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AbstractPhlogacanthus thyrsiflorusNees (Acanthaceae) is traditionally used in the North East Himalayan region to treat stomach issues, including gastritis. This study aimed to investigate the gastroprotective effect of 70% aqueous ethanol extract of Phlogacanthus thyrsiflorusflowers (PTE), standardized by HPTLC and LC-MS/MS, and to establish its possible mechanisms. The gastroprotective effect of PTE, at doses of 200 and 400 mg/kg body weight, was evaluated using both physical (pylorus ligation, PL; cold restraint stress, CRS) and chemical (ethanol, EtOH) ulcerogens-induced gastric ulcers in Wistar rats. Animals were randomly divided into control, ulcer control, positive control and PTE-treated groups, with PTE administered orally twice daily for 5 days. The protective effect of PTE was assessed through various gastric ulcer parameters, including gastric pH, gastric wall mucus, non-protein sulfhydryls (NP-SH) content, microvascular permeability, endogenous antioxidant markers, and gastric histopathology. HPTLC and LC-MS/MS confirmed the presence of gallic acid, naringenin, β-sitosterol and ascorbic acid in PTE. The active components of PTE showed significant dose-dependent inhibition of ulcer index, with reductions of 28.59-50.03% in PL, 27.69-53.23% in EtOH and 31.14-57.53% in CRS models (P< 0.01). Additionally, PTE at 400 mg/kg significantly increased gastric pH by 23.41%, mucus content by 33.69%, and NP-SH levels by 37.24%. PTE also demonstrated significant antioxidant potential and histopathological studies confirmed its protective effect. The study suggests that the anti-ulcer effect of PTE may be attributed to its ability to preserve adhered gastric mucus, exhibit antisecretory effects, and scavenge free radicals.

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Background: Literature meta-analysis results show that digital breast tomosynthesis (DBT) combined with synthesized two-dimensional (s2D) mammograms can reduce recalls and improve breast cancer detection. Uncertainty regarding the screening of patients with breast cancer presents a health economic challenge, both in terms of healthcare resource use and quality of life impact on patients. Objective: This study aims to estimate the cost effectiveness of DBT + s2D versus digital mammography (DM) used in a biennial breast cancer screening setting of women aged 40–69 years with scattered areas of fibroglandular breast density and heterogeneous dense breasts in the Brazilian supplementary health system. Methods: A cost-effectiveness analysis was performed on the basis of clinical data obtained from a systematic review with meta-analysis performed to evaluate the analytical validity and clinical utility of DBT + s2D compared with DM. The search was conducted in the PubMed, Cochrane Library and Embase databases, with the main descriptors of the technology, a comparator, and the clinical condition in question, on 9 June 2022. The hybrid economic model (decision tree plus Markov model) simulated costs and outcomes over a lifetime for women aged 40–69 years with scattered areas of fibroglandular breast density and heterogeneous dense breasts. We analyzed incremental cost-effectiveness ratio (ICER) to measure the incremental cost difference per quality-adjusted life year (QALY) of adding DBT + s2D to breast cancer screening. Results: DBT + s2D incurred a cost saving of € 954.02 per patient, in the time horizon of 30 years, compared with DM, and gained 5.1989 QALYs, which would be considered a dominant intervention. These results were confirmed in sensitivity analyses. Conclusion: Switching from DM to biennial DBT + s2D was cost effective. Furthermore, reductions in false-positive recall rates should also be considered in decision making.

Background: The words "nutrition" and "pharmaceutical" are combined to form the phrase "nutraceutical." Nutraceuticals are foods or dietary components that have an important role in regulating and sustaining normal physiological function in humans. For the treatment of dysmenorrhoea, a variety of pharmacological medications are available, however, they all have significant side effects. Dietary supplements and lifestyle management, on the other hand, were found to have a major influence on the occurrence and control of dysmenorrhea.Objective: The objective of this paper is to study a comprehensive review of the dietary and nutritional supplements with special emphasis on dysmenorrhea. This paper focuses on understanding and interpreting the details of menstrual pain and its effective nutritional diet that can be used as a treatment for avoiding menstrual discomfort.Methods: The selection of data has been done by studying a combination of various research and review papers from different databases like PubMed, NCBI, Science Direct, WHO, Cochrane Library, and Web of Science from the year 2000-2022.Results: Based on various papers and literature reviews, we have concluded about various dietary supplements and herbs that can be used to avoid pain during mensuration followed by its all-daily requirement of nutrition on different age groups and efficacy of treatments.Conclusion: According to current evidence, young women should be instructed in the proper use of dietary supplements, nutrition, and vitamins, as well as the inclusion of effective diet and lifestyle changes such as exercise and a well-balanced diet with adequate nutrition, as these are likely to reduce the negative effects of dysmenorrhea.

