Effect of Fermentation Parameters for the Mass Cultivation of Trichoderma viride via Submerged and Solid-State Fermentation Studies On Cellulase Production

The present investigation was carried out to evaluate different fermentation parameters and to optimize the fermentation parameters to cultivate Trichoderma viride (T. viride) via submerged and solid-state fermentations. The different parameters such as, effect of pH, temperature, inoculum size, media volume, incubation period and different nitrogen sources.  The highest growth yield noticed was 14.221g L-1 at 15 g L-1, 0.15 g L-1, 40 oC, 2.0, 7.0 and 200 carbon, nitrogen, temperature, volume of the medium, pH, RPM respectively. Following, 12.187 g L-1 yield of T. viride was achieved with 15 g L-1, 0.15 g L-1, 40 oC, 2.0, 7.0, 200 carbon, nitrogen, temperature, volume of the medium, pH, RPM respectively. the effect of different incubation period on the cellulase activity was ranged from 0.76U/mL/min to 3.02 U/mL/min. The effect of different incubation period on the cellulase activity was ranged from 0.63 U/mL/min to 2.88 U/mL/min. The effect of different pH on the cellulase activity was ranged from 0.436 U/mL/min to 2.481 U/mL/min. the highest cellulase activity was noticed at pH 5.5 with 2.481 Nitrogen sources, five (5) namely, NH4Cl, NH4, CH3COO, (NH4)2SO4, NH4H2PO4, NH4NO3 are identified as significant sources for cultivation of T. viride and subsequent production and activity of cellulase.  In accordance to results obtained, the inoculum size of 4mL found significant with 2.321 U/mL/min Out of Seven (7), three (3) media volumes such as 30mL, 40mL, and 50mL produced highest cellulase production with 2.964 U/mL/min, 2.331 U/mL/min

Determination of Nitrogen (N), Phosphorous (P), Potassium (K), pH and Electrical Conductivity of Jeevamrutham Samples Collected from Different Places of Telangana and Andhra Pradesh

This investigation was carried out to investigate the nitrogen, phosphorous, potassium levels of the jeevamrutham samples collected from different regions of the Telangana and Andhra Pradesh. In continuation, the collected samples are also evaluated for pH and Electrical Conductivity. Estimation of nitrogen was conducted by the Kjeldahl method. For acid soils, the Bray's method is used to measure the amount of accessible phosphorus, whereas the Olsen's method is used for neutral, alkaline, and calcareous soils. Determination of potassium was carried out using ammonium acetate at pH 7. The nitrogen percentage of the samples collected from Telangana and Andhra Pradesh was ranged from 3.0% to 5.8% and 3.5% to 6.5% respectively. The results revealed that the samples collected from Andhra Pradesh was found to exhibit highest nitrogen percentage comparing to the nitrogen percentage of the samples collected from Telangana. The concentration of phosphorus in the samples collected from Telengana is ranged from 77 ppm to 256 ppm. Whereas the concentration of phosphorus in the samples collected from Andhra Pradesh is ranged from 132 ppm to 312 ppm. The potassium levels were ranged from 66 ppm to 84 ppm and 63 ppm to 81 ppm of the samples collected from Telangana and Andhra Pradesh respectively. The pH 5.4 to 6.7 and 5.6 to 6.3 are ranged from the samples collected from Telangana and Andhra Pradesh respectively. The EC 0.19 ds m- to 0.25 ds m- and 0.21 ds m- to 0.28 ds m- are ranged from the samples collected from Telangana and Andhra Pradesh respectively. In conclusion, all collected samples contain the sufficient concentrations of Nitrogen, Phosphorous and Potassium levels in the collected jeevamrutham samples from Telangana and Andhra Pradesh. Moreover, the values of pH and EC of the samples tested found good

Longitudinal Monitoring of Lactate in Hospitalized and Ambulatory COVID-19 Patients.

