Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants.

Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA). Donor antigen presenting cells (APCs), particularly dendritic cells (DCs), orchestrate early alloimmune responses by activating recipient effector T cells. Employing a targeted approach, we investigated the impact of donor-derived conventional DCs (cDCs) and APCs on the immunogenicity of skin and skin-containing VCA grafts, using mouse models of skin and hind limb transplantation. By post-transplantation day 6, skin grafts demonstrated severe rejections, characterized by predominance of recipient CD4 T cells. In contrast, hind limb grafts showed moderate rejection, primarily infiltrated by CD8 T cells. Notably, the skin component exhibited heightened immunogenicity when compared to the entire VCA, evidenced by increased frequencies of pan (CD11b-CD11c+), mature (CD11b-CD11c+MHCII+) and active (CD11b-CD11c+CD40+) DCs and cDC2 subset (CD11b+CD11c+ MHCII+) in the lymphoid tissues and the blood of skin transplant recipients. While donor depletion of cDC and APC reduced frequencies, maturation and activation of DCs in all analyzed tissues of skin transplant recipients, reduction in DC activities was only observed in the spleen of hind limb recipients. Donor cDC and APC depletion did not impact all lymphocyte compartments but significantly affected CD8 T cells and activated CD4 T in lymph nodes of skin recipients. Moreover, both donor APC and cDC depletion attenuated the Th17 immune response, evident by significantly reduced Th17 (CD4+IL-17+) cells in the spleen of skin recipients and reduced levels of IL-17E and lymphotoxin-α in the serum samples of both skin and hind limb recipients. In conclusion, our findings underscore the highly immunogenic nature of skin component in VCA. The depletion of donor APCs and cDCs mitigates the immunogenicity of skin grafts while exerting minimal impact on VCA.

Development and characterization of pH-responsive Delonix regia/mucin co-poly (acrylate) hydrogel for controlled drug delivery of metformin HCl.

This study introduces a pH-responsive hydrogel developed from Delonix regia and mucin co-poly(acrylate) through free radical polymerization to enhance controlled drug delivery systems. Characterization using FTIR, DSC, TGA, SEM, PXRD, and EDX spectroscopy detailed the hydrogel's amorphous and crystalline structures, thermal stability, surface characteristics, and elemental composition. Tested at a pH of 7.4-mimicking intestinal conditions-the hydrogel demonstrated significant swelling, indicating its capability for targeted drug release. With Metformin HCl as a model drug, the hydrogel exhibited a promising sustained release profile, underscoring its potential for oral administration. Safety and biocompatibility were assessed through acute oral toxicity studies in albino rabbits, encompassing biochemical, hematological, and histopathological evaluations. X-ray imaging confirmed the hydrogel's navigability through the gastrointestinal tract, affirming its application in drug delivery. By potentially mitigating gastrointestinal side effects, enhancing patient compliance, and improving therapeutic efficacy, this Delonix regia/mucin co-poly(acrylate) hydrogel represents a step in pharmaceutical sciences, exploring innovative materials and methodologies for drug delivery.

Beyond the Diagnosis: A Deep Dive Into the End Stage Liver Disease Experience From the Patient Perspective.

INTRODUCTION: End-stage liver disease (ESLD) presents a multifaceted challenge that encompasses not only physical but also emotional, psychological, and social dimensions. This study aims to explore the experiences of ESLD patients within the United States healthcare system. METHODS: Utilizing a convenience sampling methodology, 15 ESLD patients from a tertiary care hospital in the USA participated in semi-structured interviews between April 2023 and January 2024. Data analysis was conducted using MAXQDA 2023, employing a phenomenological approach to identify common themes. RESULTS: The study identified six primary themes: the significance of communication style in diagnosis delivery, the crucial role of family and social support, varied understanding and preferences for palliative care, diverse attitudes towards advanced care planning, preferences for coordinated healthcare experiences, and the emotional and psychological impact of ESLD. CONCLUSION: Our study underscores the complexity of ESLD patient care beyond medical treatment, highlighting the importance of clear communication, empathetic care, and the integration of family and palliative care services.

Combined Endurance and Resistance Exercise Mitigates Age-Associated Cardiac Dysfunction.

