the incidence of PCR-positive test results in arriving passengers

Seroprevalence of camel brucellosis in Qatar

Brucellosis is a significant zoonotic disease and one of the most common neglected diseases worldwide. It can infect a wide range of domestic and wild animal species. Infected animals are usually culled, causing substantial economic losses to animal owners and the country’s economy in general. The disease is endemic among cattle, sheep, and goats in many countries around the Middle East and prevalent in most Gulf Cooperation Council countries, comprising a significant public health risk in the region. This study investigated the seroprevalence of brucellosis among camels in Qatar. Two hundred and forty-eight samples were collected from dromedary camels from 28 farms across the entire country. Each sample was tested for Brucella antibodies with both Rose Bengal and competitive enzyme-linked immunosorbent assay. Only samples that tested positive by both tests were considered seropositive for brucellosis. The overall prevalence was (20.6%, 95% CI, 15.7–26.1). The association between sex and seropositivity was slightly significant (Χ2 = 4.32, P = 0.04), with higher seroprevalence in females. Camels below breeding age (i.e., < 4 years old) showed decreased seropositivity (3.4%, 95% CI, 0.1–17.8), compared to (22.8%, 95% CI, 17.4–29.0) seropositivity in camels ≥ 4 years of age, with a significant association between age groups and seropositivity (P = 0.02). Our results indicate that the seroprevalence of brucellosis in Qatar’s camels is alarming, mandating more efforts to control the disease. The findings of this study will aid in selecting better effective measures to control camel brucellosis in Qatar. Further studies need to be conducted on Brucella infection among camels to determine the predisposing risk factors and the steps that should be followed to control brucellosis.Open Access funding provided by the Qatar National Library. This work was supported by Qatar University grant number QUCG-BRC-20/21–2 and high potential projects program QPH3P-BRC-2021–604 to Nahla O. Eltai

The Spectrum of Antibiotic Prescribing During COVID-19 Pandemic: A Systematic Literature Review

Objectives: Over the last decades, there has been a significant increase in antimicrobial prescribing and consumption associated with the development of patients’ adverse events and antimicrobial resistance (AMR) to the point of becoming a global priority. This study aims at evaluating antibiotic prescribing during COVID- 19 pandemic from November 2019 to December 2020. Materials and Methods: A systematic review was conducted primarily through the NCBI database, using PRISMA guidelines to identify relevant literature for the period between November 1, 2019 and December 19, 2020, using the keywords: COVID-19 OR SARS-Cov-2 AND antibiotics restricted to the English language excluding nonclinical articles. Five hundred twenty-seven titles were identified; all articles fulfilling the study criteria were included, 133 through the NCBI, and 8 through Google Scholar with a combined total of 141 studies. The patient’s spectrum included all ages from neonates to elderly with all associated comorbidities, including immune suppression. Results: Of 28,093 patients included in the combined studies, 58.7% received antibiotics (16,490/28,093), ranging from 1.3% to 100% coverage. Antibiotics coverage was less in children (57%) than in adults with comorbidities (75%). Broad-spectrum antibiotics were prescribed presumptively without pathogen identifications, which might contribute to adverse outcomes. Conclusions: During the COVID-19 pandemic, there has been a significant and wide range of antibiotic prescribing in patients affected by the disease, particularly in adults with underlying comorbidities, despite the paucity of evidence of associated bacterial infections. The current practice might increase patients’ immediate and long-term risks of adverse events, susceptibility to secondary infections as well as aggravating AM