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Purpose: This study aims to evaluate the association between 2 weeks wait referral and survival in the head and neck cancer. Methods: Retrospective cohort study of consecutively discussed new head and neck cancer patients at large United Kingdom Cancer Alliance including two tertiary referral hospitals and two district general hospital. Results: A total of 276 cancer patients were included for analysis. Patients referred under the 2 weeks wait had were seen and diagnosed sooner from referral (p < 0.0001 and p < 0.0001 respectively). However, this did not translate into better survival outcomes. No survival differences were seen between those patients that were managed within the proposed cancer targets and those that were not. Conclusions: The 2 weeks wait head and neck cancer pathway did not offer a survival advantage. Targeting the delay in referral as well as delay in treatment to prevent late-stage cancer presentation is paramount. Fulfilment of cancer time targets do not translate into better outcomes and should not be prioritised to clinical judgement. [ABSTRACT FROM AUTHOR]

Co-existence of life style disorders, like, Diabetes or Hypertension, increases risk of, treatment failure, deaths and developing drug-resistant TB. Concomitant administration of drugs to treat dual/multi-morbidities may alter their effectiveness, in additive/synergistic or adverse/antagonistic manner. We evaluated interactive effect of 7 anti-hyperglycaemic (HG) and 6 anti-hypertensive (HT) drugs on the inhibitory (MICs) and bactericidal (% killing of intracellular bacilli) activities of anti-TB drugs, Isoniazid (INH), Rifampicin (RFM), Ethambutol (EMB) and Streptomycin (STR) against M. tuberculosis. Five anti-HG drugs, namely, Acarbose, Acetohexamide, Glyburide, Repaglinide and Sitagliptin imparted either 'additive' or 'no effect' on the activities (inhibition or % killing) of all the four anti-TB drugs, as evident by their lower FICs (Fractional Inhibitory concentrations) and higher bacterial killing in combination. Metformin and Rosiglitazone, however, exerted adverse effect on the Ethambutol (FICs >2.0). All the six anti-HT drugs, namely, Atenolol, Hydrochlorothiazide, Ramipril, Valsartan, Nifedipine and Verapamil exerted either 'additive'/'synergistic' or 'no effect' on the activities of anti-TB drugs. These findings may help clinicians to select safe and helpful anti-HG or anti-HT drugs for TB patients, if, suffering with diabetes or hypertension like co-morbidities and receiving DOTs (a set regimen for the treatment of TB based on the WHO guidelines). [ABSTRACT FROM AUTHOR]

It is widely understood that cancer is a significant cause of morbidity and mortality worldwide. Despite numerous available treatments, prognosis for many remains poor, thus, the development of novel therapies remains essential. Given the incredible success of many immunotherapies in this field, the important contribution of the immune system to the control, and elimination, of malignancy is clear. While many immunotherapies target higher‐order pathways, for example, through promoting T‐cell activation via immune checkpoint blockade, the potential to target specific immunological pathways is largely not well researched. Precisely understanding how immunity can be tailored to respond to specific challenges is an exciting idea with great potential, and may trigger the development of new therapies for cancer. Inborn Errors of Immunity (IEI) are a group of rare congenital disorders caused by gene mutations that result in immune dysregulation. This heterogeneous group, spanning widespread, multisystem immunopathology to specific immune cell defects, primarily manifest in immunodeficiency symptoms. Thus, these patients are particularly susceptible to life‐threatening infection, autoimmunity and malignancy, making IEI an especially complex group of diseases. While precise mechanisms of IEI‐induced malignancy have not yet been fully elucidated, analysis of these conditions can highlight the importance of particular genes, and downstream immune responses, in carcinogenesis and may help inform mechanisms which can be utilised in novel immunotherapies. In this review, we examine the links between IEIs and cancer, establishing potential connections between immune dysfunction and malignancy and suggesting roles for specific immunological mechanisms involved in preventing carcinogenesis, thus, guiding essential future research focused on cancer immunotherapy and providing valuable insight into the workings of the immune system in both health and disease. [ABSTRACT FROM AUTHOR]

