Flavonoids: A treasure house of prospective pharmacological potentials.

Flavonoids are organic compounds characterized by a range of phenolic structures, which are abundantly present in various natural sources such as fruits, vegetables, cereals, bark, roots, stems, flowers, tea, and wine. The health advantages of these natural substances are renowned, and initiatives are being taken to extract the flavonoids. Apigenin, galangin, hesperetin, kaempferol, myricetin, naringenin, and quercetin are the seven most common compounds belonging to this class. A thorough analysis of bibliographic records from reliable sources including Google Scholar, Web of Science, PubMed, ScienceDirect, MEDLINE, and others was done to learn more about the biological activities of these flavonoids. These flavonoids appear to have promising anti-diabetic, anti-inflammatory, antibacterial, antioxidant, antiviral, cytotoxic, and lipid-lowering activities, according to evidence from in vitro, in vivo, and clinical research. The review contains recent trends, therapeutical interventions, and futuristic aspects of flavonoids to treat several diseases like diabetes, inflammation, bacterial and viral infections, cancers, and cardiovascular diseases. However, this manuscript should be handy in future drug discovery. Despite these encouraging findings, a notable gap exists in clinical research, hindering a comprehensive understanding of the effects of flavonoids at both high and low concentrations on human health. Future investigations should prioritize exploring bioavailability, given the potential for high inter-individual variation. As a starting point for further study on these flavonoids, this review paper may promote identifying and creating innovative therapeutic uses.

The Effect of Microballoon Volume Fraction on the Elastic and Viscoelastic Properties of Hollow Microballoon-Filled Epoxy Composites.

This paper reports the study of hollow microballoon-filled epoxy composites also known as syntactic foams with various volume fractions of microballoons. Different mechanical and thermomechanical investigations were carried out to study the elastic and viscoelastic behavior of these foams. The density, void content, and microstructure of these materials were also studied for better characterization. In addition to the experimental testing, a representative 3D model of these syntactic foams was developed to further investigate their elastic behavior. The results indicate that changes in the volume percentage of the microballoons had a substantial impact on the elastic and viscoelastic behavior of these foams. These results will help in designing and optimizing custom-tailored syntactic foams for different engineering applications.

Corrigendum: Effects of dietary nutmeg (Myristica fragrans) seed meals on growth, non-specific immune indices, antioxidant status, gene expression analysis, and cold stress tolerance in zebrafish (Danio rerio).

[This corrects the article DOI: 10.3389/fnut.2022.1038748.].

Food Color Additives in Hazardous Consequences of Human Health: An Overview.

Food color additives are used to make food more appetizing. The United States Food and Drug Administration (FDA) permitted nine artificial colorings in foods, drugs, and cosmetics, whereas the European Union (EU) approved five artificial colors (E-104, 122, 124, 131, and 142) for food. However, these synthetic coloring materials raise various health hazards. The present review aimed to summarize the toxic effects of these coloring food additives on the brain, liver, kidney, lungs, urinary bladder, and thyroid gland. In this respect, we aimed to highlight the scientific evidence and the crucial need to assess potential health hazards of all colors used in food on human and nonhuman biota for better scrutiny. Blue 1 causes kidney tumor in mice, and there is evidence of death due to ingestion through a feeding tube. Blue 2 and Citrus Red 2 cause brain and urinary bladder tumors, respectively, whereas other coloring additives may cause different types of cancers and numerous adverse health effects. In light of this, this review focuses on the different possible adverse health effects caused by these food coloring additives, and possible ways to mitigate or avoid the damage they may cause. We hope that the data collected from in vitro or in vivo studies and from clinical investigations related to the possible health hazards of food color additives will be helpful to both researchers and the food industry in the future.

Analysis of bioactive compounds present in different crude extracts of Benincasa hispida and Cucurbita moschata seeds by gas chromatography-mass spectrometry.

