Identification of small-molecule protein-protein interaction inhibitors for NKG2D.

NKG2D (natural-killer group 2, member D) is a homodimeric transmembrane receptor that plays an important role in NK, γδ+, and CD8+ T cell-mediated immune responses to environmental stressors such as viral or bacterial infections and oxidative stress. However, aberrant NKG2D signaling has also been associated with chronic inflammatory and autoimmune diseases, and as such NKG2D is thought to be an attractive target for immune intervention. Here, we describe a comprehensive small-molecule hit identification strategy and two distinct series of protein-protein interaction inhibitors of NKG2D. Although the hits are chemically distinct, they share a unique allosteric mechanism of disrupting ligand binding by accessing a cryptic pocket and causing the two monomers of the NKG2D dimer to open apart and twist relative to one another. Leveraging a suite of biochemical and cell-based assays coupled with structure-based drug design, we established tractable structure-activity relationships with one of the chemical series and successfully improved both the potency and physicochemical properties. Together, we demonstrate that it is possible, albeit challenging, to disrupt the interaction between NKG2D and multiple protein ligands with a single molecule through allosteric modulation of the NKG2D receptor dimer/ligand interface.

Trace element pollution tracking in the complex multi-aquifer groundwater system of Al-Hassa oasis (Saudi Arabia) using spatial, chemometric and index-based techniques.

In a global context, trace element pollution assessment in complex multi-aquifer groundwater systems is important, considering the growing concerns about water resource quality and sustainability worldwide. This research addresses multiple objectives by integrating spatial, chemometric, and indexical study approaches, for assessing trace element pollution in the multi-aquifer groundwater system of the Al-Hassa Oasis, Saudi Arabia. Groundwater sampling and analysis followed standard methods. For this purpose, the research employed internationally recognized protocols for groundwater sampling and analysis, including standardized techniques outlined by regulatory bodies such as the United States Environmental Protection Agency (USEPA) and the World Health Organization (WHO). Average values revealed that Cr (0.041) and Fe (2.312) concentrations surpassed the recommended limits for drinking water quality, posing serious threats to groundwater usability by humans. The trace elemental concentrations were ranked as: Li < Mn < Co < As < Mo < Zn < Al < Ba < Se < V < Ni < Cr < Cu < B < Fe < Sr. Various metal(loid) pollution indices, including degree of contamination, heavy metal evaluation index, heavy metal pollution index, and modified heavy metal index, indicated low levels of groundwater pollution. Similarly, low values of water pollution index and weighted arithmetic water quality index were observed for all groundwater points, signifying excellent groundwater quality for drinking and domestic purposes. Spatial distribution analysis showed diverse groundwater quality across the study area, with the eastern and western parts displaying a less desirable quality, while the northern has the best, making water users in the former more vulnerable to potential pollution effects. Thus, the zonation maps hinted the necessity for groundwater quality enhancement from the western to the northern parts. Chemometric analysis identified both human activities and geogenic factors as contributors to groundwater pollution, with human activities found to have more significant impacts. This research provides the scientific basis and insights for protecting the groundwater system and ensuring efficient water management.

The Pediatric Crohn Disease Morbidity Index (PCD-MI): Development of a Tool to Assess Long-Term Disease Burden Using a Data-Driven Approach.

BACKGROUND/OBJECTIVE: Heterogeneity and chronicity of Crohn disease (CD) make prediction of outcomes difficult. To date, no longitudinal measure can quantify burden over a patient's disease course, preventing assessment and integration into predictive modeling. Here, we aimed to demonstrate the feasibility of constructing a data driven, longitudinal disease burden score. METHODS: Literature was reviewed for tools used in assessment of CD activity. Themes were identified to construct a pediatric CD morbidity index (PCD-MI). Scores were assigned to variables. Data were extracted automatically from the electronic patient records at Southampton Children's Hospital, diagnosed from 2012 to 2019 (inclusive). PCD-MI scores were calculated, adjusted for duration of follow up and assessed for variation (ANOVA) and distribution (Kolmogorov-Smirnov). RESULTS: Nineteen clinical/biological features across five themes were included in the PCD-MI including blood/fecal/radiological/endoscopic results, medication usage, surgery, growth parameters, and extraintestinal manifestations. Maximal score was 100 after accounting for follow-up duration. PCD-MI was assessed in 66 patients, mean age 12.5 years. Following quality filtering, 9528 blood/fecal test results and 1309 growth measures were included. Mean PCD-MI score was 14.95 (range 2.2-32.5); data were normally distributed ( P = 0.2) with 25% of patients having a PCD-MI < 10. There was no difference in the mean PCD-MI when split by year of diagnosis, F -statistic 1.625, P = 0.147. CONCLUSIONS: PCD-MI is a calculatable measure for a cohort of patients diagnosed over an 8-year period, integrating a wide-range of data with potential to determine high or low disease burden. Future iterations of the PCD-MI require refinement of included features, optimized scores, and validation on external cohorts.

