Leveraging a rationally designed veliparib-based anilide eliciting anti-leukemic effects for the design of pH-responsive polymer nanoformulation.

Careful recruitment of the components of the HDAC inhibitory template culminated in veliparib-based anilide 8 that elicited remarkable cell growth inhibitory effects against HL-60 cell lines mediated via dual modulation of PARP [(IC50 (PARP1) = 0.02 nM) and IC50 (PARP2) = 1 nM)] and HDACs (IC50 value = 0.05, 0.147 and 0.393 µM (HDAC1, 2 and 3). Compound 8 downregulated the expression levels of signatory biomarkers of PARP and HDAC inhibition. Also, compound 8 arrested the cell cycle at the G0/G1 phase and induced autophagy. Polymer nanoformulation (mPEG-PCl copolymeric micelles loaded with compound 8) was prepared by the nanoprecipitation technique. The mPEG-PCL diblock copolymer was prepared by ring-opening polymerization method using stannous octoate as a catalyst. The morphology of the compound 8@mPEG-PCL was examined using TEM and the substance was determined to be monodispersed, spherical in form, and had an average diameter of 138 nm. The polymer nanoformulation manifested pH-sensitive behaviour as a greater release of compound 8 was observed at 6.2 pH as compared to 7.4 pH mimicking physiological settings. The aforementioned findings indicate that the acidic pH of the tumour microenvironment might stimulate the nanomedicine release which in turn can attenuate the off-target effects precedentially claimed to be associated with HDAC inhibitors.

Ossifying Fibroma: A Case Report of an Unusual Presentation of Angiodysplastic Disease with Review of Literature.

Ossifying fibroma is a nonneoplastic developmental disease of osseous tissue seen rarely in association with Sturge-Weber syndrome. It is a lesion of unknown aetiology, uncertain pathogenesis, and diverse histopathology. The aim of this study is to report an unusual case of in a 11-year-old male of SWS. The rarity of the case and the fact that ossifying fibroma may be associated with Sturge-Weber syndrome propelled us to report it. Physical examination showed facial asymmetry (due to hemifacial swelling) without any tenderness, fluctuation, ocular pain, or ophthalmoplegia. Imaging studies revealed a solid mass involving the left maxilla and orbital floor. A conservative therapeutic approach to these lesions may be sufficient to relieve signs and symptoms effectively. Periodic follow-up is indicated to detect recurrences or malignant changes in the early stages.

Microalgae harvesting using flocculation and dissolved air flotation: Selecting the right vessel for lab-scale experiments.

Flocculation combined with dissolved air flotation (DAF) is a promising technology for harvesting microalgae; therefore, optimisation of flocculant-DAF operating conditions are frequently explored in laboratory experiments. DAF systems have jars of differing volumes, height to diameter ratios, shapes and materials used to manufacture the jars; thus, the harvesting efficiency (η) may differ between these jars. The aim was to systematically compare η between different types of benchtop DAF jars. Evaluation of 30 different types of DAF jars revealed that η was not influenced by the volume of the jars, but was impacted by the height to diameter ratio, with optimal η at a ratio ranging between 1.6 and 2.05. There was no difference in η between cylindrical and cuboid jars, but jars made of hydrophobic (polypropylene) plastic resulted in a lower η. Overall, these results are useful to guide the design of lab-scale DAF microalgae harvesting experiments.

Enzyme-substrate interactions in orotate-mimetic OPRT inhibitor complexes: a QM/MM analysis.

Orotate phosphoribosyltransferase (OPRT) catalyses the reversible phosphoribosyl transfer from α-D-5-phosphoribosyl-1-pyrophosphate (PRPP) to orotic acid (OA) to yield orotidine 5'-monophosphate (OMP) during the de novo synthesis of nucleotides. Numerous studies have reported the inhibition of this reaction as a strategy to check diseases like tuberculosis, malaria and cancer. Insight into the inhibition of this reaction is, therefore, of urgent interest. In this study, we implemented a QM/MM framework on OPRT derived from Saccharomyces cerevisiae to obtain insights into the competitive binding of OA and OA-mimetic inhibitors by quantifying their interactions with OPRT. 4-Hydroxy-6-methylpyridin-2(1H) one showed the best inhibiting activity among the structurally similar OA-mimetic inhibitors, as quantified from the binding energetics. Our analysis of protein-ligand interactions unveiled the association of this inhibitory ligand with a strong network of hydrogen bonds, a large contribution of hydrophobic contacts, and bridging water molecules in the binding site. The ortho-substituted CH3 group in the compound resulted in a large population of π-electrons in the aromatic ring of this inhibitor, supporting the ligand binding further.

