Design, synthesis, biological evaluation and molecular docking studies of quinoline-anthranilic acid hybrids as potent anti-inflammatory drugs.

Despite the high global prevalence, rheumatoid arthritis lacks a satisfactory treatment. Hence, the present study is undertaken to design and synthesize novel anti-inflammatory compounds. For this, quinoline and anthranilic acid, two medicinally-privileged moieties, were linked by pharmacophore hybridization, and following their computational assessments, three hybrids 5a-c were synthesized in good over all yields. The in vitro and in vivo anti-inflammatory potential of these hybrids was determined by anti-denaturation and anti-proteinase, and carrageenan-induced paw edema models. The computational studies of these hybrids revealed their drug-likeness, optimum pharmacokinetics, and less toxicity. Moreover, they demonstrated high binding affinity (-9.4 to -10.6 kcal mol-1) and suitable binding interactions for TNF-α, FLAP, and COX-II. A three-step synthetic route resulted in the hybrids 5a-c with 83-86% yield of final step. At 50 µg mL-1, the antiprotease and anti-denaturation activity of compound 5b was significantly higher than 5a and 5c. Furthermore, 5b significantly reduced the edema in the right paw of the rats that received carrageenan. The results of this study indicate the medicinal worth of the novel hybrids in treating inflammatory disorders such as rheumatoid arthritis.

Risk surveillance with spatial distribution of Organochlorine Pesticides (OCPs) from sedimentary samples of Chenab River.

A pioneering study employed a holistic geostatistical approach to predict the spatial variability of a non sampled area in the Chenab River, Pakistan, using kriging interpolation for organochlorine pesticide (OCP)-polluted risk zones. The Present research intended to investigate the carcinogenic and non-carcinogenic human health risks, contamination levels, and spatial variation of OCPs in the Chenab River, Pakistan. The residual OCP content in sediment samples (n = 120) ranged from 0.056 to 32.14 ng/g. DDE and α-HCH were prevalent among all the samples analyzed, with mean concentrations of 15.84 ± 8.02 and 12.45 ± 6.72 ng/g, respectively. The order of magnitude of OCPs in sediment samples was DDTs > α-HCH > chlorothalonil > heptachlor > endosulfan > aldrin > dieldrin. The findings of the single (SPI) and Nemerow (Nel) pollution index of α-HCH, heptachlor, and aldrin depicted the Chenab River as a serious pollution risk zone. The outcomes of the Pearson correlation coefficient analysis represent the positive correlation among all OCPs, revealing the common origin. Distribution trends showed substantially higher (p < 0.05) contents of analyzed OCPs along the downstream zone. With regards to USEPA human health hazard assessment model, the estimated non-carcinogenic (ΣHI) and non-carcinogenic (ΣTCR) risk ranged from 1.1 × 10-5 to 1.0 × 10-1, 4.0 × 10-8 to 3.2 × 10-4 respectively. TCR >10-4 illustrated a substantial cancer health risk posed by α-HCH, heptachlor, aldrin, and dieldrin in the downstream zone. We recommend the urgent cessation of the ongoing discharge of OCPs into the Chenab River, which needs to be highlighted owing to the significant cancer risk to public health to ensure the good health and wellbeings.

Ecological and human health hazards; integrated risk assessment of organochlorine pesticides (OCPs) from the Chenab River, Pakistan.

Carcinogenic hazards to human health were investigated through oral and dermal exposure to organochlorine pesticides (OCPs) from water samples (n = 120) of River Chenab, Pakistan. The Pioneering study aimed to employ an integrated geographic information system (GIS) based geostatistical method for the determination of pollution load by GC-ECD from water of River Chenab. The residual levels of OCPs detected from water samples ranged from 0.54 to 122 ng L-1 with significant prevalence of DDE and α-HCH. Results of the Nemerrow pollution index (NeI), single pollution index (SPI), and comprehensive pollution index (CPI) reflected the downstream zone a stern pollution risk zone. The spatial distribution pattern through geostatistical approaches also revealed significantly higher (p < 0.05) OCP levels in the downstream zone. Risk quotient (RQCCC) of surface water quality with respect to heptachlor epitomized a high level of risk (RQCCC > 1). Non-carcinogenic human health risk (Σ HQ) assessment ranged from 8.39 × 10-9 to 1.7 × 10-3, which represented a marginal risk through oral and dermal exposure. However, carcinogenic risks by oral exposure route were ranged from 3.57 × 10-11 to 4.46 × 10-6. Estimated cancer risk (ΣCR) exhibited a considerable carcinogenic risk posed by heptachlor, α-HCH and dieldrin. It is suggested to employ an immediate mitigation strategy for the constant discharge of OCPs in the studied area.

Comprehensive GIS based risk surveillance of organochlorine pesticides (OCPs) in edible fish species of River Chenab, Pakistan.

