Comparative efficacy and safety of nirmatrelvir/ritonavir and molnupiravir for COVID-19: A systematic review and meta-analysis.

This study aimed to compare the efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) with molnupiravir in the treatment of coronavirus disease 2019 (COVID-19). To end this, PubMed, Cochrane Library, Web of Science, medRxiv, and Google Scholar were systematically searched to collect relevant evidence up to February 15, 2023. The risk of bias was evaluated using the risk of bias in nonrandomized studies of interventions tool. Data were analyzed using Comprehensive Meta-Analysis software. Eighteen studies involving 57 659 patients were included in the meta-analysis. The meta-analysis showed a significant difference between nirmatrelvir/ritonavir and molnupiravir in terms of all-cause mortality rate (odds ratio [OR] = 0.54, 95% confidence interval [CI]: 0.44-0.67), all-cause hospitalization rate (OR = 0.61, 95% CI: 0.54-0.69), death or hospitalization rate (OR = 0.61, 95% CI: 0.38-0.99), and negative polymerase chain reaction conversion time (mean difference = -1.55, 95% CI: -1.74 to -1.37). However, no significant difference was observed between the two groups in terms of COVID-19 rebound (OR = 0.87, 95% CI: 0.71-1.07). In terms of safety, although the incidence of any adverse events was higher in the nirmatrelvir/ritonavir group (OR = 2.52, 95% CI: 1.57-4.06), no significant difference was observed between the two treatments in terms of adverse events leading to treatment discontinuation (OR = 1.18, 95% CI: 0.69-2.00). The present meta-analysis demonstrated the significant superiority of nirmatrelvir/ritonavir over molnupiravir in improving clinical efficacy in COVID-19 patients during the prevalence of Omicron variant. These findings, however, need to be further confirmed.

Seasonal variations in the skin epidermal structure and mucosal immune parameters of rainbow trout skin (Oncorhynchus mykiss) at different stages of farming.

The aim of this study was to investigate the seasonal changes in the epidermal structure and the innate immunity parameters of skin mucus in rainbow trout. The skin epidermis and mucus samples were collected over three consecutive seasons including winter, spring and late summer from three different weight groups i.e., 2-20 g (W1), 100-200 g (W2) and 400-600 g (W3) fish. The skin mucosal immunity analysis of rainbow trout showed that the haemagglutination activity increased significantly with increasing fish size from W1 to W3 in all three seasons, while no significant seasonal changes occurred in haemagglutination activity. Moreover, the bactericidal activity against fish pathogens increased significantly with increasing water bacterial load in late summer. The SDS-PAGE analysis of mucus showed a high amount of low molecular weight proteins (<35 kDa) in the late summer that was correlated with the increase in bactericidal activity. Histological analysis of the epidermis structure of rainbow trout skin showed that the density and size of goblet cells and consequently the mucus secretion significantly increased in W3 group in all seasons. In all three weight groups of fish, the density of goblet cells significantly increased from winter to spring and late summer along with increasing water temperature. Moreover, the goblet cell density showed a significant positive relationship with the soluble protein concentration and haemagglutination activity (p < 0.01). The results of this study demonstrated the more active immune role of the skin epidermal cells and mucus in rainbow trout during summer to protect fish against the pathogenic microorganisms. Given its potent bactericidal properties and the lack of haemolytic activity, the rainbow trout mucus might be used as a safe and inexpensive source for developing antimicrobial agents to prevent and treat some bacterial diseases in human and fish.

Salmonid gene expression biomarkers indicative of physiological responses to changes in salinity and temperature, but not dissolved oxygen.