Aging is associated with a decline in cardiac function. Exercise has been shown to effectively reduce the risks of cardiovascular diseases. Here whether a combination of endurance and resistance exercises can improve cardiac function in aged mice during late life is investigated. Through transcriptome analysis, several signaling pathways activated in the hearts of 22-month-old mice after combined exercise, including cardiac muscle contraction, mitophagy, and longevity regulation are identified. Combined exercise training mitigated age-associated pathological cardiac hypertrophy, reduced oxidative stress, cardiac senescence, and enhanced cardiac function. Upstream stimulatory factor 2 (Usf2) is upregulated in the aged mouse hearts with combined exercise compared to sedentary mice. In the human cardiomyocytes senescent model, overexpression of Usf2 led to anti-senescence effects, while knockdown of Usf2 exacerbated cellular senescence. The results suggest that a combination of endurance and resistance exercises, such as swimming and resistance running, can mitigate age-related pathological cardiac remodeling and cardiac dysfunction in late life. These cardioprotective effects are likely due to the activation of Usf2 and its anti-senescence effect. Therefore, Usf2 can potentially be a novel therapeutic target for mitigating age-related cardiac dysfunction.

Halotolerant Endophytic Bacteria Regulate Growth and Field Performance of Two Durum Wheat Genotypes with Contrasting Salinity Tolerance Potential.

Soil salinity hampers durum wheat plant growth and development at various stages. The detrimental effects of salinity on plant cellular and physiological processes necessitate strategies to alleviate its negative impact and improve overall crop yield. This study investigates the efficacy of plant growth-promoting rhizobacteria (PGPR) bacteria inoculation in mitigating salinity stress on two durum wheat genotypes with contrasting degrees of salinity tolerance (Tamaroi, salt-sensitive and Line 5004, salt-tolerant) under greenhouse and field conditions. For this purpose, two halotolerant-PGPR strains, Pseudomonas jordanii strain G34 and Oceanobacillus jordanicus strain GSFE11, were utilized for the inoculation. For the greenhouse experiment, the two selected genotypes were subjected to salinity at the flag leaf stage with continuous irrigation with a Hoagland solution supplemented with 50 mM NaCl. Field experiments were conducted across two locations with contrasting salinity levels over two growing seasons. At the end of both experiments, various parameters including total weight, spike weight, grain weight, spike number, spikelet number, grains per spike and thousand kernel weight were measured. The halotolerant PGPRs, P. jordanii strain G34 and O. jordanicus strain GSFE11, proved effective in alleviating salinity-induced adverse effects and enhancing growth under greenhouse and field conditions. However, bacterial inoculation significantly improved growth in the salt-sensitive genotype and such effects were not observed in the tolerant genotype, emphasizing genotype-specific responses. Notably, inoculation with O. jordanicus increased Na+ and Ca2+ uptake in the salt-tolerant "Line 5004" without hindering growth, suggesting one of its potential mechanisms for salt tolerance. This research demonstrates the potential of halotolerant-PGPR inoculation in enhancing durum wheat production in saline environments, but also underscores the importance of understanding genotype-specific responses for tailored interventions.

Comparative efficacy of craniotomy versus craniectomy in surgical management of acute subdural hematoma: A systematic review and meta-analysis.

INTRODUCTION: Acute subdural hematoma (ASDH), a predominantly lethal neurosurgical emergency in the settings of traumatic brain injury, requires surgical evacuation of hematoma, via craniotomy or craniectomy. The clinical practices vary, with no consensus over the superiority of either procedure. AIM: To evaluate whether craniotomy or craniectomy is the optimal approach for surgical evacuation of ASDH. METHODS: After a comprehensive search of PubMed, Google Scholar, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) up to January 2024, to identify relevant studies, a meta-analysis was performed using a random-effects model, and risk ratios were calculated with 95% confidence intervals (CIs). For quality assessment, the Cochrane risk of bias tool and Newcastle-Ottawa Scale were applied. RESULTS: Out of 2143 potentially relevant studies, 1875 were deemed suitable for screening. Eighteen studies were included in the systematic review. Thirteen studies, in which 1589 patients underwent craniotomy and 1452 patients underwent craniectomy, allowed meta-analysis. Pooled estimates showed that there was no significant correlation of mortality at 6 months (RR 1.14;95 % CI; 0.94-1.38 P = 0.18) and 12 months (RR 1.17; 95 % CI; 0.84-1.63 P = 0.36) with the two surgical modalities. A positive association was observed between improved functional outcomes at 6-months and craniotomy (RR 0.76; 95 % CI; 0.62-0.93 P = 0.008), however, no significant difference was observed between the two treatment groups at 12 months follow-up (RR 0.89; 95 % CI; 0.72-1.09 P = 0.26). Craniotomy reported a significantly higher proportion of patients discharged to home (RR 0.63; 95 % CI; 0.49-0.83 P = 0.0007), whereas incidence of residual subdural hematoma was significantly lower in the craniectomy group (RR 0.70; 95 % CI; 0.52-0.94 P = 0.02). CONCLUSION: Craniectomy is associated with poor clinical outcomes. However, with long-term follow-up, no difference in mortality and functional outcomes is observed in either of the patient populations. On account of equivocal evidence regarding the efficacy of craniectomy over craniotomy in the realm of long-term outcomes, utmost preference shall be directed toward craniotomy as it is less invasive and associated with fewer complications.