A bi-directional deep learning architecture for lung nodule semantic segmentation.

Lung nodules are abnormal growths and lesions may exist. Both lungs may have nodules. Most lung nodules are harmless (not cancerous/malignant). Pulmonary nodules are rare in lung cancer. X-rays and CT scans identify the lung nodules. Doctors may term the growth a lung spot, coin lesion, or shadow. It is necessary to obtain properly computed tomography (CT) scans of the lungs to get an accurate diagnosis and a good estimate of the severity of lung cancer. This study aims to design and evaluate a deep learning (DL) algorithm for identifying pulmonary nodules (PNs) using the LUNA-16 dataset and examine the prevalence of PNs using DB-Net. The paper states that a new, resource-efficient deep learning architecture is called for, and it has been given the name of DB-NET. When a physician orders a CT scan, they need to employ an accurate and efficient lung nodule segmentation method because they need to detect lung cancer at an early stage. However, segmentation of lung nodules is a difficult task because of the nodules' characteristics on the CT image as well as the nodules' concealed shape, visual quality, and context. The DB-NET model architecture is presented as a resource-efficient deep learning solution for handling the challenge at hand in this paper. Furthermore, it incorporates the Mish nonlinearity function and the mask class weights to improve segmentation effectiveness. In addition to the LUNA-16 dataset, which contained 1200 lung nodules collected during the LUNA-16 test, the LUNA-16 dataset was extensively used to train and assess the proposed model. The DB-NET architecture surpasses the existing U-NET model by a dice coefficient index of 88.89%, and it also achieves a similar level of accuracy to that of human experts.

Mechanistic elucidations of sesquiterpenes ameliorating viral infections: A review.

Sesquiterpenes are important in human health because they can treat viral infection, cardiovascular disease, and cancer. Sesquiterpenes have also been shown to increase the sensitivity of tumor cells to conventional pharmacological therapies, in addition to their antiviral effects. The present review article was drafted with an intention to gather information regarding sesquiterpenes and its medicinal importance. The role of sesquiterpenes in the endogenous production of sesquiterpenes by plants and fungi, as well as the mechanisms by which they are effective against viral infection, are discussed in this review. Different online libraries such as PUBMED, Sciencedirect, MEDLINE were assessed to gather information, additionally, books, magzagines, journals, and scientific newspapaers were also studied to make this article more informative. This review examines novel synthesis mechanisms, their cyclization, purification techniques, and the diverse ecological roles sesquiterpenes play in the plant producer, which varies according to the plant and the chemical under consideration. In this article, we have discussed the consequences of sesquiterpenes and their properties for future crop productivity. We have addressed the many forms of sesquiterpenes that have been shown to have antiviral activity in various diseases. The consequences of sesquiterpenes and their properties are very useful for future crop productivity. We have addressed the many forms of sesquiterpenes that have been shown to have antiviral activity in the treatment of various diseases. PRACTICAL APPLICATIONS: Novel synthesis mechanisms, their cyclization, purification techniques, and the diverse ecological roles of sesquiterpenes will be very helfpul in drug development process. Sesquiterpene lactones are shown in this review to have qualities that warrant further scientific investigation in order to stimulate preclinical and clinical trials leading to the creation of novel medications. For antiviral drug development, the sesquiterpenes are a good prospective lead molecule because they can suppress viral replication by disrupting vRNA production and viral protein production.

Accommodation of ring C expanded deoxyvasicinone in the HDAC inhibitory pharmacophore culminates into a tractable anti-lung cancer agent and pH-responsive nanocarrier.

