TDDFT versus GW/BSE Methods for Prediction of Light Absorption and Emission in a TADF Emitter.

Design concepts for organic light emitting diode (OLED) emitters, which exhibit thermally activated delayed fluorescence (TADF) and thereby achieve quantum yields exceeding 25%, depend on singlet-triplet splitting energies of order kT to allow reverse intersystem crossing at ambient temperatures. Simulation methods for these systems must be able to treat relatively large organic molecules, as well as predict their excited state energies, transition energies, singlet-triplet splittings, and absorption and emission cross sections with reasonable accuracy, in order to prove useful in the design process. Here we compare predictions of TDDFT with M06-2X and ωB97X-D exchange-correlation functionals and a GoWo@HF/BSE method for these quantities in the well-studied DPTZ-DBTO2 TADF emitter molecule. Geometry optimization is performed for ground state (GS) and lowest donor-acceptor charge transfer (CT) state for each functional. Optical absorption and emission cross sections and energies are calculated at these geometries. Relaxation energies are on the order of 0.5 eV, and the importance of obtaining excited state equilibrium geometries in predicting delayed fluorescence is demonstrated. There are clear trends in predictions of GoWo@HF/BSE, and TDDFT/ωB97X-D and M06-2X methods in which the former method favors local exciton (LE) states while the latter favors DA CT states and ωB97X-D makes intermediate predictions. GoWo@HF/BSE suffers from triplet instability for LE states but not CT states relevant for TADF. Shifts in HOMO and LUMO levels on adding a conductor-like polarizable continuum model dielectric background are used to estimate changes in excitation energies on going from the gas phase to a solvated molecule.

High-flow nasal cannula versus non-invasive ventilation for acute hypercapnic respiratory failure in adults: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Non-invasive ventilation (NIV) with bi-level positive pressure ventilation is a first-line intervention for selected patients with acute hypercapnic respiratory failure. Compared to conventional oxygen therapy, NIV may reduce endotracheal intubation, death, and intensive care unit length of stay (LOS), but its use is often limited by patient tolerance and treatment failure. High-flow nasal cannula (HFNC) is a potential alternative treatment in this patient population and may be better tolerated. RESEARCH QUESTION: For patients presenting with acute hypercapnic respiratory failure, is HFNC an effective alternative to NIV in reducing the need for intubation? METHODS: We searched EMBASE, MEDLINE, and the Cochrane library from database inception through to October 2021 for randomized clinical trials (RCT) of adults with acute hypercapnic respiratory failure assigned to receive HFNC or NIV. The Cochrane risk-of-bias tool for randomized trials was used to assess risk of bias. We calculated pooled relative risks (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with corresponding 95% confidence intervals (CI) using a random-effects model. RESULTS: We included eight RCTs (n = 528) in the final analysis. The use of HFNC compared to NIV did not reduce the risk of our primary outcome of mortality (RR 0.86, 95% CI 0.48-1.56, low certainty), or our secondary outcomes including endotracheal intubation (RR 0.80, 95% CI 0.46-1.39, low certainty), or hospital LOS (MD - 0.82 days, 95% CI - 1.83-0.20, high certainty). There was no difference in change in partial pressure of carbon dioxide between groups (MD - 1.87 mmHg, 95% CI - 5.34-1.60, moderate certainty). INTERPRETATION: The current body of evidence is limited in determining whether HFNC may be either superior, inferior, or equivalent to NIV for patients with acute hypercapnic respiratory failure given imprecision and study heterogeneity. Further studies are needed to better understand the effect of HFNC on this population.