An organism's ability to respond effectively to environmental change is critical to its survival. Yet, life stage and overall condition can dictate tolerance thresholds to heightened environmental stressors, such that stress may not be equally felt across individuals and at all times. Also, the transcriptional responses induced by environmental changes can reflect both generalized responses as well as others that are highly specific to the type of change being experienced. Thus, if transcriptional biomarkers specific to a stressor, even under multi-stressor conditions, can be identified, the biomarkers could then be applied in natural environments to determine when and where an individual experiences such a stressor. Here, we experimentally challenged juvenile Chinook salmon (Oncorhynchus tshawytscha) to validate candidate gill gene expression biomarkers. A sophisticated experimental design manipulated salinity (freshwater, brackish water and seawater), temperature (10, 14 and 18°C) and dissolved oxygen (normoxia and hypoxia) in all 18 possible combinations for 6 days using separate trials for three smolt statuses (pre-smolt, smolt and de-smolt). In addition, changes in juvenile behaviour, plasma variables, gill Na+/K+-ATPase activity, body size, body morphology and skin pigmentation supplemented the gene expression responses. We identified biomarkers specific to salinity and temperature that transcended the multiple stressors, smolt status and mortality (live, dead and moribund). Similar biomarkers for dissolved oxygen were not identified. This work demonstrates the unique power of gene expression biomarkers to identify a specific stressor even under multi-stressor conditions, and we discuss our next steps for hypoxia biomarkers using an RNA-seq study.

Effect of dietary date seed meal as an alternative carbohydrate source on immune-related gene expression of Pacific white shrimp Penaeus vannamei.

Current study aimed to examine the effect of dietary date seed meal (DSM) as an alternative carbohydrate ingredient on immune-related genes expression of Pacific white shrimp (Penaeus vannamei). A total number of 750 shrimp (4.0 ±â€¯0.1 g) were randomly assigned into five experimental treatments, each with three replicates. Experimental diets contained 0, 50, 100, 150 and 230 g/kg DSM substituted for both wheat and rice flour. Shrimp were fed at a rate of 5% body weight three times daily and the mRNA expression of α2-macroglobulin (α2-M), lipopolysaccharide and beta-1,3-glucan-binding protein (LGBP), integrin ß, and peroxinectin (PX) was studied on five shrimp per treatment after 8 weeks feeding trial. The results showed that replacement of DSM up to 100 g/kg in the diet of P. vannamei caused no significant changes in the expression of α2-M and integrin ß, however both of these genes showed lower expression in shrimp fed diets containing 150 and 230 g/kg DSM compared to control group. Moreover, no significant differences were observed in the expression of PX and LGBP between shrimp fed diets containing different amounts of DSM and control group. These findings demonstrated that as an inexpensive source of carbohydrate, DSM could be substituted up to 100 g/kg for wheat and rice flour in the diet of farmed shrimp without suppressive effects on the immune status.

Developing specific molecular biomarkers for thermal stress in salmonids.

BACKGROUND: Pacific salmon (Oncorhynchus spp.) serve as good biological indicators of the breadth of climate warming effects on fish because their anadromous life cycle exposes them to environmental challenges in both marine and freshwater environments. Our study sought to mine the extensive functional genomic studies in fishes to identify robust thermally-responsive biomarkers that could monitor molecular physiological signatures of chronic thermal stress in fish using non-lethal sampling of gill tissue. RESULTS: Candidate thermal stress biomarkers for gill tissue were identified using comparisons among microarray datasets produced in the Molecular Genetics Laboratory, Pacific Biological Station, Nanaimo, BC, six external, published microarray studies on chronic and acute temperature stress in salmon, and a comparison of significant genes across published studies in multiple fishes using deep literature mining. Eighty-two microarray features related to 39 unique gene IDs were selected as candidate chronic thermal stress biomarkers. Most of these genes were identified both in the meta-analysis of salmon microarray data and in the literature mining for thermal stress markers in salmonids and other fishes. Quantitative reverse transcription PCR (qRT-PCR) assays for 32 unique genes with good efficiencies across salmon species were developed, and their activity in response to thermally challenged sockeye salmon (O. nerka) and Chinook salmon (O. tshawytscha) (cool, 13-14 °C and warm temperatures 18-19 °C) over 5-7 days was assessed. Eight genes, including two transcripts of each SERPINH1 and HSP90AA1, FKBP10, MAP3K14, SFRS2, and EEF2 showed strong and robust chronic temperature stress response consistently in the discovery analysis and both sockeye and Chinook salmon validation studies. CONCLUSIONS: The results of both discovery analysis and gene expression showed that a panel of genes involved in chaperoning and protein rescue, oxidative stress, and protein biosynthesis were differentially activated in gill tissue of Pacific salmon in response to elevated temperatures. While individually, some of these biomarkers may also respond to other stressors or biological processes, when expressed in concert, we argue that a biomarker panel comprised of some or all of these genes could provide a reliable means to specifically detect thermal stress in field-caught salmon.

