Evaluating the efficacy of microbial antagonists in inducing resistance, promoting growth, and providing biological control against powdery mildew in wheat.

This study evaluates the biocontrol efficacy of three bacterial strains (Pseudomonas fluorescens DTPF-3, Bacillus amyloliquefaciens DTBA-11, and Bacillus subtilis DTBS-5) and two fungal strains (Trichoderma harzianum Pusa-5SD and Aspergillus niger An-27) antagonists, along with their combinations at varying doses (5.0, 7.5, and 10.0 g/kg of seeds), against wheat powdery mildew. The most effective dose (10 g/kg seeds) was further analyzed for its impact on induced resistance and plant growth promotion under greenhouse conditions. The study measured defense enzyme activities, biochemical changes, and post-infection plant growth metrics. All tested microbial antagonists at 10 g/kg significantly reduced PM severity, with B. subtilis strain DTBS-5 outperforming others in reducing PM severity and achieving the highest biocontrol efficacy. It was followed by B. amyloliquefaciens strain DTBA-11 and P. fluorescens strain DTPF-3, with the fungal antagonists showing no significant effect. Wheat crops treated with B. subtilis strain DTBS-5 exhibited substantial increases in defense-related enzyme activities and biochemicals, suggesting an induced resistance mechanism. The study found a 45% increase in peroxidase (POD) activity, a 50% increase in catalase (CAT) activity, a 30% increase in phenolic content, and a 25% increase in soluble protein content in the wheat plants treated with microbial antagonists. The study highlights the effectiveness of microbial antagonists, particularly B. subtilis strain DTBS-5, in managing wheat PM through biocontrol, induced resistance, and enhanced plant growth, offering a sustainable alternative to chemical treatments.

New Investigational Drug's Targeting Various Molecular Pathways for Treatment of Cervical Cancer: Current Status and Future Prospects.

Currently, cervical cancer (CC) is the fourth recorded widespread cancer among women globally. There are still many cases of metastatic or recurring disease discovered, despite the incidence and fatality rates declining due to screening identification and innovative treatment approaches. Palliative chemotherapy continues to be the standard of care for patients who are not contenders for curative therapies like surgery and radiotherapy. This article seeks to provide a thorough and current summary of therapies that have been looked into for the management of CC. The authors emphasize the ongoing trials while reviewing the findings of clinical research. Agents that use biological mechanisms to target different molecular pathways such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), poly ADP-ribosepolymerase (PARP), and epigenetic biological mechanisms epitomize and offer intriguing research prospects.

Microbial Metabolites-Induced Epigenetic Modifications for Inhibition of Colorectal Cancer: Current Status and Future Perspectives.

Globally, one of the most prevalent cancers is colorectal cancer (CRC). Chemotherapy and surgery are two common conventional CRC therapies that are frequently ineffective and have serious adverse effects. Thus, there is a need for complementary and different therapeutic approaches. The use of microbial metabolites to trigger epigenetic alterations as a way of preventing CRC is one newly emerging field of inquiry. Small chemicals called microbial metabolites, which are made by microbes and capable of altering host cell behaviour, are created. Recent research has demonstrated that these metabolites can lead to epigenetic modifications such as histone modifications, DNA methylation, and non-coding RNA regulation, which can control gene expression and affect cellular behaviour. This review highlights the current knowledge on the epigenetic modification for cancer treatment, immunomodulatory and anti-carcinogenic attributes of microbial metabolites, gut epigenetic targeting system, and the role of dietary fibre and gut microbiota in cancer treatment. It also focuses on short-chain fatty acids, especially butyrates (which are generated by microbes), and their cancer treatment perspective, challenges, and limitations, as well as state-of-the-art research on microbial metabolites-induced epigenetic changes for CRC inhibition. In conclusion, the present work highlights the potential of microbial metabolites-induced epigenetic modifications as a novel therapeutic strategy for CRC suppression and guides future research directions in this dynamic field.

Chemoproteomic Identification of Spermidine-Binding Proteins and Antitumor-Immunity Activators.