A natural flavonoid, apigenin isolated from Clerodendrum viscosum leaves, induces G2/M phase cell cycle arrest and apoptosis in MCF-7 cells through the regulation of p53 and caspase-cascade pathway

Background With 9.6 million deaths in 2018, cancer remains the second leading cause of death worldwide. Breast cancer is the most deadly type of cancer among females, with 55.2% of crude incidence rate and 16.6% of crude mortality rate. Purpose The present study was aimed to investigate the anti-breast cancer potential of natural dietary flavonoid, apigenin isolated from Clerodendrum viscosum leaves. Methods Apigenin was evaluated for in-depth anticancer activity in MCF-7 cells using cell viability assay, cell cycle analysis, Annexin-V-FLUOS staining, ROS induction, morphological analysis, and western blot analysis. Results Apigenin showed selective cytotoxicity on MCF-7 cells with an IC50-56.72 ± 2.35 µM, while negligible cytotoxicity was observed on WI-38 cells. Further, the flow cytometer-based analysis showed that apigenin halted MCF-7 cells in the G2/M phase arrest followed by dose-dependent apoptosis. Moreover, the FACS and confocal microscopy results confirmed the elevation of intracellular ROS and nuclear fragmentation in apigenin-treated MCF-7 cells. Western blots showed up-regulation of cell cycle regulatory proteins, increased p53 expression, Bax/Bcl-2 ratio, activation of caspases, and cleavage of PARP. Finally, apigenin treatment in the presence of Pifithrin-µ showed decreased apoptotic population and it was further confirmed through western blotting study. The results revealed the vital role of p53 in apigenin-induced apoptosis in MCF-7 cells. Conclusions In the present findings, treatment of apigenin-induced intracellular ROS in MCF-7 cells followed by induction of G2/M phase cell cycle arrest and further apoptosis through the regulation of p53 and caspase-cascade signaling pathway (AU)

A natural flavonoid, apigenin isolated from Clerodendrum viscosum leaves, induces G2/M phase cell cycle arrest and apoptosis in MCF-7 cells through the regulation of p53 and caspase-cascade pathway.

BACKGROUND: With 9.6 million deaths in 2018, cancer remains the second leading cause of death worldwide. Breast cancer is the most deadly type of cancer among females, with 55.2% of crude incidence rate and 16.6% of crude mortality rate. PURPOSE: The present study was aimed to investigate the anti-breast cancer potential of natural dietary flavonoid, apigenin isolated from Clerodendrum viscosum leaves. METHODS: Apigenin was evaluated for in-depth anticancer activity in MCF-7 cells using cell viability assay, cell cycle analysis, Annexin-V-FLUOS staining, ROS induction, morphological analysis, and western blot analysis. RESULTS: Apigenin showed selective cytotoxicity on MCF-7 cells with an IC50-56.72 ± 2.35 µM, while negligible cytotoxicity was observed on WI-38 cells. Further, the flow cytometer-based analysis showed that apigenin halted MCF-7 cells in the G2/M phase arrest followed by dose-dependent apoptosis. Moreover, the FACS and confocal microscopy results confirmed the elevation of intracellular ROS and nuclear fragmentation in apigenin-treated MCF-7 cells. Western blots showed up-regulation of cell cycle regulatory proteins, increased p53 expression, Bax/Bcl-2 ratio, activation of caspases, and cleavage of PARP. Finally, apigenin treatment in the presence of Pifithrin-µ showed decreased apoptotic population and it was further confirmed through western blotting study. The results revealed the vital role of p53 in apigenin-induced apoptosis in MCF-7 cells. CONCLUSIONS: In the present findings, treatment of apigenin-induced intracellular ROS in MCF-7 cells followed by induction of G2/M phase cell cycle arrest and further apoptosis through the regulation of p53 and caspase-cascade signaling pathway.

Assessing the clinical significance of echocardiograms in determining treatment of patent ductus arteriosus in neonates.

BACKGROUND: To evaluate the utility of echocardiogram (ECHO) in detection and treatment of patent ductus arteriosus (PDA) and hemodynamically significant PDA (hsPDA) in preterm neonates. METHODS: This was a retrospective case-control study of all preterm infants born or admitted to the level III Neonatal Intensive Care Unit in McMaster Children's Hospital from January 2009 to January 2013. These cases were further classified into the following sub-groups: group A) hsPDA confirmed on ECHO; and the control, group B) PDA (but not hemodynamically significant) confirmed on ECHO. Patients without an ECHO were excluded from all analyses. The primary outcome was incidence of treatment for PDA. RESULTS: PDA treatment was administered in 83.3% and 11.2% of patients in groups A and B respectively (P < 0.05). Among patients with a hsPDA within group A, 17% did not receive treatment, while 11% of patients with non-hemodynamically significant PDA received treatment for the PDA. Within the cohort of patients who received treatment for a hsPDA, gestational age below 35 weeks as well as murmurs heard on auscultation were both found to be predictors of treatment. CONCLUSION: While the ECHO remains the gold standard for detecting pathological PDA, there is evidence that other traditional clinical measures continue to guide clinical practice and treatment decisions. Further research is required to gain an understanding of how clinical measures and ECHO may be used in conjunction to optimize resource utilization.

