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Introduction: Toxoplasma gondii infection in pregnant women is linked with higher risk of spontaneous abortion or premature infants. This study aims to investigate the seroprevalence of T. gondii infection in pregnant women in Riyadh, Saudi Arabia. Material and Methods: 1000 blood samples were collected from women visiting various regional laboratories of Riyadh. Serum was tested for toxoplasmosis using ELISA technique. Results: The result revealed that 93% pregnant women were serologically negative and only 7% were positive. The study concludes that youngand aged women who have T. gondii infection should have more awareness about this infection and its complications. Conclusion: The study would be valuable in improving pregnancy care by encouraging the health workers to implement clinical and protective care plans side by side. [ABSTRACT FROM AUTHOR]

Background & Objective:- BCL-G is a novel protein of Bax (BCL-G associated protein X) that induces caspase-mediated apoptosis. These proteins play important roles in regulating apoptosis in both normal or neoplastic cells, however their cellular and tissue distribution remains to be determined. Thus, the current study objective was to elucidate the distribution and expression pattern of BCL-G in normal and malignant gastrointestinal human tissues. Methods:- The distribution and expression of BCL-G was measured by immunohistochemistry using a rabbit monoclonal antibody against BCL-G in formalin-fixed, paraffin embedded, benign or malignant human tissue. Results:- A variable pattern of positive expression of BCL-G was observed within all the tissues studied. BCL-G expression was found to be localized to the cytoplasmic paranuclear granules of the epithelialium in the majority of organs examined. Intensity of BCL-G staining was associated withthe maturation state of benign tissue. Conclusion:- Here we demonstrate that BCL-G exhibits a specific tissue distribution pattern that appears to correlate with cellular differentiation. While such distribution patterns are complex they provide an intriguing insight into overall function that would require further investigation to fully elucidate their physiological/pathological significance. [ABSTRACT FROM AUTHOR]

The study was designed to validate the previously reported 34 SSR markers using 78 chilli genotypes to detect significant trait specific markers as well as superior genotypes resistant to Phytophthora capsici root rot (PcRR). In this context, the identification of germplasm with higher yield per plant (YPP) leads to hype in stress tolerance index (STI) in genotypes, Chakwal3 (11.98), Greenfire (10.14), Advanta5017 (9.94) and Chakwal4 (7.8). The identified genotypes were also found as resistant and moderately resistant due to existence of below 50% of disease incidence. Moreover, biplot showed the interrelation of STI with YPP through the formation of acute angle by their respective vectors. In the current study, the markers Hpms1172 and CAMS177 was found significant for STI. However, the marker CAMS066 was found associated with relative cell injury, CA06g27450 with disease incidence and CAMS173 with relative leaf damage. The bright bands on gel pictures of significant markers showed the association of these markers with resistant genotypes i.e. Chakwal3, Advanta-5017 and Chakwal4 as well as with a single moderately resistant genotype i.e. Greenfire. The markerstudes confirmed the phenotypic data by showing association of markers i.e. Hpms1172 and CAMS177, r with stress tolerance index. The principal coordinate analysis aligned with the results obtained from marker-assisted selection. Thus, currently practiced marker assisted selection detected high yielding genotypes in PcRR disease stress condition that will be helpful in progressing breeding programs in chilli., Competing Interests: Declarations Ethics approval and consent to participate This study does not include human or animal subjects. Consent for publication Not applicable. Competing interests The authors stated that they had no interest which might be perceived asposing a conflict or bias. Statement on guidelines All experimental studies and experimental materials involved in this research are in full compliance with relevant institutional, national and international guidelines and legislation., (© 2024. The Author(s).)

Background: Microsporidia MB (MB) is a naturally occurring symbiont of Anopheles and has recently been identified as having a potential to inhibit the transmission of Plasmodium in mosquitoes. MB intensity is high in mosquito gonads, with no fitness consequences for the mosquito, and is linked to horizontal (sexual) and vertical (transovarial) transmission from one mosquito to another. Maximising MB intensity and transmission is important for maintaining heavily infected mosquito colonies for experiments and ultimately for mosquito releases. We have investigated how diet affects the MB-Anopheles arabiensis symbiosis phenotypes, such as larval development and mortality, adult size and survival, as well as MB intensity in both larvae and adults., Methods: F 1 larvae of G 0 females confirmed to be An. arabiensis and infected with MB were either combined (group lines [GLs]) or reared separately (isofemale lines [IMLs]) depending on the specific experiment. Four diet regimes (all mg/larva/day) were tested on F 1 GLs: Tetramin 0.07, Tetramin 0.3, Gocat 0.3 and Cerelac 0.3. GLs reared on Tetramin 0.3 mg/larva/day were then fed either a 1% or 6% glucose diet to determine adult survival. Larvae of IMLs were fed Tetramin 0.07 mg and Tetramin 0.3 mg for larval experiments. The mosquitoes in the adult experiments with IMLs were reared on 1% or 6% glucose., Results: Amongst the four larval diet regimes tested on An. arabiensis development in the presence of MB, the fastest larval development highest adult emergence, largest body size of mosquitoes, highest prevalence and highest density of MB occurred in those fed Tetramin 0.3 mg/larva/day. Although adult MB-positive mosquitoes fed on 6% glucose survived longer than MB-negative mosquitoes, there was no such effect for those fed on the 1% glucose diet. Development time, wing length and adult survival were not significantly different between MB-infected and uninfected An. arabiensis fed on the Tetramin 0.07 mg/larva/day diet, demonstrating that the MB-conferred fitness advantage was diet-dependent., Conclusions: Microsporidia MB does not adversely impact the development and fitness of An. arabiensis, even under limited dietary conditions. The diet regime of Tetramin 0.3 mg/larva/day + 6% glucose for adults is the superior diet for the mass rearing of MB-infected An. arabiensis mosquitoes. These results are important for rearing MB-infected An. arabiensis in the laboratory for experiments and the mass rearing required for field releases., (© 2024. The Author(s).)