Effective voltammetric tool for Nano-detection of triazine herbicide (1-Chloro-3-ethylamino-5-isopropylamino-2,4,6-triazine) by naphthalene derivative.

The development and operation of a nanosensor for detecting the poisonous 1-chloro-3-ethylamino-5-isopropylamino-2,4,6-triazine (Atrazine) are described in this study for the first time. The carbon electrode (CE) surface was modified with cysteine-substituted naphthalene diimide to create this sensitive platform. The developed nanosensor (NDI-cys/GCE) was evaluated for its ability to sense Atrazine using differential pulse voltammetry and cyclic voltammetry. To achieve the best response from the target analyte, the effects of several parameters were examined to optimize the conditions. The cysteine-substituted naphthalene diimide significantly improved the signals of the Atrazine compared to bare GCE due to the synergistic activity of substituted naphthalene diimide and cysteine molecules. Under optimal conditions, atrazine detection limits at the (NDI-cys/GCE) were reported to be 94 nM with a linear range of 10-100 µM. The developed sensing platform also showed positive results when used to detect the atrazine herbicide in real tap water, wastewater, and milk samples. Furthermore, a reasonable recovery rate for real-time studies, repeatability, and stability revealed that the developed electrochemical platform could be used for sample analysis.

Graphene oxide-based novel MOF nanohybrid for synergic removal of Pb (II) ions from aqueous solutions: Simulation and adsorption studies.

Heavy metals represent a considerable threat, and the current study deals with synthesizing a novel MOF nanocomposite by intercalating graphene oxide (GO) and linker UiO-66-NDC. It was shown that UiO-66-NDC/GO had enhanced the removal efficiency of Pb (II) ions at pH 6. The adsorption kinetics data followed the PSO (Type 2) representing chemisorption. Adsorption data were also fitted with three different isotherms, namely Temkin, Freundlich, & Langmuir, and the Temkin model exhibited the best correlation (R2 0.99), representing the chemisorption nature of the adsorption process. The maximum adsorption capacity (qmax) of Pb (II) ions using Langmuir was found to be 254.45 mg/g (298 K). The Pb (II) adsorption process was confirmed to be exothermic and spontaneous as the thermodynamic parameters H° and G° were determined to have negative values. MOF nanocomposite also represents significant reusability for up to four regeneration cycles using 0.01 M HCl; for the next four, it works quite efficiently after regeneration. Meanwhile, the simulation findings confirm the superior dynamic stability (∼08 times) of the MOF nanocomposite as compared to the GO system. The removal of Pb (II) from simulated wastewater samples using a super nano-adsorbent using a MOF nanocomposite is described here for the first time.

Comparison of constructed wetland performance coupled with aeration and tubesettler for pharmaceutical compound removal from hospital wastewater.

Pharmaceutical compounds being able to alter, retard, and enhance metabolism has gained attention in recent time as emerging pollutant. However, hospitals which are part of every urban landscape have yet to gain attention in terms of its hospital wastewater treatment to inhibit pharmaceutical compounds from reaching environment. Hence this study evaluated performance of constructed wetland in combination with tubesettler and aeration based on removal efficiency and ecological risk assessment (HQ). The removal efficiency of constructed wetland with plantation was higher by 31% (paracetamol), 102% (ibuprofen), 46%, (carbamazepine), 57% (lorazepam), 54% (erythromycin), 31% (ciprofloxacin) and 20% (simvastatin) against constructed wetland without plantation. Constructed wetland with aeration efficiency increased for paracetamol, ibuprofen, carbamazepine, lorazepam, erythromycin, ciprofloxacin, and simvastatin removal efficiency were higher by 58%, 130%, 52%, 79%, 107%, 57%, and 29% respectively. In constructed wetland with plantation, removal efficiency was higher by 20% (paracetamol), 13% (ibuprofen), 4% (carbamazepine), 14% (lorazepam), 34% (erythromycin), 19% (ciprofloxacin) and 7% (simvastatin). High ecological risk was observed for algae, invertebrate and fish with hazard quotient values in range of 2.5-484, 10-631 and 1-78 respectively. This study concludes that if space is the limitation at hospitals aeration with constructed wetland can be adopted. If space is available, constructed wetland with tubesettler is suitable, economic and environmentally friendly option. Future research works can focus on evaluating other processes combination with constructed wetland.