A fragment recruitment process was conducted to pinpoint a suitable fragment for installation in the HDAC inhibitory template to furnish agents endowed with the potential to treat lung cancer. Resultantly, Ring C expanded deoxyvasicinone was selected as an appropriate surface recognition part that was accommodated in the HDAC three-component model. Delightfully, fused quinazolinone 6 demonstrating a magnificent anticancer profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80-0.96 µM) was identified. Results of the mechanistic studies confirmed that the cell growth inhibitory effects of compound 6 stems for HDAC6 (IC50 = 12.9 nM), HDAC1 (IC50 = 49.9 nM) and HDAC3 inhibition (IC50 = 68.5 nM), respectively. Compound 6 also suppressed the colony formation ability of A549 cells, induced apoptosis, and increased autophagic flux. Key interactions of HDAC inhibitor 6 within the active site of HDAC isoforms were figured out through molecular modeling studies. Furthermore, a pH-responsive nanocarrier (Hyaluronic acid - fused quinazolinone 6 nanoparticles) was designed and assessed using a dialysis bag approach under both normal and acidic circumstances that confirmed the pH-sensitive nature of NPs. Delightfully, the nanoparticles demonstrated selective cell viability reduction potential towards the lung cancer cell lines (A549 lung cancer cell lines) and were found to be largely devoid of cell growth inhibitory effects under normal settings (L929, mouse fibroblast cells).

Niraparib Shows Superior Tissue Distribution and Efficacy in a Prostate Cancer Bone Metastasis Model Compared with Other PARP Inhibitors.

Patients with prostate cancer whose tumors bear deleterious mutations in DNA-repair pathways often respond to PARP inhibitors. Studies were conducted to compare the activity of several PARP inhibitors in vitro and their tissue exposure and in vivo efficacy in mice bearing PC-3M-luc-C6 prostate tumors grown subcutaneously or in bone. Niraparib, olaparib, rucaparib, and talazoparib were compared in proliferation assays, using several prostate tumor cell lines and in a cell-free PARP-trapping assay. PC-3M-luc-C6 cells were approximately 12- to 20-fold more sensitive to PARP inhibition than other prostate tumor lines, suggesting that these cells bear a DNA damage repair defect. The tissue exposure and efficacy of these PARP inhibitors were evaluated in vivo in PC-3M-luc-C6 subcutaneous and bone metastasis tumor models. A steady-state pharmacokinetic study in PC-3M-luc-C6 tumor-bearing mice showed that all of the PARP inhibitors had favorable subcutaneous tumor exposure, but niraparib was differentiated by superior bone marrow exposure compared with the other drugs. In a PC-3M-luc-C6 subcutaneous tumor efficacy study, niraparib, olaparib, and talazoparib inhibited tumor growth and increased survival to a similar degree. In contrast, in the PC-3M-luc-C6 bone metastasis model, niraparib showed the most potent inhibition of bone tumor growth compared with the other therapies (67% vs. 40%-45% on day 17), and the best survival improvement over vehicle control [hazard ratio (HR), 0.28 vs. HR, 0.46-0.59] and over other therapies (HR, 1.68-2.16). These results show that niraparib has superior bone marrow exposure and greater inhibition of tumor growth in bone, compared with olaparib, rucaparib, and talazoparib.

Evaluation of Nicotine Dependence in Adult Population of Eastern Nepal.

Background Tobacco consumption is a leading cause of premature death in the world. Tobaccorelated deaths are associated with cardiovascular diseases, pulmonary diseases, oral potentially malignant disorders, cancer, others. Moreover there is also associated nicotine dependence which might result to numerous tobacco-associated diseases. Objective This study was conducted to analyze the degree of nicotine dependence considering its potential health risk, in the Eastern region of Nepal. Method A descriptive questionnaire based study was conducted among current tobacco users of six districts of Eastern Nepal. Fagerstrom Test for Nicotine Dependence (FTND) and Fagerstrom Test for Nicotine Dependency for Smokeless Tobacco (FTNDST) questionnaire were used for tobacco smokers and chewers, respectively. Result Of the total participants, 836 were males and 359 females, among whom 736 were active tobacco smokers and 432 chewers, 34.8% had tried to stop consuming tobacco and 306 (25.6%) had oral lesions in white or red forms. Very low nicotine dependence was found among 244 (31.47%) tobacco smokers and 37 (8.56%) chewers whereas 36 (4.71%) smokers and 103 (23.84%) chewers had very high nicotine dependence. The mean score for FTND was 3.73±2.37 and 5.74±2.12 for FTND-ST. A significant difference in duration and age group with FTND score was observed, however not with FTND-ST. Conclusion The information regarding degree of nicotine dependence can be used as baseline information for planning of preventive strategies and implementation of tobacco cessation and control programs.