Artificial Intelligence (AI) is a branch of computer science that deals with mathematical algorithms to mimic the abilities and intellectual work performed by the human brain. Nowadays, AI is being effectively utilized in addressing difficult healthcare challenges, including complex biological abnormalities, diagnosis, treatment, and clinical prognosis of various life-threatening diseases, like cancer. Deep neural networking (DNN), a subset of AI, is prominently being applied in clinical research programs on cancer. AI acts as a promising tool in radiotherapy, mammography, imaging, cancer prognosis, cancer genomics and molecular signaling, pathology, drug discovery, chemotherapy, immunotherapy, and clinical decision support system. This article provides an elaborative view concerning the application of AI in cancer, an explorative review that how AI has been used as a trenchant tool in the past, present and future of cancer. This review article provides a new prospective that how the mimic of human intellectual (AI technology) has put forward an unprecedented accuracy in the field of clinical research of cancer.

AbstractThe synthesized 1,5 diarylpenta-1,4-dien-3-one derivatives (compounds 1-6) as synthetic curcumin analogues were tested for their potential anticancer activity against human ovarian and lung adenocarcinoma cells. The absorption, distribution, metabolism, excretion, and toxicity (ADMET/pharmacokinetic) parameters of all the compounds were predicted by admetSAR software. The pharmacokinetics, pharmacodynamics and bioactivity scores properties based on Lipinski rule and Ghose filter, calculated with the help of Molinspiration and ChemDraw. Molecular docking evaluation of all the compounds was also performed by using AutoDock Vina and iGEMDOCK against three most common human anticancer targets; epidermal growth factor receptor (EGFR), heat shock protein (Hsp 90-α), and vascular endothelial growth factor receptor-2 (VEGFR2). The obtained results were compared with the reference compound 7 and drugs 8-10 (7: GO-035; 8: Quinazolin; 9: Naquotinib and 10: Ribofuranuronamide). Finding indicates, all the compounds were potentially interacting with VEGFR2 through the average –9.1 binding energy (BE) with closer contact <5.0 Å deep in the active site of the ligand-receptor complex. All the compounds showed excellent oral bioavailability, bioactivity score, and none of the compounds are virtually found to be toxic. Compounds 1-6 were also successfully characterized by the physical properties as well as spectroscopic techniques (FT-IR and 1H-NMR). In vitroanti-proliferative activity was tested viaMTT method against human ovarian carcinoma (PA-1) and human lung adenocarcinoma (A549) cells and further screened for apoptotic parameters such as nuclear fragmentation and ROS generation. Compound 4 exhibits good dose-dependent anti-proliferative activity (IC5073 and 79.7 µM) against human ovarian carcinoma and human lung adenocarcinoma, respectively.Communicated by Ramaswamy H. Sarma

Maximizing water productivity amid agricultural water scarcity demands accurate crop evapotranspiration (ETc) estimation. While the Penman–Monteith method is standard, its dependence on extensive meteorological data restricts use in data-scarce regions. Eddy covariance offers precise ETcestimation but is resource-intensive. Satellite remote sensing, like MOD16, offers a promising alternative for ET estimation. Several empirical models are also available, out of which suitable alternatives can also be identified for the regions with limited weather data availability, where eddy covariance and remote sensing techniques become limitations. Consequently, a study was undertaken to investigate the performance of eddy covariance method (Eddy Tower based), empirical models, and a remote sensing technique for computing crop evapotranspiration under rice–wheat cropping system at Naraingarh Seed Farm of Punjab Agricultural University, Ludhiana, for the years 2022–2023. The performance evaluation of all the methods was performed using statistical indicators, including mean absolute error, mean bias error, root mean squared error, coefficient of determination, and index of agreement. The eddy covariance method, selected empirical models, and remote sensing technique demonstrated a good correlation with FAO Penman–Monteith ET, with coefficient of determination values greater than 0.85. The eddy covariance tower gives precise ETcestimates, with MOD-16 satellite data closely trailing. When Eddy Tower data is inaccessible, MODIS products provide a reliable alternative on a broader scale. In the absence of MODIS data, such as during cloud cover, empirical models offer effective EToand hence ETcestimation. Moreover, for regions lacking weather data, models like Hargreaves and Samani (1985) or Priestley and Taylor (1972) stand out as optimal choices for accurate EToand thereafter ETcestimation.