Effectiveness of trastuzumab as adjuvant therapy in patients with early stage breast cancer: A systematic review and meta-analysis.

Background: Trastuzumab in combination with chemotherapy has long been established as a standard treatment for HER2-positive patients in early stage breast cancer (BC). The present study aimed at assessing the effectiveness of trastuzumab adjuvant therapy in early stage BC in overall survival (OS) and disease-free survival (DFS). Methods: A systematic review and meta-analysis was performed to evaluate the effectiveness of trastuzumab adjuvant therapy. PubMed, Cochrane library, Scopus, Web of Science, and Embase databases were searched for relevant RCTs from the beginning to February 2017. Quality assessment of studies was conducted using the Cochrane Risk of Bias Tool. The desired outcomes were OS and DFS. Results: A total of 1818 articles were identified first, however, only 11 studies were eligible to be included in this study. Our findings and meta-analysis results revealed that trastuzumab is effective in increasing OS (OS hazard ratio: -0.286 ± 0.049, 95%CI (-0.381, - 0.191)) and improving DFS (DFS hazard ratio: -0.419± 0.077, 95%CI (-0.569, -0.269)). The most serious but negligible side effect of trastuzumab is congestive heart failure. Conclusion: Adding trastuzumab as adjuvant therapy in early stages of BC in HER2 positive patients could increase OS and DFS of the patients effectively.

Acclimation of killifish to thermal extremes of hot spring: Transcription of gonadal and liver heat shock genes.

In this study, we explored the hypothesis that killifish acclimate to thermal extremes through regulation of genes involved in stress and metabolism. We examined the liver and gonadal transcription of heat shock proteins (hsp70, hsp90a, hsp90b), glucokinase (gck), and high mobility group b1 (hmgb1) protein in wild killifish species from hot springs and rivers using quantitative real-time PCR. Moreover, we exposed a river killifish species to a long-term thermal regime of hot spring (37-40°C) and examined the liver transcription of the heat shock genes. Our results showed that hot spring killifish showed a significant, strong upregulation of liver hsp90a. Moreover, the testicular transcript levels of hsp90a, hsp90b, and hsp70 were higher in hot spring killifish than the river ones. The results of the common garden experiments showed that the transcripts of hsp70, hsp90b, and hmgb1 were mildly induced (> twofold) at the time when temperature reached to 37-40°C, while the transcripts of hsp90a were strongly induced (17-fold increase). The level of hsp90a was dramatically more upregulated when fish were maintained in thermal extreme (42-fold change higher than in ambient temperature). Moreover, a significant downregulation of gck transcripts was observed at the time when temperature was raised to 37-40°C (80-fold decrease) and during exposure to long-term thermal extreme (56-fold decrease). It can be concluded that the regulation of heat shock genes particularly hsp90a might be a key factor of the acclimation of fish to high temperature environments like hot springs.

Subjective Mental Workload and Its Correlation With Musculoskeletal Disorders in Bank Staff.

OBJECTIVE: The purpose of this study was to evaluate the rate of subjective mental workload (SMWL) and its correlation with musculoskeletal disorders among bank staff members in Kurdistan Province located in western Iran. METHODS: This cross-sectional study was conducted among 200 bank staff members in Kurdistan Province, Iran. The mental workload was assessed using the National Aeronautics and Space Administration-Task Load Index (NASA-TLX) computerized version. NASA-TLX is a multidimensional rating procedure that derives an overall workload score based on a weighted average of ratings on 6 subscales. These subscales include Mental Demands, Physical Demands, Temporal Demands, Performance, Effort, Effectiveness, and Frustration. The musculoskeletal disorders (MSDs) were documented with the Nordic Musculoskeletal Questionnaire and generic body diagram. RESULTS: Of the staff members, 78.5% experienced pain at least once during the past year in 1 of their 9 musculoskeletal body regions. The highest frequencies of pain were in the neck and lower back. The NASA-TLX estimated the Effort and Performance scales with mean ± SD of 72.8 ± 25.2 and 36 ± 22.6, respectively, as the maximal and minimal scores among the 6 subscales of SMWL. The statistical analysis of the data revealed that there was a significant correlation between the overall mental workload score and also among the 6 subscales of SMWL separately with MSDs (P < .05). CONCLUSION: SMWL appears to be a risk factor in the incidence of MSDs, so that the odds of MSDs increased by 11% with each additional 1-point increase in SMWL score.