Arthropod vectors are responsible for a multitude of human and animal diseases affecting poor communities in sub-Saharan Africa. Their control still relies on chemical agents, despite growing evidence of insecticide resistance and environmental health concerns. Biorational agents, such as the entomopathogenic fungus Metarhizium anisopliae , might be an alternative for vector control. Recently, the M. anisopliae isolate ICIPE 7 has been developed into a commercial product in Kenya for control of ticks on cattle. We were interested in assessing the potential of controlling not only ticks but also disease-transmitting mosquitoes and tsetse flies using cattle as blood hosts, with the aim of developing a product for integrated vector management. Laboratory bioassays were carried out with M. anisopliae , isolate ICIPE 7 and isolate ICIPE 30, to compare efficacy against laboratory-reared Anopheles arabiensis . ICIPE 7 was further tested against wild Glossina fuscipes and Rhipicephalus spp. Dose-response tests were implemented, period of mosquito exposure was evaluated for effects on time to death, and the number of spores attached to exposed vectors was assessed. Exposure to 10 9 spores/mL of ICIPE 7 for 10 min resulted in a similar mortality of An. arabiensis as exposure to ICIPE 30, albeit at a slower rate (12 vs. 8 days). The same ICIPE 7 concentration also resulted in mortalities of tsetse flies (LT 50 : 16 days), tick nymphs (LT 50 : 11 days), and adult ticks (LT 50 : 20 days). Mosquito mortality was dose-dependent, with decreasing LT 50 of 8 days at a concentration of 10 6 spores/mL to 6 days at 10 10 spores/mL. Exposure period did not modulate the outcome, 1 min of exposure still resulted in mortality, and spore attachment to vectors was dose-dependent. The laboratory bioassays confirmed that ICIPE 7 has the potential to infect and cause mortality to the three exposed arthropods, though at slower rate, thus requiring further validation under field conditions.

Background: Microsporidia MB, an endosymbiont naturally found in Anopheles mosquitoes inhibits transmission of Plasmodium and is a promising candidate for a transmission-blocking strategy that may involve mosquito release. A rapid assessment was carried out to develop insight into sociodemographic factors, public health concerns, and malaria awareness, management, and prevention practices with the willingness to accept and participate in Microsporidia MB-based transmission-blocking strategy to develop an informed stakeholder engagement process., Methods: The assessment consisted of a survey conducted in two communities in western Kenya that involved administering a questionnaire consisting of structured, semi-structured, and open questions to 8108 household heads., Results: There was an overall high level of willingness to accept (81%) and participate in the implementation of the strategy (96%). Although the willingness to accept was similar in both communities, Ombeyi community was more willing to participate (OR 22, 95% CI 13-36). Women were less willing to accept (OR 0.8, 95% CI 0.7-0.9) compared to men due to fear of increased mosquito bites near homes. Household heads with incomplete primary education were more willing to accept (OR 1.6, 95% CI 01.2-2.2) compared to those educated to primary level or higher. Perceiving malaria as a moderate or low public health issue was also associated with a lower willingness to accept and participate. Experience of > 3 malaria cases in the family over the last six months and knowledge that malaria is transmitted by only mosquito bites, increased the willingness to accept but reduced the willingness to participate. Awareness of malaria control methods based on mosquitoes that cannot transmit malaria increases the willingness to participate., Conclusion: The study showed a high level of willingness to accept and participate in a Microsporidia MB-based strategy in the community, which is influenced by several factors such as community, disease risk perception, gender, education level, knowledge, and experience of malaria. Further research will need to focus on understanding the concerns of women, educated, and employed community members, and factors that contribute to the lower disease risk perception. This improved understanding will lead to the development of an effective communication strategy., (© 2024. The Author(s).)