Cancer immune therapies, particularly programmed cell death protein 1 (PD-1) blockade immunotherapy, falter in aged individuals due to compromised T-cell immunity. Spermidine, a biogenic polyamine that declines along with aging, shows promise in restoring antitumor immunity by enhancing mitochondrial fatty acid oxidation (FAO). Herein, we report a spermidine-based chemoproteomic probe (probe 2) that enables profiling of spermidine-binding proteins and screening for small-molecule enhancers of mitochondrial FAO. Chemoproteomic profiling by the probe revealed 140 proteins engaged in cellular interaction with spermidine, with a significant majority being mitochondrial proteins. Hydroxyl coenzyme A (CoA) dehydrogenase subunits α (HADHA) and other lipid metabolism-linked proteins are among the mitochondrial proteins that have attracted considerable interest. Screening spermidine analogs with the probe led to the discovery of compound 13, which interacts with these lipid metabolism-linked proteins and activates HADHA. This simple and biostable synthetic compound we named "spermimic" mirrors spermidine's ability to enhance mitochondrial bioenergetics and displays similar effectiveness in augmenting PD-1 blockade therapy in mice. This study lays the foundation for developing small-molecule activators of antitumor immunity, offering potential in combination cancer immunotherapy.

The Effect of Vitamin D Deficiency as a Risk Factor of Early Fragmentation in Legg-Calve-Perthes Disease: A Prospective Study.

INTRODUCTION: Legg-Calve-Perthes disease (LCPD) is a disorder involving the hips in young children of preschool and school-going age groups, more common in 4-8 years. The insufficient blood supply to the femoral head is the main reason behind various etiologic theories. Multiple factors affect the natural progression of the disease. The natural progression of the disease involves early avascular necrosis, fragmentation, reconstitution, and healed stages. In the fragmentation stage, the bony epiphysis begins to fragment, and the subchondral radiolucent zone (crescent sign) is the result of a subchondral stress fracture, which later on determines the extent of a necrotic fragment of the femoral head. These changes later contribute to changes in the shape of the femur head and the extent of deformity. As vitamin D plays a vital role in the onset of the fragmentation stage, we conducted a study to assess the effect of vitamin D deficiency as a risk factor for early fragmentation in Legg-Calve-Perthes disease. METHODS: In our study, 50 patients aged 4-12 years were examined over three years and classified according to Catterall and Herring's lateral pillar classification; the length of the fragmentation stage and the vitamin D level were considered. A vitamin D level of less than 20 ng/mL was labeled as the deficient group, 20-30 ng/mL as the insufficient group, and more than 30 ng/mL as the sufficient (normal) group. RESULTS: The critical fragmentation stage was significantly longer (more than 12 months) in vitamin D deficiency (34%), leading to a higher risk of deformity and extrusion of the femoral head, which led to higher rates of surgical intervention and containment procedures. CONCLUSION: The fragmentation stage is critical in the course of LCPD. Vitamin D levels play a vital role in predicting the prognostic of LCPD, and it should be measured in all patients of LCPD. Patients with normal vitamin D levels have a comparatively shorter fragmentation stage duration than patients with insufficient or deficient levels, leading to a lesser duration of femoral head damage.

Selective fluoride sensing by a novel series of lanthanide-based one-dimensional coordination polymers through intramolecular proton transfer.

A novel series of one-dimensional coordination polymers (CPs) is achieved via a facile one-pot synthesis strategy employing the nitrate salts of trivalent lanthanides, a pentadentate chelating ligand, and triphenylphosphine oxide at a controlled stoichiometry under ambient conditions. All the CPs are characterized comprehensively using spectroscopic, X-ray crystallographic and magnetometric studies. The CPs are found to be thermally stable up to a significantly high temperature and resistant to water for an indefinite time. They are photoactive and exhibit selective fluoride ion (F-) sensing with excellent efficiency both colorimetrically and fluorimetrically in the solid-state as well as in solution. The presence of F- concomitantly sensitizes the photoluminescence enhancement and visual decolourization of the CPs in solution owing to the ground-state intra-molecular proton transfer. The photophysical response of the CPs to F- in solution was found to be instantaneous (<30 s). The sensitivity of detection is observed to be significantly high over a wide range of F- concentrations, covering the beneficial and detrimental domains of F- concentrations in drinking water. The limit of detection (LoD) under ambient conditions was found to be in the micromolar (µM) range-the best being 0.22 µM found using UV-vis spectrometry and 7.5 µM using fluorimetry. In comparison, the USEPA standard cut-off for the upper limit of F- concentration in drinking water is 211 µM, and the LoD of measuring F- concentration using the USEPA standard method using a fluoride-selective electrode is 26.3 µM. The CPs display markedly high selectivity toward F- with negligible-to-no interference from the commonly abundant ions (Cl-, Br-, I-, CH3CO2-, CO32-, SO42-, HPO42-, NH4+, Na+, K+, Mg2+, and Ca2+) in terms of UV-vis spectral change. Moreover, they also exhibit solid-state IR-spectrometric sensitivity towards F- under ambient conditions.