Cuticle is the first layer protecting plants against external biotic and abiotic factors and is responsive to climatic factors as well as determined by genetic adaptations. In this study, the chemical composition of bilberry fruit cuticular wax was investigated through a latitudinal gradient from Latvia (56°N 24°E) through Finland (65°N 25°E) to northern Norway (69°N 18°E) in two seasons 2018 and 2019. Changes in the major cuticular wax compounds, including triterpenoids, fatty acids, alkanes, aldehydes, ketones, and primary alcohols, were detected by GC-MS analysis. Generally, a decreasing trend in the proportion of triterpenoids from southern to northern latitudes, accompanied with an increase in proportion of fatty acids, aldehydes, and alkanes, in bilberry fruit cuticular wax was observed. A correlation analysis between climatic factors with proportion of wax compounds indicated that temperature was the main factor affecting the cuticular wax composition in bilberries. A controlled phytotron experiment with southern and northern bilberry ecotypes confirmed the major effect of temperature on bilberry fruit cuticular wax load and composition. Elevated temperature increased wax load most in berries of northern ecotypes. The level of triterpenoids was higher, while levels of fatty acids and alkanes were lower, in wax of bilberry fruits ripened at 18°C compared to 12°C in both northern and southern ecotypes. Based on our results, it can be postulated that the predicted increase in temperature due to climate change leads to alterations in fruit cuticular wax load and composition. In northern ecotypes, the alterations were especially evident. [ABSTRACT FROM AUTHOR]

In vitro anti-tubercular activity of a series of 15 novel 2,3-dihydroquinazolin-4(1H)-one analogues were evaluated against Mycobacterium tuberculosis H37Ra (ATCC 25177 strain). Among the series, seven compounds showed moderate to good anti-TB activity with minimum inhibitory concentration (MIC) values ranging from 25.0–12.5 μg/mL. Further, in silico experiments were carried out to identify the probable ligand-protein interaction. Molecular docking of the target compounds into the active site of enzymes 1DQY Antigen 85C from Mycobacterium Tuberculosis and 2NSD Enoyl Acyl Carrier Protein Reductase reveals notable information on the possible binding interactions. [ABSTRACT FROM AUTHOR]

A silica‐supported iron complex has been identified as a highly active and reusable catalyst for the synthesis of medicinally important 2,3‐dihydroquinazolin‐4(1H)‐ones. The catalyst was fully characterized by various spectroscopic analyses such as Fourier‐transform infrared spectroscopy (FT‐IR), ultraviolet‐visible (UV–VIS), scanning electron microscopy (SEM), scanning electron microscopy with energy‐dispersive X‐ray spectroscopy (SEM–EDX), energy‐dispersive spectroscopy (EDS) mapping, X‐ray diffraction (XRD), X‐ray photoelectron spectroscopy (XPS), electron paramagnetic resonance (EPR), inductively coupled plasma atomic emission spectroscopy (ICP‐AES), elemental analysis, Brunauer–Emmett–Teller (BET) isotherm and thermogravimetric analysis (TGA) analysis. A diverse library of 2,3‐dihydroquinazolin‐4(1H)‐ones including some new analogues were successfully synthesized in good to excellent yields with parts‐per‐million (ppm) levels of Fe using water as a solvent. The active catalyst has high turnover number (TON) and turnover frequency (TOF) at the optimized condition, which were 30,087 and 30,087 h−1, respectively. Ppm level catalysis, wide substrate scope, shorter reaction time, reusability of the catalyst, green solvent media and gram‐scale synthesis make this protocol eco‐friendly and sustainable. [ABSTRACT FROM AUTHOR]

The aerial parts of land plants are covered by a hydrophobic layer called cuticle that limits non-stomatal water loss and provides protection against external biotic and abiotic stresses. The cuticle is composed of polymer cutin and wax comprising a mixture of very-long-chain fatty acids and their derivatives, while also bioactive secondary metabolites such as triterpenoids are present. Fleshy fruits are also covered by the cuticle, which has an important protective role during the fruit development and ripening. Research related to the biosynthesis and composition of cuticles on vegetative plant parts has largely promoted the research on cuticular waxes in fruits. The chemical composition of the cuticular wax varies greatly between fruit species and is modified by developmental and environmental cues affecting the protective properties of the wax. This review focuses on the current knowledge of the cuticular wax biosynthesis during fleshy fruits development, and on the effect of environmental factors in regulation of the biosynthesis. Bioactive properties of fruit cuticular waxes are also briefly discussed, as well as the potential for recycling of industrial fruit residues as a valuable raw material for natural wax to be used in food, cosmetics and medicine. [ABSTRACT FROM AUTHOR]

