Decoration of phytochemicals contributes to the majority of metabolic diversity in nature, whereas how this process alters the biological functions of their precursor molecules remains to be ...investigated. Flavones, an important yet overlooked subclass of flavonoids, are most commonly conjugated with sugar moieties by UDP-dependent glycosyltransferases (UGTs). Here, we report that the natural variation of rice flavones is mainly determined by OsUGT706D1 (flavone 7-O-glucosyltransferase) and OsUGT707A2 (flavone 5-O-glucosyltransferase). UV-B exposure and transgenic evaluation demonstrate that their allelic variation contributes to UV-B tolerance in nature. Biochemical characterization of over 40 flavonoid UGTs reveals their differential evolution in angiosperms. These combined data provide biochemical insight and genetic regulation into flavone biosynthesis and additionally suggest that adoption of the positive alleles of these genes into breeding programs will likely represent a potential strategy aimed at producing stress-tolerant plants.
The purpose of this study is to examine the relationship between renewable energy sources and sustainable economic growth of the South Asian Association for Regional Cooperation (SAARC) countries. ...This study uses three main renewable energy sources such as geothermal, hydro and wind. This study collects dataset from SAARC countries from 1995 to 2018. This study applies a fixed-effect test and panel vector error correction model (PVECM) test for data analysis. The overall results show that all three renewable energy sources have positively significant impacts on economic development among SAARC countries’ economies. Moreover, the hydropower renewable energy source has more effects and influences on economic growth as relatively compared with the rest of the two individual sources of renewable energy.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Hepatic diseases are one of the chief reasons for worldwide morbidity and mortality. The increased incidence in Asian countries is driving researchers to explore preventive ways from nature. It is ...more practical to go with healthy routine edibles like vegetable oils to avoid environmental and chemical hepatic injuries. With the use of thermally oxidized oils overproduction of reactive oxygen species (ROS) with overwhelmed cellular antioxidants defense system results in oxidative stress, the known cause of cardiovascular diseases (CVDs), cancers and neurodegenerative disorders. Little is investigated about the effect of daily used oxidized cooking oils on hepatic function changes with oxidative stress especially in the animal model that mimics the human situation.
In this study, healthy adult male rabbits of local strain were divided into 4 groups (n = 12). First, two sets of rabbits were treated with 1 and 2 ml/kg/day of repeatedly heated mix vegetable oils (RHMVO) respectively. The third set of rabbits was given 1 ml/kg/day of single time heated mix vegetable oils (STHMVO) and the fourth set of rabbits served as controls and fed with normal rabbit diet to for 16 weeks. Serum liver function markers including total-protein, albumin, serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) and alkaline phosphatase (ALP) along with the activity of hepatic antioxidant-enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) for lipid peroxidation were compared among different groups of rabbits. Histopathological examination was performed for all four groups.
Significantly (p < 0.05) elevated hepatic enzymes and MDA levels, with lower total protein, serum albumin, GPx, SOD and CAT levels were found in high and low doses RHMVO treated groups, in comparison to control. In the STHMVO group, all mentioned markers were insignificantly changed. Accumulation of liver fat in low and high dose oil-treated groups was further confirmed under the microscopic examination of liver tissues, presented significant fat accumulation in liver tissues, in addition, 40-60% increased oxidative stress compared to control, in a dose-dependent manner.
These results conclude that consumption of thermally oxidized mix vegetable oils for longer duration can impair the liver function and destroy its histological structure significantly through fat accumulation and oxidative stress both in high as well as low doses.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Infections with multidrug-resistant organisms (MDROs) such as Gram-negative bacteria have high morbidity and mortality with limited treatment options. Colistin, an antibiotic active against MDRO, was ...rarely used due to frequent adverse effects, but its use has now been recommended among adults. In this study, we determined the efficacy of colistin for the treatment of sepsis in neonates.
We conducted a retrospective record review of all neonates admitted to the neonatal intensive care unit of Aga Khan University Hospital, Karachi, Pakistan, between June 2015 and June 2018, who had sepsis and received colistin by intravenous, inhalation and/or intrathecal routes. Predictors of colistin efficacy, for neonatal survival and microbial clearance, were assessed using multiple logistic regression.