Insights into chitosan-based cellulose nanowhiskers reinforced nanocomposite material via deep eutectic solvent in green chemistry.

In the present work, the synthesis of cellulose nanowhiskers (CNW)/chitosan nanocomposite films via deep eutectic solvents (DES) changing the chemical structures were carried out. It was observed that a pure chitosan film has broadband at 3180-3400 cm-1, indicating amide and hydroxyl groups. Upon CNW incorporation, the peak gets sharper and stronger and shifts to a greater wavelength. Further, the addition of DES infuses more elements of amide into the nanocomposite films. Moreover, the mechanical properties incorporating CNW filler into a chitosan matrix show an enhancement in tensile strength (TS), Young's modulus (YM), and elongation at break. The TS and YM increase while the elongation decrease as the CNW concentration increases. The YM of biocomposite films is increased to 723 MPa at 25% CNW into chitosan films. Besides, the TS has enhanced to 11.48 MPa at 15% CNW concentration in the biocomposite films. The elongation at break has decreased to 11.7% at 25% CNW concentration. Hence, incorporating CNW into the chitosan matrix via DES can still improve the mechanical properties of the nanocomposite films. Therefore, the application of DES results in a lower YM and TS as the films are hygroscopic. In conclusion, DES can be considered the new green solvent media for synthesizing materials. It has the potential to replace ionic liquids due to its biodegradability and non-toxic properties while preserving the character of low-vapour pressure. Besides that, chitosan can be used as potential material for applications in process industries, such as the biomedical and pharmaceutical industries. Thus, DES can be used as a green solvent and aim to reduce the toxic effect of chemicals on the environment during chemical production.

Green synthesis of nickel-doped magnesium ferrite nanoparticles via combustion for facile microwave-assisted optical and photocatalytic applications.

NixMg1-xFe2O4(x = 0, 0.2, 0.4, 0.6) nanoparticles were symphonized via combustion with microwave assistance in the presence of Tamarindus indica seeds extract as fuel. Nanoparticles nature, size, morphology, oxidation state, elemental composition, and optical and luminescence properties were analysed using PXRD, FTIR, SEM, EDX, and HRTEM with SAED, XPS, UV-Visible and photoluminescence spectroscopy. PXRD analysis confirms that synthesized nanoparticles are spinel cubic and have a 17-18 nm average crystalline size. Tetrahedral and octahedral sites regarding stretching vibrations were confirmed by FTIR analysis. SEM and HRTEM data it is disclosed that the morphology of synthesized nanoparticles has nano flakes-like structure with sponge-like agglomeration. Elemental compositions of prepared nanoparticles were confirmed through EDX spectroscopy. XPS Spectroscopy confirmed and revealed transition, oxidation states, and elemental composition. The band gap and absorption phenomenon were disclosed using UV-visible spectroscopy, where the band gap declines (2.1, 2, 1.6, 1.8 eV), with increase in nickel NixMg1-xFe2O4(x = 0, 0.2, 0.4, 0.6) doping. Photoluminescence intensity reduces with an incline in nickel doping, was confirmed and disclosed using photoluminescence spectroscopy. Dyes (Methylene blue and Rhodamine B) degradation activity was performed in the presence of NDMF nanoparticles as a photocatalyst, which disclosed that 98.1% of MB dye and 97.9% of RB dye were degraded in 0-120 min. Regarding initial dye concentration and catalyst load, 5 ppm was initiated as the ideal initial concentration for both RB and MB dyes. 50 mg catalyst dosage was found to be most effective for the degradation of MB and RB dyes. In comparison, pH studies revealed that photodegradation efficiency was higher in neutral (MB-98.1%, RB-97.9%) and basic (MB-99.6%, RB-99.3%) conditions than in acidic (MB-61.8%, RB-60.4%) conditions.