The present study was conducted to evaluate Carcinogenic (TR) and non-carcinogenic (THQ) human health risk of organochlorine pesticides (OCPs) in three edible fish species (Labeo boga, Channa marulius and Wallago attu) of River Chenab, Pakistan using USEPA human health risk assessment model. Holistic GIS (Geographic information system) based Geo-Statistical approach has been employed for the first time in River Chenab, Pakistan to categorize contaminated risk zones of OCPs based on single pollution index. The ∑OCPs concentrations in fish species were ranged from 5.09 to 414 ng/g with the prevalence of dieldrin. Results of single pollution index of DDE, aldrin, dieldrin and ∑endosulfan revealed River Chenab as polluted and risk zone area. Distribution pattern assessed significantly higher (p < 0.05) concentrations of OCPs in downstream area suggesting substantial pollution of surrounded industrial region. The human health risk assessment depicted no harmful non-carcinogenic (THQ) risk except for ΣOCPs concentration of C. marulius. Significant carcinogenic (TR) health risk exhibited by all examined OCPs from maximum of the studied sites. Therefore, the high carcinogenic human health risk had highlighted an immediate removal of continuous disposal of OCPs in the River Chenab.

The lived experiences of radiotherapists treating paediatric patients: Gauteng, South Africa.

BACKGROUND: Paediatric cancers are rare and more complex than adult cancers. Consequently, treatment for paediatric cancers is complex, requiring absolute precision and accuracy in delivering the prescribed dose. For radiotherapists, the complexity of performing paediatric radiotherapy treatment is augmented by its rarity, time and pressure constraints, the patient's lack of cooperation, anxiety and emotional challenges. These multiple challenges may affect the quality of patient care if they are not recognised and reduced. Therefore, this study explored radiotherapists experience of treating paediatric patients. OBJECTIVE: The purpose of this study was to explore and describe the lived experiences of radiotherapists treating paediatric patients. METHODS: This qualitative phenomenological study purposively sampled qualified radiotherapists involved in paediatric treatment planning and delivery in Gauteng, South Africa. Data were collected through 17 individual, in-depth interviews and underwent thematic analysis. RESULTS: Thematic analysis identified the emotional context in which radiotherapists work when treating paediatric patients and how radiotherapists' familiarity affects their experience of treating paediatric patients. The closeness of contact with the paediatric patient, parents and family dimension impacted participants positively and negatively. CONCLUSION: The study confirmed that radiotherapists treating paediatric patients work within a highly intense emotional context. The importance of gaining familiarity and experience in paediatric radiotherapy to enhance competency, was identified. Radiotherapist's experienced both positive and negative implications due to their close contact with the paediatric patient, parents and family dimension. The necessity to advance the practical infrastructural areas and strive for enhanced professionalism to improve paediatric radiotherapy was thus emphasised.

Monitoring and spatiotemporal variations of pyrethroid insecticides in surface water, sediment, and fish of the river Chenab Pakistan.

There is a serious concern regarding freshwater resources of Pakistan which have been mismanaged and now are depleting extensively due to other reasons like intensive application of agricultural pesticides and insecticides. The present study was conducted to determine the concentrations of cypermethrin, deltamethrin, permethrin, and bifenthrin in the samples of water, sediments, and fish collected from various locations of River Chenab, Pakistan, during summer and winter seasons. These locations include namely Marala, Khanki, Qadirabad, and Trimu Headworks. High-performance liquid chromatography (HPLC) was deployed for analysis and determination of pyrethroid concentrations in these samples. The analytics show the order of pyrethroid concentrations in river as fish> sediment>water. Whereas maximum concentrations of 0.472 µg g-1 found in fish and minimum concentrations were determined in water, i.e., 0.087 µg L-1 at the sampling locations of Trimu and Marala headworks, respectively. Moreover, highest mean concentrations of pyrethroid, i.e., 1.248 µg g-1 in fish were detected in winter season as compared to summers, i.e., 0.087 µg L-1. However, all the values of pyrethroid were found to be lower than the maximum permissible levels specified by EU and WHO-FAO. Whereas the levels of deltamethrin and permethrin in water were found much higher than the specific limits set by EU.

Ecological risk assessment of an open dumping site at Mehmood Booti Lahore, Pakistan.

A robust risk assessment of Mehmood Booting Open Dumping (MBOD) site has been carried out by developing holistic risk assessment framework. Framework mainly comprises on baseline study, hazard identification, and risk quantification and evaluation. Physico-chemical analysis of groundwater and leachate, health risk assessment, and estimation of gas emissions from the site were carried out for risk evaluation. LandGEM 3.02 modelling software was used to measure the gas emissions. Analysis of leachate showed that all parameters were exceeding the WHO standard limit. Water samples were found polluted with heavy metals and total coliform contamination. Health survey inferred that problems which were faced by the majority of respondents were respiratory problems (80%). LandGEM model estimated that total landfill gas (TLG) emitted from the site for the year 2014 was 1.760E+05 Mg/year, CH4 emission was 5.445E+06 Mg/year, CO2 emission was 1.290E+05 Mg/year and for non-methane organic compound emission was 2.021E+03 Mg/year. It can be concluded that in the near future, almost all the water locations are possibly threatened with leachate contamination due to the continued accumulation of solid waste at MBOD site. The study recommends that new sanitary landfill sites should be designed to minimize the adverse effects associated with solid waste disposal and to preclude further pollution to surface water, groundwater, soil, and air.