AbstractAchyranthes asperais an economically important medicinal plant, exhibiting a wide range of cytomorphological diversity. Taking into account, its pharmacological activities, as well as variability, found within the species, the present attempt was made to study the detailed meiotic course in 13 plant samples collected from different areas of North India. The anti-diabetic activity of three different cytotypes (diploid, tetraploid, and hexaploid) and two different morphotypes (obovate-leaf morphotype and ovate-leaf morphotype) was investigated in alloxan-induced Swiss albino male rats. Additionally, phytochemical analysis of aerial parts of these cytotypes and morphotypes was performed using the UPLC technique. The meiotic analysis depicts the presence of three cytotypes with 2n=14, 28, and 42. The results indicated that the diploid cytotype of A. asperahas maximum activity against diabetes in alloxan-induced diabetic rats. Out of the two morphotypes, the obovate-leaf morphotype showed a potent anti-diabetic effect as compared to the ovate-leaf morphotype. UPLC results showed that the maximum percentage of active component oleanolic acid was present in diploid cytotype followed by tetraploid and hexaploid cytotypes. A comparative study of the two morphotypes within the tetraploid cytotype revealed that the obovate-leaf morphotype possessed a higher percentage of oleanolic acid as compared to the ovate-leaf morphotype.

Boerhavia diffusais an herbaceous plant of the family Nyctaginaceae. It is mentioned to have anti-aging, disease prevention, and life-enhancing activities that hold enormous influence on disease burden and affordability/availability of healthcare in the world. In the present study, various populations of this plant species were characterized using morphological markers, cytogenetic and phytochemical analyses. Besides, biological activity was also studied for anti-diabetic and anti-bacterial effects using rats and bacterial systems respectively. For the three cytotypes i.e. diploid, tetraploid and octaploid, twelve morphological traits were studied. HPLC system was used for the identification of bioactive compounds present in extracts. The in vivo anti-hyperglycemic effects of the extract in alloxan- induced diabetes were determined using Swiss albino rats. Rats with fasting plasma glucose vary ≥ 300–315 mg/dl were treated to be diabetic and utilized for the examination. Anti-bacterial activities of three cytotypes of B. diffusawere screened by using the Disc diffusion method against two strains of Gram-positive bacteria and three strains of Gram-negative bacteria. The present study reports the existence of diploid, tetraploid and octaploid cytotypes which was new report from India. The diploid cytotype of B. diffusashowed maximum activity against diabetes in alloxan-induced diabetic rats and more anti-bacterial activity in Gram-positive and Gram-negative bacteria as compared to tetraploid and octaploid cytotypes. HPLC results showed that the concentration of phytoconstituents showed a negative correlation with the ploidy level being maximum in plants with lower ploidy levels. The present paper represents the first report of the pharmacognostic study based on different plant parts and cytotypes in B. diffusa. Results of the present study will be useful for exploiting appropriate cytotypes for various purposes such as formulating new anti-diabetic and anti-bacterial drugs from B. diffusa.

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This research aims to examine the influence of altering the relative arrangement of (0°/90°) and (± 45°) angle plies with respect to the midplane of a laminate on the flexural and fatigue characteristics of fiber-reinforced composites composed of carbon and basalt fibers with an epoxy matrix. Three laminate configurations of carbon and basalt fiber-reinforced laminate were examined: These configuration included an eight-layer symmetric [(0°/90°)/(± 45°)2/(0°/90°)]//[(0°/90°)/(± 45°)2/(0°/90°)] and an eight layer asymmetric having [(0°/90°)/(± 45°)2/(0°/90°)//(± 45°)/(0°/90°)2/(± 45°)], and (± 45°)/(0°/90°)2/(± 45°)//(0°/90°)/(± 45°)2/(0°/90) stacking sequence. Flexure and fatigue tests were conducted on FRP composites under monotonic and cyclic loading. Varied parameters were carefully chosen, including load range (90–50%), loading frequency (f = 1 Hz), stress ratio (R= 0.1), and different stacking sequences. The findings of this study unveiled noteworthy insights. (1) The flexural and fatigue properties of the C-SYM and B-SYM specimens surpassed those of their respective asymmetric specimens, indicating their superior performance in bending applications. (2) The flexural modulus of the fibers played a pivotal role in determining the failure mode observed in the composite coupons, underscoring the significance of fiber properties in composite behavior. (3) Fatigue failure in the composites was attributed to the progressive propagation of damage, highlighting the cumulative nature of structural deterioration under cyclic loading conditions.