Hypoxemia is readily detectable by assessing SpO2 levels, and these are important in optimizing COVID-19 patient management. Hyperlactatemia is a marker of tissue hypoxia, particularly in patients with increased oxygen requirement and microvascular obstruction. We monitored peripheral venous lactate concentrations in hospitalized patients with moderate to severe COVID-19 (n = 18) and in mild ambulatory COVID-19 patients in home quarantine (n = 16). Whole blood lactate decreased significantly during the clinical course and recovery in hospitalized patients (P = 0.008). The blood lactate levels were significantly higher in hospitalized patients than ambulatory patients (day 1: hospitalized versus ambulatory patients P = 0.002; day 28: hospitalized versus ambulatory patients P = < 0.0001). Elevated lactate levels may be helpful in risk stratification, and serial monitoring of lactate may prove useful in the care of hospitalized COVID-19 patients

Host genetic factors determining COVID-19 susceptibility and severity.

The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) poses an unprecedented challenge to humanity. SARS-CoV-2 infections range from asymptomatic to severe courses of COVID-19 with acute respiratory distress syndrome (ARDS), multiorgan involvement and death. Risk factors for disease severity include older age, male sex, increased BMI and pre-existing comorbidities. Ethnicity is also relevant to COVID-19 susceptibility and severity. Host genetic predisposition to COVID-19 is now increasingly recognized and whole genome and candidate gene association studies regarding COVID-19 susceptibility have been performed. Several common and rare variants in genes related to inflammation or immune responses have been identified. We summarize research on COVID-19 host genetics and compile genetic variants associated with susceptibility to COVID-19 and disease severity. We discuss candidate genes that should be investigated further to understand such associations and provide insights relevant to pathogenesis, risk classification, therapy response, precision medicine, and drug repurposing

Comprehensive characterization of molecular interactions based on nanomechanics

Molecular interaction is a key concept in our understanding of the biological mechanisms of life. Two physical properties change when one molecular partner binds to another. Firstly, the masses combine and secondly, the structure of at least one binding partner is altered, mechanically transducing the binding into subsequent biological reactions. Here we present a nanomechanical micro-array technique for bio-medical research, which not only monitors the binding of effector molecules to their target but also the subsequent effect on a biological system in vitro. This label-free and real-time method directly and simultaneously tracks mass and nanomechanical changes at the sensor interface using micro-cantilever technology. To prove the concept we measured lipid vesicle (approximately 748*10(6) Da) adsorption on the sensor interface followed by subsequent binding of the bee venom peptide melittin (2840 Da) to the vesicles. The results show the high dynamic range of the instrument and that measuring the mass and structural changes simultaneously allow a comprehensive discussion of molecular interactions

Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study.

BACKGROUND: The recombinant vesicular stomatitis virus (rVSV) vaccine expressing the Zaire Ebola virus (ZEBOV) glycoprotein is efficacious in the weeks following single-dose injection, but duration of immunity is unknown. We aimed to assess antibody persistence at 1 and 2 years in volunteers who received single-dose rVSV-ZEBOV in three previous trials. METHODS: In this observational cohort study, we prospectively followed-up participants from the African and European phase 1 rVSV-ZEBOV trials, who were vaccinated once in 2014-15 with 300 000 (low dose) or 10-50 million (high dose) plaque-forming units (pfu) of rVSV-ZEBOV vaccine to assess ZEBOV glycoprotein (IgG) antibody persistence. The primary outcome was ZEBOV glycoprotein-specific IgG geometric mean concentrations (GMCs) measured yearly by ELISA compared with 1 month (ie, 28 days) after immunisation. We report GMCs up to 2 years (Geneva, Switzerland, including neutralising antibodies up to 6 months) and 1 year (Lambaréné, Gabon; Kilifi, Kenya) after vaccination and factors associated with higher antibody persistence beyond 6 months, according to multivariable analyses. Trials and the observational study were registered at ClinicalTrials.gov (Geneva: NCT02287480 and NCT02933931; Kilifi: NCT02296983) and the Pan-African Clinical Trials Registry (Lambaréné PACTR201411000919191). FINDINGS: Of 217 vaccinees from the original studies (102 from the Geneva study, 75 from the Lambaréné study, and 40 from the Kilifi study), 197 returned and provided samples at 1 year (95 from the Geneva study, 63 from the Lambaréné, and 39 from the Kilifi study) and 90 at 2 years (all from the Geneva study). In the Geneva group, 44 (100%) of 44 participants who had been given a high dose (ie, 10-50 million pfu) of vaccine and who were seropositive at day 28 remained seropositive at 2 years, whereas 33 (89%) of 37 who had been given the low dose (ie, 300 000 pfu) remained seropositive for 2 years (p=0·042). In participants who had received a high dose, ZEBOV glycoprotein IgG GMCs decreased significantly between their peak (at 1-3 months) and month 6 after vaccination in Geneva (p0·05). Neutralising antibodies seem to be less durable, with seropositivity dropping from 64-71% at 28 days to 27-31% at 6 months in participants from the Geneva study. INTERPRETATION: Antibody responses to single-dose rVSV-ZEBOV vaccination are sustained across dose ranges and settings, a key criterion in countries where booster vaccinations would be impractical. FUNDING: The Wellcome Trust and Innovative Medicines Initiative 2 Joint Undertaking