Plant seeds are the resources of many different bioactive components. The chemical composition of the different crude extracts from Benincasa hispida (White pumpkin) and Cucurbita moschata (Pumpkin) seeds with three different polarity-based solvents (n-hexane, n-hexane-chloroform (2:1), and methanol) was analyzed to identify the biologically active compounds. Each of the extracts was analyzed by gas chromatography-mass spectrometry. Different extracts of targeted seeds showed different biologically active compounds that have different pharmacological potentialities. 9, 12-Octadecadienoic acid (ZZ) was the most potent bioactive compound present in three different extracts of both B. hispida and C. moschata. Another bioactive compound comparatively low percentage present in both plants was n-hexadecanoic acid. Other major pharmacologically active compounds present in both plants were 9- Octadecenoic acid (Z)-, methyl ester, and 9, 12-Octadecadienoic acid methyl ester (E, E). Besides these compounds, a few more biologically active compounds were present in the two plants separately. The findings of this study support the use of these seeds in modern functional foods, nutraceuticals, and medicinal purposes, and the whole seeds would give better health benefits rather than use any extract. Although further pharmacological examinations should be carried out to conclude the medicinal application of the seeds of these two plants as well as to understand the mechanism of the potential health benefits.

Ferroelectric nematic droplets in their isotropic melt.

The isotropic to ferroelectric nematic liquid transition was theoretically studied over one hundred years ago, but its experimental studies are rare. Here we present experimental results and theoretical considerations of novel electromechanical effects of ferroelectric nematic liquid crystal droplets coexisting with the isotropic melt. We find that the droplets have flat pancake-like shapes that are thinner than the sample thickness as long as there is room to increase the lateral droplet size. In the center of the droplets a wing-shaped defect with low birefringence is present that moves perpendicular to a weak in-plane electric field, and then extends and splits in two at higher fields. Parallel to the defect motion and extension, the entire droplet drifts along the electric field with a speed that is independent of the size of the droplet and is proportional to the amplitude of the electric field. After the field is increased above 1 mV µm-1 the entire droplet gets deformed and oscillates with the field. These observations led us to determine the polarization field and revealed the presence of a pair of positive and negative bound electric charges due to divergences of polarization around the defect volume.

Prevalence and associated factors for elevated fear and depressive symptoms among the private service holders in Bangladesh during the Covid-19 pandemic: A cross-sectional study.

Background and Aims: The ongoing public health emergency has created incredible fear of getting the infection and a terrible psychological burden among all levels. The pandemic has severely affected private job holders' economic status and lifestyle factors in Bangladesh. Here we aimed to assess fear and depressive symptoms among private job holders in Bangladesh during the Covid-19 pandemic and associated risk factors. Methods: We conducted this online cross-sectional survey between January 15, 2021, and March 15, 2021, among 510 private job holders aged above 18 years. We followed the convenience sampling method for data collection. We assessed sociodemographic factors and two psychometric parameters. We applied the Fear of Covid-19 Scale and Patient Health Questionnaire-9 to assess increased fear and depressive symptoms, respectively. Chi-square test, independent sample t-test, and binary logistic regression analysis were performed for data analysis. Results: The prevalence of increased fear and depressive symptoms were 86.27% and 42.16%, respectively. Factors associated with increased fear among private job holders during COVID-19 were economic class, obesity, on-time salary, company's downsizing policy, salary reduction, home office, and transportation facilities. However, depressive symptoms were associated with marital status, education level, residence area, the organizational practice of health safety rules, company performance, on-time salary, health insurance, downsizing, salary reduction policy, organization type, transportation, and mental health support at work. The present study also noticed some interrelations among the above factors with mental health issues. Conclusion: Based on the present findings, we recommend actionable items to improve the mental health of private job holders in Bangladesh due to the ongoing pandemic. Authorities can develop mental health support programs and efficient Covid-19 response systems. The policymakers and regulatory bodies might take some initiatives to promote mental health in the private sector in Bangladesh.

Development and analysis of a geospatial database for maritime spatial planning in Bangladesh.