AbstractThe present work identifies the essential oil components of Azadirachta indicaleaves from three different locations viz. Haryana, Punjab, and Uttar Pradesh. The yields of essential oils obtained by hydro- distillation were 0.018 %, 0.038 %, and 0.047 % from Haryana, Punjab, and Uttar Pradesh, respectively. The detailed chemical composition of essential oils was analyzed by GC-MS, and thirty-six, thirty-two, and thirty- four compounds were identified. The results indicated that the most abundant components of sample AzP were germacrene-B (40.31 %), β-caryophyllene (10.89 %), mintsulfide (9.41 %), γ-elemene (7.24 %), α-humulene (2.87 %), bicyclogermacrene (2.70 %), phytol (2.64 %), and α-cadinol (2.00 %). Compared with the constituents of sample AzP, several chemical compounds such as γ-Elemene, bicyclogermacrene, and phytol were not detected in sample AzB and sample AzS and were unique to sample AzP only. Sample-AzB was dominated by tetracosane (52.44 %), β-caryophyllene (5.16 %), palmitic acid (3.70 %), mintsulfide (2.92 %), docosane (2.79 %), spathulenol (2.28 %), hexadeca-7, 10, 13-trienal (2.12 %), and α-cadinol (2.08 %). Sample AzS was found to be rich in n- docosane (21.26 %), phytol (21.09 %), 1-docosene (20.28 %), octadecanol acetate (10.04 %), palmitic acid (2.88 %), and germacrene B (1.94 %). The present study identifies the best site where the cultivation of A. indicacan preferably be done commercially, for the use of plant in preparation of medicines and other formulations.

AbstractSyzygium cumini, is a medicinally important plant and exhibits a wide range of cytomorphological diversity. The present attempt was made to study the detailed meiotic course in five different populations from North India. The meiotic analysis depicts the presence of three cytotypes with 2n = 22, 44, and 66. These cytotypes were further subjected to the chemical analysis of the content and composition of leaf essential oil by GC-MS. All three-leaf samples (SLS-1, SLS-2, and SLS-3) collected from the same study area (Patiala, Punjab) were reported to be different in the content and composition of their essential oil components. The extraction yields of oils from leaves were 0.37 % (SLS-1), 0.42 % (SLS-2), and 0.39 % (SLS-3), respectively. The essential oil constituents identified were 38, 39, and 39 out of total 40 constituents for each oil sample representing 99.08 %, 99.52 %, and 99.39 % of the compositions, respectively. The major constituents of leaf essential oil of sample SLS-1 were: Iso-dihydrocarveol (14.61 %); (Z)-β-ocimene (12.02 %). From sample SLS-2 were (Z)-β-ocimene (19.45 %); α-pinene (14.80 %). From the sample, SLS-3 was: (Z)-β-ocimene (13.75 %); α-pinene (9.08 %), respectively. The present study identifies the best cytotype which can be preferably cultivated commercially for their use in the preparation of medicines and other formulations.

AbstractDue to the dynamic nature of Mobile Ad hoc NETwork (MANET) the designing and development of protocols is very challenging. MANET has a limited number of resources i.e., power, infrastructure, etc. The need for an optimized path for communication amongst node has attracted the use of Swarm Intelligence (SI) based techniques such as Ant-Colony Optimization (ACO), Particle Swarm Optimization (PSO). In sort to broaden the duration of communication availability, the protocol needs to be optimized for finding out the greatest path. SI based techniques are able to solve these numerous routing problems. ACO provides the optimized packet delivery rate, throughput with low power consumption and packet delay. This paper compares the performance of various existing routing protocols viz. AODV, AOMDV as reactive, DSDV as proactive and ACOP using Random Waypoint Mobility Model. The purpose of using this mobility model is generating different scenarios for the same purpose. The analysis of these protocols has been made by implementing irregularities in the scenario using Network Simulator (NS2). Various performance metrics including Packet Delivery Fraction, Throughput and End to end Delay are used for validating the comparative study. Experimental results of the simulation indicate that the performance of the ACOP protocol is found better than other protocols of study.