Appraisal of vulnerable zones of non-cancer-causing health risks associated with exposure of nitrate and fluoride in groundwater from a rural part of India.

The present investigation carried out from a rural part of Nalgonda district, Telangana, India was to know the general groundwater quality and also to measure the vulnerable zones of non-cancer-causing health risks with respect to infants, children, and adults due to the consumption of nitrate and fluoride contaminated groundwater. Groundwater samples were collected from the study area and analyzed for the major physicochemical parameters. Nitrate and fluoride contents ranged from 2 to 700 mg/L and 0.3 to 4.7 mg/L, in which 59.09% and 31.82% of the groundwater samples exceed the safe drinking water limits of 45 mg/L and 1.5 mg/L, which spread over an area of 77.59% and 25.41%, respectively. Domestic wastes, septic tank spillages, animal wastes, and nitrate composts are the prime sources of nitrate, while the fluoride-bearing minerals and phosphate fertilizers are the main sources of fluoride in the aquifer regime. Individual non-cancer-causing health index obviously suggested the nitrate as the higher health risk than fluoride. The total non-cancer-causing health index was observed to be more than the acceptable limit of 1.0 in 95.5% of the total groundwater samples concerning infants, children, and adults. The vulnerable intensity of this index appeared to be higher in infants than in children and adults due to the differences in their body weights. The spatial coverage area of very health risk is more in infants (37.45%) than that of children (36.78%) and adults (30.34%). Thus, the present study suggested suitable measures for the improvement of groundwater quality and consequently the health conditions of the locals.

Prediction of the drug-drug interaction potential of the α1-acid glycoprotein bound, CYP3A4/CYP2C9 metabolized oncology drug, erdafitinib.

Erdafitinib is a potent oral pan-fibroblast growth factor receptor inhibitor being developed as oncology drug for patients with alterations in the fibroblast growth factor receptor pathway. Erdafitinib binds preferentially to α1-acid glycoprotein (AGP) and is primarily metabolized by cytochrome P450 (CYP) 2C9 and 3A4. This article describes a physiologically based pharmacokinetic (PBPK) model for erdafitinib to assess the drug-drug interaction (DDI) potential of CYP3A4 and CYP2C9 inhibitors and CYP3A4/CYP2C9 inducers on erdafitinib pharmacokinetics (PK) in patients with cancer exhibiting higher AGP levels and in populations with different CYP2C9 genotypes. Erdafitinib's DDI potential as a perpetrator for transporter inhibition and for time-dependent inhibition and/or induction of CYP3A was also evaluated. The PBPK model incorporated input parameters from various in vitro and clinical PK studies, and the model was verified using a clinical DDI study with itraconazole and fluconazole. Erdafitinib clearance in the PBPK model consisted of multiple pathways (CYP2C9/3A4, renal, intestinal; additional hepatic clearance), making the compound less susceptible to DDIs. In poor-metabolizing CYP2C9 populations carrying the CYP2C9*3/*3 genotype, simulations shown clinically relevant increase in erdafitinib plasma concentrations. Simulated luminal and enterocyte concentration showed potential risk of P-glycoprotein inhibition with erdafitinib in the first 5 h after dosing, and simulations showed this interaction can be avoided by staggering erdafitinib and digoxin dosing. Other than a simulated ~ 60% exposure reduction with strong CYP3A/2C inducers such as rifampicin, other DDI liabilities were minimal and considered not clinically relevant.

Clinical diagnostic criteria versus advanced imaging in prediction of cervical lymph node metastasis in oral squamous cell carcinomas: A magnetic resonance imaging based study.