Sundew plant, a potential source of anti-inflammatory agents, selectively induces G2/M arrest and apoptosis in MCF-7 cells through upregulation of p53 and Bax/Bcl-2 ratio.

The worldwide cancer incidences are remarkable despite the advancement in cancer drug discovery field, highlighting the need for new therapies focusing on cancer cell and its microenvironment, including inflammation. Several species of Drosera (family: Droseraceae) are used in various traditional as well as homeopathic systems of medicine. Drosera burmannii Vahl. is also enlisted in French Pharmacopoeia in 1965 for the treatment of inflammatory diseases, including chronic bronchitis, asthma and whooping cough. The present study is designed to substantiate the potential of D. burmannii in in vitro anticancer activity and its relation with anti-inflammatory property. In vitro anticancer study revealed that DBME is inhibiting the proliferation of MCF-7 cells without affecting the viability of other malignant and non-malignant cells. DBME induced G2/M phase arrest and apoptosis in MCF-7 cells by suppressing the expression of cyclin A1, cyclin B1 and Cdk-1 and increasing the expression of p53, Bax/Bcl-2 ratio leading to activation of caspases and PARP degradation. Presence of caspase-8 (Z-IETD-fmk) and caspase-9 (Z-LEHD-fmk) inhibitors alone did prevent the apoptosis partially while apoptosis prevention was significantly observed when used in combination, suggesting vital role of caspases in DBME-induced apoptosis in MCF-7 cells. DBME also downregulated LPS-induced increased expression of iNOS, COX-2 and TNF-α along with suppression on intracellular ROS production that confirms the potential of DBME as anti-inflammatory extract. GCMS analysis revealed the presence of four major compounds hexadecanoic acid, tetradecanoic acid, hexadecen-1-ol, trans-9 and 1-tetradecanol along with some other fatty acid derivatives and carotenoids (Beta-doradecin) in DBME. These findings confirmed the anti-inflammatory activity of DBME, which is already listed in French Pharmacopeia in 1965. Here we have additionally reported the anti-breast cancer activity of DBME and its relation to the anti-inflammatory potential. Hence, an ethnopharmacological approach can be considered as useful tool for the discovery of new drug leads.

Ab initio theory for femtosecond spin dynamics, angle-resolved fidelity analysis, and the magneto-optical Kerr effect in the Ni3(CH3OH) and Co3(+)(CH3OH) clusters.

We present a systematic analysis of the ab initio controlled femtosecond spin dynamics in Ni3(CH3OH) and Co3(+)(CH3OH) clusters achieved by a spin-orbit-coupling enabled Λ process. The distortion caused by the attachment of CH3OH to one of the active magnetic centers of the Ni3 and the Co3(+) clusters induces asymmetric geometries which result in well localized spin densities on the magnetic centers. With the use of high-level quantum chemistry methods, successful spin-flip scenarios are demonstrated for both clusters. In order to assess the experimental accessibility of those effects, we compute their tolerance with respect to two laser pulse parameters, i.e., the energy detuning as well as the deviation of the polar angle ϕ from its optimized value. Finally, we calculate the magneto-optical Kerr effect in order to connect to the susceptibility tensor χ as an experimentally measurable quantity.

Reduction of plasma aldosterone and arterial stiffness in obese pre- and stage1 hypertensive subjects after aerobic exercise.

