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The aryl hydrocarbon receptor is a ligand dependent transcription factor which functions as an environmental sensor. Originally discovered as the sensor for man made pollutants such as 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) it has recently gained prominence as an important mediator for environmental triggers via the diet or microbiota which influences many physiological functions in different cell types and tissues across the body. Notably AHR activity contributes to prevent excessive inflammation following tissue damage in barrier organs such as skin, lung or gut which has received wide attention in the past decade. In this review we will focus on emerging common AHR functions across cell types and tissues and discuss ongoing issues that confound the understanding of AHR physiology. Furthermore, we will discuss the need for deeper molecular understanding of the functional activity of AHR in different contexts with respect to development of potential therapeutic applications.

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OBJECTIVE: Violence against children (VAC) is a global public health and human rights issue that can lead to long-lasting negative consequences for individual and societal outcomes. While extensive evidence indicates that parenting programmes might be effective in preventing VAC, there are several unsolved questions on how to ensure interventions are acceptable, feasible, effective and sustainable, particularly in low- and- middle-income countries (LMICs). METHOD: In this study, we report findings from a qualitative examination of policymakers' (N = 10), early childhood and parenting programme facilitators' (N = 20) and parents' and other caregivers' (N = 38) perspectives on VAC prevention to examine the implementation ecosystem of parenting programmes in Colombia, including contextual risk and protection factors, features of existing programmes, and stakeholders' needs. We conducted interviews and focus groups using a semistructured format, along with a thematic approach, to analyse the data from each group of participants (i.e., policymakers, facilitators and caregivers) independently. RESULTS: Overall, the data revealed the critical role of intersecting and interacting factors at the micro (e.g., caregivers' capabilities and beliefs), meso (e.g., programme content and delivery approaches) and macro (e.g., policymakers' vision and existing infrastructure) levels in exacerbating risks/imposing barriers versus protecting/promoting VAC prevention. CONCLUSIONS: These findings provide evidence on the implementation ecosystem of prevention programmes to inform the design of novel strategies and programmes aimed at preventing violence and promoting families' well-being and young children's development.

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Chlorinated paraffins (CPs) are complex mixtures of polychlorinated n-alkanes with multiple carbon- (C-, nC = 9-30) and chlorine homologues (Cl-, nCl = 3-18). The mass spectrometric analysis of CPs is time-consuming and challenging, especially when interferences between CPs, their transformation products, or from the matrix are numerous. These analytical challenges and the lack of appropriate and accessible data evaluation tools are obstacles to their analysis. CP-Hunter is a web-based, open-access data processing platform for the automatic analysis of mass spectra of CPs and their transformation products. Extracts of two consumer plastic materials and sewage sludge were evaluated with CP-Hunter. C- and Cl-homologue distributions were obtained in quasi-real-time and the posterior calculated fingerprints were in agreement with the ones obtained by traditional methods. However, the data extraction and evaluation time were now reduced from several minutes to seconds. The implemented signal deconvolution method, i.e., to resolve mass spectrometric interferences, provides robust results, even when severe matrix effects are present. CP-Hunter facilitates the untargeted analysis of unknown products and the detection and elimination of false positive signals. Finally, data evaluation with CP-Hunter is performed locally without the transfer of data to external servers. The tool is safe, public, and accessible at https://cphunter.cheminfo.org/.

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Background: Surgeons face challenges associated with adherent cutaneous scalp malignancy. Traditional general anesthetic excision involves periosteal removal and burring of the outer table of the calvaria for deep margin clarity and tissue reconstruction. Research on this practice is limited, and graft survival in burr-treated bones is underexplored. This study aimed to assess the clinical margin accuracy for immobile scalp malignancies, identify deep-invading malignancy types, and evaluate graft survival in burr-treated calvariae. It compares split-thickness grafts (STSGs) and full-thickness grafts (FTSGs). Methods: Twelve fixed scalp malignancies were excised under anesthesia, allowing immediate STSG or FTSG for defect reconstruction. Postsurgery, graft take, malignancy type, and margin clearance were evaluated. Results: Histopathological diagnosis identified seven squamous cell carcinomas, two melanomas, one basal cell carcinoma, one adenocarcinoma, and one metastatic squamous cell carcinoma. Deep margins ranged from 0 to 0.9 mm, and peripheral margins ranged from 0 to 15 mm. The graft take was 100% in eight cases, with total failure in two cases, and 75%-90% in two cases. The five STSGs had 100% take and 90% take. The three FTSGs had 100%, 75%, and two failed. Conclusions: Clinical examination effectively gauges the tumor fixation depth, but large lesions may require imaging. Most deep-invading tumors were SCCs. STSGs performed better on burr-treated Calvaria than FTSGs.