Gastrointestinal nematodes are re-emerging in countries where the popularity of free-range poultry production systems is increasing. Amongst all gastrointestinal nematodes, Ascaridia galliis of significant concern due to the parasite's direct life cycle and ability to survive extreme environmental conditions. In laying hens, A. galliparasites have been associated with reduced health, welfare, immunity, and egg production. Direct losses are caused by obstruction and damage of the intestinal tract in hens when high worm burdens are present. These result in reduction in egg production and body weight of infected laying hens, consequently leading to significant economic losses for farmers. Furthermore, heavy infections with A. gallimay lead to increased mortality within the flock. Indirect losses are due to suppression of immune system function which can increase susceptibility to secondary infections. Infection with A. gallican also alter nutrient utilization and absorption. Levels of anti- A. galliserum and egg yolk antibodies increase following A. galliinfection. Elevated antibodies can be used as an indicator of current or previous infections and therefore can be used as a diagnostic tool. The impact of A. gallion hen health and welfare manifests through the depletion of liver lipid reserves and increased use of energy reserves to mount immune responses against the parasite. This review highlights the variable effects of A. galliinfection on the performance, health, egg quality, and emphasizes especially on immune responses of free-range laying hens as well as it evaluates various potential detection methods and preventive and control measures of this parasitic disease.

Systemic chemotherapy for retinoblastoma comes with various haematological side effects, hence, require newer treatment approaches. This study developed carboplatin (CPT) and etoposide (ETP) loaded biodegradable PLGA microparticles as a combination therapy for extended action decreasing frequency of administration. CPT and ETP loaded PLGA microparticles (CE-MIP) were prepared by emulsification-spray drying technique. The optimized drug loaded PLGA microparticles were characterized for particle size (3–14 μm), zeta potential (−23.0 to −34.2 mV), entrapment efficiency (ETP - >80 % & CPT - >60 %) and in vitrorelease (CPT – 4 h & ETP – 72 h). In vitrocytotoxicity studies of CE-MIP showed greater anti-cancer effect (25.33 % cell viability) compared to plain drug mixture (38.56 % cell viability) in Y-79 cells. In WERI-Rb cell lines, the CE-MIP and plain drug mixture at 100 μM showed percent cell viability as 37.82 % and 66.08 % respectively. In the soft agar assay, the CE-MIP treatment demonstrated a significant reduction in the number of colonies (∼50 % reduction) formed compared to control. In orthotropic mouse model of retinoblastoma, the apoptotic effect of subconjunctival CE-MIP (15.7 %) was greater compared to control (7.9 %). Mean tumor burden of CE-MIP treated eyes was significantly smaller compared to the untreated control eyes showing the anti-tumor efficacy of developed CE-MIP.

ObjectiveTo explore how the number and type of breast cancers developed after screen detected atypia compare with the anticipated 11.3 cancers detected per 1000 women screened within one three year screening round in the United Kingdom.DesignObservational analysis of the Sloane atypia prospective cohort in England.SettingAtypia diagnoses through the English NHS breast screening programme reported to the Sloane cohort study. This cohort is linked to the English Cancer Registry and the Mortality and Birth Information System for information on subsequent breast cancer and mortality.Participants3238 women diagnosed as having epithelial atypia between 1 April 2003 and 30 June 2018.Main outcome measuresNumber and type of invasive breast cancers detected at one, three, and six years after atypia diagnosis by atypia type, age, and year of diagnosis.ResultsThere was a fourfold increase in detection of atypia after the introduction of digital mammography between 2010 (n=119) and 2015 (n=502). During 19 088 person years of follow-up after atypia diagnosis (until December 2018), 141 women developed breast cancer. Cumulative incidence of cancer per 1000 women with atypia was 0.95 (95% confidence interval 0.28 to 2.69), 14.2 (10.3 to 19.1), and 45.0 (36.3 to 55.1) at one, three, and six years after atypia diagnosis, respectively. Women with atypia detected more recently have lower rates of subsequent cancers detected within three years (6.0 invasive cancers per 1000 women (95% confidence interval 3.1 to 10.9) in 2013-18 v24.3 (13.7 to 40.1) in 2003-07, and 24.6 (14.9 to 38.3) in 2008-12). Grade, size, and nodal involvement of subsequent invasive cancers were similar to those of cancers detected in the general screening population, with equal numbers of ipsilateral and contralateral cancers.ConclusionsMany atypia could represent risk factors rather than precursors of invasive cancer requiring surgery in the short term. Women with atypia detected more recently have lower rates of subsequent cancers detected, which might be associated with changes to mammography and biopsy techniques identifying forms of atypia that are more likely to represent overdiagnosis. Annual mammography in the short term after atypia diagnosis might not be beneficial. More evidence is needed about longer term risks.