In this research we collect, prepare and analyze a geospatial database of maritime activities located in the northern Bay of Bengal with the final aim to simulate maritime spatial planning (MSP) - ready information source for future sectoral and multi-sector MSP in Bangladesh. The database is composed of 28 anthropogenic and environmental layers categorized into seven Blue Economy sectors. The database is analyzed with a set of geospatial models aimed at understanding the intensity distribution of human activities at sea and the potential marine use conflicts emerging from the aggregation of human activities. Ecological resources were characterized in terms of marine mammals, lobsters, commercially important and threatened fish species, and pelagic birds and mapped as biodiversity hotspots using geographic cluster analysis. Results show that the most intensely used sea areas are located along the northeastern coast of Bangladesh, as well as in the Swatch of No Ground (SoNG) area, with maximum Marine Use Intensity (MUI) scores ranging from 5 to 8. Offshore waters of Saint Martin's Island have higher MUI scores (≥ 5) as well. The pairwise spatial conflict analysis shows that nature protection sites particularly SoNG Marine Protected Area (MPA), Nijhum Dwip Marine Reserve (MR), and Saint Martin's Island MPA are exposed to the high Marine Use Conflicts (MUC) induced by fishing and shipping activities. Fishing operations generate the highest MUC value (MUC = 30) in SoNG MPA, whereas shipping activities produce the highest MUC value (MUC = 24) in Nijhum Dwip MR. Both of the MPAs exhibit 6 to 12 MUC scores induced by shipping. The proposed database together with the illustrated analytical techniques used in this study and key findings can provide the first understanding of the priorities for Ecosystem Based Management of Bangladesh's marine space and provide valuable insights on the urgency for MSP process in the country. The study concludes with an outlook on the utility of the database for future analysis.

Incorporating the mutational landscape of SARS-COV-2 variants and case-dependent vaccination rates into epidemic models.

Coronavirus Disease (COVID-19), which began as a small outbreak in Wuhan, China, in December 2019, became a global pandemic within months due to its high transmissibility. In the absence of pharmaceutical treatment, various non-pharmaceutical interventions (NPIs) to contain the spread of COVID-19 brought the entire world to a halt. After almost a year of seemingly returning to normalcy with the world's quickest vaccine development, the emergence of more infectious and vaccine resistant coronavirus variants is bringing the situation back to where it was a year ago. In the light of this new situation, we conducted a study to portray the possible scenarios based on the three key factors: impact of interventions (pharmaceutical and NPIs), vaccination rate, and vaccine efficacy. In our study, we assessed two of the most crucial factors, transmissibility and vaccination rate, in order to reduce the spreading of COVID-19 in a simple but effective manner. In order to incorporate the time-varying mutational landscape of COVID-19 variants, we estimated a weighted transmissibility composed of the proportion of existing strains that naturally vary over time. Additionally, we consider time varying vaccination rates based on the number of daily new cases. Our method for calculating the vaccination rate from past active cases is an effective approach in forecasting probable future scenarios as it actively tracks people's attitudes toward immunization as active case changes. Our simulations show that if a large number of individuals cannot be vaccinated by ensuring high efficacy in a short period of time, adopting NPIs is the best approach to manage disease transmission with the emergence of new vaccine breakthrough and more infectious variants.

Effects of dietary nutmeg (Myristica fragrans) seed meals on growth, non-specific immune indices, antioxidant status, gene expression analysis, and cold stress tolerance in zebrafish (Danio rerio).