Pharmacogene sequencing of a Gabonese population with severe Plasmodium falciparum malaria reveals multiple novel variants with putative relevance for antimalarial treatment.

Malaria remains one of the most deadly diseases in Africa, particularly for children. While successful in reducing morbidity and mortality, antimalarial treatments are also a major cause of adverse drug reactions (ADRs). Host genetic variation in genes involved in drug disposition or toxicity constitutes an important determinant of ADR risk and can prime for parasite drug resistance. Importantly however, the genetic diversity in Africa is substantial and thus genetic profiles in one population cannot be reliably extrapolated to other ethnogeographic groups. Gabon is considered a high-transmission country with more than 460,000 malaria cases per year. Yet, the pharmacogenetic landscape of the Gabonese population or its neighboring countries has not been analyzed. Using targeted sequencing, we here profiled 21 pharmacogenes with importance for antimalarial treatment in 48 Gabonese pediatric patients with severe Plasmodium falciparum malaria. Overall, we identified 347 genetic variants of which 18 were novel and each individual was found to carry 87.3±9.2 SD variants across all analyzed genes. Importantly, 16.7% of these variants were population-specific, highlighting the need for high-resolution pharmacogenomic profiling. Between one in three and one in six individuals harbored reduced activity alleles of CYP2A6, CYP2B6, CYP2D6 and CYP2C8 with important implications for artemisinin, chloroquine and amodiaquine therapy. Furthermore, one in three patients harbored at least one G6PD deficient allele, suggesting considerably increased risk of hemolytic anemia upon exposure to aminoquinolines. Combined, our results reveal the unique genetic landscape of the Gabonese population and pinpoint the genetic basis for inter-individual differences in antimalarial drug response and toxicity

A systematic review of interactive multimedia interventions to promote children's communication with health professionals: implications for communicating with overweight children

Background: Interactive multimedia is an emerging technology that is being used to facilitate interactions between patients and health professionals. The purpose of this review was to identify and evaluate the impact of multimedia interventions (MIs), delivered in the context of paediatric healthcare, in order to inform the development of a MI to promote the communication of dietetic messages with overweight preadolescent children. Of particular interest were the effects of these MIs on child engagement and participation in treatment, and the subsequent effect on health-related treatment outcomes. Methods: An extensive search of 12 bibliographic databases was conducted in April 2012. Studies were included if: one or more child-participant was 7 to 11 years-of-age; a MI was used to improve health-related behaviour; child-participants were diagnosed with a health condition and were receiving treatment for that condition at the time of the study. Data describing study characteristics and intervention effects on communication, satisfaction, knowledge acquisition, changes in self-efficacy, healthcare utilisation, and health outcomes were extracted and summarised using qualitative and quantitative methods. Results: A total of 14 controlled trials, published between 1997 and 2006 met the selection criteria. Several MIs had the capacity to facilitate engagement between the child and a clinician, but only one sought to utilise the MI to improve communication between the child and health professional. In spite of concerns over the quality of some studies and small study populations, MIs were found useful in educating children about their health, and they demonstrated potential to improve children’s health- related self-efficacy, which could make them more able partners in face-to-face communications with health professionals. Conclusions: The findings of this review suggest that MIs have the capacity to support preadolescent child-clinician communication, but further research in this field is needed. Particular attention should be given to designing appropriate MIs that are clinically relevant

Molecular markers of anti-malarial drug resistance in Central, West and East African children with severe malaria.