Obesity-related hypertension is associated with increased activity of the renin-angiotensin-aldosterone system (RAAS), increasing arterial stiffness. Aerobic exercise decreases pulse wave velocity (PWV), therefore a treatment option for hypertension and obesity. Assess RAAS activity and PWV before and after 4 weeks of aerobic training in unmedicated, pre-to-stage-1 hypertensives. Ten obese subjects (52±3.2 years, body mass index=33.5±1.4) performed 30 min of aerobic exercise on a treadmill 3 days per week at 65% of peak oxygen consumption (VO2peak). Descriptive characteristics, systolic and diastolic blood pressure (SBP and DBP), PWV, and a blood draw was performed at baseline, following the 4-week control and training interventions. No differences in descriptive characteristics during the control period were observed, however, a significant decrease in plasma aldosterone (ALDO) (255.4±75 to 215.8±66 pg ml(-1), P=0.001), SBP (140±12 to 136±10.4 mm Hg; P=0.02), DBP (89±4.2 to 85±6.3 mm Hg; P=0.03) and central PWV (11.2±0.6 to 9.8±0.8 m s(-1); P=0.04) was shown pre-to-post exercise training. Four weeks of moderate-intensity aerobic training in obese, hypertensives decreases plasma ALDO independently of body weight and is significantly correlated to decreases in PWV reductions.

Phytochemical profile of a microalgae Euglena tuba and its hepatoprotective effect against iron-induced liver damage in Swiss albino mice.

AIMS: This study was aimed to evaluate different phytochemical constituents and the ameliorating effect of 70% methanol extract of Euglena tuba (ETME) on iron overload-induced liver injury, along with its in vitro iron-chelating and DNA protection effects. METHODS AND RESULTS: Phytochemicals of ETME were identified by GC-MS analysis. Iron chelation and protection of Fenton reaction-induced DNA damage was conducted in vitro. Post oral administration of ETME to iron-overloaded mice, the levels of serum parameters, antioxidant enzymes, liver iron, lipid peroxidation, protein carbonyl and hydroxyproline contents were measured. ETME showed inhibition of lipid peroxidation, protein oxidation and liver fibrosis. The serum markers and liver iron were lessened, whereas enhanced levels of liver antioxidant enzymes were detected in ETME-treated group. Furthermore, the histopathological observations also substantiated the protective effects of the extract. CONCLUSIONS: Several bioactive compounds identified by GC-MS may be the basis of hepatoprotective as well as antioxidant and iron-chelating effect of ETME. SIGNIFICANCE AND IMPACT OF THE STUDY: Currently available iron-chelating agents show several side effects and limitations which may be overcome by ETME, which suggest its benefit against pathology of iron overload-linked diseases. Hence, ETME can be used as a promising hepatoprotective agent.

In vitro assessment of praziquantel and a novel nanomaterial against protoscoleces of Echinococcus granulosus.

The present study describes the activity of a nanomaterial on protoscoleces of Echinococcus granulosus, which exhibited morphological changes and apoptosis. Apoptotic changes were deduced on the basis of effector caspase activation and nucleosomal laddering. Invaginated protoscoleces maintained in vitro became evaginated and had hooks, presumptive suckers and stalks. Degenerative changes of protoscoleces were evidenced after treatment with praziquantel and nano-combination. Protoscoleces treated with praziquantel had distinct attestation of necrosis and nano-combination-treated protoscoleces had signatures of apoptosis.

Inheritance of plumage colour variations in a large flock of Japanese quail.

1. The inheritance of various plumage colour variants and their underlying interactions were investigated in a large flock of Japanese quail maintained at CARI (India) by conducting reciprocal crosses between four breeding stocks inheriting Pharaoh, White Breasted, White and Brown plumages, followed by test crosses. 2. Based on the proportion of plumage-colour types in the progeny, putative genotypes were determined for parents and offspring for each of the crosses. 3. The White and Brown phenotypes were attributed to the Panda (S) and Roux (Br) loci respectively in agreement with contemporary quail stocks. 4. The White Breasted plumage type present in our stock was caused by a novel mutation with dominant gene action at an autosomal locus that was not allelic to either Panda or the White feather locus. 5. A recessive epistatic action of the Panda locus (S) on White Breasted (Wb) resulted in a White colour phenotype. 6. A novel phenotype, White Breasted-Brown was co-expressed with the Br and Wb loci. 7. It was concluded that breeding for customized feather colour phenotypes in Japanese quail using colour mutations was feasible and would be advantageous in order to overcome the limitations of legislation to protect wildlife in India.