Introduction: A medicinal plant, Myristica fragrans seed meal (nutmeg), was utilized to evaluate its impact on the growth, immunity, and antioxidant defense of zebrafish (Danio rerio). Methods: In this regard, zebrafish (0.47 ± 0.04 g) (mean ± S.D.) were fed with 0% (control), 1% (T1-nutmeg), 2% (T2-nutmeg), and 3% (T3-nutmeg) of powdered nutmeg for 70 days. At the end of the feeding trial, growth performance, survival rate of fish, and temperature-challenge effects were recorded. Immune and antioxidant parameters were also assessed through the collection of serum and skin mucus samples. Results: The results indicated that nutmeg supplementation did not significantly influence the growth of zebrafish (P > 0.05); however, the survival rate of fish fed with 2 and 3% of nutmeg supplementation significantly decreased (P < 0.05). The skin mucus and serum total protein, total immunoglobulin (Ig), and lysozyme activity were significantly increased in T3-nutmeg treatment in comparison to the control (P < 0.05). Superoxide dismutase (SOD) and catalase (CAT) activities were also enhanced in the T3-nutmeg group (P < 0.05). Nutmeg supplementation significantly upregulated the mRNA expression of growth hormone (gh) and insulin growth factor-1 (igf-1). Moreover, the nutmeg inclusion upregulated the expression of interleukin-1ß (IL-1ß), lysozyme, sod, and cat. The dietary supplementation of nutmeg significantly increased the resistance of zebrafish against cold-water shock and survivability afterward (P < 0.05). Discussion: In conclusion, the supplementation of 3% powdered nutmeg in zebrafish diets could be suggested as an effective immune stimulator that improves antioxidant defense and stress tolerance.

Insect (black soldier fly larvae) oil as a potential substitute for fish or soy oil in the fish meal-based diet of juvenile rainbow trout (Oncorhynchus mykiss).

Alternative sources of fish oil (FO) are one of the major problems in aquaculture; therefore, the goal of the present study was to examine insect (black soldier fly larvae) oil (BSLO) as a potential replacer of fish/soy oil in juvenile rainbow trout (initial average weight of 32 ± 0.15 g) feed. Four diets were formulated wherein FO (control diet) was completely replaced with either soybean oil (SO) or BSLO, and an additional BSLO-based diet supplemented with 1.5% bile acid (BSLO + BA) were fed to the fish for 10 weeks. Growth performance of the BSLO fed group was similar (P > 0.05) to that of the FO and SO fed groups, however, the fish fed BSLO + BA diet registered the lowest growth (P < 0.05). Oil sources did not (P > 0.05) affect the major nutrient content of whole-body, however, the fatty acid composition of the muscle and liver was influenced (P < 0.05), with the highest 14:0, 16:0, and total saturated fatty acid detected in BSLO or BSLO + BA fed trout compared to the others (P < 0.001). No significant differences were observed in eicosapentaenoic acid + docosahexaenoic acid (EPA + DHA) or total n-3 polyunsaturated fatty acid (PUFA) content in muscle among the groups, whereas, the highest EPA:DHA and n-3:n-6 ratios were detected in the FO group. Gene expression for fatty acid binding protein (fabp), fatty acid synthase (fas), and Δ5 desaturase in the liver was lower in FO (P < 0.05), while BSLO + BA registered the highest Δ6 expression (P = 0.006). Supplementation of BA in the BSLO diet increased superoxide dismutase (SOD) and catalase (CAT) activities compared to the other groups (P < 0.05). In conclusion, BSLO could serve as a substitute for FO and SO in rainbow trout diet without negatively impacting growth performance, whole-body composition and nutrient retention, and modulate the expression of fatty acid metabolism-related genes in rainbow trout.

Evaluation of Loopamp™ Leishmania Detection Kit and Leishmania Antigen ELISA for Post-Elimination Detection and Management of Visceral Leishmaniasis in Bangladesh.