Efficacy and safety of bamlanivimab in patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: Monoclonal antibodies (mAbs) have shown clinical benefits against coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several studies have reported the use of bamlanivimab as a promising treatment option for COVID-19. AIM: To synthesize the latest evidence for the efficacy and safety of bamlanivimab alone in the treatment of adult patients with COVID-19. METHODS: A literature search was conducted in PubMed, Cochrane Library, Web of Science, medRxiv, and Google Scholar using "SARS-CoV-2", "COVID-19", "LY-CoV555", and "Bamlanivimab" keywords up to January 25, 2023. The quality of included studies was assessed using the Cochrane bias tools. The Comprehensive Meta-Analysis software version 3.0 was used to analyze the data. RESULTS: A total of 30 studies involving 47368 patients were included. A significant difference was observed between the bamlanivimab and standard of care/placebo groups in terms of mortality rate [risk ratio (RR) = 50, 95% confidence interval (CI): 0.36-0.70], hospitalization rate (RR = 0.51; 95%CI: 0.39-0.68), and emergency department (ED) visits (RR = 0.69; 95%CI: 0.47-0.99); while the two groups exhibited no significant difference in terms of intensive care unit (ICU) admission (P > 0.05). Compared to other mAbs, bamlanivimab was associated with a higher rate of hospitalization (RR = 1.44; 95%CI: 1.07-1.94). However, no significant difference was detected between the bamlanivimab and other mAbs groups in terms of mortality rate, ICU admission, and ED (P > 0.05). The incidence of any adverse events was similar between the bamlanivimab and control groups (P > 0.05). CONCLUSION: Although the results suggest the efficacy and safety of bamlanivimab in COVID-19 patients, further research is required to confirm the efficacy of this drug for the current circulating SARS-CoV-2 variants.

Developmental transcription of genes putatively associated with growth in two sturgeon species of different growth rate.

In the present study, we surveyed developmental changes in the transcription of growth hormone (gh), insulin-like growth factor-I (igf-I), ghrelin (ghrl) and vascular endothelial growth factor (vegf) genes in the largest freshwater fish, European sturgeon (Beluga, Huso huso) and compared the same parameters to that of its phylogenically close moderate-sized species, Persian sturgeon (Acipenser persicus). The transcripts of gh, igf-I, ghrl and vegf were detected at all developmental time-points of Persian sturgeon and Beluga from embryos to juvenile fish. Changes in normalized gh, igf-I, ghrl and vegf transcription by using the geometric average of genes encoding ribosomal protein L6 (RPL6) and elongation factor (EF1A) over the time of development of Persian sturgeon and Beluga were statistically significant (P<0.05). Our results showed that the mRNA expression levels of both igf-I and ghrl were low during early larval development and then increased significantly to the late larval time-points when larvae started exogenous feeding. In both Beluga and Persian sturgeon, after a low mRNA expression during the embryonic stage, the transcript levels of vegf displayed an increasing trend during yolk-sac fry, consistent with organogenesis. The vegf level remained constantly high in the time of exogenous feeding. The highest detection of gh transcripts coincided with the end of the embryonic stage (hatching time) in Persian sturgeon and 3 days-post-hatching (dph) in Beluga. In Persian sturgeon, the gh transcript started to decrease to the rest of the developmental time-points, whereas in Beluga gh transcript had a marked second increase from the time of exogenous feeding (20-dph). This Beluga specific increase in gh transcription may be associated with the marked growth rate and extraordinary size of this fish species.

Site-specific gene knock-in and bacterial phytase gene expression in Chlamydomonas reinhardtii via Cas9 RNP-mediated HDR.