Removal of Pb ions using green Co3O4 nanoparticles: Simulation, modeling, adsorption, and biological studies.

Chemical co-precipitation synthesized novel and green cobalt-oxide nanoparticles (Co3O4-NPs) utilizing cobalt nitrate as cobalt precursors. FTIR, Raman, scanning electron microscopy, UV visible, X-ray powder diffraction, and BET was used to analyze the surface characteristics, composition, and morphology, of the NPs. These green Co3O4-NPs were employed to remove Pb ions from simulated wastewater solutions at various pH, adsorbate, temperature, and dose concentrations. At dose 20 mg/L, pH 6.0, 20 mg/L (Pb(II) solution, 25 °C of temperature, and 45 min for equilibrium, nearly 99.44% of Pb ions were removed. To evaluate the kinetic data, four different kinetic equations were used. The data fit the Elovich rate equation better than the other three models. Thermodynamic and isothermal studies were also evaluated, and the maximum adsorption capacity of 450.45 mg/g was observed at 298.15 K. 0.1 M HNO3, and 0.1 HCl were used to regenerate used Co3O4-NPs. Simulation results show the strong correlation of the Co atom in the Co3O4-NPs generates active delocalized surface states, which are energetically most favorable for heavy metal (Pb ions) adsorption and removal, supporting the experimental outcomes. In concluding remarks, green Co3O4-NPs can also be used as an adsorbent to remove Pb ions from wastewater bodies.

Pharmacological treatment of gastro-oesophageal reflux in children.

