Engineering and evolution of the complete Reductive Glycine Pathway in Saccharomyces cerevisiae for formate and CO2 assimilation.

Using captured CO2 and C1-feedstocks like formate and methanol derived from electrochemical activation of CO2 are key solutions for transforming industrial processes towards a circular carbon economy. Engineering formate and CO2-based growth in the biotechnologically relevant yeast Saccharomyces cerevisiae could boost the emergence of a formate-mediated circular bio-economy. This study adopts a growth-coupled selection scheme for modular implementation of the Reductive Glycine Pathway (RGP) and subsequent Adaptive Laboratory Evolution (ALE) to enable formate and CO2 assimilation for biomass formation in yeast. We first constructed a serine biosensor strain and then implemented the serine synthesis module of the RGP into yeast, establishing glycine and serine synthesis from formate and CO2. ALE improved the RGP-dependent growth by 8-fold. 13C-labeling experiments reveal glycine, serine, and pyruvate synthesis via the RGP, demonstrating the complete pathway activity. Further, we re-established formate and CO2-dependent growth in non-evolved biosensor strains via reverse-engineering a mutation in GDH1 identified from ALE. This mutation led to significantly more 13C-formate assimilation than in WT without any selection or overexpression of the RGP. Overall, we demonstrated the activity of the complete RGP, showing evidence for carbon transfer from formate to pyruvate coupled with CO2 assimilation.

Association of serum digoxin concentration with morbidity and mortality in patients with atrial fibrillation, heart failure and reduced ejection fraction of 45 % or below.

BACKGROUND: Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) are common cardiovascular conditions linked to significant health burdens. This review aims to study the relationship of serum digoxin concentration and mortality and morbidity outcomes in defined population. METHODS: We conducted a thorough search of databases such as PubMed, Google Scholar, and Cochrane Library, from inception until 20th Aug 2023. Studies that explored the relationship between serum digoxin concentration and mortality, morbidity, or other clinical endpoints in AF and HFrEF patients (ejection fraction ≤45 %) were eligible for inclusion. RESULTS: The selected studies exhibited a wide range of designs, patient cohorts, and measured outcomes. The association between serum digoxin concentration, mortality and morbidity endpoints like hospitalization rates and cardiovascular events were assessed in these studies. Despite the methodological diversity, our systematic review uncovered consistent trends across the studies, suggesting that elevated serum digoxin concentrations may correlate with higher mortality and morbidity in AF and HFrEF patients. CONCLUSION: This systematic review emphasizes the need for cautious management of serum digoxin levels in patients with concurrent AF and HFrEF. While digoxin remains a valuable treatment for heart failure, its potential adverse effects on outcomes in this specific patient subgroup call for vigilant monitoring and individualized treatment approaches. Further research is required to elucidate the dose-response relationship and potential confounding factors influencing outcomes associated with serum digoxin concentration in AF and HFrEF patients. Clinicians should consider these findings when making therapeutic decisions to enhance patient care and outcomes.

Energetic and informational masking place dissociable demands on listening effort: Evidence from simultaneous electroencephalography and pupillometrya).

The task of processing speech masked by concurrent speech/noise can pose a substantial challenge to listeners. However, performance on such tasks may not directly reflect the amount of listening effort they elicit. Changes in pupil size and neural oscillatory power in the alpha range (8-12 Hz) are prominent neurophysiological signals known to reflect listening effort; however, measurements obtained through these two approaches are rarely correlated, suggesting that they may respond differently depending on the specific cognitive demands (and, by extension, the specific type of effort) elicited by specific tasks. This study aimed to compare changes in pupil size and alpha power elicited by different types of auditory maskers (highly confusable intelligible speech maskers, speech-envelope-modulated speech-shaped noise, and unmodulated speech-shaped noise maskers) in young, normal-hearing listeners. Within each condition, the target-to-masker ratio was set at the participant's individually estimated 75% correct point on the psychometric function. The speech masking condition elicited a significantly greater increase in pupil size than either of the noise masking conditions, whereas the unmodulated noise masking condition elicited a significantly greater increase in alpha oscillatory power than the speech masking condition, suggesting that the effort needed to solve these respective tasks may have different neural origins.