In the present study, we applied the HDR (homology-directed DNA repair) CRISPR-Cas9-mediated knock-in system to accurately insert an optimized foreign bacterial phytase gene at a specific site of the nitrate reductase (NR) gene (exon 2) to achieve homologous recombination with the stability of the transgene and reduce insertion site effects or gene silencing. To this end, we successfully knocked-in the targeted NR gene of Chlamydomonas reinhardtii using the bacterial phytase gene cassette through direct delivery of the CRISPR/Cas9 system as the ribonucleoprotein (RNP) complex consisting of Cas9 protein and the specific single guide RNAs (sgRNAs). The NR insertion site editing was confirmed by PCR and sequencing of the transgene positive clones. Moreover, 24 clones with correct editing were obtained, where the phytase gene cassette was located in exon 2 of the NR gene, and the editing efficiency was determined to be 14.81%. Additionally, site-specific gene expression was analyzed and confirmed using RT-qPCR. Cultivation of the positive knocked-in colonies on the selective media during 10 generations indicated the stability of the correct editing without gene silencing or negative insertion site effects. Our results demonstrated that CRISPR-Cas9-mediated knock-in could be applied for nuclear expression of the heterologous gene of interest, and also confirmed its efficacy as an effective tool for site-specific gene knock-in, avoiding nuclear positional effects and gene silencing in C. reinhardtii. These findings could also provide a new perspective on the advantageous application of RNP-CRISPR/Cas9 gene-editing to accelerate the commercial production of complex recombinant proteins in the food-grade organism "C. reinhardtii".

Sex and reproductive development impact skin mucosal epithelium immunity, antimicrobial capacity, and up-regulation of immune-related gene of goldfish (Carassius auratus).

This study evaluated the epidermis mucosal capacity of goldfish (Carassius auratus) during different stages of reproductive development in both females and males. In this regard, the activity of mucolytic immune enzymes, i.e., lysozyme, complement and peroxidase, as well as the activity of alkaline phosphatase (ALP) were evaluated. There were five stages for females i.e., immature (f1), cortical alveoli (f2), early and late-vitellogenesis (vtg) (f3 and f4) and ripe (f5); as well as two stages for males spermatogenesis (m1) and spermiation (m2). Some stages were also examined for the mucosal antimicrobial activity against specific pathogens. The results showed that the mucosal lysozyme activity increased significantly during vitellogenesis (P < 0.05), but no lysozyme activity was detected in plasma. On the contrary, the complement activity was only observed in female plasma, and it was significantly higher at f3 compared to the other developmental stages. Both the plasma and mucosal ALP and peroxidase activities showed a significant increase by female reproductive development with the highest amounts at f4. Contrary to the female, no significant changes were observed in plasma and mucosal immune agents and biochemistry of the male. The f5-staged goldfish showed the highest antimicrobial activities against Gram-positive bacteria, i.e., Streptococcus faecium, Staphylococcus aureus and Micrococcus luteus (P < 0.05). Our results also represented the up-regulation of lysozyme (c-lys) gene expression by effects of female maturational development in ovary, liver and skin, while male goldfish showed no significant changes in c-lys expression. Moreover, there were positive correlations between c-lys expression, mucosal lysozyme activity and calcium levels in females (P < 0.01). Overall, our findings revealed that vtg process improves mucosal innate immunity that leads to activate antimicrobial components at spawning season.

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.].

Artesunate, imatinib, and infliximab in COVID-19: A rapid review and meta-analysis of current evidence.

BACKGROUND AND OBJECTIVE: Despite the pervasive vaccination program against coronavirus disease 2019 (COVID-19), fully vaccinated people are still being infected by severe acute respiratory syndrome coronavirus 2, making an effective and safe therapeutic intervention a crucial need for the patients' survival. The purpose of the present study is to seek available evidence for the efficacy and safety of three promising medications artesunate, imatinib, and infliximab against COVID-19. METHODS: A literature search was conducted in PubMed, Cochrane Library, medRxive, and Google Scholar up to January 2022. Furthermore, the clinical trial databases were screened to find more citations. The Cochrane Collaboration tool and Newcastle-Ottawa scale were used to assess the included studies. Meta-analysis was performed using RevMan 5.4.1. RESULTS: Five published studies were identified as eligible. Meta-analysis showed that there was no significant difference between the infliximab and control groups in terms of mortality rate (risk ratio [RR]: 0.65; 95% confidence interval [CI]: 0.40-1.07; p = 0.09). However, a significant difference was observed between the two groups for the hospital discharge (RR: 1.37; 95% CI: 1.04-1.80; p = 0.03). No remarkable clinical benefit was observed in favor of using imatinib for COVID-19 patients. Artesunate showed significant improvement in patients with COVID-19. CONCLUSION: In the present, limited evidence exists for the efficacy and safety of artesunate, imatinib, and infliximab in patients with COVID-19. The findings of WHO's Solidarity international trial will provide further information regarding these therapeutic interventions.