Commissioning of a novel PET-Linac for biology-guided radiotherapy (BgRT).

BACKGROUND: Biology-guided radiotherapy (BgRT) is a novel radiotherapy delivery technique that utilizes the tumor itself to guide dynamic delivery of treatment dose to the tumor. The RefleXion X1 system is the first radiotherapy system developed to deliver SCINTIX® BgRT. The X1 is characterized by its split arc design, employing two 90-degree positron emission tomography (PET) arcs to guide therapeutic radiation beams in real time, currently cleared by FDA to treat bone and lung tumors. PURPOSE: This study aims to comprehensively evaluate the capabilities of the SCINTIX radiotherapy delivery system by evaluating its sensitivity to changes in PET contrast, its adaptability in the context of patient motion, and its performance across a spectrum of prescription doses. METHODS: A series of experimental scenarios, both static and dynamic, were designed to assess the SCINTIX BgRT system's performance, including an end-to-end test. These experiments involved a range of factors, including changes in PET contrast, motion, and prescription doses. Measurements were performed using a custom-made ArcCHECK insert which included a 2.2 cm spherical target and a c-shape structure that can be filled with a PET tracer with varying concentrations. Sinusoidal and cosine4 motion patterns, simulating patient breathing, was used to test the SCINTIX system's ability to deliver BgRT during motion-induced challenges. Each experiment was evaluated against specific metrics, including Activity Concentration (AC), Normalized Target Signal (NTS), and Biology Tracking Zone (BTZ) bounded dose-volume histogram (bDVH) pass rates. The accuracy of the delivered BgRT doses on ArcCHECK and EBT-XD film were evaluated using gamma 3%/2 mm and 3%/3 mm analysis. RESULTS: In static scenarios, the X1 system consistently demonstrated precision and robustness in SCINTIX dose delivery. The end-to-end delivery to the spherical target yielded good results, with AC and NTS values surpassing the critical thresholds of 5 kBq/mL and 2, respectively. Furthermore, bDVH analysis consistently confirmed 100% pass rates. These results were reaffirmed in scenarios involving changes in PET contrast, emphasizing the system's ability to adapt to varying PET avidities. Gamma analysis with 3%/2 mm (10% dose threshold) criteria consistently achieved pass rates > 91.5% for the static tests. In dynamic SCINTIX delivery scenarios, the X1 system exhibited adaptability under conditions of motion. Sinusoidal and cosine4 motion patterns resulted in 3%/3 mm gamma pass rates > 87%. Moreover, the comparison with gated stereotactic body radiotherapy (SBRT) delivery on a conventional c-arm Linac resulted in 93.9% gamma pass rates and used as comparison to evaluate the interplay effect. The 1 cm step shift tests showed low overall gamma pass rates of 60.3% in ArcCHECK measurements, while the doses in the PTV agreed with the plan with 99.9% for 3%/3 mm measured with film. CONCLUSIONS: The comprehensive evaluation of the X1 radiotherapy delivery system for SCINTIX BgRT demonstrated good agreement for the static tests. The system consistently achieved critical metrics and delivered the BgRT doses per plan. The motion tests demonstrated its ability to co-localize the dose where the PET signal is and deliver acceptable BgRT dose distributions.