Application of an MTT reduction assay for assessing sperm quality and predicting fertilising ability of domestic fowl semen.

1. The ability of domestic fowl spermatozoa to reduce MTT tetrazolium to its coloured formazan was compared with other tests of sperm quality and fertilising ability. 2. MTT reduction was highly correlated with sperm ATP content (r2 = 0.85); sperm mobility (r2 = 0.62.); sperm:perivitelline layer interaction (r2 = 0.80) and fertilizing ability (r2 = 0.83). 3. The simple, robust, MTT-reduction assay may therefore be used to select male chickens on the basis of their sperm quality and thus potential fertilising ability.

Genotypic diversity in species of Scilla.

Two cytotypes of Scilla indica and three other species, namely S. nervosa, S. siberica and S. vindobonensis were investigated. The estimation of nuclear DNA content was utilized as a measure of genetic diversity at inter- and intraspecific levels and as an index of the trends of evolution. S. siberica with a very high DNA value was regarded as indicative of a primitive state. The heavy intraspecific difference in DNA content in S. indica has been attributed to amplification of the DNA.

Primary osteogenic sarcoma of the tongue.

A 56-year-old man presented with the difficulty of swallowing and respiratory distress due to a large tumour arising from the tongue and occupying the entire oral cavity. Histological examination revealed it to be an extraskeletal osteogenic sarcoma. The tumour was excised. After six weeks, he came back with massive local recurrence and bleeding from the tumour, but died despite chemotherapy. Review of the literature revealed only four other such cases of this rare tumour. A brief review of these four cases is also made.

Modeling of pile footings and drilled shafts for seismic design

This report documents two studies that were conducted to review, assess, and provide recommendations regarding the seismic design of bridge foundations. Specifically, the report addresses modeling approaches and parameters that affect the seismic design and response of pile groups and drilled shafts. The report attempts to bridge the interface between the structural and geotechnical design process-in so doing, it describes a two-step design and analysis procedure for these bridge foundation components. Recent research results on pile group effects and the design of pile foundations to resist lateral spreading of liquefiable soils are also reviewed. Recommendations are provided concerning: modifications to p-y curves to account for cyclic loading conditions, pile group effects and soil-pile interaction behavior, and development of p-y curves for the design of drilled shafts.(AU)

Ortner's syndrome revisited.

Hoarseness of voice due to paralysis of the left recurrent laryngeal nerve caused by a dilated left atrium in mitral stenosis as discussed by Ortner, is a subject of controversy. Different authors have cited different mechanisms as explanation. A variety of cardiac problems such as primary pulmonary hypertension, ischaemic heart disease, various congenital heart disorders can all lead to paralysis of the left recurrent laryngeal nerve. Most authors believe that pressure in the pulmonary artery causes the nerve compression. In Papua New Guinea cor pulmonale and rheumatic heart disease are the commonest cardiac disorders seen. Ortner's syndrome is a rarity and has never been reported from here before. Here three different case reports are presented with mitral stenosis, primary pulmonary hypertension and combined mitral stenosis and regurgitation and the pathogenesis of hoarseness is discussed.

Recurrence of kala-azar after PKDL: role of co-factors.

Recurrence of kala-azar after post kala-azar dermal leishmaniasis (PKDL) has remained uncommon. We report here two patients with recurrence of kala-azar (KA) after development of PKDL. In one case the second attack of KA was preceded by repeated attacks of malaria and tuberculosis, and in the other the recurrence of KA followed an attack of measles. While measles has earlier been suggested as co-factor in inducing transformation from sub-clinical to clinical kala-azar, malaria was demonstrated to enhance the virulence and invasiveness of Leishmania in an experimental model as well as under natural condition. We propose that in our cases, measles and repeated attacks of malaria or tuberculosis led to immunosuppression and recurrence of visceral leishmaniasis (VL).