BACKGROUND: Gastro-oesophageal reflux (GOR) is characterised by the regurgitation of gastric contents into the oesophagus. GOR is a common presentation in infancy, both in primary and secondary care, affecting approximately 50% of infants under three months old. The natural history of GOR in infancy is generally of a self-limiting condition that improves with age, but older children and children with co-existing medical conditions can have more protracted symptoms. The distinction between gastro-oesophageal reflux disease (GORD) and GOR is debated. Current National Institute of Health and Care Excellence (NICE) guidelines define GORD as GOR causing symptoms severe enough to merit treatment. This is an update of a review first published in 2014. OBJECTIVES: To assess the effects of pharmacological treatments for GOR in infants and children. SEARCH METHODS: For this update, we searched CENTRAL, MEDLINE, Embase, and Web of Science up to 17 September 2022. We also searched for ongoing trials in clinical trials registries, contacted experts in the field, and searched the reference lists of trials and reviews for any additional trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared any currently-available pharmacological treatment for GOR in children with placebo or another medication. We excluded studies assessing dietary management of GORD and studies of thickened feeds. We included studies in infants and children up to 16 years old. DATA COLLECTION AND ANALYSIS: We used standard methodology expected by Cochrane. MAIN RESULTS: We included 36 RCTs involving 2251 children and infants. We were able to extract summary data from 14 RCTs; the remaining trials had insufficient data for extraction. We were unable to pool results in a meta-analysis due to methodological differences in the included studies (including heterogeneous outcomes, study populations, and study design). We present the results in two groups by age: infants up to 12 months old, and children aged 12 months to 16 years old. Infants Omeprazole versus placebo: there is no clear effect on symptoms from omeprazole. One study (30 infants; very low-certainty evidence) showed cry/fuss time in infants aged three to 12 months had altered from 246 ± 105 minutes/day at baseline (mean +/- standard deviation (SD)) to 191 ± 120 minutes/day in the omeprazole group and from 287 ± 132 minutes/day to 201 ± 100 minutes/day in the placebo group (mean difference (MD) 10 minutes/day lower (95% confidence interval (CI) -89.1 to 69.1)). The reflux index changed in the omeprazole group from 9.9 ± 5.8% in 24 hours to 1.0 ± 1.3% and in the placebo group from 7.2 ± 6.0% to 5.3 ± 4.9% in 24 hours (MD 7% lower, 95% CI -4.7 to -9.3). Omeprazole versus ranitidine: one study (76 infants; very low-certainty evidence) showed omeprazole may or may not provide symptomatic benefit equivalent to ranitidine. Symptom scores in the omeprazole group changed from 51.9 ± 5.4 to 2.4 ± 1.2, and in the ranitidine group from 47 ± 5.6 to 2.5 ± 0.6 after two weeks: MD -4.97 (95% CI -7.33 to -2.61). Esomeprazole versus placebo: esomeprazole appeared to show no additional reduction in the number of GORD symptoms compared to placebo (1 study, 52 neonates; very low-certainty evidence): both the esomeprazole group (184.7 ± 78.5 to 156.7 ± 75.1) and placebo group (183.1 ± 77.5 to 158.3 ± 75.9) improved: MD -3.2 (95% CI -4.6 to -1.8). Children Proton pump inhibitors (PPIs) at different doses may provide little to no symptomatic and endoscopic benefit. Rabeprazole given at different doses (0.5 mg/kg and 1 mg/kg) may provide similar symptom improvement (127 children in total; very low-certainty evidence). In the lower-dose group (0.5 mg/kg), symptom scores improved in both a low-weight group of children (< 15 kg) (mean -10.6 ± SD 11.13) and a high-weight group of children (> 15 kg) (mean -13.6 ± 13.1). In the higher-dose groups (1 mg/kg), scores improved in the low-weight (-9 ± 11.2) and higher-weight groups (-8.3 ± 9.2). For the higher-weight group, symptom score mean difference between the two different dosing regimens was 2.3 (95% CI -2 to 6.6), and for the lower-weight group, symptom score MD was 4.6 (95% CI -2.9 to 12). Pantoprazole: pantoprazole may or may not improve symptom scores at 0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg pantoprazole in children aged one to five years by week eight, with no difference between 0.3 mg/kg and 1.2 mg/kg dosing (0.3 mg/kg mean -2.4 ± 1.7; 1.2 mg/kg -1.7 ± 1.2: MD 0.7 (95% CI -0.4 to 1.8)) (one study, 60 children; very low-certainty evidence). There were insufficient summary data to assess other medications. AUTHORS' CONCLUSIONS: There is very low-certainty evidence about symptom improvements and changes in pH indices for infants. There are no summary data for endoscopic changes. Medications may or may not provide a benefit (based on very low-certainty evidence) for infants whose symptoms remain bothersome, despite nonmedical interventions or parental reassurance. If a medication is required, there is no clear evidence based on summary data for omeprazole, esomeprazole (in neonates), H2antagonists, and alginates for symptom improvements (very low-certainty evidence). Further studies with longer follow-up are needed. In older children with GORD, in studies with summary data extracted, there is very low-certainty evidence that PPIs (rabeprazole and pantoprazole) may or may not improve GORD outcomes. No robust data exist for other medications. Further RCT evidence is required in all areas, including subgroups (preterm babies and children with neurodisabilities).

Characterization of municipal solid waste: Measures towards management strategies using statistical analysis.

Implementing unified municipal solid waste management (MSWM) is often difficult due to socio-economic variables. However, spatial GIS models and statistical analysis of solid waste characterized by the weekdays, weekends, and festivals can somewhat mitigate the variance and assist with selecting suitable waste management methods. This paper presents the example of Rajouri, India, to propose a suitable MSWM based on Inverse Distance Weighted (IDW) intensity maps and statistical findings. The considered region was divided into different sample sites based on the local population density, and Municipal Solid Waste (MSW) was collected from four locations in each site on weekdays, weekends, and festivals. Compositional analysis of the MSW was then used to generate spatial IDW models in QGIS 3.22.7 to interpolate MSW generation over the entire area. Finally, statistical analysis was conducted to gain insight into the waste generation and accumulation trends. The results show that Rajouri produces 245 tonnes of waste daily (per capita: 0.382 kg/day) with a large organic fraction compared to other waste categories. Besides, waste generation is observed to increase over weekends and festivals due to increased consumption of material goods. Composting could serve as a vector for municipal solid waste because of its increased organic component and cost constraints. However, further research on the potential segregation techniques for the organic fraction of solid waste is needed.

Experimental investigation of H3PO4 activated papaya peels for methylene blue dye removal from aqueous solution: Evaluation on optimization, kinetics, isotherm, thermodynamics, and reusability studies.