Background: There are concerns about indiscriminate prescriptions and the inappropriate use of proton pump inhibitors (PPIs) without any clear indications, especially among noncritically hospitalized patients., Objective: This study aimed to characterize PPI prescriptions among non-critically hospitalized patients in a tertiary care hospital in Saudi Arabia., Methods: A retrospective cross-sectional study was conducted at the King Abdulaziz University Hospital between June and August 2021. The data of adult patients who received PPIs on hospital admission in the medical and surgical wards were collected and analyzed for appropriateness based on the current international guidelines and recommendations., Results: A total of 174 patient records were included in this study. The proportion of patients with appropriate and inappropriate PPI prescriptions was 67.24% (n=117) and 32.76% (n=57), respectively. Female patients (risk=50.00%, 95% CI: 36.89-63.11, p<0.001) were more likely to receive an inappropriate PPI prescription than their male counterparts (risk=33.33%, 95% CI: 24.56-43.43, p<0.001). Intravenous omeprazole 40 mg once daily was the most frequently prescribed PPI (n=62). The hospital length of stay differed significantly between the groups of patients who received appropriate and inappropriate PPIs (24.56 ± 47.14 vs. 13.50 ± 13.84; t=2.34, 95% CI: 1.72-20.4; p=0.02). However, there was no significant difference in the total therapy duration in both the groups (3.76 ± 2.50 vs. 4.75 ± 3.32, t=-1.62, 95%CI: -1.79-0.17; p=0.11)., Conclusion: The findings show a high trend of inappropriate PPI prescriptions. Hence, educational programs are recommended to encourage healthcare professionals to stick to the approved guidelines when prescribing PPIs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: The aim of this study was to analyze the antibiotic resistance in ocular samples over a 16-year period., Methods: This was a retrospective cohort study conducted at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia (2003-2019). The study included corneal and conjunctival swabs and aqueous and vitreous samples., Results: Coagulase-negative staphylococci exhibited a significant trend of increasing resistance over time to erythromycin (p < 0.001), oxacillin (p < 0.001), fusidic acid (p < 0.001), and moxifloxacin (p = 0.003). Staphylococcus aureus also showed a significant increase in oxacillin (p = 0.001), ofloxacin (p = 0.003), and moxifloxacin (p = 0.001) resistance patterns. Streptococcus pneumoniae demonstrated a significant increase in resistance to erythromycin (p = 0.01) and ofloxacin, which jumped from 0.80% in 2003 to 80% in 2019 (p = 0.015). No statistically significant increase in antibiotic resistance trend was observed for Pseudomonas., Conclusions: An increasing antibiotic resistance pattern was demonstrated, particularly among gram-positive organisms. Such findings warrant revision of the common ocular antibiotic prescribing strategy and consideration of alternative antibiotics., (Copyright © 2022 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Generalized pustular psoriasis (GPP) is a rare, immune-mediated inflammatory disease with characteristic cutaneous and systemic manifestations. Mutations in the interleukin-36 receptor antagonist (IL36RN) gene have been implicated in its pathogenesis. Spesolimab is a novel systemic biologic therapy that selectively inhibits interleukin-36. It was recently approved by Health Canada and the US FDA for the treatment of GPP flares in adults. Results from phase 1 and 2 studies have been promising. Herein, we review the efficacy and safety of spesolimab for the treatment of GPP flares, as demonstrated in clinical trials., Competing Interests: Ronald Vender has been an advisor, consultant, speaker, and/or investigator for AbbVie, Actelion, Amgen, Aralez, Arcutis, Astellas, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Centocor, Dermira, Dermavant, Eli Lilly, Galderma, GSK, Innovaderm, Janssen, Kabi-Care, LEO Pharma, Merck, Novartis, Palladin, Pfizer, Regeneron, Sandoz, Sun Pharma, Takeda, UCB, and Viatris-Mylan. Jensen Yeung has been an advisor, consultant, speaker, and/or investigator for AbbVie, Allergan, Amgen, Astellas, Boehringer Ingelheim, Celgene, Centocor, Coherus, Dermira, Eli Lilly, Forward, Galderma, GSK, Janssen, LEO Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Takeda, UCB, Valeant, and Xenon. Alim R. Devani has been an advisor, consultant, speaker, and/or investigator for AbbVie, Amgen, AnaptysBio, Arcutis, Arena, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, Dermavant, Dermira, Eli Lilly, Galderma, GSK, Incyte, Janssen, LEO Pharma, Medexus, Nimbus Lakshmi, Novartis, Pediapharm, Pfizer, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Takeda, Tribute, UCB, and Valeant. Vimal H. Prajapati has been an advisor, consultant, speaker, and/or investigator for AbbVie, Actelion, Amgen, AnaptysBio, Apogee Therapeutics, Aralez, Arcutis, Arena, Asana, Aspen, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Concert, CorEvitas, Dermavant, Dermira, Eli Lilly, Galderma, GSK, Homeocan, Incyte, Janssen, LEO Pharma, Medexus, Nimbus Lakshmi, Novartis, Pediapharm, Pfizer, RAPT Therapeutics, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Takeda, Tribute, UCB, and Valeant. Tuba Bukhari, Mariya Markovina, Abrahim Abduelmula, and Brian D. Rankin have no relevant disclosures. Funding sources: None.

Background: Centers for Disease Control and Prevention (CDC) light traps are widely used for sampling mosquitoes. However, this trap, manufactured in the USA, poses challenges for use in sub-Saharan Africa due to procurement costs and shipping time. Traps that are equally efficient than the CDC light trap, but which are amenable for use in remote African settings and made in Africa, are desirable to improve local vector surveillance. This study evaluated a novel solar-powered light trap made in South Africa (Silver Bullet trap; SB), for its efficiency in malaria vector sampling in western Kenya., Methods: Large cage (173.7 m 3 ) experiments and field evaluations were conducted to compare the CDC-incandescent light trap (CDC-iLT), CDC-UV fluorescent tube light trap (CDC-UV), SB with white diodes (SB-White) and SB with UV diodes (SB-UV) for sampling Anopheles mosquitoes. Field assessments were done indoors and outdoors following a Latin square design. The wavelengths and absolute spectral irradiance of traps were compared using spectrometry., Results: The odds of catching a released Anopheles in the large cage experiments with the SB-UV under ambient conditions in the presence of a CDC-iLT in the same system was three times higher than what would have been expected when the two traps were equally attractive (odds ratio (OR) 3.2, 95% confidence interval CI 2.8-3.7, P < 0.01)). However, when the white light diode was used in the SB trap, it could not compete with the CDC-iLT (OR 0.56, 95% CI 0.48-0.66, p < 0.01) when the two traps were provided as choices in a closed system. In the field, the CDC and Silver Bullet traps were equally effective in mosquito sampling. Irrespective of manufacturer, traps emitting UV light performed better than white or incandescent light for indoor sampling, collecting two times more Anopheles funestus sensu lato (s.l.) (RR 2.5; 95% CI 1.7-3.8) and Anopheles gambiae s.l. (RR 2.5; 95% 1.7-3.6). Outdoor collections were lower than indoor collections and similar for all light sources and traps., Conclusions: The solar-powered SB trap compared well with the CDC trap in the field and presents a promising new surveillance device especially when charging on mains electricity is challenging in remote settings., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Chilli is an important commercial crop with positive returns tendency. Phytophthora root rot causes drastic damage to chilli plant. Dearth of detecting marker trait associations is a major hinderance in practicing marker assisted selection in chilli breeding., Methods and Results: Herein, 110 chilli accessions were assessed for 15 agronomic traits under control and disease infected conditions for two crop seasons (2018-2019). The SSR genotyping revealed high values of major allele frequency (MAF = 0.70), genetic diversity (GD = 0.39) and Polymorphic Information Content (PIC = 0.31). Principal coordinate analysis and population structure analysis showed distribution of diverse genotypes in all groups by dividing 110 genotypes in three populations and nine sub-populations. The UPGMA based Archaeopteryx tree was in concordance with population structure analysis. Linkage disequilibrium analysis evaluated that LD decays within 3-10 bp. Marker trait association (MTA) revealed the associations of 35 SSRs with 14 morphological traits. The significant MTA for marker CAeMS073 with relative leaf damage (RLD, 0.183 R 2 ) under control and treated conditions was consistently observed in both models. The markers, CAMS173 and CAMS194 were found to be strongly associated with RLD and Disease Index (DI), respectively. The absence of MTA was detected for height of first branch., Conclusion: The MTAs reported in this study can facilitate marker assisted breeding for developing chilli germplasm resistant against Phytophthora capsici., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Entomopathogenic fungi have been explored as a potential biopesticide to counteract the insecticide resistance issue in mosquitoes. However, little is known about the possibility that genetic resistance to fungal biopesticides could evolve in mosquito populations. Here, we detected an important genetic component underlying Anopheles coluzzii survival after exposure to the entomopathogenic fungus Metarhizium anisopliae. A familiality study detected variation for survival among wild mosquito isofemale pedigrees, and genetic mapping identified two loci that significantly influence mosquito survival after fungus exposure. One locus overlaps with a previously reported locus for Anopheles susceptibility to the human malaria parasite Plasmodium falciparum. Candidate gene studies revealed that two LRR proteins encoded by APL1C and LRIM1 genes in this newly mapped locus are required for protection of female A. coluzzii from M. anisopliae, as is the complement-like factor Tep1. These results indicate that natural Anopheles populations already segregate frequent genetic variation for differential mosquito survival after fungal challenge and suggest a similarity in Anopheles protective responses against fungus and Plasmodium. However, this immune similarity raises the possibility that fungus-resistant mosquitoes could also display enhanced resistance to Plasmodium, suggesting an advantage of selecting for fungus resistance in vector populations to promote naturally diminished malaria vector competence., (© 2022. The Author(s).)