Evolutionary trends of respiratory syncytial viruses: Insights from large-scale surveillance and molecular dynamics of G glycoprotein.

Human respiratory syncytial virus (RSV) is an underlying cause of lower respiratory illnesses in children, elderly and immunocompromised adults. RSV contains multiple structural and non-structural proteins with two major glycoproteins that control the initial phase of infection, fusion glycoprotein and the attachment (G) glycoprotein. G protein attaches to the ciliated cells of airways initiating the infection. The hypervariable G protein plays a vital role in evolution of RSV strains. We employed multiple bioinformatics tools on systematically accessed large-scale data to evaluate mutations, evolutionary history, and phylodynamics of RSV. Mutational analysis of central conserved region (CCR) on G protein-coding sequences between 163 and 189 positions revealed frequent mutations at site 178 in human RSV (hRSV) A while arginine to glutamine substitutions at site 180 positions in hRSV B, remained prevalent from 2009 to 2014. Phylogenetic analysis indicates multiple signature mutations within G protein responsible for diversification of clades. The USA and China have highest number of surveillance records, followed by Kenya. Markov Chain Monte Carlo Bayesian skyline plot revealed that RSV A evolved steadily from 1990 to 2000, and rapidly between 2003 and 2005. Evolution of RSV B continued from 2003 to 2022, with a high evolution stage from 2016 to 2020. Throughout evolution, cysteine residues maintained their strict conserved states while CCR has an entropy value of 0.0039(±0.0005). This study concludes the notion that RSV G glycoprotein is continuously evolving while the CCR region of G protein maintains its conserved state providing an opportunity for CCR-specific monoclonal antibodys (mAbs) and inhibitors as potential candidates for immunoprophylaxis.

Navigating autism treatment: unlocking new frontiers with ChatGPT.

Autism Spectrum disorder is a significant neurodevelopmental behavioral disorder. Children with Autism display a wide array of ambiguous symptoms resulting making the diagnosis quite challenging thus resulting in delayed management. Traditionally, its diagnosis and management require the collaboration of services from the three P's namely the pediatrician, psychiatrist, and child psychologist. The management requires an intensive multi-disciplinary approach which would help minimize the disease symptoms and facilitate development and learning during childhood.Recently, with the advent of widespread testing and usage of various artificial intelligence tools across various domains, AI tools such as Chatbots are being incorporated into medical treatments, especially in behavioral therapy. Considering the increasing use of AI, we believe that the natural language processing techniques employed by ChatGPT algorithms have the potential to identify speech and linguistic patterns in children with ASD. Therefore, through this letter, we have tried to explore the scope of Artificial intelligence (ChatGPT) for behavioral therapy in children affected with autism spectrum disorder.

Identifying alkaline phosphatase inhibitory potential of cyclooxygenase-2 inhibitors: Insights from molecular docking, MD simulations, molecular expression analysis in MCF-7 breast cancer cell line and in vitro investigations.

Alkaline phosphatases (APs, EC 3.1.3.1) belong to a superfamily of biological macromolecules that dephosphorylate many phosphometabolites and phosphoproteins and their overexpression is intricated in the spread of cancer to liver and bones, neuronal disorders including Alzheimer's disease (AD), inflammation and others. It was hypothesized that cyclooxygenase-2 (COX-2) selective inhibitors may possess anti-APs potential and may be involved in anticancer proceedings. Three COX-2 inhibitors including nimesulide, piroxicam and lornoxicam were evaluated for the inhibition of APs using in silico and in vitro methods. Molecular docking studies against tissue nonspecific alkaline phosphatase (TNAP) offered the best binding affinities for nimesulide (-11.14 kcal/mol) supported with conventional hydrogen bonding and hydrophobic interactions. MD simulations against TNAP for 200 ns and principal component analysis (PCA) reiterated the stability of ligand-receptor complexes. Molecular expression analysis of TNAP enzyme in the breast cancer cell line MCF-7 exhibited 0.24-fold downregulation with 5 µM nimesulide as compared with 0.26-fold standard 10 µM levamisole. In vitro assays against human placental AP (hPAP) displayed potent inhibitions of these drugs with IC50 values of 0.52 ±â€¯0.02 µM to 3.46 ±â€¯0.13 µM and similar results were obtained for bovine intestinal AP (bIAP). The data when generalized collectively emphasizes that the inhibition of APs by COX-2 inhibitors provides another target to work on the development of anticancer drugs.