CONTEXT AND AIM: The inaccuracies in clinical examination have been well documented, while advanced imaging modalities, including computed tomography and magnetic resonance imaging (MRI), have been shown to have superior diagnostic accuracy in detecting occult and nodal metastasis. The aim of the present study was to identify as well as evaluate the inaccuracies in clinical examination and of clinical diagnostic criteria in known cases of oral squamous cell carcinomas (OSCCs) with the help of MRI. MATERIALS AND METHODS: A total of 24 patients attending as outpatients were included in the study, while clinically diagnosed and histopathologically proven cases of OSCC were examined clinically and then subjected to advanced imaging with the help of MRI. STATISTICAL ANALYSIS USED: Statistical analysis was done using Statistical Package for the Social Sciences (SPSS) version 17.0 (SPSS Inc., Chicago, IL, USA), while paired t-test was performed for evaluating the size of tumor and lymph node recorded on clinical and imaging findings. A P < 0.05 was considered statistically significant. RESULTS: Detection of tumor size and lymph node metastasis was found to be higher in case of MRI than when accomplished by clinical staging alone, while paired t-test values for difference in results were found to be statistically significant (P < 0.05). CONCLUSIONS: The present study showed that clinical diagnostic criteria alone were not sufficient and reliable for detecting metastatic lymphadenopathy, highlighting the significance of advanced imaging modalities such as MRI for an efficient preoperative diagnostic workup, as well a tool for planning treatment in patients with OSCCs.

Efficient Design to Monitor the Site-specific Sustained Release of a Non-Emissive Anticancer Drug.

A pH-responsive smart nanocarrier with significant components was synthesized by conjugating the non-emissive anticancer drug methyl orange and polyethylene glycol derived folate moiety to the backbone of polynorbornene. Complete synthesis procedure and characterization methods of three monomers included in the work: norbornene-derived Chlorambucil (Monomer 1), norbornene grafted with polyethylene glycol, and folic acid (Monomer 2) and norbornene attached methyl orange (Monomer 3) connected to the norbornene backbone through ester linkage were clearly discussed. Finally, the random copolymer CHO PEG FOL METH was synthesized by ring-opening metathesis polymerization (ROMP) using Grubbs' second-generation catalyst. Advanced polymer chromatography (APC) was used to find the final polymer's molecular weight and polydispersity index (PDI). Dynamic light scattering, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were utilized to explore the prodrug's size and morphology. Release experiments of the anticancer drug, Chlorambucil and the coloring agent, methyl orange, were performed at different pH and time. Cell viability assay was carried out for determining the rate of survived cells, followed by the treatment of our final polymer named CHO PEG FOL METH.

Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE).

PURPOSE: To assess the safety and pharmacokinetics and determine the recommended phase 2 dose (RP2D) of niraparib with apalutamide or abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: BEDIVERE was a multicenter, open-label, phase 1b study of niraparib 200 or 300 mg/day with apalutamide 240 mg or AAP (abiraterone acetate 1000 mg; prednisone 10 mg). Patients with mCRPC were previously treated with ≥ 2 lines of systemic therapy, including ≥ 1 androgen receptor-axis-targeted therapy for prostate cancer. RESULTS: Thirty-three patients were enrolled (niraparib-apalutamide, 6; niraparib-AAP, 27). No dose-limiting toxicities (DLTs) were reported when combinations included niraparib 200 mg; five patients receiving niraparib 300 mg experienced DLTs [niraparib-apalutamide, 2/3 patients (66.7%); niraparib-AAP, 3/8 patients (37.5%)]. Although data are limited, niraparib exposures were lower when given with apalutamide compared with historical niraparib monotherapy exposures in patients with solid tumors. Because of the higher incidence of DLTs, the niraparib-apalutamide combination and niraparib 300 mg combination with AAP were not further evaluated. Niraparib 200 mg was selected as the RP2D with AAP. Of 19 patients receiving niraparib 200 mg with AAP, 12 (63.2%) had grade 3/4 treatment-emergent adverse events, the most common being thrombocytopenia (26.3%) and hypertension (21.1%). Five patients (26.3%) had adverse events leading to treatment discontinuation. CONCLUSIONS: These results support the choice of niraparib 200 mg as the RP2D with AAP. The niraparib-AAP combination was tolerable in patients with mCRPC, with no new safety signals. An ongoing phase 3 study is further assessing this combination in patients with mCRPC. TRIAL REGISTRATION NO: NCT02924766 (ClinicalTrials.gov).