This article highlights the recent publications and changing trends in practice regarding management of high-risk lesions of the breast. Traditional management has always been a surgical operation but this is recognized as overtreatment. It is recognized that over diagnosis is inevitable but what we can control is overtreatment. Vacuum assisted excision is now established as an alternative technique to surgery for further sampling of these high-risk lesions in the UK. The use in Europe is also increasing. Guidelines from UK and Europe now recognize this alternative pathway and data is available showing that VAE is a safe alternative to surgery.

Present study synthesized stimuli-sensitive drug delivery systems for anti-cancer drug doxorubicin hydrochloride (Dox) and antibiotic drug gentamicin sulphate (GS) using sterculia gum, gelatin, and Fe3O4nanoparticles. The approach involved oxidizing sterculia gum with NaIO4, followed by self-crosslinking with gelatin resulting a pH-responsive protein hybrid crosslinked network. Further gel matrix was reinforced with Fe3O4nanoparticles formed magnetic nanocomposite hydrogel. FTIR, powdered XRD, and FESEM had used to characterize the functionalized drug-loaded hydrogels. In vitrorelease behavior of Dox and GS had been studied in pH 2.2, 7.0, 7.4, simulated gastric fluid (SGF) and in simulated intestinal fluid (SIF). For both drugs, highest release in pH 2.2 and SGF has been achieved, while minimum in physiological pH 7.4. The release mechanisms adopted by Dox and GS from drug loaded OSG-cl-Gelatin and OSG-cl-Gelatin/Fe3O4matrix have been assessed using different mathematical models viz Zero order, First order, Higuchi kinetic model and Korsmeyer Peppas model in different release mediums. Drug release mainly had occurred through Case-II diffusion mechanism. In acidic pH, Dox release followed Higuchi kinetic model while GS release occurred through Korsmeyer Peppas model. Hydrolytic degradation potential, thrombogenicity and haemocompatible behavior of functionalized gel matrix had also been screened.

•NEPi and ACE2 activator combination increased cGMP, inhibited fibrosis and apoptosis in diabetic heart.•Ability to reverse H3K4Me2 and its methyl transferases expressions may add to its cardioprotective potential.•NEPi and ACE2 activator combination can be a novel therapeutic strategy against diabetic cardiomyopathy.

Background: Neprilysin inhibitors (NEPi) are assisting the renin-angiotensin system (RAS) inhibitors in halting diabetic cardiomyopathy (DCM). Away from conventional tactic, a recent report revealed the renoprotective potential of NEPi and angiotensin-converting enzyme (ACE2) activator combination therapy against diabetic nephropathy. However, this combination so far not evaluated against DCM, thus the present investigation aiming the same. Methods: Streptozotocin-induced (55 mg/kg, ip) type 1 diabetic (T1 D) male Wistar rats were treated with either monotherapy of thiorphan (0.1 mg/kg/day, po)or diminazene aceturate (5 mg/kg/day, po), or their combination therapy, for four weeks. After hemodynamic measurements, all the rats’ heart and plasma were collected for biochemistry, ELISA, histopathology, and immunoblotting. Results: Metabolic perturbations and failing cardiac functions associated with diabetes were markedly attenuated by combination therapy. Besides, unfavourable alterations in RAS and natriuretic peptides system (NPS) were corrected by combination therapy. Interestingly, combination therapy significantly increased plasma and heart cGMP levels compared to T1D and monotherapy receiving rats. Moreover, rats receiving combination therapy exhibited significant inhibition of activated NF-KB, TGF-p and apoptotic signalling, and a notable reduction in cardiac fibrosis when compared to Tl D rats. Expressions of posttranslational histone modifications markers; H3K4Me2 and its methyltransferases (SET7/9 and RBBP5) were significantly enhanced in T1D hearts, which were significantly reduced by combination therapy. Conclusions: The NEPi and ACE2 activator combination therapy effectively prevented DCM by normalising RAS and NPS activities, increasing cGMP, inhibiting inflammatory, pro-fibrotic and apoptotic signalling, and reversing H3K4Me2 and its methyl transferases expressions.

Digital breast tomosynthesis in the breast cancer screening setting can reduce the benign biopsy rate while maintaining the cancer detection rate.