Antibiotic choices among healthcare professionals for enterococcal bacteremia with patterns of resistance and risk factors of mortality, in settings of poor antibiotic stewardship program - a five-year retrospective cohort study.

BACKGROUND: Enterococcal bacteremia has become prevalent in the recent decade, especially in hospitalized patients. Moreover, the rise in resistance patterns against antibiotic drugs regarding enterococci infection, such as cephalosporins, ampicillin and vancomycin, is prevailing. The major driving force behind this is the incongruous use of antibiotics with a minor contribution from environmental stressors which calls for vigilant and prudent administration of evidence-based antibiotics. METHODS: A retrospective study was conducted from January 1 2017 until December 31 2021, at the tertiary care center, Dr Ziauddin Hospital in Karachi, Pakistan. RESULTS: Our research revealed ampicillin resistance in 87 (63.5%), with an estimated 25 (18.8%) mortality. Male gender 19 (76%) and vancomycin resistance 13 (52%) were associated with increased mortality. Furthermore, appropriate antibiotic therapy reduced the risk of death compared with inappropriate and excessive use of antibiotics 10 (40%) vs. 15 (60%) vs. 20 (80%) respectively. Targeted therapy with amoxicillin/clavulanic acid was associated with lower mortality 1 (4%) and higher discharge rates 34 (32.1%). On Kaplan-Meier survival, targeted therapy with amoxicillin/clavulanic acid was associated with shorter hospital stays and prolonged survival. UTI was found as the most common source of enterococcal bacteremia 57 (41.6%), followed by respiratory 21 (15.3%) and intra-abdominal 13 (9.5%). In 26 (19%) patients, no identifiable source of infection was found. CONCLUSION: Vancomycin resistance and male gender were found independent risk factors for mortality. The use of inappropriate antibiotics significantly increases mortality in these patients. The appropriate antibiotic therapy reduces the risk of death. Furthermore, overuse of antibiotics didn't reduce mortality; instead increased the financial burden and chances of developing multi-drug resistant strains of other organisms by increasing hospital stays of patients.

Medical applicant general practice experience and career aspirations: a questionnaire study.

BACKGROUND: Increasing access to general practice work experience placements for school students is a strategy for improving general practice recruitment, despite limited evidence and concerns surrounding equity of access to general practice experiences. AIMS: To examine the association between undertaking general practice experience and the perceptions of general practice as an appealing future career among prospective medical applicants. To identify socioeconomic factors associated with obtaining general practice experience. DESIGN & SETTING: Cross-sectional questionnaire study in the UK. METHOD: Participants were UK residents aged ≥16 years and seriously considering applying to study medicine in 2019/2020. They were invited to take part via the University Clinical Aptitude Test (UCAT). Questionnaire data were analysed using a linear regression of general practice appeal on general practice experience, adjusting for career motivations and demographics, and a logistic regression of general practice experience on measures of social capital and demographics. RESULTS: Of 6391 responders, 4031 were in their last year of school. General practice experience predicted general practice appeal after adjusting for career motivation and demographics (b = 0.37, standard error [SE] = 0.06, P<0.00001). General practice experience was more common among students at private (odds ratio [OR] = 1.65, 95% confidence interval [CI] = 1.31 to 2.08, P<0.0001) or grammar schools (OR = 1.33, 95% CI = 1.02 to 1.72, P = 0.03) and in the highest socioeconomic group (OR = 1.62, 95% CI = 1.28 to 2.05, P<0.0001), and less likely among students of 'other' ethnicity (OR = 0.37, 95% CI = 0.20 to 0.67, P = 0.0011). CONCLUSION: Having general practice experience prior to medical school was associated with finding general practice appealing, which supports its utility in recruitment. Applicants from more deprived backgrounds were less likely to have had a general practice experience, possibly through lack of accessible opportunities.

Notch Signaling & MicroRNAs - two tumblers of neurogenesis and Gliomas.