A new bicornuate model of rat uterus transplantation.

INTRODUCTION: Uterus transplantation has revolutionized reproductive medicine for women with absolute uterine factor infertility, resulting in more than 40 reported successful live births worldwide to date. Small animal models are pivotal to refine this surgical and immunological challenging procedure aiming to enhance safety for both the mother and the child. MATERIAL AND METHODS: We established a syngeneic bicornuate uterus transplantation model in young female Lewis rats. All surgical procedures were conducted by an experienced and skilled microsurgeon who organized the learning process into multiple structured steps. Animals underwent meticulous preoperative preparation and postoperative care. Transplant success was monitored by sequential biopsies, monitoring graft viability and documenting histological changes long-term. RESULTS: Bicornuate uterus transplantation were successfully established achieving an over 70% graft survival rate with the passage of time. The bicornuate model demonstrated safety and feasibility, yielding outcomes comparable to the unicornuate model in terms of ischemia times and complications. Longitudinal biopsies were well-tolerated, enabling comprehensive monitoring throughout the study. CONCLUSIONS: Our novel bicornuate rat uterus transplantation model provides a distinctive opportunity for sequential biopsies at various intervals after transplantation and, therefore, comprehensive monitoring of graft health, viability, and identification of potential signs of rejection. Furthermore, this model allows for different interventions in each horn for comparative studies without interobserver differences contrary to the established unicornuate model. By closely replicating the clinical setting, this model stands as a valuable tool for ongoing research in the field of uterus transplantation, promoting further innovation and deeper insights into the intricacies of the uterus transplant procedure.

Pervasive influence of heavy metals on metabolic pathways is potentially relieved by hesperidin to enhance the phytoremediation efficiency of Bassia scoparia.

Hesperidin (HSP), a flavonoid, is a potent antioxidant, metal chelator, mediator of signaling pathways, and regulator of metal uptake in plants. The study examined the ameliorative effects of HSP (100 µM) on Bassia scoparia grown under excessive levels of heavy metals (zinc (500 mg kg-1), copper (400 mg kg-1), cadmium (100 mg kg-1), and chromium (100 mg kg-1)). The study clarifies the underlying mechanisms by which HSP lessens metabolic mayhem to enhance metal stress tolerance and phytoremediation efficiency of Bassia scoparia. Plants manifested diminished growth because of a drop in chlorophyll content and nutrient acquisition, along with exacerbated deterioration of cellular membranes reflected in elevated reactive oxygen species (ROS) production, lipid peroxidation, and relative membrane permeability. Besides the colossal production of cytotoxic methylglyoxal, the activity of lipoxygenase was also higher in plants under metal toxicity. Conversely, hesperidin suppressed the production of cytotoxic ROS and methylglyoxal. Hesperidin improved oxidative defense that protected membrane integrity. Hesperidin caused a more significant accumulation of osmolytes, non-protein thiols, and phytochelatins, thereby rendering metal ions non-toxic. Hydrogen sulfide and nitric oxide endogenous levels were intricately maintained higher in plants treated with HSP. Hesperidin increased metal accumulation in Bassia scoparia and thereby had the potential to promote the reclamation of metal-contaminated soils.

Salicylic Acid and Gemma-Aminobutyric Acid Mediated Regulation of Growth, Metabolites, Antioxidant Defense System and Nutrient Uptake in Sunflower (Helianthus annuus L.) Under Arsenic Stress.

