Aflatoxin is considered a "hidden poison" due to its slow and adverse effect on various biological pathways in humans, particularly among children, in whom it leads to delayed development, stunted ...growth, liver damage, and liver cancer. Unfortunately, the unpredictable behavior of the fungus as well as climatic conditions pose serious challenges in precise phenotyping, genetic prediction and genetic improvement, leaving the complete onus of preventing aflatoxin contamination in crops on post-harvest management. Equipping popular crop varieties with genetic resistance to aflatoxin is key to effective lowering of infection in farmer's fields. A combination of genetic resistance for in vitro seed colonization (IVSC), pre-harvest aflatoxin contamination (PAC) and aflatoxin production together with pre- and post-harvest management may provide a sustainable solution to aflatoxin contamination. In this context, modern "omics" approaches, including next-generation genomics technologies, can provide improved and decisive information and genetic solutions. Preventing contamination will not only drastically boost the consumption and trade of the crops and products across nations/regions, but more importantly, stave off deleterious health problems among consumers across the globe.
Patients with COVID-19 infection are commonly reported to have an increased risk of venous thrombosis. The choice of anti-thrombotic agents and doses are currently being studied in randomized ...controlled trials and retrospective studies. There exists a need for individualized risk stratification of venous thromboembolism (VTE) to assist clinicians in decision-making on anticoagulation. We sought to identify the risk factors of VTE in COVID-19 patients, which could help physicians in the prevention, early identification, and management of VTE in hospitalized COVID-19 patients and improve clinical outcomes in these patients.
This is a multicenter, retrospective database of four main health systems in Southeast Michigan, United States. We compiled comprehensive data for adult COVID-19 patients who were admitted between 1st March 2020 and 31st December 2020. Four models, including the random forest, multiple logistic regression, multilinear regression, and decision trees, were built on the primary outcome of in-hospital acute deep vein thrombosis (DVT) and pulmonary embolism (PE) and tested for performance. The study also reported hospital length of stay (LOS) and intensive care unit (ICU) LOS in the VTE and the non-VTE patients. Four models were assessed using the area under the receiver operating characteristic curve and confusion matrix.
The cohort included 3531 admissions, 3526 had discharge diagnoses, and 6.68% of patients developed acute VTE (N = 236). VTE group had a longer hospital and ICU LOS than the non-VTE group (hospital LOS 12.2 days vs. 8.8 days, p < 0.001; ICU LOS 3.8 days vs. 1.9 days, p < 0.001). 9.8% of patients in the VTE group required more advanced oxygen support, compared to 2.7% of patients in the non-VTE group (p < 0.001). Among all four models, the random forest model had the best performance. The model suggested that blood pressure, electrolytes, renal function, hepatic enzymes, and inflammatory markers were predictors for in-hospital VTE in COVID-19 patients.
Patients with COVID-19 have a high risk for VTE, and patients who developed VTE had a prolonged hospital and ICU stay. This random forest prediction model for VTE in COVID-19 patients identifies predictors which could aid physicians in making a clinical judgment on empirical dosages of anticoagulation.
Background: Urinary tract infection (UTI) is one of the most common bacterial infections seen in children. A wide range of organisms with varying antibiotic sensitivity patterns have been known to ...cause UTI. The objective of the study was to analyse the clinical presentation of UTI in children between 1-month to15 years of age and to analyse the causative microorganism and their drug susceptibility in UTI in children between 1 month to 15 years of age.Methods: A retrospective study was conducted in a teaching hospital in Kerala, between July 2018 and June 2020 among children 1 month to 15 years of age who presented with symptoms of UTI. Patients who had culture positive UTI were included in the study. Clinical data was obtained from inpatient and outpatient records. Antimicrobial susceptibility was done for positive urine culture by Kirby-Bauer disk diffusion method. Statistical analysis was done using Statistical package for social sciences (SPSS) software version 16.Results: Of the 1057 urine samples analysed, 18.44% had significant bacteuria. 43.07% were children less than one year of age with male predominance. Fever and dysuria were the most common clinical presentation. E. coli was the most prevalent pathogen isolated followed by Klebsiella pneumoniae. Enterococcus faecalis was the only gram-positive bacilli isolated. Highest resistance was shown to ampicillin, third generation cephalosporins and co-trimoxazole. Least resistance was shown to nitrofurantoin, fluoroquinolones, aminoglycosides, piperacillin- tazobactam and carbapenems.Conclusions: Regular surveillance programme is necessary for implementation of guidelines for empiric treatment of UTI.
Background and aims
Though cyclooxygenase inhibitors are employed in rheumatoid arthritis treatment, modulators of leukotrienes are underexplored. We investigated the therapeutic potential of ...montelukast, a known cysteinyl leukotriene receptor-1 (CysLT1) inhibitor in an experimental rat model of arthritis.
Methods
Arthritis was induced in rats, and montelukast (5 mg/kg body wt.) was administered prophylactically (PAM) and therapeutically (TAM) through oral route.
Results and discussion
Blood and joint tissue markers of oxidative stress (lipid peroxidation, protein carbonyls, and nitric oxides) were significantly (
p
< 0.05) reduced in montelukast administered rats. Paw inflammation, RA markers (RF and CRP), eicosanoids (PGE
2
, LTB
4
, and LTC
4
), cytokines (IL-1β and MCP-1), activity of hydrolytic enzymes (collagenase, elastase, and hyaluronidase), expression of matrix metalloproteinases (MMP), and EP-4 receptor were significantly (
p
< 0.05) reduced in montelukast administered rats. This study established that leukotriene inhibition through montelukast lowered the severity of arthritis and thus a potential strategy for reducing the severity of arthritis.