Gliomas are one of the most annihilating types of brain tumours having a high rate of annual incidence worldwide. Notch signaling is an evolutionary conserved pathway that regulates differentiation and development. Aberrations in Notch signalling pathways lead to severe pathological state such as the Gliomas. MicroRNAs (miRNAs) are the tiny molecules less than 200 bps in length and regulate a myriad of cellular processes. Categorically, miRNAs are divided in to oncogenic and tumours suppressor miRNAs. Accumulating data have identified miRNAs, which positively or negatively regulate Notch signaling in Gliomas. Here, we have assessed status of our understanding of the interplay between miRNA-base regulation of Notch signaling in gliomas, interaction between Notch signaling and other signaling cascades and have also discussed use of natural compounds that will help us get closer to personalized medicine for gliomas.

Pollen morphological assessment of specific selected species of district Sheikhupura, Punjab, Pakistan under LM and SEM.

Around 30 pollen samples, 16 families and 25 genera that were gathered, identified and preserved from 6 different localities of District Sheikhupura. Light and scanning electron microscopy was done for all collected flora. Out of the total samples, 43% specie was identified as herbs, 23% as shrubs, and 33% were identified as trees. The flora was both wild and cultivated. Wild plants were 33%, cultivated 40% and 26% of them were both wild and cultivated. Qualitative and Quantitative survey of pollens revealed polar shape of pollens were 37% spheroidal, 20% prolate spheroidal, 17% oblate spheroidal, remaining were rectangular and pecolpate. Sexine and nexine were available in 100% of samples. Thirty-three percentage of pollen grains were having spines on them. The presence of spines on pollen grains represents the evolutionary relationship amongst the plants. Current study was conducted to record and analyze palynomorphic diversity in district Sheikhupura, Punjab, Pakistan.

Highly selective colorimetric detection and estimation of Hg2+ at nano-molar concentration by silver nanoparticles in the presence of glutathione.

The present study investigated the colorimetric detection of mercury (Hg(2+)) ions by using silver nanoparticles (Ag NPs) in the presence of glutathione. The nanoparticles used in the study were synthesized biologically by using Polyalthia longifolia leaf extract. The synthesized nanoparticles were characterized by UV-visible spectrophotometer, transmission electron microscope, X-ray diffraction, particle size analyzer and zeta sizer. The particles were spherical in shape and it possesses the effective diameter of 5 nm. The zeta potential of the particles was determined to be -28.6 mV. Ag NPs-glutathione conjugates were able to detect Hg(2+) in nanomolar level. Ag NPs-glutathione conjugates upon interaction with Hg(2+) changes from yellowish brown to pale yellow and finally colorless. The study may be applied for the qualitative and quantitative estimation of mercury at very low concentration.

Identification of natural compounds which inhibit biofilm formation in clinical isolates of Klebsiella pneumoniae.

Klebsiella pneumoniae, an important opportunistic pathogen, exists as a biofilm in persistent infections and in-dwelling medical devices. With the objective of identifying natural compounds inhibiting biofilm formation in K. pneumoniae, 35 clinical isolates were screened,out of which 7 strong biofilm producers were identified. Six natural compounds were tested for their inhibitory effects on bacterial growth and biofilm formation by determining the minimum inhibitory concentration and minimum concentration for biofilm inhibition (MBIC) for each compound. The results show that reserpine followed by linoleic acid, were the most potent biofilm inhibitors. Reserpine, an efflux pump inhibitor was effective at biofilm inhibition at a concentration of 0.0156 mg/mL, 64-fold lower concentration than its MIC. Linoleic acid, an essential fatty acid was effective as a biofilm inhibitor at 0.0312 mg/mL, which is 32-fold lower than its MIC. Berberine, another plant derived antimicrobial, chitosan and eugenol had an MBIC value of 0.0635 mg/mL. Curcumin, a natural phenolic compound was effective at biofilm inhibition at a concentration of 0.25 mg/mL, which is 50 fold less than its MIC. Notably, the MIC and MBIC data on these 6 natural compounds was reproducible in all seven high biofilm forming isolates of K. pneumoniae. The present report is a comprehensive comparative analysis of the dose dependent inhibition of various natural compounds on biofilm formation in K. pneumoniae.