With reduced prevalence of visceral leishmaniasis (VL) in the Indian subcontinent (ISC), direct and field deployable diagnostic tests are needed to implement an effective diagnostic and surveillance algorithm for post-elimination VL control. In this regard, here we investigated the diagnostic efficacies of a loop-mediated isothermal amplification (LAMP) assay (Loopamp™ Leishmania Detection Kit, Eiken Chemical CO., Ltd, Japan), a real-time quantitative PCR assay (qPCR) and the Leishmania antigen ELISA (CLIN-TECH, UK) with different sampling techniques and evaluated their prospect to incorporate into post-elimination VL control strategies. Eighty clinically and rK39 rapid diagnostic test confirmed VL cases and 80 endemic healthy controls were enrolled in the study. Peripheral blood and dried blood spots (DBS) were collected from all the participants at the time of diagnosis. DNA was extracted from whole blood (WB) and DBS via silica columns (QIAGEN) and boil & spin (B&S) methods and tested with qPCR and Loopamp. Urine was collected from all participants at the time of diagnosis and was directly subjected to the Leishmania antigen ELISA. 41 patients were followed up and urine samples were collected at day 30 and day 180 after treatment and ELISA was performed. The sensitivities of the Loopamp-WB(B&S) and Loopamp-WB(QIA) were 96.2% (95% CI 89·43-99·22) and 95% (95% CI 87·69-98·62) respectively. The sensitivity of Loopamp-DBS(QIA) was 85% (95% CI 75·26- 92·00). The sensitivities of the qPCR-WB(QIA) and qPCR-DBS(QIA) were 93.8% (95% CI 86·01-97·94) and 72.5% (95% CI 61·38-81·90) respectively. The specificity of all molecular assays was 100%. The sensitivity and specificity of the Leishmania antigen ELISA were 97.5% (95% CI 91·47-99·70) and 91.95% (95% CI 84·12-96·70) respectively. The Leishmania antigen ELISA depicted clinical cure at day 180 in all the followed-up cases. Efficacy and sustainability identify the Loopamp-WB(B&S) and the Leishmania antigen ELISA as promising and minimally invasive VL diagnostic tools to support VL diagnostic and surveillance activities respectively in the post-elimination era.

Detection of asymptomatic Leishmania infection in Bangladesh by antibody and antigen diagnostic tools shows an association with post-kala-azar dermal leishmaniasis (PKDL) patients.

BACKGROUND: Asymptomatic Leishmania infections outnumber clinical infections on the Indian subcontinent (ISC), where disease reservoirs are anthroponotic. Diagnostics which detect active asymptomatic infection, which are suitable for monitoring and surveillance, may be of benefit to the visceral leishmaniasis (VL) elimination campaign on the ISC. METHODS: Quantitative polymerase chain reaction (qPCR), loop-mediated isothermal amplification (LAMP), and the direct agglutination test (DAT) were carried out on blood samples, and the Leishmania antigen ELISA was carried out on urine samples collected from 720 household and neighbouring contacts of 276 VL and post-kala-azar dermal leishmaniasis (PKDL) index cases, with no symptoms or history of VL or PKDL, in endemic regions of Bangladesh between September 2016 and March 2018. RESULTS: Of the 720 contacts of index cases, asymptomatic infection was detected in 69 (9.6%) participants by a combination of qPCR (1.0%), LAMP (2.1%), DAT (3.9%), and Leishmania antigen ELISA (3.3%). Only one (0.1%) participant was detected positive by all four diagnostic tests. Poor agreement between tests was calculated using Cohen's kappa (κ) statistics; however, the Leishmania antigen ELISA and DAT in combination captured all participants as positive by more than one test. We find evidence for a moderately strong association between the index case being a PKDL case (OR 1.94, p = 0.009), specifically macular PKDL (OR 2.12, p = 0.004), and being positive for at least one of the four tests. CONCLUSIONS: Leishmania antigen ELISA on urine detects active asymptomatic infection, requires a non-invasive sample, and therefore may be of benefit for monitoring transmission and surveillance in an elimination setting in combination with serology. Development of an antigen detection test in a rapid diagnostic test (RDT) format would be of benefit to the elimination campaign.

Insect (black soldier fly, Hermetia illucens) meal supplementation prevents the soybean meal-induced intestinal enteritis in rainbow trout and health benefits of using insect oil.