153 neonates received colistin; 120 had culture-proven sepsis; and 93 had MDR-GNB (84 colistin-sensitive). 111 (72.5%) neonates survived and were discharged from hospital; 82.6% had microbial clearance. Neonates with colistin-sensitive bacteria (adjusted OR (AOR)=3.2, 95% CI 2.8 to 4.0), and those in which colistin therapy started early (AOR=7.2, 95% CI 3.5 to 13.6) were more likely to survive. Neonates with increased gestational age (AOR=1.9, 95% CI 1.5 to 3.0), higher weight (AOR=5.4, 95% CI 3.3 to 11.8) and later onset of sepsis (AOR=4.3, 95% CI 2.0 to 9.0) had higher survival. Adverse events included nephrotoxicity in 5.2%; 13.7% developed seizures and 18.3% had electrolyte imbalance.
Colistin therapy was associated with survival among neonates suffering from MDR-GNB sepsis. The frequency of side effects was moderate.
Caffeine is available in an ampoule, used via parenteral and enteral routes in preterm neonates to treat apnea of prematurity (AOP) in neonates of gestational age greater than or equal to 35-40 ...weeks. A longer duration of therapy has a higher risk of medication non-adherence due to higher costs and inappropriate dosage forms. Pharmaceutically compounded oral caffeine (PCC) could be an appropriate alternate dosage form. The researchers aimed to determine the impact of PCC on medication-related factors influencing medication adherence (MA) and the frequency of hospital readmission with apnea (HRA) in preterm neonates. We conducted a single-center quasi-experimental study for this quality improvement project using PCC among the preterm neonates admitted in a tertiary care level-III NICU at the Aga Khan University Hospital Karachi, Pakistan, received caffeine therapy, and survived at discharge. The researchers compared pre-PCC data (April-December 2017) with post-PCC data (April-Dec 2018) each for nine months, with three months intervals (January-March 2018) of PCC formulation and implementation phase. The study was conducted according to the SQUIRE2.0 guidelines. The Data were collated on factors influencing MA, including the cost of therapy, medication refill rates, and parental complaints as primary outcome measures. The Risk factors of HRA were included as secondary outcomes. After PCC implementation cost of therapy was reduced significantly from Rs. 97000.0 (729.0 USD) to Rs. 24500.0 (185.0 USD) (p<0.001), significantly higher (p<0.001) number of patients completed remaining refills (77.6% pre-phase vs 97.5% post-phase). The number of parental complaints about cost, ampoule usage, medication drawing issue, wastage, inappropriate dosage form, and longer duration of therapy reduced significantly in post-phase. HRA reduced from 25% to 6.6% (p<0.001). Post-implementation of PCC (RR 0.14; 95% CI: 0.07-0.27) was a significant independent risk factor for reducing HRA using a multivariate analysis model. Longer duration of caffeine therapy after discharge (RR 1.05; 95% CI: 1.04-1.04), those who were born in multiple births (RR 1.15; 95% CI: 1.15-1.15), and those who had higher number of siblings were other significant independent risk factors for HRA. PCC dispensation in the appropriate dosage form at discharge effectively reduced cost, non-adherence to therapy, and risk of hospital readmissions. This neonatal clinical and compounding pharmacist-led model can be replicated in other resource-limiting setting.