Background: Understanding the ecology and behaviour of disease vectors, including the olfactory cues used to orient and select hosts and egg-laying sites, are essential for the development of novel, insecticide-free control tools. Selected graminoid plants have been shown to release volatile chemicals attracting malaria vectors; however, whether the attraction is selective to individual plants or more general across genera and families is still unclear., Methods: To contribute to the current evidence, we implemented bioassays in two-port airflow olfactometers and in large field cages with four live graminoid plant species commonly found associated with malaria vector breeding sites in western Kenya: Cyperus rotundus and C. exaltatus of the Cyperaceae family, and Panicum repens and Cynodon dactylon of the Poaceae family. Additionally, we tested one Poaceae species, Cenchrus setaceus, not usually associated with water. The volatile compounds released in the headspace of the plants were identified using gas chromatography/mass spectrometry., Results: All five plants attracted gravid vectors, with the odds of a mosquito orienting towards the choice-chamber with the plant in an olfactometer being 2-5 times higher than when no plant was present. This attraction was maintained when tested with free-flying mosquitoes over a longer distance in large field cages, though at lower strength, with the odds of attracting a female 1.5-2.5 times higher when live plants were present than when only water was present in the trap. Cyperus rotundus, previously implicated in connection with an oviposition attractant, consistently elicited the strongest response from gravid vectors. Volatiles regularly detected were limonene, β-pinene, β-elemene and β-caryophyllene, among other common plant compounds previously described in association with odour-orientation of gravid and unfed malaria vectors., Conclusions: The present study confirms that gravid Anopheles gambiae sensu stricto use chemical cues released from graminoid plants to orientate. These cues are released from a variety of graminoid plant species in both the Cyperaceae and Poaceae family. Given the general nature of these cues, it appears unlikely that they are exclusively used for the location of suitable oviposition sites. The utilization of these chemical cues for attract-and-kill trapping strategies must be explored under natural conditions to investigate their efficiency when in competition with complex interacting natural cues., (© 2021. The Author(s).)

The recently discovered Anopheles symbiont, Microsporidia MB , has a strong malaria transmission-blocking phenotype in Anopheles arabiensis , the predominant Anopheles gambiae species complex member in many active transmission areas in eastern Africa. The ability of Microsporidia MB to block Plasmodium transmission together with vertical transmission and avirulence makes it a candidate for the development of a symbiont-based malaria transmission blocking strategy. We investigate the characteristics and efficiencies of Microsporidia MB transmission between An. arabiensis mosquitoes. We show that Microsporidia MB is not transmitted between larvae but is effectively transmitted horizontally between adult mosquitoes. Notably, Microsporidia MB was only found to be transmitted between male and female An. arabiensis , suggesting sexual horizontal transmission. In addition, Microsporidia MB cells were observed infecting the An. arabiensis ejaculatory duct. Female An. arabiensis that acquire Microsporidia MB horizontally are able to transmit the symbiont vertically to their offspring. We also investigate the possibility that Microsporidia MB can infect alternate hosts that live in the same habitats as their An. arabiensis hosts, but find no other non-anopheline hosts. Notably, Microsporidia MB infections were found in another primary malaria African vector, Anopheles funestus s.s . The finding that Microsporidia MB can be transmitted horizontally is relevant for the development of dissemination strategies to control malaria that are based on the targeted release of Microsporidia MB infected Anopheles mosquitoes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nattoh, Maina, Makhulu, Mbaisi, Mararo, Otieno, Bukhari, Onchuru, Teal, Paredes, Bargul, Mburu, Onyango, Magoma, Sinkins and Herren.)