AimsThe clinical significance of radial scar (RS)/complex sclerosing lesion (CSL) with high-risk lesions (epithelial atypia) diagnosed on needle core biopsy is not well defined. We aimed at assessing the upgrade rate to ductal carcinoma in situ (DCIS) and invasive carcinoma on the surgical excision specimen in a large cohort with RS/CSL associated with atypia.Methods157 women with a needle core biopsy diagnosis of a RS/CSL with atypia and follow-up histology were studied. Histological findings, including different forms of the atypical lesions and final histological outcome in the excision specimens, were retrieved and analysed, and the upgrade rates for malignancy and for invasive carcinoma were calculated.Results69.43% of the cases were associated with atypical ductal hyperplasia (ADH) or atypia not otherwise classifiable, whereas lobular neoplasia was seen in 21.66%. On final histology, 39 cases were malignant (overall upgrade rate of 24.84%); 12 were invasive and 27 had DCIS. The upgrade differed according to the type of atypia and was highest for ADH (35%). When associated with lobular neoplasia, the upgrade rate was 11.76%. The upgrade rate’s variability was also considerably lower when considering the upgrade to invasive carcinoma alone for any associated lesion.ConclusionsThe upgrade rate for ADH diagnosed on needle core biopsy with RS is similar to that of ADH without RS and therefore should be managed similarly. RS associated with lobular neoplasia is less frequently associated with malignant outcome. Most lesions exhibiting some degree of atypia showed a similar upgrade rate to invasive carcinoma. Management of RS should be based on the concurrent atypical lesion.

Background: Natriuretic peptide system (NPS) alterations are involved in pathogenesis of diabetic cardiomyopathy (DCM) and nephropathy (DN), however its epigenetic regulation is still unclear. Interestingly, histone acetylation epigenetically regulates neprilysin expression in Alzheimer’s disease. Objectives: The present study was aimed at delineating role of histone acetylation in regulation of NPS in DCM and DN. Methods: Streptozotocin (55 mg/kg, i.p.)-induced diabetic male Wistar rats were used to mimic pathogenesis of DCM and DN. After haemodynamic measurements, all the rat’s plasma, heart and kidney were collected for biochemistry, ELISA, protein isolation and western blotting, RT-PCR and chromatin immunoprecipitation (ChIP) assay. Results: Diabetic rats heart and kidney exhibited activation of NF-κB and TGF-β signalling with increased histone acetyl transferases (PCAF/CBP) expressions and augmented H2AK5Ac, H2BK5Ac, H3K18Ac, and H4K8Ac levels. ChIP assay results showed increased enrichment of H3K18Ac and H2BK5Ac at Nppa, Nppb (Heart) and Mme promoter (Heart/Kidney) in diabetic rats. Enrichment of H2AK5Ac was augmented on Nppa and Mme promoters in diabetic heart, while it remained unchanged on Nppb promoter in heart and Mme promoter in kidney. Conclusion: Augmented histone acetylation at promoter regions of NPS gene(s), at least in a part, is responsible for increased expressions of ANP, BNP and NEP in diabetic heart and kidney. Hence, histone acetylation inhibitors can be considered as novel therapeutic targets against DCM and DN.

Background and Objectives: Dermatophytosis (topical fungal infection) is the 4th common disease in the last decade, affecting 20-25% world’s population. Patients of AIDS, cancer, old age senescence, diabetes, cystic fibrosis become more vulnerable to dermatophytosis. The conventional topical dosage proves effective as prophylactic in preliminary stage. In the advanced stage, the therapeutics interacts with healthy tissues before reaching the pathogen site, showing undesirable effects, thus resulting in pitiable patient compliance. The youngest carbon nano-trope “Graphene” is recently used to manipulate bioactive agents for therapeutic purposes. Here, we explore graphene via smart engineering by virtue of high surface area and high payload for therapeutics and developed graphene–ketoconazole nanohybrid (Gn-keto) for potent efficacy towards dermatophytes in a controlled manner. Methods: Polymethacrylate derivative Eudragit (ERL100 and ERS 100) microspheres embedded with keto and Gn-keto nanohybrid were formulated and characterized through FTIR, TGA, and SEM. In vitro drug release and antifungal activity of formulated Gn-keto microspheres were assessed for controlled release and better efficacy against selected dermatophytes. Results: Presence of numerous pores within the surface of ERL100 microspheres advocated enhanced solubility and diffusion at the site of action. Controlled diffusion across the dialysis membrane was observed with ERS100 microspheres owing to the nonporous surface and poor permeability. Antifungal activity against T. rubrum and M. canis using microdilution method focused on a preeminent activity (99.785 % growth inhibition) of developed nanohybrid loaded microspheres as compared to 80.876% of keto loaded microspheres for T. rubrum. The culture of M. canis was found to be less susceptible to formulated microspheres. Conclusion: Synergistic antifungal activity was achieved by nanohybrid Gn-Keto loaded microspheres against selected topical fungal infections suggesting a vital role of graphene towards fungi.