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ObjectiveNutrition societies recommend using standardised parenteral nutrition (SPN) solutions. We designed evidence-based SPN formulations for neonates admitted to our neonatal intensive care unit ...(NICU) and evaluated their outcomes.DesignThis was a quality improvement initiative. Data were collected retrospectively before and after the intervention.SettingA tertiary-care level 3 NICU at the Aga Khan University in Karachi, Pakistan.PatientsAll NICU patients who received individualised PN (IPN) from December 2016 to August 2017 and SPN from October 2017 to June 2018.InterventionsA team of neonatologists and nutrition pharmacists collaborated to design two evidence-based SPN solutions for preterm neonates admitted to the NICU.Main outcome measuresWe recorded mean weight gain velocity from days 7 to 14 of life. The other outcomes were change in weight expressed as z-scores, metabolic abnormalities, PN-associated liver disease (PNALD), length of NICU stay and episodes of sepsis during hospital stay.ResultsNeonates on SPN had greater rate of change in weight compared with IPN (β=13.40, 95% CI: 12.02 to 14.79) and a smaller decrease in z-scores (p<0.001). Neonates in the SPN group had fewer hyperglycemic episodes (IPN: 37.5%, SPN: 6.2%) (p<0.001), electrolyte abnormalities (IPN: 56.3%, SPN: 21%) (p<0.001), PNALD (IPN: 52.5%, SPN: 18.5%) (p<0.001) and sepsis (IPN: 26%, SPN: 20%) (p<0.05). The median length of stay in NICU was 14.0 (IQR 12.0–21.0) for the IPN and 8.0 (IQR 5.0–13.0) days for the SPN group.ConclusionsWe found that SPN was associated with shorter NICU stay and greater weight gain. In-house preparation of SPN can be used to address the nutritional needs in resource-limited settings where commercially prepared SPN is not available.
BP in Dialysis: Results of a Pilot Study Miskulin, Dana C; Gassman, Jennifer; Schrader, Ronald ...
Journal of the American Society of Nephrology,
01/2018, Volume:
29, Issue:
1
Journal Article
Peer reviewed
Open access
The optimal BP target for patients receiving hemodialysis is unknown. We randomized 126 hypertensive patients on hemodialysis to a standardized predialysis systolic BP of 110-140 mmHg (intensive arm) ...or 155-165 mmHg (standard arm). The primary objectives were to assess feasibility and safety and inform the design of a full-scale trial. A secondary objective was to assess changes in left ventricular mass. Median follow-up was 365 days. In the standard arm, the 2-week moving average systolic BP did not change significantly during the intervention period, but in the intensive arm, systolic BP decreased from 160 mmHg at baseline to 143 mmHg at 4.5 months. From months 4-12, the mean separation in systolic BP between arms was 12.9 mmHg. Four deaths occurred in the intensive arm and one death occurred in the standard arm. The incidence rate ratios for the intensive compared with the standard arm (95% confidence intervals) were 1.18 (0.40 to 3.33), 1.61 (0.87 to 2.97), and 3.09 (0.96 to 8.78) for major adverse cardiovascular events, hospitalizations, and vascular access thrombosis, respectively. The intensive and standard arms had similar median changes (95% confidence intervals) in left ventricular mass of -0.84 (-17.1 to 10.0) g and 1.4 (-11.6 to 10.4) g, respectively. Although we identified a possible safety signal, the small size and short duration of the trial prevent definitive conclusions. Considering the high risk for major adverse cardiovascular events in patients receiving hemodialysis, a full-scale trial is needed to assess potential benefits of intensive hypertension control in this population.
Key message
Second generation
Bt
insecticidal toxin in comibination with
Allium sativum
leaf agglutinin gene has been successfully expressed in cotton to develop sustainable resistance against ...major chewing and sucking insects. The first evidence of using the Second-generation
Bt
gene in combination with
Allium sativum
plant lectin to develop sustainable resistance against chewing and sucking insects has been successfully addressed in the current study.