Nasal vestibule and columella cancer: a therapeutic and reconstructive conundrum.

PURPOSE OF REVIEW: Nasal vestibular cancers are rare entities among the head and neck cancers. The treatment options are varied. Although surgical treatment plays an important role, postablative defects are difficult to reconstruct. This review aims to discuss the current views in the management of these cancers and issues related to the reconstruction of the complex surgical defects. RECENT FINDINGS: Nasal vestibular cancers are a distinct rare entity of head and neck cancers. These cancers are staged using the AJCC-TNM system for nonmelanoma cutaneous cancers of head and neck or the Wang classification. Early lesions are best treated by either surgery or radiation giving excellent cure rates. Advanced stages tumours need combined treatment with surgery and adjuvant radiation therapy. Primary radiation therapy can be offered by external beam or interstitial brachytherapy. Surgical treatment varies from endonasal resections, Mohs' chemosurgery to open excisions. SUMMARY: Even though the Wang system of classification is used by majority of reports due its clinical utility, it has a drawback of not taking into account the tumour size as done by the AJCC system. Brachytherapy has been reported to be offering excellent cure rates with low morbidity in early tumours. Surgical treatment is also effective in early lesions, but its role is more established in advanced lesions. Reconstruction of the surgical defects is often a challenge, to preserve functional integrity and cosmesis. Various techniques, including skin grafts, local flaps, free flaps and prosthetics, form part of the reconstructive armamentarium.

A report of a novel approach for the management of paediatric mandibular fracture using a prefabricated adaptable surgical splint.

Paediatric facial fractures are relatively rare. The inherent elasticity of the bones with more of the cartilage than that of the mineralised bone accounts for this. The principles involved in the management of facial fractures are the same irrespective of the age of the patient; however, in children, the techniques used are necessarily modified by certain anatomical, physiological, psychological and feeding factors related to childhood and the parents. In an attempt to keep the treatment and fixation technique simple, the case, presented here, describes the management of a mandibular parasymphyseal fracture in a 16-month-old child with the use of a prefabricated adaptable surgical splint.

Applications of geochemical and multivariate statistical approaches for the evaluation of groundwater quality and human health risks in a semi-arid region of eastern Maharashtra, India.

A qualitative approach, including geochemical and multivariate statistical approaches, is applied to evaluate the groundwater quality and human health risk, based on analytical data of 72 samples collected from a semi-arid region of eastern Maharashtra, India. The shifting of hydrochemical type from Ca2+-Na+-[Formula: see text] to Na+-Ca2+-Cl- type was observed along different flow paths. The main controlling processes observed from the chemical characterisation of the groundwater are water-rock interactions, dedolomitisation and reverse ion exchange. Simulation analysis (mass transfer) exposes the dissolution of dolomite, gypsum, halite, k-feldspar and CO2 down the simulated pathways. Around 77% of the total variance was observed from the first three principal component analyses. The high positive loadings of EC, TDS, Na+, K+, Ca2+, Cl-, [Formula: see text] and [Formula: see text] of PC1 revealed silicate weathering and reverse ion exchange followed by human activities as the contamination sources. The sources identified for high positive loadings on [Formula: see text] and [Formula: see text] of PC2 are soil CO2 and human activities. The high loadings of pH and F- in PC3 revealed fluorite dissolution and calcite precipitation. The human health risk calculated for [Formula: see text] revealed that 58% and 44% of the total groundwater samples surpassed the tolerance limit for non-carcinogenic risk of 1.0 in children and adults. The human health risk assessment for fluoride showed high hazard index values in 40% and 23% of the total groundwater samples for children and adults, respectively. The study suggests some management measures for protection of groundwater resources.

Hyaluronic Acid Derived Hypoxia-Sensitive Nanocarrier for Tumor Targeted Drug Delivery.