This investigation is centered on the effectiveness of methylene blue (MB), a cationic dye, adsorbed from an aqueous media by H3PO4 activated papaya skin/peels (PSPAC), with initial pH (2-10), contact time (30-180 min), MB dye concentration (varying from 10 to 50 mg/L), and MB dose (0.1-0.5 gm). The findings show that the best optimal conditions for MB dye removal occur at a 6 pH, 0.3 gm dose of PSPAC adsorbent for 10 mg/L MB dye concentration, with 90 min of contact time. To optimize and validate the extraction efficiency of MB dye, a response surface methodology (RSM) study was conducted using a central composite design (CCD) with a regression model showing R2 = 0.9940. FT-IR spectroscopy shows, CO, and O-H stretching functional groups while FE-SEM is assessed to supervise morphological features of the PSPAC adsorbent. The peak adsorption capacity with 46.95 mg/g for the Langmuir isotherm model conveniently satisfies the adsorption process with R2 = 0.9984 while with R2 = 0.999, a kinetic model, pseudo-second-order, confirms MB dye adsorption by PSPAC adsorbent. Moreover, thermodynamic parameters including ΔGᵒ, ΔH°, and ΔS° were computed and found to be spontaneous and exothermic. Furthermore, regeneration studies employed with NaOH (0.1 M) and HCl (0.1 M) solution media show an acceptable MB removal efficiency consecutive up to three cycles. The study highlights that H3PO4 papaya skin/peel (PSPAC) is an effectual, sustainable, reasonably available biosorbent to remove industrial cationic dyes disposal.

Zinc oxide nanoparticles adsorb emerging pollutants (glyphosate pesticide) from aqueous solutions.

The present study captures the precipitation synthesis of zinc nanoparticles and modification with alumina and oleic acid. The crystalline size evaluated from the XRD profile of the zinc oxide nanoparticles was 18.05 nm but was reduced to 14.20 and 14.50 nm upon modification with oleic acid and alumina. The XRD spectra also showed evidence of the amorphous nature of zinc oxide nanoparticles and subsequent enhancement upon modification. A porous appearance was observed in the SEM instrumentation but seems to be enhanced by modification. The FTIR absorption spectra of the nanoparticles showed a peak associated with ZnO vibration around 449 cm, but the enhanced intensity was observed due to modification. The prepared ZnO-NPs and the modified samples were good materials for the adsorption removal of glyphosate from water, recording efficiencies above 94% at neutral pH and showing a possible incremental trend with an enhanced period of contact and adsorbent dosage. The adsorbents showed maximum capacity that ranged from 82.85 to 82. 97 mg/g. The adsorption models of Freundlich, Temkin, Dubinin-Radushkevich and BET showed excellent fitness. Results from computational results complemented experimental data and were used to identify the sites for adsorption and characteristics of molecular descriptors for the systems.

Incidence and Prevalence of Paediatric Inflammatory Bowel Disease Continues to Increase in the South of England.

OBJECTIVE: The incidence of paediatric inflammatory bowel disease (IBD) has been increasing over 25 years; however, contemporary trends are not established and the impact of COVID-19 on case rates is unclear. METHODS: Data from Southampton Children's hospital prospective IBD database were retrieved for 2002-2021. Incidence rates were calculated based on referral area populations and temporal trends analysed. Disease prevalence for those aged <18 years was calculated for 2017-2021. Monoclonal prescriptions were reported. RESULTS: In total, 1150 patients were included (mean age at diagnosis 12.63 years, 40.5% female). An estimated 704 patients had Crohn's disease (61.2%), 385 had ulcerative colitis (33.5%), and 61 had IBD unclassified (5.3%). Overall IBD incidence increased, ß = 0.843, P = 3 × 10 -6 , driven by Crohn's disease, ß = 0.732, P = 0.00024 and ulcerative colitis, ß = 0.816, P = 0.000011. There was no change in IBDU incidence, ß = 0.230, P = 0.33. From 2002-2021, 51 patients were diagnosed <6 years of age, 160 patients aged 6 to <10 years and 939 patients aged 10 to <18 years of age. Increased incidence was observed in patients aged 10 to <18 years of age (ß = 0.888, P = 1.8 × 10 -7 ). There was no significant change in incidence of IBD in <6 years (ß = 0.124, P = 0.57), or 6 to <10 years (ß = 0.146, P = 0.54). IBD prevalence increased by an average of 1.71%/year from 2017 to 2021, ß = 0.979, P = 0.004. The number of new monoclonal prescriptions increased from 6 in 2007 to 111 in 2021. CONCLUSIONS: IBD incidence continues to increase in Southern England. Compounding prevalence and increased monoclonal usage has implications for service provision.