Excessive use of
Bt
δ-endotoxins in the field is delimiting its insecticidal potential. Second-generation
Bt
Vip3Aa could be the possible alternative because it does not share midgut receptor sites with any known cry proteins. Insecticidal potential of plant lectins against whitefly remains to be evaluated. In this study, codon-optimized synthetic
Bt
Vip3Aa gene under CaMV35S promoter and
Allium sativum
leaf agglutinin gene under phloem-specific promoter were transformed in a local cotton variety. Initial screening of putative transgenic cotton plants was done through amplification, histochemical staining and immunostrip assay. The mRNA expression of Vip3Aa gene was increased to be ninefold in transgenic cotton line L
6
P
3
than non-transgenic control while ASAL expression was found to be fivefold higher in transgenic line L
34
P
2
as compared to non-transgenic control. The maximum Vip3Aa concentration was observed in transgenic line L
6
P
3
. Two copy numbers in homozygous form at chromosome number 9 and one copy number in hemizygous form at chromosome number 10 was observed in transgenic line L
6
P
3
through fluorescent in situ hybridization. Significant variation was observed in transgenic cotton lines for morphological characteristics, whereas physiological parameters of plants and fiber characteristics (as assessed by scanning electron microscopic) remained comparable in transgenic and non-transgenic cotton lines. Leaf-detach bioassay showed that all the transgenic lines were significantly resistant to
Helicoverpa armigera
showing mortality rates between 78% and 100%. Similarly, up to 95% mortality of whiteflies was observed in transgenic cotton lines when compared with non-transgenic control lines.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Background
Therapeutic drug monitoring (TDM) of Vancomycin (VCM) is required to prevent inappropriate dosage-associated bacterial resistance, therapeutic failure, and toxicities in ...pediatrics. Anecdotal experience and studies show that many healthcare institutions confront barriers while implementing TDM services, this study aimed to assess a pharmacist-directed VCM–TDM service for optimizing patient care in our institution.
Materials and methods
Patients aged 1 month–18 years who received intravenous VCM were included in this quasi-experimental study. The pre-implementation phase (March–June 2018) consisted of retrospective assessment of pediatric patients, the interventional phase (July 2018 to February 2020) included educational programs and the post-implementation phase (March–June 2020) evaluated the participants based on pharmacist-directed VCM–TDM services as a collaborative-practice model including clinical and inpatient pharmacists to provide 24/7 TDM services. Outcomes of the study included the mean difference in the number of optimal (i) prescribed initial VCM doses (primary) (ii) dosage adjustments and (iii) VCM-sampling time (secondary). After ethical approval, data were collected retrospectively.
Results
A hundred patients were there in each phase. The number of cases who were correctly prescribed initial VCM doses was significantly higher in the post-implementation phase, mean difference of 0.22, 95% CI (0.142–0.0.358),
p
< 0.0001. Patients who had correct dosage adjustments in the post-implementation phase also had higher statistical significance, mean difference of 0.29, 95% CI (0.152–0.423),
p
< 0.05. More correct practices of VCM-levels timing were observed in the post-implementation phase, mean difference of 0.15, 95% CI (− 0.053–0.264),
p
= 0.079.
Conclusion
This study showed the significant role of pharmacist-directed TDM services to optimize the correct prescribing of initial VCM doses and dose adjustments.
Whitefly infestation of cotton crop imparts enormous damage to cotton yield by severely affecting plant health, vigour and transmitting Cotton Leaf Curl Virus (CLCuV). Genetic modification of cotton ...helps to overcome both the direct whitefly infestation as well as CLCuV based cotton yield losses. We have constitutively overexpressed asparaginase (ZmASN) gene in Gossypium hirsutum to overcome the cotton yield losses imparted by whitefly infestation. We achieved 2.54% transformation efficiency in CIM-482 by Agrobacterium-mediated shoot apex transformation method. The relative qRT-PCR revealed 40-fold higher transcripts of asparaginase in transgenic cotton line vs. non-transgenic cotton lines. Metabolic analysis showed higher contents of aspartic acid and glutamic acid in seeds and phloem sap of the transgenic cotton lines. Phenotypically, the transgenic cotton lines showed vigorous growth and height, greater number of bolls, and yield. Among six representative transgenic cotton lines, line 14 had higher photosynthetic rate, stomatal conductance, smooth fiber surface, increased fiber convolutions (SEM analysis) and 95% whitefly mortality as compared to non-transgenic cotton line. The gene integration analysis by fluorescence in situ hybridization showed single copy gene integration at chromosome number 1. Collectively, asparaginase gene demonstrated potential to control whitefly infestation, post-infestation damages and improve cotton plant health and yield: a pre-requisite for farmer's community.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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