Ligand-gated ion channels as potential biomarkers for ADT-mediated cognitive decline in prostate cancer patients.

Men with prostate cancer are at increased risk of developing cognitive decline by the use of second-generation androgen signaling inhibitors. To date, reliable and sensitive biomarkers that could distinguish men at high risk of cognitive dysfunction under androgen deprivation therapy (ADT) have not been characterized. We used high-throughput transcriptional profiling utilizing human prostate cancer cell culture models mimicking ADT, biomarker selection using minimal common oncology data elements-cytoscape, and bioinformatic analyses employing Advaita® iPathwayGuide and DisGeNET for identification of disease-related gene associations. Validation analysis of genes was performed on brain neuronal and glial cells by quantitative real-time polymerase chain reaction assay. Our systematic analysis of androgen deprivation-associated genes involved multiple biological processes, including neuroactive ligand-receptor interaction, axon guidance, cytokine-cytokine receptor interaction, and metabolic and cancer signaling pathways. Genes associated with neuroreceptor ligand interaction, including gamma-aminobutyric acid (GABA) A and B receptors and nuclear core proteins, were identified as top upstream regulators. Functional enrichment and protein-protein interaction network analysis highlighted the role of ligand-gated ion channels (LGICs) and their receptors in cognitive dysfunction. Gene-disease association assigned forgetfulness, intellectual disability, visuospatial deficit, bipolar disorder, and other neurocognitive impairment with upregulation of type-1 angiotensin II receptor, brain-derived neurotrophic factor, GABA type B receptor subunit 2 (GABBR2), GABRA3, GABRA5, GABRB1, glycine receptor beta, glutamate ionotropic receptor N-methyl-D-aspartate receptor (NMDA) type subunit 1, glutamate ionotropic receptor NMDA type subunit 2D, 5-hydroxytryptamine receptor 1D, interferon beta 1, and nuclear receptor subfamily 3 group C member 1 as top differentially expressed genes. Validation studies of brain glial cells, neurons, and patients on ADT demonstrated the association of these genes with cognitive decline. Our findings highlight LGICs as potential biomarkers for ADT-mediated cognitive decline. Further validation of these biomarkers may lead to future practical clinical use.

Emerging Trends of Nanomedicines in the Management of Prostate Cancer: Perspectives and Potential Applications.

Prostate cancer is one of the most life-threatening disorders that occur in males. It has now become the third most common disease all over the world, and emerging cases and spiking mortality rates are becoming more challenging day by day. Several approaches have been used to treat prostate cancer, including surgery, radiation therapy, chemotherapy, etc. These are painful and invasive ways of treatment. Primarily, chemotherapy has been associated with numerous drawbacks restricting its further application. The majority of prostate cancers have the potential to become castration-resistant. Prostate cancer cells exhibit resistance to chemotherapy, resistance to radiation, ADT (androgen-deprivation therapy) resistance, and immune stiffness as a result of activating tumor-promoting signaling pathways and developing resistance to various treatment modalities. Nanomedicines such as liposomes, nanoparticles, branched dendrimers, carbon nanotubes, and quantum dots are promising disease management techniques in this context. Nanomedicines can target the drugs to the target site and enhance the drug's action for a prolonged period. They may also increase the solubility and bioavailability of poorly soluble drugs. This review summarizes the current data on nanomedicines for the prevention and treatment of prostate cancer. Thus, nanomedicine is pioneering in disease management.

Targeting Lysosomes: A Strategy Against Chemoresistance in Cancer.