In situ current–voltage characteristics of Nb-doped TiO2/p-Si-based heterojunction diode have been studied under dense electronic excitations of 84-MeV Si6+ ions. The diode parameters such as ideality factor ($\eta $), barrier height ($\phi _{B}$), reverse saturation current (${J}_{s}$), and series resistance (${R}_{s}$) are found to be a strong function of ion irradiation fluence. The observed anomalies of fluence dependence of barrier height and ideality factor are explained in terms of irradiation-induced created defects complexes, modification of interface states and structural properties of Nb-doped TiO2 (NTO) layer. Several mechanisms such as barrier height inhomogeneity, donor defects-induced enchantment in n-NTO layer conductivity, and various current conduction mechanisms involved at different voltage ranges are discussed as a function of fluence with the help of constructed energy band diagram. Such in situ studies on n-NTO/p-Si heterojunction diode under radiation harsh environment are very appropriate for the better understanding of heterojunction interface properties and make it suitable for use in aerospace industry and nuclear reactors. [ABSTRACT FROM AUTHOR]

We present the results of studies on the dielectric properties of polycrystalline Bi1-xCaxFeO3(x = 0.05, 0.10, 0.20) (BCFO) multiferroics. Rietveld refined XRD patterns confirm the single phasic nature of 5% & 10% Ca – doped samples crystallizing in superimposed R3c (Rhombohedral) + Pm 3m (Cubic) space group symmetry while 20% Ca – doped sample crystallize in Pm 3m symmetry. Frequency and temperature dependent dielectric constant (ϵ) studies show the contribution of grain and grain boundaries in the system. Complex impedance graph exhibits a single semicircular arc for all the samples, indicating the contribution of grain interior (bulk) property of the material. [ABSTRACT FROM AUTHOR]

The present study for the first time explores the use of Central composite design (CCD) of RSM to optimize the process parameters of biosynthesis of AgNPs from rhizome extract of Curculigo orchioides based on the absorbance of surface plasmon resonance (SPR) band at 430 nm that corresponds to the synthesis of mono-disperse, spherical AgNPs. A polynomial model was established as a functional relationship between the synthesis of AgNPs and four independent variables such as concentration of AgNO, % rhizome extract, pH and temperature. The optimum conditions for maximum AgNPs synthesis were 2 mM concentration of AgNO, 20 % rhizome extract, pH 8, and temperature of 60 °C. A significant correlation ( R = 0.8947) was observed between the experimental data and the predicted values indicating the adequacy of the model. Transmission electron microscopy (TEM) revealed spherical particles with size range of 5-28 nm. Selected area electron diffraction pattern and X-ray diffraction analysis confirmed the face-centered cubic structure of metallic silver. The plausible mechanism for the reduction of AgNO to AgNPs was proposed following the identification of functional groups by FTIR. The antioxidative activity of AgNPs was demonstrated with scavenging of hydrogen peroxide (HO), 1,1-Diphenyl-2-picrylhydrazyl (DPPH) and superoxide radicals. [ABSTRACT FROM AUTHOR]

It remains challenging to produce decisive vaccines against MUC1, a tumor-associated antigen widely expressed by pancreas, breast and other tumors. Employing clinically relevant mouse models, we ruled out such causes as irreversible T-cell tolerance, inadequate avidity, and failure of T-cells to recognize aberrantly glycosylated tumor MUC1. Instead, every tested MUC1 preparation, even non-glycosylated synthetic 9mer peptides, induced interferon gamma-producing CD4+ and CD8+ T-cells that recognized glycosylated variants including tumor-associated MUC1. Vaccination with synthetic peptides conferred protection as long as vaccination was repeated post tumor challenge. Failure to revaccinate post challenge was associated with down-regulated tumor MUC1 and MHC molecules. Surprisingly, direct admixture of MUC1-expressing tumor with MUC1-hyperimmune T-cells could not prevent tumor outgrowth or MUC1 immunoediting, whereas ex vivo activation of the hyperimmune T-cells prior to tumor admixture rendered them curative. Therefore, surrogate T-cell preactivation outside the tumor bed, either in culture or by repetitive vaccination, can overcome tumor escape. [ABSTRACT FROM AUTHOR]