Background: Arsenic (As) is a highly toxic and carcinogenic pollutant commonly found in soil and water, posing significant risks to human health and plant growth. Objective: The objectives of this study to evaluate morphological, biochemical, and physiological markers, as well as ion homeostasis, to alleviate the toxic effects of As in sunflowers through the exogenous application of salicylic acid (SA), γ-aminobutyric acid (GABA), and their combination. Methods: A pot experiment was conducted using two sunflower genotypes, FH-779 and FH-773, subjected to As stress (60 mg kg-1) to evaluate the effects of SA at 100 mg L-1, GABA at 200 mg L-1, and their combination on growth and related physiological and biochemical attributes under As stress. Results: The study revealed that As toxicity had a detrimental effect on various growth parameters, chlorophyll pigments, relative water content, total proteins, and nutrient uptake in sunflower plants. It also led to increased oxidative stress, as indicated by higher levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2), along with As accumulation in the roots and leaves. However, the application of SA and GABA protected against As-induced damage by enhancing the enzymatic antioxidant defense system. This was achieved through the activation of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities, as well as an increase in osmolytes. They also improved nutrient acquisition and plant growth under As toxicity. Conclusions: We investigated the regulatory roles of SA and GABA in mitigating arsenic-induced phytotoxic effects on sunflower. Our results revealed a significant interaction between SA and GABA in regulating growth, photosynthesis, metabolites, antioxidant defense systems, and nutrient uptake in sunflower under As stress. These findings provide valuable insights into plant defense mechanisms and strategies to enhance stress tolerance in contaminated environments. In the future, SA and GABA could be valuable tools for managing stress in other important crops facing abiotic stress conditions.

Copper Oxide Nanoparticles Induced Growth and Physio-Biochemical Changes in Maize (Zea mays L.) in Saline Soil.

Research on nanoparticles (NPs) is gaining great attention in modulating abiotic stress tolerance and improving crop productivity. Therefore, this investigation was carried out to evaluate the effects of copper oxide nanoparticles (CuO-NPs) on growth and biochemical characteristics in two maize hybrids (YH-5427 and FH-1046) grown under normal conditions or subjected to saline stress. A pot-culture experiment was carried out in the Botanical Research Area of "the University of Lahore", Lahore, Pakistan, in a completely randomized design. At two phenological stages, both maize hybrids were irrigated with the same amount of distilled water or NaCl solution (EC = 5 dS m-1) and subjected or not to foliar treatment with a suspension of CuO-NPs. The salt stress significantly reduced the photosynthetic parameters (photosynthetic rate, transpiration, stomatal conductance), while the sodium content in the shoot and root increased. The foliar spray with CuO-NPs improved the growth and photosynthetic attributes, along with the N, P, K, Ca, and Mg content in the roots and shoots. However, the maize hybrid YH-5427 responded better than the other hybrid to the saline stress when sprayed with CuO-NPs. Overall, the findings of the current investigation demonstrated that CuO-NPs can help to reduce the adverse effects of salinity stress on maize plants by improving growth and physio-biochemical attributes.

Antiurease Activity of Antibiotics: In Vitro, In Silico, Structure Activity Relationship, and MD Simulations of Cephalosporins and Fluoroquinolones.

Helicobacter pylori infection is widespread in 50% of the world's population and is associated with gastric ulcers and related disorders that ultimately culminate in gastric cancer. Levofloxacin-based, or clarithromycin-based, triple therapy is frequently used to inhibit the bacterial urease enzyme for the eradication of H. pylori. A comprehensive investigation based on the urease inhibitory profiles of antibiotics and their computational implications is lacking in the scientific literature. The present study was aimed specifically to determine the antiurease activities within the realms of cephalosporins and fluoroquinolones by in vitro methods supported with in silico investigations. The results demonstrate the jack bean urease inhibitory activity of cephalosporins, wherein cefadroxil, cefpodoxime, cefotaxime, and cefaclor displayed inhibitions (IC50 21.35 ± 0.64 to 62.86 ± 0.78 µM) compared with the standard thiourea (IC50 21.25 ± 0.15 µM). Among fluoroquinolones, levofloxacin, ofloxacin, and gemifloxacin (IC50 7.24 ± 0.29 to 16.53 ± 0.85 µM) unveiled remarkable inhibitory profiles. Levofloxacin and ofloxacin exhibited competitive inhibition against the said enzyme. Ciprofloxacin and moxifloxacin displayed weak urease inhibitions. During molecular docking studies, Asp362, Gly279, Arg338, Asn168, Asp223, Gln364, and Met366 were involved in hydrogen bonding in fluoroquinolones, and hydrogen bonding was established with Arg338, His248, Asn168 residues, and metal Ni601 and Ni602 of the enzyme. MD simulations and MMPBSA results demonstrated the existence of significant protein-ligand binding. Overall, these results warrant further investigations into the significance of these active molecules in relation to their inhibitory potential against the targeted urease enzyme.