Graphic abstract
The electron transport chain (ETC) in the cell membrane consists of a series of redox complexes that transfer electrons from electron donors to acceptors and couples this electron transfer with the ...transfer of protons (H+) across a membrane. This process generates proton motive force which is used to produce ATP and a myriad of other functions and is essential for the long-term survival of Mycobacterium tuberculosis (Mtb), the causative organism of tuberculosis (TB), under the hypoxic conditions present within infected granulomas. Menaquinone (MK), an important carrier molecule within the mycobacterial ETC, is synthesized de novo by a cluster of enzymes known as the classic/canonical MK biosynthetic pathway. MenA (1,4-dihydroxy-2-naphthoate prenyltransferase), the antepenultimate enzyme in this pathway, is a verified target for TB therapy. In this study, we explored structure-activity relationships of a previously discovered MenA inhibitor scaffold, seeking to improve potency and drug disposition properties. Focusing our campaign upon three molecular regions, we identified two novel inhibitors with potent activity against MenA and Mtb (IC50 = 13–22 μM, GIC50 = 8–10 μM). These analogs also displayed substantially improved pharmacokinetic parameters and potent synergy with other ETC-targeting agents, achieving nearly complete sterilization of Mtb in combination therapy within two weeks in vivo. These new inhibitors of MK biosynthesis present a promising new strategy to curb the continued spread of TB.
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•Inhibitors of 1,4-dihydroxy-2-naphthoate prenyltransferase.•Antibiotic for Mycobacterium tuberculosis.•SAR studies.
Though present in small amounts, the minor constituents of dietary oils may supplement the dietary therapies for rheumatoid arthritis (RA). Hence, in the present study, we assessed the effect of ...minor constituents from sesame oil (SO) and rice bran oil (RBO) and their fatty acids on the severity of adjuvant-induced arthritis in experimental rats. Rats were gavaged with 1 mL of SO or RBO or groundnut oil (GNO, control) with or without its minor components for a period 15 days before and 15 days after the induction of arthritis. Oxidative stress, markers of RA, eicosanoids, cytokines, paw swelling and joint integrity were measured in experimental and control rats. Results demonstrated that native SO and RBO but not SO and RBO stripped of their minor components decreased severity of paw inflammation, oxidative stress (lipid peroxides, protein carbonyls, nitric oxide), RA markers (RF and CRP), inflammatory eicosanoids (PGE
2
, LTB
4
and LTC
4
) and cytokines (IL-1β, IL-6, MCP-1 and TNF-α) compared to control rats. Native SO and RBO inhibited hydrolytic enzymes (collagenase, elastase and hyaluronidase) in the synovial tissue compared to SO and RBO without minor components. The arthritic scores assessed based on the digital and X-ray images indicated that native oils but not those without their minor components reduced the paw swelling and bone loss. Our results indicated that minor components of SO and RBO possess a significant degree of an anti-arthritic effect and are responsible for down regulating inflammation in the experimentally induced arthritis in rats.
Predischarge cardiac testing (PDT) in low-risk patients evaluated for acute coronary syndrome in a chest pain unit (CPU) remains a challenge. It is unclear whether PDT varies by gender. We analyzed ...consecutive low-risk women and men evaluated in our CPU over a 2-year period and compared the utilization of PDT (exercise treadmill test, myocardial stress perfusion scintigraphy, exercise stress echocardiography, invasive coronary angiography, or no test), and incidence of major adverse cardiac events (MACE) at 30 days and 6 months. The study group comprised 619 patients (54% women). A large proportion of both genders did not undergo PDT, although this finding was more frequent in women (50% women vs 40% men, p = 0.01). At 30 days, there were no MACE in either gender. After 6 months of follow-up, MACE remained very low in both women and men (2 1% vs 2 1%), and in patients who did and did not receive PDT (2 1% vs 2 1%). Mean length of stay in the CPU was 5.4 hours in patients without PDT and 9.8 hours in those with PDT (p <0.0001) without altering postdischarge MACE. When referred for PDT, women more often underwent myocardial stress perfusion scintigraphy than men (22% vs 14%, p = 0.005) and less often received exercise treadmill test (20% vs 39%, p <0.0001). Yield of abnormal PDT was low in both women and men although it was lower in women (1% vs 5%, p = 0.02). In conclusion, many low-risk women and men evaluated in a CPU for acute coronary syndrome can be safely and rapidly discharged without PDT and with low risk for MACE at 30 days and at 6 months. Exclusion of PDT was associated with significantly reduced length of stay while maintaining safety in terms of postdischarge MACE.
Aspirin resistance (AR) commonly refers to the concept of reduced aspirin efficacy in preventing cardiovascular disease and platelet inhibition. Obesity increases the risk of heart disease three- to ...four-fold and has been associated with AR. Aspirin is used as a tool for both primary and secondary prevention, but recent studies suggest that its lack of efficacy for primary prevention is partly attributable to obesity. Several mechanisms have been described that contribute to AR in obese patients using pharmacokinetics and pharmacodynamics. AR may be attenuated through weight loss, alternative dosing regimens, and different drug formulations. With the global rise of obesity, it is imperative to find preventive therapies that adequately address atherosclerotic cardiovascular disease (ASCVD) risk in this population.
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