Black solider fly larvae (BSFL) and their oils (BSFLO) are receiving increasing attention as sustainable ingredients in fish feeds, but mostly as replacements to marine sources. There were two aims to this study; in exp. 1, soybean meal (SBM)-based diets were formulated to contain BSFL as supplements at 0 (SBM), 8 (SBM + BSFLlow) or 16% (SBM + BSFLhigh) with a control diet being fishmeal-based (FM). In exp. 2, diets included only fish oil (FO), soybean oil (SBO), BSFLO or BSFLO + bile acid (BA), and all lipid sources were added at 16%. Both experiments were run at the same time and fed to rainbow trout (32 g) with each treatment being triplicated. After 10 weeks the fish were sampled for liver and distal intestine histology, expression of genes responsible for inflammation in the intestine and kidneys, and serum peroxidase and lysozyme activities. In exp. 1, supplementations of BSFL effectively prevented SBM-induced intestinal enteritis, down-regulated intestinal prostaglandin and interferon regulatory factor 1 (IRF-1), while the SBM + BSFLhigh diet significantly increased serum lysozyme activity. In exp. 2, BSFLO caused no histomorphological change to the liver or intestine, but kidney interluekin-8, tumor necrosis factor and IRF-1 were significantly upregulated along with significantly higher serum peroxidase activity. The inclusion of BA in the BSFLO diets significantly upregulated intestinal prostaglandin gene expression. Overall, BSFL supplementations of 8 or 16% prevented SBM-induced intestinal enteritis based on histological observations, which was supported by a down-regulation in pro-inflammatory genes and enhanced innate immunity. Meanwhile, the use of BSFLO showed some immunological benefits. Therefore, these sustainable resources are recommended in the diets of rainbow trout, especially when using elevated levels of plant-based proteins.

Efficacy of mozuku fucoidan in alternative protein-based diet to improve growth, health performance, and stress resistance of juvenile red sea bream, Pagrus major.

We evaluated the efficacy of mozuku fucoidan supplementation to alternative dietary proteins used in fish meal (FM) replacement to enhance growth, immunity, and stress resistance of Pagrus major. Seven isonitrogenous (45% protein) experimental diets were formulated where diet 1 (D1) was FM-based control diet. Diets 2 to 7 were formulated by replacing 25, 50, and 75% of FM protein with soy protein isolate (SPI) protein, and each replacement level was supplemented without or with fucoidan at 0.4% for diet groups D2 (FM25), D3 (FM25Fu), D4 (FM50), D5 (FM50Fu), D6 (FM75), and D7(FM75Fu), respectively. Each diet was randomly allocated to triplicate groups of fish (4.1 g) for 56 days. Significantly higher weight gain and specific growth rate were observed in fish fed FM50Fu diet group, and it was not differed (P > 0.05) with fish fed FM25Fu diet group. FM-based control diet showed intermediate value, and it was not differed (P > 0.05) with or without fucoidan-supplemented ≤ 50% FM replacement groups and FM75Fu diet group. Significantly lower growth performances were observed in FM75 diet group. At each replacement level, fucoidan-supplemented groups showed nonsignificant improvement of feed utilization performances. Fish fed fucoidan-supplemented diets showed best condition of oxidative and freshwater stress resistance. Lysozyme activity, NBT, and peroxidase activity showed higher (P > 0.05) values in fucoidan-supplemented groups compared with the non-supplemented groups. Catalase activity was significantly lower in FM75Fu diet group. Catalase activity is significantly influenced by the interaction effects of fucoidan and FM replacement level. In conclusion, fucoidan supplementation could increase the efficiency of utilizing SPI (≥ 75%) without any adverse effects on red sea bream performance.

The effect of dietary fucoidan on growth, immune functions, blood characteristics and oxidative stress resistance of juvenile red sea bream, Pagrus major.