Context: Cytarabine (Ara-C) is an effective chemotherapeutic drug for the treatment of acute leukaemias. It inhibits the DNA synthesis and repair, thereby causes cytotoxicity in the proliferating cells. Objective: This study was aimed to investigate the effects of pre-pubertal exposure of Ara-C on testesticular development in juvenile SD rats and their function at puberty. Materials and methods: Ara-C was injected at the doses of 50, 100 and 200 mg/kg/day from postnatal day (PND) 29-42 (14 days) by intraperitoneal ( i.p.) route. Half of the animals were sacrificed on PND 43 and remaining on PND 70. End points of the evaluation included gross pathological examination, histomorphometric analysis, sperm count and sperm head morphology, cell proliferation and DNA damage as well as apoptosis analysis. Results: Ara-C treatment significantly decreased food and water intake, weight gain, testes and epididymis weight and increased histological alterations in the seminiferous tubule. Furthermore, Ara-C treatment significantly decreased the PCNA-positive cells and sperm count in a dose-dependent manner. Ara-C treatment also increased the DNA damage and apoptosis in testes and sperm as evident from the comet and TUNEL assays results. Discussion: The present study results clearly indicated that Ara-C treatment impaired spermatogenesis and adversely affects the testicular development and its function in rats by reducing the germ cell proliferation and the inducing DNA damage and apoptosis. [ABSTRACT FROM AUTHOR]

Ulcerative colitis is an idiopathic, chronic and relapsing inflammatory bowel disease, which elicits the risk of colorectal cancer, the third most common malignancy in humans. It has been known for a long time that oxidative stress is a major pathogenic factor in the inflamed tissue that can pave the way towards DNA damage and carcinogenesis. However, the DNA damage produced due to oxidative stress in the inflamed tissue is not limited to the local site but extends globally, thereby augmenting the risk of global carcinogenesis. Targeting oxidative stress may provide an exciting avenue to combat inflammation-associated local as well as global DNA damage and the subsequent carcinogenesis. The present review portrays the role of oxidative stress in the pathogenesis of ulcerative colitis and the associated local as well as global DNA damage, which may lead to carcinogenesis. [ABSTRACT FROM AUTHOR]

Micelle-mediated extraction and cloud-point preconcentration method was developed for the separation and determination of andrographolide (ANDRO) and neo-andrographolide (NEO) from Andrographis paniculata by planar and high performance liquid chromatography with photodiode array detection. Comparative efficiency and feasibility of employing non-ionic surfactants, namely, Triton X-100, Triton X-114, and Genapol X-80 as an alternative and effective solvent have been demonstrated. Ultrasonic assisted extraction, when compared with common organic solvents, at 5% surfactant (Triton X-100) concentration has yielded higher extraction efficiency of ANDRO and NEO than common organic solvents. The preconcentration factor was approximately 7.0 and the cloud-point extraction recoveries for the two labdane diterpenoids were 90.28 and 98.80%, respectively. The HPLC method consisting monolithic column and isocratic elution with water: acetonitrile (75:25, v/v) has shown advantages over C18 column, in terms of noninterference of surfactant peak elution. The elution was monitored with a photodiode array detector and quantitation was performed at 220 nm. The method has shown good sensitivities (LOD- 10, 30 µg/mL; LOQ- 33, 99 µg/mL of ANDRO and NEO, respectively). The results showed that micelle-mediated extraction and cloud-point preconcentration could be employed as an alternative and ecofriendly approach for the rapid analysis of targeted diterpenoids from A. paniculata. [ABSTRACT FROM AUTHOR]