Microplastics: Occurrences, treatment methods, regulations and foreseen environmental impacts.

Microplastics are a silent threat that represent a high degree of danger to the environment in its different ecosystems and of course will also have an important impact on the health of living organisms. It is evident the need to have effective treatments for their treatment, however this is not a simple task, this as a result of the behavior of microplastics in wastewater treatment plants due to their different types and nature, their long molecular chain, reactivity against water, size, shape and the functional groups they carry. Wastewater treatment plants are at the circumference of the release of these wastes into the environment. They often act as a source of many contaminations, which makes this problem more complex. Challenges such as detection in the current scenario using the latest analytical techniques impede the correct understanding of the problem. Due to microplastics, treatment plants have operational and process stability problems. This review paper will present the in-depth situation of occurrence of microplastics, their detection, conventional and advanced treatment methods as well as implementation of legislations worldwide in a comprehensive manner. It has been observed that no innovative or new technologies have emerged to treat microplastics. Therefore, in this article, technologies targeting wastewater treatment plants are critically analyzed. This will help to understand their fate, but also to develop state-of-the-art technologies or combinations of them for the selective treatment of microplastics. The pros and cons of the treatment methods adopted and the knowledge gaps in legislation regarding their implementation are also comprehensively analyzed. This critical work will offer the development of new strategies to restrict microplastics.

Growth failure is rare in a contemporary cohort of paediatric inflammatory bowel disease patients.

AIM: We assessed growth in a paediatric inflammatory bowel disease (PIBD) cohort. METHODS: Paediatric inflammatory bowel disease patients were eligible if they were diagnosed at Southampton Children's Hospital from 2011 to 2018. Weight and height standard deviation scores (SDS) were retrieved. Mean SDS values, SDS change and anti-TNF status were analysed at diagnosis and during follow-up. RESULTS: Four hundred and ninety patients were included, 313 with Crohn's disease (CD). CD patients presented with mean height SDS -0.13, -0.1 at 1-year, -0.11 at 2-years and -0.03 at 5 years, reflecting preserved linear growth. There was no significant height-SDS change from diagnosis to 5-year follow-up, +0.12, 95%-CI: 0.48 to -0.24. Mean weight-SDS at diagnosis was -0.39, driven by CD patients (-0.65). Mean weight-SDS approached 0 after 1 year and remained at the 50th centile throughout follow-up. Growth in ulcerative colitis was maintained. In multivariable regression males had worse height growth from diagnosis to transition (P = .036). Anti-TNF treatment (P = .013) and surgical resection (P = .005) were also associated with poorer linear growth. Patients treated with anti-TNF therapy had lower height-SDS compared to those never treated with anti-TNF at 1 year (-0.2 vs -0.01, P = .22), 2-years (-0.27 vs -0.01, P = .07) and 5 years (-0.21 vs 0.25, P = .051). CONCLUSION: Height was generally maintained in Crohn's disease, and impaired linear growth was rare in this cohort.

Understanding the impacts of the COVID-19 pandemic on sustainable agri-food system and agroecosystem decarbonization nexus: A review.