Objective: Dental caries is one of the most common problems of the oral cavity which is frequently observed in older people. The aim of this study is to evaluate serum C-reactive proteins (CRP) levels and to identify the correlation between dental caries and CRP levels., Methodology: The study included 12 aged patients with an average age of 65-years; the patients were diagnosed with dental caries and did not have clinical history of heart diseases, rheumatoid arthritis or any other infection. The control group consisted of 10 healthy donors with an average age of 60-years. The CRP level of positive samples was measured by using CRP Enzyme-linked immunosorbent assay-ELISA Kit., Results: The currents study showed that only 5 out of 12 patients were CRP positive., Conclusions: Because of study limitations, it is early to conclude of close relationship between serum CRP and dental caries from the findings of this study; however, this study will give a clearer picture to understand the relationship between serum CRP, inflammatory cytokines and dental caries., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Exposure of mosquitoes to numerous eukaryotic and prokaryotic microbes in their associated microbiomes has probably helped drive the evolution of the innate immune system. To our knowledge, a metagenomic catalog of the eukaryotic microbiome has not been reported from any insect. Here we employ a novel approach to preferentially deplete host 18S ribosomal RNA gene amplicons to reveal the composition of the eukaryotic microbial communities of Anopheles larvae sampled in Kenya, Burkina Faso and Republic of Guinea (Conakry). We identified 453 eukaryotic operational taxonomic units (OTUs) associated with Anopheles larvae in nature, but an average of 45% of the 18S rRNA sequences clustered into OTUs that lacked a taxonomic assignment in the Silva database. Thus, the Anopheles microbiome contains a striking proportion of novel eukaryotic taxa. Using sequence similarity matching and de novo phylogenetic placement, the fraction of unassigned sequences was reduced to an average of 4%, and many unclassified OTUs were assigned as relatives of known taxa. A novel taxon of the genus Ophryocystis in the phylum Apicomplexa (which also includes Plasmodium ) is widespread in Anopheles larvae from East and West Africa. Notably, Ophryocystis is present at fluctuating abundance among larval breeding sites, consistent with the expected pattern of an epidemic pathogen. Species richness of the eukaryotic microbiome was not significantly different across sites from East to West Africa, while species richness of the prokaryotic microbiome was significantly lower in West Africa. Laboratory colonies of Anopheles coluzzii harbor 26 eukaryotic OTUs, of which 38% ( n = 10) are shared with wild populations, while 16 OTUs are unique to the laboratory colonies. Genetically distinct An. coluzzii colonies co-housed in the same facility maintain different prokaryotic microbiome profiles, suggesting a persistent host genetic influence on microbiome composition. These results provide a foundation to understand the role of the Anopheles eukaryotic microbiome in vector immunity and pathogen transmission. We hypothesize that prevalent apicomplexans such as Ophryocystis associated with Anopheles could induce interference or competition against Plasmodium within the vector. This and other members of the eukaryotic microbiome may offer candidates for new vector control tools., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cuesta, Coulibaly, Bukhari, Eiglmeier, Kone, Coulibaly, Zongo, Barry, Gneme, Guelbeogo, Beavogui, Traore, Sagnon, Vernick and Riehle.)

Introduction Hepatic osteodystrophy is an osteoporotic bone disease that occurs in chronic liver disease patients. The global prevalence of osteoporosis in patients with chronic liver disease is 30% to 40%. The pathogenesis of hepatic bone disease is not clear, but it occurs due to unstable bone remodeling with increased bone resorption and decreases bone formation. There has been an interest in determining the clinical utility of bone turnover markers (BTMs) in the assessment of osteoporosis in chronic liver patients. Methods This was a cross-sectional study conducted in patients with chronic liver disease at the section of chemical pathology, department of pathology and laboratory medicine, Aga Khan University (AKU). A total of 50 patients with age >8 years and a history of liver disease >6 months were recruited from January to October 2019. Liver function tests, i.e. aspartate aminotransferase (AST), alanine transaminase (ALT), albumin, and bilirubin, along with clinical signs of liver disease chronicity, were noted. The samples for BTMs, i.e. total serum alkaline phosphatase (ALP) and serum C-terminal telopeptide of type-1 collagen (CTX) were withdrawn and analyzed on Microlab (ELItech Group, Puteaux, France) and ADVIA Centaur (Siemens Diagnostics, NY), respectively. Results The majority of patients were males (n=34, 68%). Twenty-four (48%) patients suffered from fibrosis while 26 (52%) were without fibrosis. Median platelet count (68×10 9 /L (102.5-50)) and median cholesterol levels (102.5 mg/dl (147-99.5)) were decreased, whereas gamma-glutamyl transferase (GGT) levels were higher in the fibrosis group as compared to the non-fibrosis group. The median levels of total ALP were 91.5 IU/L (103-82), and the median levels of CTX were 0.24 pg/ml (0.34-0.21). Conclusion In the present study, no significant difference was found in the BTMs of patients with and without chronic liver disease (CLD). However, there was a positive and significant correlation of BTMs, particularly CTX with age, bilirubin levels, and hepatomegaly., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Bukhari et al.)

Introduction Liver cirrhosis is an irreversible and end-stage disease. It results from chronic liver damage characterized by the replacement of normal liver tissue by fibrosis, leading to the progressive loss of liver function. Making an early diagnosis of cirrhosis is important for patients with chronic hepatitis because early antiviral therapy can prevent the progression of cirrhosis and even induce regression. There have been efforts to develop surrogate markers for liver cirrhosis as the biopsy is invasive, costly, and difficult to standardize. Methods This was a cross-sectional study conducted at the Section of Chemical Pathology, the Department of Pathology and Laboratory Medicine in Collaboration with the Section of Gastroenterology, Department of Medicine, the Aga Khan University, from January to December 2018. A total of 90 patients (>18 years of age) with a history of chronic viral hepatitis, who were attending the FibroScan® (Echosens, Paris, France) clinic were included. Patients with a history of autoimmune liver diseases and hepatocellular carcinoma were excluded from the study. Blood samples withdrawn were analyzed on ADVIA Centaur ® (Siemens Healthineers, Erlangen, Germany), and Forns scores were calculated based on the following four parameters: patient age, total cholesterol, gamma-glutamyl transferase (GGT), and platelet count. Results The median age of the patients was 38.5 years [interquartile range (IQR): 21]. Among the study population, 59 (65.6%) were males and 31 (34.4%) were females; 26 patients showed reactivity for hepatitis B surface antigen (HBsAg), and 63 patients were found chronic with hepatitis C virus (HCV). The proportion of HCV was observed to be higher as compared with that of Hepatitis B virus (HBV). Nineteen patients were found to have jaundice and only one patient had ascites. An Area Under the Receiver Operating Curve (AUROC) was generated to determine the diagnostic accuracy of the Forns score. It was observed that the Forn score value of >7.110 had an AUROC of 0.9928 (95% CI: 0.9821-1.003, p-value: <0.001) with a sensitivity of 100% (95% CI: 91.19-100.0%) and specificity of 94% (95% CI: 83.45-98.75%), with a higher positive likelihood ratio of 16.67. Conclusion This study found the Forns score to be sensitive and specific in diagnosing liver cirrhosis in patients with chronic hepatitis. The Forns score at a cutoff of 7.11 is highly sensitive as well as a specific noninvasive method that can be used to ascertain the status of fibrosis in chronic hepatitis patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Bukhari et al.)