Investigating the internal structure of multiple mini interviews-A perspective from Pakistan.

BACKGROUND: Healthcare professionals require many personal attributes in addition to cognitive abilities and psychomotor skills for competent practice. Multiple Mini- Interviews are being employed globally to assess personality attributes of candidates for selection in health professions education at all level of entry; these attributes are namely, communication skills, critical thinking, honesty, responsibility, health advocacy, empathy and sanctity of life. Considering the high stakes involved for students, faculty, institutions and the society, rigorous quality assurance mechanisms similar to those used for student assessment must be employed for student selection, throughout the continuum of medical education. It is a difficult undertaking as these psychological constructs are difficult to define and measure. Though considered to yield reliable and valid scores, studies providing multiple evidences of internal structure especially dimensionality of Multiple Mini-Interviews are sparse giving rise to questions if they are measuring a single or multiple constructs and even if they are measuring what they are purported to be measuring. OBJECTIVE: The main objective is to provide statistical support of the multi-dimensional nature of our Multiple Mini Interviews, hypothesized a-priori, through CFA. Another objective is to provide multiple evidences for the internal structure. Our study highlights the link between content and internal structure evidences of the constructs, thus establishing that our Multiple Mini Interviews measure what they were intended to measure. METHOD: After securing permission from the Institutional review board, an a-priori seven factor-model was hypothesized based on the attributes considered most essential for the graduating student of the institution. After operationally defining the attributes through extensive literature search, scenarios were constructed to assess them. A 5-point rating scale was used to rate each item on the station. A total 259 students participated in the multiple mini interviews over a period of three days. A training workshop had been arranged for the participating faculty. RESULTS: The reliability coefficient using Cronbach's alpha were calculated (range from 0.73 to 0.94), Standard Error of Measurement (ranged from 0.80 to1.64), and item to station-total correlation ranged from 0.43-0.50 to 0.75-0.83. Inter-station correlation was also determined. Confirmatory factor analysis endorsed the results of Exploratory factor analysis in the study revealing a seven model fit with multiple indices of Goodness-of-fit statistics such as Root mean square error of approximation (RMSEA) value 0.05, Standardized root mean square residual (SRMR) value with less than 0.08. All these indices showed that model fit is good. The Confirmatory factor analysis confirmed the multi-dimensional nature of our MMIs and also confirmed that our stations measured the attributes that they were supposed to measure. CONCLUSION: This study adds to the validity evidence of Multiple Mini-Interviews, in selection of candidates, with required personality traits for healthcare profession. It provides the evidence for the multi-dimensional structure of Multiple Mini interviews administered with multiple evidences for its internal structure and demonstrates the independence of different constructs being measured.

Plastic footprint deteriorates dryland carbon footprint across soil-plant-atmosphere continuum.

Plastic fragments are widely found in the soil profile of terrestrial ecosystems, forming plastic footprint and posing increasing threat to soil functionality and carbon (C) footprint. It is unclear how plastic footprint affects C cycling, and in particularly permanent C sequestration. Integrated field observations (including 13C labelling) were made using polyethylene and polylactic acid plastic fragments (low-, medium- and high-concentrations as intensifying footprint) landfilling in soil, to track C flow along soil-plant-atmosphere continuum (SPAC). The result indicated that increased plastic fragments substantially reduced photosynthetic C assimilation (p < 0.05), regardless of fragment degradability. Besides reducing C sink strength, relative intensity of C emission increased significantly, displaying elevated C source. Moreover, root C fixation declined significantly from 21.95 to 19.2 mg m-2, and simultaneously root length density, root weight density, specific root length and root diameter and surface area were clearly reduced. Similar trends were observed in the two types of plastic fragments (p > 0.05). Particularly, soil aggregate stability was significantly lowered as affected by plastic fragments, which accelerated the decomposition rate of newly sequestered C (p < 0.05). More importantly, net C rhizodeposition declined averagely from 39.77 to 29.41 mg m-2, which directly led to significant decline of permanent C sequestration in soil. Therefore, increasing plastic footprint considerably worsened C footprint regardless of polythene and biodegradable fragments. The findings unveiled the serious effects of plastic residues on permanent C sequestration across SPAC, implying that current C assessment methods clearly overlook plastic footprint and their global impact effects.