Hyaluronic acid (HA) is conjugated with BHQ3 moiety with azo bonds to prepare hypoxia-responsive polymer conjugate. Because of the amphiphilic nature, the polymer conjugate self-assembles to HA-BHQ3 nanoparticles (NPs). The anticancer drug doxorubicin (DOX) is loaded into the NPs. In the physiological environment, DOX is released slowly. In contrast, under hypoxic conditions, the azo bond in BHQ3 is cleaved, thus significantly enhancing the DOX release rate. For instance, after 24 h, 25% of DOX is released under normal conditions, while 74% of DOX is released under hypoxic conditions. In vitro cytotoxicity demonstrates higher toxicity in the hypoxic conditions. DOX@HA-BHQ3 NPs exhibit greater toxicity levels against 4T1 cells in hypoxic conditions. The fluorescent microscope images confirm the oxygen-dependent intracellular DOX release from the NPs. The in vivo biodistribution results suggest the tumor targetability of HA-BHQ3 NPs in 4T1 tumor-bearing mice.

Colitis and Crohn's Foundation (India): a first nationwide inflammatory bowel disease registry.

BACKGROUND/AIMS: The national registry for inflammatory bowel disease (IBD) was designed to study epidemiology and prescribing pattern of treatment of IBD in India. METHODS: A multicenter, cross-sectional, prospective registry was established across four geographical zones of India. Adult patients with ulcerative colitis (UC) or Crohn's disease (CD) were enrolled between January 2014 and December 2015. Information related to demographics; disease features; complications; and treatment history were collected and analyzed. RESULTS: A total of 3,863 patients (mean age, 36.7 ± 13.6 years; 3,232 UC [83.7%] and 631 CD [16.3%]) were enrolled. The majority of patients with UC (n = 1,870, 57.9%) were from north, CD was more common in south (n = 348, 55.5%). The UC:CD ratio was 5.1:1. There was a male predominance (male:female = 1.6:1). The commonest presentation of UC was moderately severe (n = 1,939, 60%) and E2 disease (n = 1,895, 58.6%). Patients with CD most commonly presented with ileocolonic (n = 229, 36.3%) inflammatory (n = 504, 79.9%) disease. Extraintestinal manifestations were recorded among 13% and 20% of patients in UC and CD respectively. Less than 1% patients from both cohorts developed colon cancer (n = 26, 0.7%). The commonly used drugs were 5-aminosalicylates (99%) in both UC and CD followed by azathioprine (34.4%). Biologics were used in only 1.5% of patients; more commonly for UC in north and CD in south. CONCLUSIONS: The national IBD registry brings out diversities in the 4 geographical zones of India. This will help in aiding research on IBD and improving quality of patient care.

Spatial distribution of quality of groundwater and probabilistic non-carcinogenic risk from a rural dry climatic region of South India.

Having safe drinking water is a fundamental human right, which affects directly the human health. In view of this, an effort has been made for understanding the spatial distribution of quality of groundwater in a rural dry climatic region of Andhra Pradesh, South India, and associated health risks with respect to pollutants of NO3- and F-, which cause the potential production of non-carcinogenic risk, using entropy-weighted water quality index (EWWQI) and total chronic hazard index (TCHI), where the population rely on the groundwater resource for drinking purpose. Groundwater quality observed from the present study region has an alkaline character with brackish type. The concentrations of K+, HCO3-, TDS, Na+, NO3-, F-, Mg2+ and Cl- come under the non-permissible limits in 100%, 100%, 96.67%, 90%, 73.33%, 46.67%, 13.33% and 6.67% of the groundwater samples, which deteriorate the groundwater quality, causing the health disorders. The overall groundwater quality computed, using EWWQI, ranges from 53.64 to 216.59 (122.22), which classifies the region spatially into 55%, 10% and 35% due to influences of the geogenic and anthropogenic pollutants, which are the respective medium, poor and very poor groundwater quality types prescribed for potable water. According to the TCHI evaluated with respect to pollutants of NO3- and F-, the values of TCHI for men (1.194 to 4030), women (1.411 to 4.763) and children (1.614 to 5.449) are more than its acceptable limit of one. So, the health risk of non-carcinogenic is spatially in the decreasing order of children > women > men, depending upon their sensitiveness to pollutants and also their body weights. Further, the spatial distributions of both TCH1 and EWWQI are more or less similar, following the pollution activities, which help for establishment of the fact to recognize the intensity of various vulnerable zones. Therefore, the present study suggests the suitable environmental safety measures to control the NO3-- and F--contaminated drinking water and subsequently to increase the health conditions.