BACKGROUND: The Plasmodium falciparum multidrug resistance 1 (PfMDR1), P. falciparum Ca(2+)-ATPase (PfATP6) and Kelch-13 propeller domain (PfK13) loci are molecular markers of parasite susceptibility to anti-malarial drugs. Their frequency distributions were determined in the isolates collected from children with severe malaria originating from three African countries. METHODS: Samples from 287 children with severe malaria [(Gabon: n = 114); (Ghana: n = 89); (Kenya: n = 84)] were genotyped for pfmdr1, pfatp6 and pfk13 loci by DNA sequencing and assessing pfmdr1 copy number variation (CNV) by real-time PCR. RESULTS: Pfmdr1-N86Y mutation was detected in 48, 10 and 10% in Lambaréné, Kumasi and Kisumu, respectively. At codon 184, the prevalence of the mutation was 73% in Lambaréné, 63% in Kumasi and 49% Kisumu. The S1034C and N1042D variants were absent at all three sites, while the frequency of the D1246Y mutation was 1, 3 and 13% in Lambaréné, Kumasi and Kisumu, respectively. Isolates with two pfmdr1 gene copy number predominantly harboured the N86Y wild-type allele and were mostly found in Kumasi (10%) (P < 0.0001). Among the main pfmdr1 haplotypes (NFD, NYD and YFD), NYD was associated with highest parasitaemia (P = 0.04). At the pfatp6 locus, H243Y and A623E mutations were observed at very low frequency at all three sites. The prevalence of the pfatp6 E431K variant was 6, 18 and 17% in Lambaréné, Kumasi and Kisumu, respectively. The L263E and S769N mutations were absent in all isolates. The pfk13 variants associated with artemisinin resistance in Southeast Asia were not observed. Eleven novel substitutions in the pfk13 locus occurring at low frequency were observed. CONCLUSIONS: Artemisinins are still highly efficacious in large malaria-endemic regions though declining efficacy has occurred in Southeast Asia. The return of chloroquine-sensitive strains following the removal of drug pressure is observed. However, selection of wild-type alleles in the multidrug-resistance gene and the increased gene copy number is associated with reduced lumefantrine sensitivity. This study indicates a need to constantly monitor drug resistance to artemisinin in field isolates from malaria-endemic countries

A call to caution when hydroxychloroquine is given to elderly COVID-19 patients.

INTRODUCTION: Hydroxychloroquine use in COVID-19 patients was widespread and uncontrolled until recently. Patients vulnerable to severe COVID-19 are at risk for hydroxychloroquine interactions with comorbidities and co-medications contributing to detrimental, including fatal adverse treatment effects. METHODS: This is a retrospective survey of health conditions and co-medications of COVID-19 patients who were pre-screened for enrolment into a randomized, double-blind, placebo-controlled hydroxychloroquine multicenter trial. RESULTS: Our survey involved 305 patients (median age 71 (IQR: 59-81) years). The majority of patients (N = 279, 92%) considered for inclusion into the clinical trial were not eligible mainly due to safety concerns caused by health conditions or co-medications. Most common were QT prolonging drugs (N = 188, 62%) and hematologic/hemato-oncologic diseases (N = 39, 13%) which prohibited the administration of hydroxychloroquine in our clinical trial. Additionally, 165 (54%) patients had health conditions and 167 (55%) were on co-medications that did not prohibit hydroxychloroquine treatment but had a risk of adverse interactions with hydroxychloroquine. Most common were diabetes (N = 86, 28%), renal insufficiency (N = 69, 23%) and heart failure (N = 58, 19%). CONCLUSION: The majority of hospitalized COVID-19 patients had health conditions or took co-medications precluding safe treatment with hydroxychloroquine. Therefore, especially in elderly, hydroxychloroquine should be administered with extreme caution and only in clinical trials