The combined assessment of breast cancer subtype and evidence of complete radiologic response at MR imaging may enable breast conservation surgery to be performed in patients with luminal B and nonluminal human epidermal growth factor receptor 2 (HER2)–positive breast cancer treated with neoadjuvant chemotherapy and anti-HER2 therapy, notwithstanding the presence of nonlocalized mammographic malignant-appearing microcalcification

Targeting the main three networking systems, viz.Las, RhI, and PQS, vianatural quenchers is a new ray of hope for combating the persistent behavior of Pseudomonas aeruginosa. In the bacterial chemical vocabulary pyocyanin, N-AHLs and rhamnolipids are the main keywords, which are responsible for the social and nomadic behavior of P. aeruginosa. In the present work, LC-MS based real-time qualitative and quantitative analysis of pyocyanin, green phenazine, N-AHLs, and rhamnolipids were performed on P. aeruginosaPAO1. The quantitative analysis indicates that the production of pyocyanin and NHSLs increases with time while the production of rhamnolipids discontinued after 16 h. This indicates the emergence of persisters in the medium instead of planktonic cells. Rhamnolipids acting as a surfactant enhances the motility of the bacterial cells, whereas the pyocyanin is responsible for the biofilm formation. In a microtiter plate based assay, an effect of capsaicin and 6-gingerol was recorded. In the presence of capsaicin and 6-gingerol, a substantial decrease in the production of rhamnolipids, phenazine, quinolone, and N-AHLs was observed. Most interestingly, the 6-gingerol treatment led to a drastic decrease of rhamnolipids, phenazine, quinolone, and N-AHLs versus capsaicin. These studies demonstrate the effectiveness of the capsaicin and 6-gingerol on Las, PQS, and Rhl circuits in a bacterium in order to understand the persistent and social behavior. Here, we are reporting LC-MS/MS based qualitative and quantitative analysis of QS molecules by taking a low volume of culture (up to 200 μL). This method can be used as a platform to screen the new antivirulence agents for fighting the resistant behavior of P. aeruginosaduring biofilm formation.

This experiment was carried out with 375 male broilers (Ross 308) from days 1 to 28 to evaluate the influence of crimped kernel maize silage (CKMS) on the manifestation of subclinical necrotic enteritis, microbiota counts, organic acid production and relative weights of gastrointestinal segments. A necrotic enteritis disease model was applied. Birds were allocated into 3 different dietary treatments: a maize-based feed (MBF, control diet), and 2 diets supplemented with 15% (CKMS15) or 30% (CKMS30) of crimped ensiled kernel maize. The disease model involved a 10-time overdose of an attenuated live vaccine against coccidiosis given orally on day 17, followed by oral inoculation of Clostridium perfringensType A (S48, 108to 109bacteria/bird) twice daily on days 18, 19, 20 and 21. Scoring of intestinal lesions was performed on days 22, 23, 25 and 28. Ileal and caecal digesta samples were collected for the quantification of selected bacterial groups and organic acids. The results showed that there was no effect of dietary treatments on small intestinal lesion scores (P > 0.05). Lesions scores peaked on days 23 and 25 and decreased again on day 28 (P = 0.001). No effect of age on microbiota counts was observed, but feeding of CKMS30 reduced the number of coliforms in ileal contents (P = 0.01). Dietary treatments did not affect organic acid concentrations in ileum and caeca, but there was an effect of age; butyric acid was higher on days 22, 23 and 25 than on day 28 (P = 0.04). Acetic acid and propionic acid concentrations in caeca were the highest on days 22 and 28 but the lowest on days 23 and 25. Relative gizzard and caeca weights were increased, and relative ileum weights were decreased when birds were fed CKMS30 (P < 0.05). In conclusion, the inclusion of CKMS in broiler diets had no effects on the course of necrotic enteritis but had potential benefits in terms of inhibition of potentially harmful microorganisms.