Background : Strategies that involve manipulations of the odour-orientation of gravid malaria vectors could lead to novel attract-and-kill interventions. Recent work has highlighted the potential involvement of graminoid plants in luring vectors to oviposition sites. This study aimed to analyse the association between water-indicating graminoid plants (Cyperaceae, sedges), other abiotic and biotic factors and the presence and abundance of early instar Anopheles larvae in aquatic habitats as a proxy indicator for oviposition. Methods : A cross-sectional survey of 110 aquatic habitats along the shores of Lake Victoria was done during the rainy season. Habitats were sampled for mosquito larvae using the sweep-net method and habitat characteristics recorded. Results : Anopheles arabiensis was the dominant species identified from aquatic habitats. Larvae of the secondary malaria vectors such as Anopheles coustani, An. rufipes and An. maculipalpis were found only in habitats covered with graminoids, whereas An. arabiensis, An. ziemanni and An. pharoensis were found in both habitats with and without graminoid plants. The hypothesis that sedges might be positively associated with the presence and abundance of early instar Anopheles larvae could not be confirmed. The dominant graminoid plants in the habitats were Panicum repens , Cynodon dactylon in the Poaceae family and Cyperus rotundus in the Cyperaceae family. All of these habitats supported abundant immature vector populations. The presence of early instar larvae was significantly and positively associated with swamp habitat types (OR=22, 95% CI=6-86, P<0.001) and abundance of late Anopheles larvae (OR=359, CI=33-3941, P<0.001), whilst the association was negative with tadpole presence (OR=0.1, CI=0.0.01-0.5, P=0.008). Conclusions : Early instar malaria vectors were abundant in habitats densely vegetated with graminoid plants in the study area but specific preference for any of the graminoids could not be detected. In search for oviposition cues, it might be useful to screen for chemical volatiles released from all dominant plant species., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Bokore GE et al.)

Background: A good understanding of mosquito ecology is imperative for integrated vector control of malaria. In breeding sites, Anopheles larvae are concurrently exposed to predators and parasites. However, to our knowledge, there is no study on combined effects of predators and parasites on development and survival of larvae and their carry-over effects on adult survivorship and susceptibility to further parasite infection., Methods: This study focused on effects of the nymphs of the dragonfly Pantala flavescens and the parasitic fungus Beauveria bassiana on Anopheles gambiae, to determine: predation efficacy of nymphs against An. gambiae larvae; development rate of An. gambiae larvae in the presence of one, two or four constrained nymphs; efficacy of B. bassiana against An. gambiae larvae at doses of 3, 6 and 12 mg; and survival of adult mosquitoes exposed to B. bassiana, following pre-exposure to a constrained predator and/or parasite at the larval stage. The experiments consisted of survival bioassays quantified as pupation day, or dead larvae and/or adults., Results: Nymphs had an average predation efficacy of 88.3% (95% CI: 87.5-89.1) at 24 hours, against An. gambiae larvae. The presence of one or two nymphs reduced development time of larvae by 0.65 and 0.35 days, respectively. However, development time of larvae exposed to four nymphs was similar to the control larvae. Larvae exposed to 3, 6 and 12 mg of B. bassiana were 2.0, 2.5 and 3.5 times more likely to die, respectively, compared to control larvae. Adults not pre-exposed, those pre-exposed to predator, parasite, or both were 45.8, 67.4, 50.9 and 112.0 times more likely to die, respectively, compared to control that were unexposed to predator or parasite, at larval and adult stage., Conclusions: This study shows that both predator and parasite can reduce larval population of An. gambiae, and presence of predator cues decreases development time in breeding sites, as well as, increases the susceptibility of emerging adult to fungus. Predator and parasite both have an additive effect on survival of adults exposed to B. bassiana. Field studies are required for an in-depth understanding of predator and parasite influence on mosquito development time, survival and susceptibility in nature.

Chromosome inversions suppress genetic recombination and establish co-adapted gene complexes, or supergenes. The 2La inversion is a widespread polymorphism in the Anopheles gambiae species complex, the major African mosquito vectors of human malaria. Here we show that alleles of the 2La inversion are associated with natural malaria infection levels in wild-captured vectors from West and East Africa. Mosquitoes carrying the more-susceptible allele (2L+ a ) are also behaviorally less likely to be found inside houses. Vector control tools that target indoor-resting mosquitoes, such as bednets and insecticides, are currently the cornerstone of malaria control in Africa. Populations with high levels of the 2L+ a allele may form reservoirs of persistent outdoor malaria transmission requiring novel measures for surveillance and control. The 2La inversion is a major and previously unappreciated component of the natural malaria transmission system in Africa, influencing both malaria susceptibility and vector behavior.

Introduction: The aim of this study was to compare two gamma camera-based methods (Gates' method and Inoue's method) for measuring glomerular filtration rate (GFR) with Russell's two plasma sample clearance method (2-PSC), which was taken as the gold standard., Materials and Methods: In 94 healthy potential kidney donors (25 women and 69 men), GFR was measured by means of the 2-PSC method and was compared with Gates' and Inoue's methods of assessing GFR after technetium-99m-labeled diethylene triamine penta-acetic acid (⁹⁹ mTc-DTPA) injection., Results: Inoue's method showed no statistically significant difference (P=0.22) with the gold standard (2-PSC); there was good correlation (r=0.69) and least bias (-1.91 ml/min/1.73 m², root mean squared error=11.85 ml/min/1.73 m²). Gates' method showed weak correlation (r=0.36) and tended to underestimate GFR by 21% with bias of 25 ml/min/1.73 m² and root mean squared error of 29.97., Conclusion: For a normal healthy adult population, Inoue's method gives a better measure of GFR in contrast to Gates' method when compared with 2-PSC method of GFR calculation.