The existing finite natural resources have witnessed unsustainable usage in the past few years, especially for food production, with accompanying environmental devastation and ecosystem damage. Regrettably, the global population and consumption demands are increasing ceaselessly, leading to the need for more resources for food production, which could potentially aggravate the sustainability and ecosystem degradation issues, while stimulating drastic climate change. Meanwhile, the unexpected emergence of the COVID-19 pandemic and some implemented measures to combat its spread disrupted agricultural activities and the food supply chain, which also led to a reduction in ecosystem carbonization. This study sets out to explore policy framework and selected feasible actions that are being adopted during the COVID-19 pandemic, which could potentially reduce the emissions even after the pandemic to promote a resilient and sustainable agri-food system. In this study, we reviewed 27 articles that focus on the current state of the agri-food system in light of the COVID-19 pandemic and its impact on the decarbonization of the agroecosystem. This review has taken the form of a systematic methodology in analyzing the adoption and implementation of various measures to mitigate the spread of COVID-19 on the impact of the agri-food system and reduction in ecosystem degradation. Up to 0.3 Mt of CO2 reduction from the agri-food system alone was reportedly achieved during the first 6 months of the pandemic in 23 European countries. The various adopted measures indicate that the circular economy approach is a panacea to achieve the needed sustainability in the agri-food system. Also, it dictates a need for a paradigm change towards improvement on localized food production that promotes sustainable production and consumption.

COVID-19 transmission, vulnerability, persistence and nanotherapy: a review.

End 2019, the zoonotic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), named COVID-19 for coronavirus disease 2019, is the third adaptation of a contagious virus following the severe acute respiratory syndrome coronavirus in 2002, SARS-CoV, and the Middle East respiratory syndrome virus in 2012, MERS-CoV. COVID-19 is highly infectious and virulent compared to previous outbreaks. We review sources, contagious routes, preventive measures, pandemic, outbreak, epidemiology of SARS-CoV, MERS-CoV and SARS-CoV-2 from 2002 to 2020 using a Medline search. We discuss the chronology of the three coronaviruses, the vulnerability of healthcare workers, coronaviruses on surface and in wastewater, diagnostics and cures, and measures to prevent spreading.

SNP discovery and population structure analysis in Lassi and Marecha camel breeds using a genotyping by sequencing method.

Pakistani camels have been classified socio-geographically into 20 breeds, but they have not yet been subjected to substantial selective pressures and the genetic basis for these breeds is not understood. However, it should be possible to distinguish them by use of molecular data. This study investigated the genetic diversity and population structure within and between two major Pakistani camel breeds, Marecha and Lassi. As no SNP array is currently available, we first identified 63 619 SNPs using a genotyping by sequencing approach. After quality control, a panel of 36 926 SNPs was used in the analysis. Population structure was investigated with a principal coordinate analysis as well as a cluster analysis using NetView, and multilocus heterozygosity analysis to explore between- and within-breed genetic variation. In addition, between-breed variation was explored using the fixation index, FST . We also compared relationship matrices computed using the VanRaden SNP-based method and a method developed specifically for genotyping by sequencing data. Among the two camel breeds, Lassi showed a lower level of genetic diversity whereas Marecha showed a higher level. As a genotyping platform has not yet been developed for the camel, the SNPs discovered in this study will be useful in future genetic studies in camels.

Impact of varying agrometeorological indices on peel color and composition of Kinnow fruit (Citrus nobilis Lour x Citrus deliciosa Tenora) grown at different ecological zones.

BACKGROUND: Kinnow orchards were selected in different ecological zones in districts Sargodha, Toba Tek Singh (TTS) and Vehari of the Punjab province, Pakistan. Three biological replicates in block form were applied by using analysis of variance techniques to assess varying agrometeorological indices impact on fruit color-development and peel composition. RESULTS: Fruit samples were randomly collected on each month's end starting from August up to February. Chromameter was used for measuring coloring parameters and its values a*, b*, C* and L* were increased from August till February with a rapid elevation started at color-break stage, while hue angle (h*) rotated from 120° to 60° of portraying green to yellow shade. An increasing level of chlorophyll contents were noted in August till color-break at the end of October and then diminished afterwards. Whereas, carotenoids increased rapidly upon yellow tinting peel of Kinnow fruits till fully attained deep orange color at the end of February. Ascorbic acid content and total phenolic content (TPC) showed a decreasing trend whereas anthocyanins and antioxidant activity were increased from August to February, with unchanged flavonoids and flavonols level. Fruit firmness was gradually reduced till color-break with rapid reduction noted subsequently. Maturity index represented internal ripening directly increased with color-development. CONCLUSION: Color development has directly influenced on maturity index and both were increased rapidly after color-break to afterwards. More color development with rapid reduction in chlorophyll, ascorbic acid and TPC level were seen in warm districts namely TTS and Vehari after color-break stage due to accumulating more agrometeorological indices. © 2020 Society of Chemical Industry.