We determined the supplementation effects of dietary fucoidan on growth, immune responses, blood characteristics, and oxidative stress resistance of juvenile red sea bream. A fishmeal (FM)-based basal diet supplemented with 0% (D1, control), 0.05% (D2), 0.1% (D3), 0.2% (D4), 0.4% (D5), and 0.8% (D6) mozuku fucoidan to formulate six experimental diets. Each diet was randomly allocated to triplicate groups of fish (3.8 g) for 60 days. Results showed that fish-fed diet D5 showed significantly higher (P < 0.05) growth performance compared to the control (D1). Diet groups D2 to D4 also showed intermediate values compared to D1. Feed conversion efficiency and protein efficiency ratio were significantly higher in diet group D5, which was not significantly different with D3. Fucoidan supplementation increased whole-body lipid, which was significantly higher in the D5 group. Condition factor (CF) was significantly higher in fish fed ≥ 0.2% fucoidan-supplemented diet groups. Diet group D5 and D4 showed significantly lower blood urea nitrogen (BUN) and aspartate aminotransferase (AST) level, respectively. Dietary fucoidan reduced the oxidative stress of fish. Among the measured nonspecific immune parameters, only peroxidase activity (PA) and total serum protein (TSP) were significantly influenced by dietary supplementation and it was higher in D4 group. Fucoidan supplementation reduces thiobarbituric acid reactive substance (TBARS) values numerically and it was lowest in fish-fed diet group D5. Under the present experimental condition, finally, we concluded that 0.3-0.4% dietary fucoidan supplementation enhanced the growth and health performance of red sea bream by increasing growth, immune response, blood characteristics, and oxidative stress resistance.

Fishmeal replacement by soya protein concentrate with inosine monophosphate supplementation influences growth, digestibility, immunity, blood health, and stress resistance of red sea bream, Pagrus major.

We assessed the effects of fishmeal (FM) replacement by soy protein concentrate (SPC) with inosine monophosphate (IMP) supplementation on growth, digestibility, immunity, blood health, and stress resistance of red sea bream, Pagrus major. FM protein of a FM-based control diet (FM100) was replaced with 25 (FM75), 50 (FM50), 75 (FM25), and 100% (FM0) by SPC protein, and each replacement group was supplemented with 0.4% IMP to formulate five experimental diets. Each diet was randomly allocated to triplicate groups of fish (4.8 g) for 56 days. Results demonstrated that fish fed diet groups FM50 and FM75 had significantly the highest final weight, weight gain, specific growth rate, and feed intake. Meanwhile, in comparison to the control, growth performance and feed utilization did not significantly differ with the 75% FM-replaced diet group by SPC with IMP supplementation. Apparent digestibility coefficient of dry matter, protein, and lipid also followed a similar trend. All growth, feed utilization, and digestibility parameters were significantly lower in the FM0 diet group. Triglyceride level was increased (P < 0.05) with the increasing replacement level and it was significantly highest in the FM0 diet group. The fish fed diet groups FM100 and FM50 showed the best condition of oxidative and freshwater stress resistance, respectively. Meanwhile, the groups with up to 75% FM-replaced diet also showed acceptable stress resistance status. Overall, enhanced innate immune responses were observed in the entire FM replaced with IMP-supplemented diet groups in comparison to the control. Considering SGR as a model, the regression analysis determined that 71.7% FM protein could be replaced by SPC protein with IMP supplementation in diets for the growth of red sea bream.

Using focused pharmacovigilance for ensuring patient safety against antileishmanial drugs in Bangladesh's National Kala-azar Elimination Programme.