Background and Objective: Endothelial dysfunction in diabetes mellitus (DM) is an important factor in the pathogenesis of micro and macrovascular complications. We aimed to measure soluble endothelial protein C receptor (sEPCR) and high sensitivity C reactive protein (hsCRP) levels as markers of endothelial damage in both types of diabetes mellitus and to determine if they can be used as predictors of vascular complications., Methods: Fifty patients with DM, 20 with type 1 and 30 with type 2 as well as 30 healthy subjects were included. All were subjected to measurement of sEPCR and hsCRP by enzyme linked immunosorbent assay., Results: sEPCR and hsCRP were significantly increased when compared to the control group in both types of DM. sEPCR was a significant predictor of macrovascular complications and thrombosis in type 1 p=0.02, and p=0.015, respectively. hsCRP was a significant predictor of macrovascular complications in type 2 p=0.04., Conclusion: Patients with type 1 and type 2 DM exhibit higher sEPCR and hsCRP levels compared to healthy controls which suggesting endothelial damage. sEPCR could be used as a predictor of macrovascular complications and thrombosis in type 1 DM, whereas, hsCRP might be used as a predictor of macrovascular complications in type 2 DM., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Entomopathogenic fungi have shown to be effective in biological control of both larval and adult stages of malaria mosquitoes. However, a small fraction of mosquitoes is still able to emerge after treatment with fungus during the larval stage. It remains unclear whether fitness of these adults is affected by the treatment during the larval stage and whether they are still susceptible for another treatment during the adult stage. Therefore, we tested the effects of larval exposure to the entomopathogenic fungus Beauveria bassiana on fitness of surviving Anopheles stephensi females. Furthermore, we tested whether larval exposed females were still susceptible to re-exposure to the fungus during the adult stage. Sex ratio, survival and reproductive success were compared between non-exposed and larval exposed A. stephensi. Comparisons were also made between survival of non-exposed and larval exposed females that were re-exposed to B. bassiana during the adult stage. Larval treatment did not affect sex ratio of emerging mosquitoes. Larval exposed females that were infected died significantly faster and laid equal numbers of eggs from which equal numbers of larvae hatched, compared to non-exposed females. Larval exposed females that were uninfected had equal survival, but laid a significantly larger number of eggs from which a significantly higher number of larvae hatched, compared to non-exposed females. Larval exposed females which were re-exposed to B. bassiana during the adult stage had equal survival as females exposed only during the adult stage. Our results suggest that individual consequences for fitness of larval exposed females depended on whether a fungal infection was acquired during the larval stage. Larval exposed females remained susceptible to re-exposure with B. bassiana during the adult stage, indicating that larval and adult control of malaria mosquitoes with EF are compatible., (Copyright © 2014. Published by Elsevier Inc.)

Background: The entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana have demonstrated effectiveness against anopheline larvae in the laboratory. However, utilising these fungi for the control of anopheline larvae under field conditions, relies on development of effective means of application as well as reducing their sensitivity to UV radiation, high temperatures and the inevitable contact with water. This study was conducted to develop formulations that facilitate the application of Metarhizium anisopliae and Beauveria bassiana spores for the control of anopheline larvae, and also improve their persistence under field conditions., Methods: Laboratory bioassays were conducted to test the ability of aqueous (0.1% Tween 80), dry (organic and inorganic) and oil (mineral and synthetic) formulations to facilitate the spread of fungal spores over the water surface and improve the efficacy of formulated spores against anopheline larvae as well as improve spore survival after application. Field bioassays were then carried out to test the efficacy of the most promising formulation under field conditions in western Kenya., Results: When formulated in a synthetic oil (ShellSol T), fungal spores of both Metarhizium anisopliae and Beauveria bassiana were easy to mix and apply to the water surface. This formulation was more effective against anopheline larvae than 0.1% Tween 80, dry powders or mineral oil formulations. ShellSol T also improved the persistence of fungal spores after application to the water. Under field conditions in Kenya, the percentage pupation of An. gambiae was significantly reduced by 39 - 50% by the ShellSol T-formulated Metarhizium anisopliae and Beauveria bassiana spores as compared to the effects of the application of unformulated spores., Conclusions: ShellSol T is an effective carrier for fungal spores when targeting anopheline larvae under both laboratory and field conditions. Entomopathogenic fungi formulated with a suitable carrier are a promising tool for control of larval populations of malaria mosquitoes. Additional studies are required to identify the best delivery method (where, when and how) to make use of the entomopathogenic potential of these fungi against anopheline larvae.

Background: Rice paddies harbour a large variety of organisms including larvae of malaria mosquitoes. These paddies are challenging for mosquito control because their large size, slurry and vegetation make it difficult to effectively apply a control agent. Aquatain, a monomolecular surface film, can be considered a suitable mosquito control agent for such breeding habitats due to its physical properties. The properties allow Aquatain to self-spread over a water surface and affect multiple stages of the mosquito life cycle., Methodology/principal Findings: A trial based on a pre-test/post-test control group design evaluated the potential of Aquatain as a mosquito control agent at Ahero rice irrigation scheme in Kenya. After Aquatain application at a dose of 2 ml/m(2) on rice paddies, early stage anopheline larvae were reduced by 36%, and late stage anopheline larvae by 16%. However, even at a lower dose of 1 ml/m(2) there was a 93.2% reduction in emergence of anopheline adults and 69.5% reduction in emergence of culicine adults. No pupation was observed in treated buckets that were part of a field bio-assay carried out parallel to the trial. Aquatain application saved nearly 1.7 L of water in six days from a water surface of 0.2 m(2) under field conditions. Aquatain had no negative effect on rice plants as well as on a variety of non-target organisms, except backswimmers., Conclusions/significance: We demonstrated that Aquatain is an effective agent for the control of anopheline and culicine mosquitoes in irrigated rice paddies. The agent reduced densities of aquatic larval stages and, more importantly, strongly impacted the emergence of adult mosquitoes. Aquatain also reduced water loss due to evaporation. No negative impacts were found on either abundance of non-target organisms, or growth and development of rice plants. Aquatain, therefore, appears a suitable mosquito control tool for use in rice agro-ecosystems.