Chemotherapy is still the major method of treatment for many types of cancer. Curative cancer therapy is hampered significantly by medication resistance. Acidic organelles like lysosomes serve as protagonists in cellular digestion. Lysosomes, however, are gaining popularity due to their speeding involvement in cancer progression and resistance. For instance, weak chemotherapeutic drugs of basic nature permeate through the lysosomal membrane and are retained in lysosomes in their cationic state, while extracellular release of lysosomal enzymes induces cancer, cytosolic escape of lysosomal hydrolases causes apoptosis, and so on. Drug availability at the sites of action is decreased due to lysosomal drug sequestration, which also enhances cancer resistance. This review looks at lysosomal drug sequestration mechanisms and how they affect cancer treatment resistance. Using lysosomes as subcellular targets to combat drug resistance and reverse drug sequestration is another method for overcoming drug resistance that is covered in this article. The present review has identified lysosomal drug sequestration as one of the reasons behind chemoresistance. The article delves deeper into specific aspects of lysosomal sequestration, providing nuanced insights, critical evaluations, or novel interpretations of different approaches that target lysosomes to defect cancer.

Dietary Plant Metabolites Induced Epigenetic Modification as a Novel Strategy for the Management of Prostate Cancer.

Prostate cancer is a widespread malignancy among men, with a substantial global impact on morbidity and mortality. Despite advances in conventional therapies, the need for innovative and less toxic treatments remains a priority. Emerging evidence suggests that dietary plant metabolites possess epigenetic-modifying properties, making them attractive candidates for prostate cancer treatment. The present work reviews the epigenetic effects of dietary plant metabolites in the context of prostate cancer therapy. We first outline the key epigenetic mechanisms involved in prostate cancer pathogenesis, including histone modifications, DNA methylation, and miRNA or Long Noncoding RNA (lncRNA) dysregulation. Next, we delve into the vast array of dietary plant metabolites that have demonstrated promising anti-cancer effects through epigenetic regulation. Resveratrol, minerals, isothiocyanates, curcumin, tea polyphenols, soy isoflavones and phytoestrogens, garlic compounds, anthocyanins, lycopene, and indoles are among the most extensively studied compounds. These plant-derived bioactive compounds have been shown to influence DNA methylation patterns, histone modifications, and microRNA expression, thereby altering the gene expression allied with prostate cancer progression, cell proliferation, and apoptosis. We also explore preclinical and clinical studies investigating the efficacy of dietary plant metabolites as standalone treatments or in combination with traditional treatments for people with prostate cancer. The present work highlights the potential of dietary plant metabolites as epigenetic modulators to treat prostate cancer. Continued research in this field may pave the way for personalized and precision medicine approaches, moving us closer to the goal of improved prostate cancer management.

Chemo-profiling of Purpureocillium lilacinum and Paecilomyces variotii isolates using GC-MS analysis, and evaluation of their metabolites against M. incognita.

Nematophagous fungi are the best alternatives to chemical nematicides for managing nematodes considering environmental health. In the current study, activity of metabolites from ten isolates of Purpureocillium lilacinum (Thom) Luangsa-ard (Hypocreales: Ophiocordycipitaceae) and two isolates of Paecilomyces variotii Bainier (Eurotiales: Trichocomaceae), were examined to inhibit the hatching of Meloidogyne incognita (Kofoid & White) Chitwood (Tylenchida: Heteroderidae) eggs. At 100%, 50%, and 25% concentrations, respectively, the culture filtrate of the isolate P. lilacinum 6887 prevented 97.55%, 90.52%, and 62.97% of egg hatching. Out of all the isolates, Pl 6887, Pl 6553, and Pl 2362 showed the greatest results in the hatching inhibition experiment.Gas chromatography-mass spectrometry (GC-MS) analysis revealed a variety of nematicidal compounds from different isolates. A total of seven nematicidal compounds, including four very potent nematicidal fatty acids were found in the isolate Pl 6553. Secondary metabolites of the same isolate possess the highest M. incognita juvenile mortality, i.e., 43.33% and 92% after 48 hrs of treatment at 100 and 200 ppm concentrations, respectively. Significant difference was observed in juvenile mortality percentage among the isolate having highest and lowest nematicidal compounds. Nematicidal fatty acids like myristic and lauric acid were found for the first time in P. lilacinum. Multiple vacuole-like droplets were found inside the unhatched eggs inoculated with the culture filtrate of isolate Pl 6887, and also in the juveniles that perished in the ethyl acetate extract of isolate Pl 6553.

The Role of Cytokines in Activation of Tumour-promoting Pathways and Emergence of Cancer Drug Resistance.