BACKGROUND: Adverse effects of antileishmanial drugs can affect patients' quality of life and adherence to therapy for visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). In Bangladesh, there are 26 treatment centers that manage leishmaniasis cases coming from 100 endemic upazilas (subdistricts) of 26 districts (these include VL, PKDL, treatment failure, and relapse VL and cutaneous leishmaniasis cases). This study aimed to investigate the feasibility of using focused pharmacovigilance for VL (VLPV) in Bangladesh's National Kala-azar Elimination Programme for the early detection and prevention of expected and unexpected adverse drug reactions (ADRs). METHODS: This activity has been going on since December 2014. Activity area includes secondary public hospital or Upazila health complex (UHC) in hundred sub districts and Surya Kanta Kala-azar Research Center (SKKRC) in Mymensingh District, a specialized center for management of complicated VL and PKDL cases. Communicable Disease Control (CDC) of the Directorate General of Health Services (DGHS) assigned twenty five of hundred UHCs and SKKRC (total 26) as treatment centers depending on their suitable geographical location. This was implemented for better management of VL cases with Liposomal Amphotericin B (AmBisome®) to ensure patient convenience and proper utilization of this expensive donated drug. A VLPV expert committee and a UHC VLPV team were established, an operational manual and pharmacovigilance report forms were developed, training and refresher training of health personnel took place at UHCs and at the central level, collected information such as patient data including demographics, treatment history and response, adverse events were analyzed. This report includes information for the period from December 2014 to December 2016. RESULTS: From December 2014 to December 2016, 1327 leishmaniasis patients were treated and 1066 (80%) were available for VLPV. Out of these, 57, 33, 9, and 1% were new VL, PKDL, VL relapse, and other cases, respectively. Liposomal amphotericin B was mostly used (82%) for case management, followed by miltefosine (20%) and paromomycin (3%). Out of the 1066 patients, 26% experienced ADRs. The most frequent ADR was fever (17%, 176/1066), followed by vomiting (5%, 51/1066). Thirteen serious adverse events (SAEs) (eight deaths and five unexpected SAEs) were observed. The expert committee assessed that three of the deaths and all unexpected SAEs were possibly related to treatment. Out of the five unexpected SAEs, four were miltefosine-induced ophthalmic complications and the other was an AmBisome®-induced avascular necrosis of the nasal alae. The Directorate General of the Drug Administration entered the ADRs into the World Health Organization Uppsala Monitoring Centre (WHO-UMC) VigiFlow database. CONCLUSIONS: This study found that VLPV through NKEP is feasible and should be continued as a routine activity into the public health system of Bangladesh to ensure patient safety against anti-leishmanial drugs.

Influence of dietary inosine and vitamin C supplementation on growth, blood chemistry, oxidative stress, innate and adaptive immune responses of red sea bream, Pagrus major juvenile.

Both inosine (INO) and vitamin C (l-ascorbic acid, AsA) play important roles in growth performance, feed utilization and health status of fish. Therefore, a 56 days feeding trial was conducted to determine the interactive effects of dietary INO and AsA on growth performance, oxidative status, innate and adaptive immune responses of red sea bream. Fish growth performance and fed utilization parameters were significantly affected by dietary INO supplementation but not by AsA. Fish fed diets with INO at 4 g kg-1 diet in combination of high and low levels of AsA (3.1 g kg-1 and 9.3 g kg-1) produced the highest growth and feed utilization performances. In terms of growth and feed utilization performances no significant interaction effects were observed between INO and AsA. Dietary INO significantly influenced hematocrit, glucose and glutamyl oxaloacetic transaminase (GOT) content of red sea bream meanwhile AsA also significantly influenced hematocrit, glucose, total cholesterol, blood urea nitrogen (BUN) and glutamic-pyruvate transaminase (GPT) content of the test fish. No significant interaction effects was also observed between INO and AsA on measured hematological parameters. Reactive oxygen metabolites (d-ROMs) significantly influenced by both INO and AsA. Fish fed diet groups D1, D4 and D6 showed best oxidative stress resistance. Only INO was a significant factor on nitro-blue-tetrazolium activity (NBT) and bactericidal activity (BA). Neither INO nor AsA was a significant factor on serum catalase activity (CAT), total serum protein (TSP), peroxidase activity (PA) and lysozyme activity (LA). No significant interaction effects was observed between INO and AsA on measured innate immune parameters. Agglutination antibody titer was significantly influenced by dietary supplementation, after 15 days of vaccination but not in 21 days. In the day 15th fish and diet group D3 and D5 showed significantly higher values compared to diet groups control and D1. INO was the only significant factor of increasing agglutination antibody titer in 15 t h day. While AsA was not a significant factor on agglutination antibody titer values in day 15 t h, there was an interaction between dietary INO and AsA levels. Finally under the experimental conditions, fish fed high INO and low AsA levels (4 g kg-1 and 0.31 g kg-1 diet, respectively) showed best growth and feed utilization performance. Simultaneously, low level of INO and high level of AsA (2 g kg-1 and 0.93 g kg-1 diet, respectively) improved blood chemistry and immunological parameters. Furthermore, combined use of INO and AsA is possible to improve hemato-immunological responses of red sea bream.