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.

Endangered Cultus Lake sockeye salmon exhibit genomic evidence of hypoxic and thermal stresses while rearing in degrading freshwater lacustrine critical habitat.

Water quality degradation due to lake eutrophication and climate change contributes to the risk of extirpation for the endangered Cultus Lake sockeye salmon. Sockeye salmon juveniles experience both low-oxygen water in profundal lake habitats and elevated temperatures above the thermocline during diel vertical migrations in summer and fall when the lake is thermally stratified. We used a transcriptomic tool (Salmon Fit-Chip) to determine whether salmon were experiencing thermal and/or hypoxic stress during this period. The results showed that over one-third of the fish were responding to either hypoxic (35.5%) or thermal stress (40.9%) during periods when these environmental stressors were pronounced within the lake, but not during periods when profundal dissolved oxygen was elevated and the water column was isothermal and cool. The most consistent signs of hypoxic stress occurred during July (52.2%) and September (44.4%). A total of 25.7% of individual fish sampled during months when both stressors were occurring (July, September, October) showed signatures of both stressors. When a combination of hypoxic and thermal stress biomarkers was applied, 92% of fish showed evidence of one or both stressors; hence, for at least several months of the year, most sockeye salmon juveniles in Cultus Lake are experiencing anthropogenically environmentally induced stress. We also detected the presence of pathogenic ciliate Ichthyoptherius multifiliis in the gill tissue of juveniles, with a higher infection signal in Cultus Lake compared to juveniles from nearby Chilliwack Lake. These data provide powerful new evidence that Cultus Lake sockeye salmon, which experience relatively lower juvenile survival than Chilliwack sockeye salmon, are more compromised by stress and carry a higher level of infection of at least one pathogenic agent. Thus, we hypothesize that the cumulative or synergistic interplay between stressors and diseases, clearly documented to be occurring within Cultus Lake, are contributing to increased mortality of endangered sockeye salmon.

Microplastic ingestion in important commercial fish in the southern Caspian Sea.

The ubiquitous distribution of microplastics (MPs) across marine habitats has led to an increased investigation of their potential impacts on the marine food chain and consequent human exposure. The two fish species Chelon aurata and Rutilus kutum that account for over 50% of the total catch in the Caspian Sea were assessed relative to the presence of MPs in their digestive system. Samples were collected from 6 stations in the southern Caspian Sea from February to March 2017. MPs were reported to be present in 67.56% of the 111 individuals analyzed, with an average concentration of 2.29 MP/Fish; the majority were fibers (≈50%) and fragments (≈30%). The baseline data have become more relevant since the population in the region has consumed the whole fish. The presence and prevalence of MP in the two commercially important fish in the Caspian Sea warranted a comprehensive assessment in the water column, marine sediments, and fish from the different trophic levels as over 130 rivers drain into the water body.

Seasonal changes of hydrolytic enzyme activities in the skin mucus of rainbow trout, Oncorhynchus mykiss at different body sizes.