Scientists are constantly researching and launching potential chemotherapeutic agents as an irreplaceable weapon to fight the battle against cancer. Despite remarkable advancement over the past several decades to wipe out cancer through early diagnosis, proper prevention, and timely treatment, cancer is not ready to give up and leave the battleground. It continuously tries to find some other way to give a tough fight for its survival, either by escaping from the effect of chemotherapeutic drugs or utilising its own chemical messengers like cytokines to ensure resistance. Cytokines play a significant role in cancer cell growth and progression, and the present article highlights their substantial contribution to mechanisms of resistance toward therapeutic drugs. Multiple clinical studies have even described the importance of specific cytokines released from cancer cells as well as stromal cells in conferring resistance. Herein, we discuss the different mechanism behind drug resistance and the crosstalk between tumor development and cytokines release and their contribution to showing resistance towards chemotherapeutics. As a part of this review, different approaches to cytokines profile have been identified and employed to successfully target new evolving mechanisms of resistance and their possible treatment options.

Diagnosis of Covid-19 from CT slices using Whale Optimization Algorithm, Support Vector Machine and Multi-Layer Perceptron.

BACKGROUND: The coronavirus disease 2019 is a serious and highly contagious disease caused by infection with a newly discovered virus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OBJECTIVE: A Computer Aided Diagnosis (CAD) system to assist physicians to diagnose Covid-19 from chest Computed Tomography (CT) slices is modelled and experimented. METHODS: The lung tissues are segmented using Otsu's thresholding method. The Covid-19 lesions have been annotated as the Regions of Interest (ROIs), which is followed by texture and shape extraction. The obtained features are stored as feature vectors and split into 80:20 train and test sets. To choose the optimal features, Whale Optimization Algorithm (WOA) with Support Vector Machine (SVM) classifier's accuracy is employed. A Multi-Layer Perceptron (MLP) classifier is trained to perform classification with the selected features. RESULTS: Comparative experimentations of the proposed system with existing eight benchmark Machine Learning classifiers using real-time dataset demonstrates that the proposed system with 88.94% accuracy outperforms the benchmark classifier's results. Statistical analysis namely, Friedman test, Mann Whitney U test and Kendall's Rank Correlation Coefficient Test has been performed which indicates that the proposed method has a significant impact on the novel dataset considered. CONCLUSION: The MLP classifier's accuracy without feature selection yielded 80.40%, whereas with feature selection using WOA, it yielded 88.94%.

Combining biophysical parameters with thermal and RGB indices using machine learning models for predicting yield in yellow rust affected wheat crop.

Evaluating crop health and forecasting yields in the early stages are crucial for effective crop and market management during periods of biotic stress for both farmers and policymakers. Field experiments were conducted during 2017-18 and 2018-19 with objective to evaluate the effect of yellow rust on various biophysical parameters of 24 wheat cultivars, with varying levels of resistance to yellow rust and to develop machine learning (ML) models with improved accuracy for predicting yield by integrating thermal and RGB indices with crucial plant biophysical parameters. Results revealed that as the level of rust increased, so did the canopy temperature and there was a significant decrease in crop photosynthesis, transpiration, stomatal conductance, leaf area index, membrane stability index, relative leaf water content, and normalized difference vegetation index due to rust, and the reductions were directly correlated with levels of rust severity. The yield reduction in moderate resistant, low resistant and susceptible cultivars as compared to resistant cultivars, varied from 15.9-16.9%, 28.6-34.4% and 59-61.1%, respectively. The ML models were able to provide relatively accurate early yield estimates, with the accuracy increasing as the harvest approached. The yield prediction performance of the different ML models varied with the stage of the crop growth. Based on the validation output of different ML models, Cubist, PLS, and SpikeSlab models were found to be effective in predicting the wheat yield at an early stage (55-60 days after sowing) of crop growth. The KNN, Cubist, SLR, RF, SpikeSlab, XGB, GPR and PLS models were proved to be more useful in predicting the crop yield at the middle stage (70 days after sowing) of the crop, while RF, SpikeSlab, KNN, Cubist, ELNET, GPR, SLR, XGB and MARS models were found good to predict the crop yield at late stage (80 days after sowing). The study quantified the impact of different levels of rust severity on crop biophysical parameters and demonstrated the usefulness of remote sensing and biophysical parameters data integration using machine-learning models for early yield prediction under biotically stressed conditions.