Background: Entomopathogenic fungi have shown great potential for the control of adult malaria vectors. However, their ability to control aquatic stages of anopheline vectors remains largely unexplored. Therefore, how larval characteristics (Anopheles species, age and larval density), fungus (species and concentration) and environmental effects (exposure duration and food availability) influence larval mortality caused by fungus, was studied., Methods: Laboratory bioassays were performed on the larval stages of Anopheles gambiae and Anopheles stephensi with spores of two fungus species, Metarhizium anisopliae and Beauveria bassiana. For various larval and fungal characteristics and environmental effects the time to death was determined and survival curves established. These curves were compared by Kaplan Meier and Cox regression analyses., Results: Beauveria bassiana and Metarhizium anisopliae caused high mortality of An. gambiae and An. stephensi larvae. However, Beauveria bassiana was less effective (Hazard ratio (HR) <1) compared to Metarhizium anisopliae. Anopheles stephensi and An. gambiae were equally susceptible to each fungus. Older larvae were less likely to die than young larvae (HR < 1). The effect of increase in fungus concentration on larval mortality was influenced by spore clumping. One day exposure to fungal spores was found to be equally effective as seven days exposure. In different exposure time treatments 0 - 4.9% of the total larvae, exposed to fungus, showed infection at either the pupal or adult stage. Mortality rate increased with increasing larval density and amount of available food., Conclusions: This study shows that both fungus species have potential to kill mosquitoes in the larval stage, and that mortality rate depends on fungus species itself, larval stage targeted, larval density and amount of nutrients available to the larvae. Increasing the concentration of fungal spores or reducing the exposure time to spores did not show a proportional increase and decrease in mortality rate, respectively, because the spores clumped together. As a result spores did not provide uniform coverage over space and time. It is, therefore, necessary to develop a formulation that allows the spores to spread over the water surface. Apart from formulation appropriate delivery methods are also necessary to avoid exposing non-target organisms to fungus.

Monomolecular films are used for mosquito control because of their asphyxiating effect on larvae and pupae. Compared with other films, Aquatain mosquito formulation (AMF) has an improved spreading ability and flexibility on a water surface. In the laboratory, AMF showed larvicidal, pupicidal, and oviposition deterrent effects against the malaria vectors Anopheles stephensi and An. gambiae. At a dose of 1 mL/m(2), the median lethal time to death for late larval instars was 3.02 (95% confidence interval [CI] = 2.76-3.25) and 0.98 (95% CI = 0.75-1.20) days for An. stephensi and An. gambiae, respectively. None of the treated larvae pupated. Pupal mortality reached 100% within two hours for both species. AMF repelled gravid females from ovipositing in treated oviposition cups. Without the choice of an untreated cup, the lowered water surface tension caused most females to drown while attempting to oviposit. This physical control method has the potential to become a safe, cost-effective, and resistance-proof malaria vector control tool.

In the mol-ecule of the title compound, C(13)H(17)N(3)O, the two rings make a dihedral angle of 56.63 (13)°. Mol-ecules are linked by strong N-H⋯O inter-molecular hydrogen bonds into chains running along the c axis.

Background: The majority of early trauma deaths are related to uncontrolled, noncompressible, parenchymal hemorrhage from truncal injuries. The purpose of this study was to formulate a fibrin sealant foam (FSF) able to control severe parenchymal bleeding without compression or vascular control., Materials and Methods: FSF with high fibrinogen concentration (20 mg/mL) and low thrombin activity (5 U/mL) was prepared and pressurized by addition of liquid gas propellant. The efficacy of this foam was tested against a severe parenchymal hemorrhage, created by partial resection of liver lobes in anticoagulated rabbits (n = 7) and compared to untreated injury (n = 8) and placebo treatment (n = 7). The hemostatic efficacy of pressurized FSF (n = 8) was also compared to a commercially available liquid fibrin sealant (n = 8) and a developing dry powdered fibrin sealant product (n = 8) in the same model., Results: The liver injury resulted in 122 +/- 11.5 mL blood loss and death of 75% of untreated rabbits (3.2-3.4 kg) within 1 h. Treatment with placebo foam had no effect on blood loss or mortality rate. Pressurized FSF significantly reduced bleeding, resulting in 56% (P < 0.05) and 66% (P < 0.01) reduction in blood loss as compared to untreated or placebo-treated animals, respectively, and 100% survival (P = 0.008). When pressurized FSF was compared with liquid and powdered forms of fibrin sealant, only foam significantly reduced blood loss (49%, P < 0.05) and mortality rate (54%, P < 0.05) of rabbits as compared to untreated control animals (n = 9)., Conclusion: Biological nature, rapid preparation, coverage of large wound areas, and effective hemostatic properties make pressurized FSF an ideal candidate for treating nonoperable parenchymal injuries in damage control procedures.

Libraries of random peptides displayed by bacteriophage can be screened to select phage expressing peptides that specifically bind antibodies, so that the peptide sequence motifs expressed by the phage can help to define the epitopes of the antibodies. It is often desirable to screen antibody-selected phage for binding of the selecting antibody in an immunoassay in order to verify the specificity of the interaction. Enzyme-linked immunosorbent assays (ELISAs) are commonly used for this purpose. However, for many antibodies, the best techniques for measuring specific, high affinity interactions are immuno-precipitation assays. Immuno-precipitation was therefore investigated as a means of measuring interactions between antibodies and phage clones selected from random peptide display libraries. Three mouse monoclonal antibodies specific for glutamic acid decarboxylase were used to select peptides as 9-mers on T7 phage, linear 12-mers on pIII of M13 phage, or constrained 15-mers on pVIII of M13 phage. Following the cloning and sequencing of selected phage, mixtures of antibody and phage were incubated in solution and the immune complexes were precipitated with Protein G bound to Sepharose beads. In order to detect and quantitate the phage that had formed immune complexes and been precipitated, advantage was taken of the biological properties of the phage by inducing infection of Escherichia coli by the precipitated phage. The aim was to quantitate the phage precipitated by determining the number of plaques produced, which would therefore be proportional to the degree of interaction between the phage and the antibody in solution. The results presented here indicate that this method of measuring monoclonal antibody interactions with phage selected for expression of peptides recognised by the monoclonal antibody is highly specific and sensitive.