The innate immune factors in the skin mucus of fish are affected by the ecological and physiological conditions such as developmental stage and seasonal cycle. The aim of this study was to investigate the seasonal changes in soluble protein and the hydrolytic enzyme activities of the skin mucus of rainbow trout including lysozyme, alkaline phosphatase (ALP) and proteases at different body sizes. Skin mucus samples were collected over three consecutive season periods including winter, spring and late summer. In each season, sampling was performed separately from three different weight groups including 2-20 g (W1), 100-200 g (W2) and 400-600 g (W3) fish. Our results showed a significant increase of soluble protein in all three weight groups from winter to spring when water temperature elevated from 9 °C to 14 °C. Moreover lysozyme activity was remarkably elevated in W1 fish from winter to late summer. In all three seasons, the activity of lysozyme was significantly decreased along with increasing the fish size. Contrary to lysozyme, the activity of proteases and ALP showed a decreasing trend from winter to late summer. A significant positive correlation was found between the proteases and ALP activity, proposing that both proteases and ALP might have important synergic roles in the mucosal innate immune function of rainbow trout. Moreover, using reverse transcription PCR (RT-PCR) analysis of some proteases genes including cathepsin-L and cathepsin-D, we demonstrated that the proteases are transcribed and likely synthesized in epidermal mucus cells of rainbow trout. The present study confirmed seasonal changes of hydrolytic enzyme activities in the skin mucus of rainbow trout across all three weight groups, with the highest variation in juvenile fish.

Pregabalin and gabapentin in neuropathic pain management after spinal cord injury: a systematic review and meta-analysis.

Neuropathic pain after spinal cord injury (SCI) has a significant negative impact on the patients' quality of life. The objective of this systematic review is to examine the safety and efficacy of pregabalin (PGB) and gabapentin (GBP) in the treatment of neuropathic pain due to SCI. PubMed, the Cochrane Library, Embase, Scopus, and the Web of Science were searched up to December 2018. The reference lists of key and review studies were reviewed for additional citations. The quality of the studies was evaluated using the Cochrane Collaboration's tools for assessing the risk of bias. A meta-analysis was performed for primary and secondary outcomes. Eight studies were eligible for inclusion. Meta-analysis of PGB vs. placebo showed that PGB was effective for neuropathic pain (standardized mean difference [SMD] = -0.40; 95% confidence interval [CI]: -0.78, -0.01), anxiety (MD = -0.68; 95% CI: -0.77, -0.59), depression (mean difference [MD] = -0.99; 95% CI: -1.08, -0.89), and sleep interference (MD = -1.08; 95% CI: -1.13, -1.02). Also, GBP was more effective than a placebo for reducing pain. No significant difference was observed between the efficacy of the two drugs (MD = -0.37; 95% CI: -1.67, 0.93). There was no significant difference between the two drugs for discontinuation due to adverse events (risk ratio = 3.00; 95% CI: 0.81, 11.15). PGB and GBP were effective vs. placebos in decreasing neuropathic pain after SCI. Also, there was no significant difference between the two drugs for decreasing pain and adverse events.

Identification of Hypoxia-Specific Biomarkers in Salmonids Using RNA-Sequencing and Validation Using High-Throughput qPCR.

Identifying early gene expression responses to hypoxia (i.e., low dissolved oxygen) as a tool to assess the degree of exposure to this stressor is crucial for salmonids, because they are increasingly exposed to hypoxic stress due to anthropogenic habitat change, e.g., global warming, excessive nutrient loading, and persistent algal blooms. Our goal was to discover and validate gill gene expression biomarkers specific to the hypoxia response in salmonids across multi-stressor conditions. Gill tissue was collected from 24 freshwater juvenile Chinook salmon (Oncorhynchus tshawytscha), held in normoxia [dissolved oxygen (DO) > 8 mg L-1] and hypoxia (DO = 4‒5 mg L-1) in 10 and 18° temperatures for up to six days. RNA-sequencing (RNA-seq) was then used to discover 240 differentially expressed genes between hypoxic and normoxic conditions, but not affected by temperature. The most significantly differentially expressed genes had functional roles in the cell cycle and suppression of cell proliferation associated with hypoxic conditions. The most significant genes (n = 30) were selected for real-time qPCR assay development. These assays demonstrated a strong correlation (r = 0.88; P < 0.001) between the expression values from RNA-seq and the fold changes from qPCR. Further, qPCR of the 30 candidate hypoxia biomarkers was applied to an additional 322 Chinook salmon exposed to hypoxic and normoxic conditions to reveal the top biomarkers to define hypoxic stress. Multivariate analyses revealed that smolt stage, water salinity, and morbidity status were relevant factors to consider with the expression of these genes in relation to hypoxic stress. These hypoxia candidate genes will be put into application screening Chinook salmon to determine the identity of stressors impacting the fish.