Cortisol as a Target for Treating Mental Disorders: A Promising Avenue for Therapy.

Cortisol, commonly known as the "stress hormone," plays a critical role in the body's response to stress. Elevated cortisol levels have been associated with various mental disorders, including anxiety, depression, and post-traumatic stress disorder. Consequently, researchers have explored cortisol modulation as a promising avenue for treating these conditions. However, the availability of research on cortisol as a therapeutic option for mental disorders is limited, and existing studies employ diverse methodologies and outcome measures. This review article aimed to provide insights into different treatment approaches, both pharmacological and non-pharmacological, which can effectively modulate cortisol levels. Pharmacological interventions involve the use of substances, such as somatostatin analogs, dopamine agonists, corticotropin-releasing hormone antagonists, and cortisol synthesis inhibitors. Additionally, non-pharmacological techniques, including cognitivebehavioral therapy, herbs and supplements, transcranial magnetic stimulation, lifestyle changes, and surgery, have been investigated to reduce cortisol levels. The emerging evidence suggests that cortisol modulation could be a promising treatment option for mental disorders. However, more research is needed to fully understand the effectiveness and safety of these therapies.

Small-Molecule Drug Repurposing for Counteracting Phototoxic A2E Aggregation.

Despite the well-established role of oxidative stress in the pathogenesis of age-related macular degeneration (AMD), the mechanism underlying phototoxicity remains unclear. Herein, we used a drug repurposing approach to isolate an FDA-approved drug that blocks the aggregation of the photoinducible major fluorophore of lipofuscin, the bis-retinoid N-retinylidene-N-retinylethanolamine (A2E). Our fluorescence-based screening combined with dynamic light scattering (DLS) analysis led to the identification of entacapone as a potent inhibitor of A2E fluorescence and aggregation. The entacapone-mediated inhibition of A2E aggregation blocks its photodegradation and offers photoprotection in A2E-loaded retinal pigment epithelial (RPE) cells exposed to blue light. In-depth mechanistic analysis suggests that entacapone prevents the conversion of toxic aggregates by redirecting A2E into off-pathway oligomers. These findings provide evidence that aggregation contributes to the phototoxicity of A2E.

Surviving Pneumonia: A Rare Outcome of Compensatory Hyperinflation in Fibrotic Lung Disease.

Chronic respiratory insufficiency can result from respiratory infections like pneumonia, which can permanently harm the lungs and respiratory system. A 21-year-old female patient arrived at our emergency medicine department (ED) complaining of acute lower-limb pain that worsened when she walked. She also reported feeling weak and having an acute, undiagnosed fever that was resolved by taking medicine two days after the day of admission. She was found to have a body temperature of 99.4°F, decreased air entry on the left side of the chest, and diminished bilateral plantar responsiveness. With the exception of a low calcium level and an increased liver function test, her biochemical indicators were normal. The left lung's basal region had fibrosis, and the right lung's hyperplasia served as a compensatory mechanism, according to the chest radiograph and CT scan of the thorax. The patient underwent treatment with intravenous pantoprazole, ondansetron, ceftriaxone, multivitamin supplementation, gabapentin, and tablets of amitriptyline. On Day 7, her lower limb pain had significantly recovered. After an eight-day hospital stay, she was discharged with instructions to follow up with the pulmonary medicine outpatient department (OPD) and the neurology OPD. A well-known occurrence known as compensatory hyperinflation of the lung happens when one lung is severely injured or rendered inoperable, leading the other lung to enlarge to make up for the loss of respiratory function. This case demonstrates the ability of the respiratory system to compensate for significant damage to one of the lungs.

Strong Field Double Ionization of Formaldehyde Investigated Using Momentum Resolved Covariance Imaging and Trajectory Surface Hopping.

We use covariance velocity map imaging of fragment ions from the strong field double ionization of formaldehyde in conjunction with trajectory surface hopping calculations to determine the ionization yields to different singlet and triplet states of the dication. The calculated kinetic energy release for trajectories initiated on different electronic states is compared with the experimental values based on momentum resolved covariance measurements. We determine the state resolved double ionization yields as a function of laser intensity and pulse duration down to 6 fs (two optical cycles).