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OBJECTIVE: To study the white matter connections between anterior cingulate cortex, anterior insula and amygdala as key regions of the frontal-limbic network that have been related to meditation. DESIGN: Twenty experienced practitioners of Sahaja Yoga Meditation and twenty nonmeditators matched on age, gender and education level, were scanned using Diffusion Weighted Imaging, using a 3T scanner, and their white matter connectivity was compared using diffusion tensor imaging analyses. RESULTS: There were five white matter fiber paths in which meditators showed a larger number of tracts, two of them connecting the same area in both hemispheres: the left and right amygdalae and the left and right anterior insula; and the other three connecting left anterior cingulate with the right anterior insula, the right amygdala and the left amygdala. On the other hand, non-meditators showed larger number of tracts in two paths connecting the left anterior insula with the left amygdala, and the left anterior insula with the left anterior cingulate. CONCLUSIONS: The study shows that long-term practice of Sahaja Yoga Meditation is associated with larger white matter tracts strengthening interhemispheric connections between limbic regions and connections between cingulo-amygdalar and cingulo-insular brain regions related to top-down attentional and emotional processes as well as between top-down control functions that could potentially be related to the witness state perceived through the state of mental silence promoted with this meditation. On the other hand, reduced connectivity strength in left anterior insula in the meditation group could be associated to reduced emotional processing affecting top-down processes.

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Background: Operating on temporal cutaneous tumors is challenging because of the intricate facial nerve system, particularly the frontal branches, and the possibility of brow dysfunction. Surgery for deep margin clearance is difficult because of the fragile and sensitive soft tissue in the temporal region. To address this research gap, this study assessed clearance margins, types of skin tumors, and nerve injuries in this critical anatomical position. This retrospective study assessed temporal skin cancer surgery, malignancy types, and clearance margins in patients with frontal-branch facial nerve injuries. Methods: Forty-five patients with temporal skin carcinoma biopsies were analyzed. The deep and peripheral excision margins of skin malignancies were examined. Medical records were reviewed for clinically injured frontal nerve. Results: Thirty-four patients were men (75%), and basal cell carcinoma was the most prevalent histological malignancy, followed by squamous cell carcinoma. The mean age of the patients was 77.8 years (39-107 years). Two patients experienced damage to the frontal branch nerve. Twenty-six percent of the skin malignancies had inadequate deep margin excision. Conclusions: Removing temporal skin lesions is difficult. We discovered a 26% and 4% probability of inadequate deep margin excision and frontal branch facial nerve injury, respectively. Temporal skin lesions must be removed safely by surgeons to preserve the branches of the facial nerves. Insufficiently removed tumors require multidisciplinary teamwork and patient discussions regarding the advantages and risks to improve results.

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Exposure of humans to chlorinated paraffins (CPs) and chlorinated olefins (COs) can occur via contact with CP-containing plastic materials. Such plastic materials can contain short-chain CPs (SCCPs), which are regulated as persistent organic pollutants (POPs) under the Stockholm Convention since 2017. Municipal wastewater treatment plants (WWTP) collect effluents of thousands of households and their sludge is a marker for CP exposure. We investigated digested sewage sludge collected in the years 1993, 2002, 2007, 2012, and 2020 from a Swiss WWTP serving between 20000 and 23000 inhabitants. A liquid chromatography mass spectrometry (R > 100000) method, in combination with an atmospheric pressure chemical ionization source (LC-APCI-MS), was used to detect mass spectra of CPs and olefinic side products. A R-based automated spectra evaluation routine (RASER) was applied to search for ∼23000 ions whereof ∼6000 ions could be assigned to CPs, chlorinated mono- (COs), di- (CdiOs) and tri-olefins (CtriOs). Up to 230 CP-, 120 CO-, 50 CdiO- and 20 CtriO-homologues could be identified in sludge. Characteristic fingerprints were deduced describing C- and Cl-homologue distributions, chlorine- (nCl) and carbon- (nC) numbers of CPs and COs. In addition, proportions of saturated and unsaturated material were determined together with proportions of different chain length classes including short- (SC), medium- (MC), long- (LC) and very long-chain (vLC) material. A substantial reduction of SCCPs of 84% was observed from 1993 to 2020. Respective levels of MCCPs, LCCPs and vLCCPs decreased by 61, 69 and 58%. These trends confirm that banned SCCPs and non-regulated CPs are present in WWTP sludge and higher-chlorinated SCCPs were replaced by lower chlorinated MCCPs. Combining high-resolution mass spectrometry with a selective and fast data evaluation method can produce characteristic fingerprints of sewage sludge describing the long-term trends in a WWTP catchment area.

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Commensal-specific clusters of differentiation (CD)4+ T cells are expanded in patients with inflammatory bowel disease (IBD) compared to healthy individuals. How and where commensal-specific CD4+ T cells get activated is yet to be fully understood. We used CBir1 TCR-transgenic CD4+ T cells, specific to a commensal bacterial antigen, and different mouse models of IBD to characterize the dynamics of commensal-specific CD4+ T-cells activation. We found that CBir1 T cells proliferate following intestinal damage and cognate antigen presentation is mediated by CD11c+ cells in the colon-draining mesenteric lymph nodes. Using assay for transposase-accessible chromatin sequencing and flow cytometry, we showed that activated CBir1 T cells preferentially acquire an effector rather than regulatory phenotype, which is plastic over time. Moreover, CBir1 T cells, while insufficient to initiate intestinal inflammation, contributed to worse disease outcomes in the presence of other CD4+ T cells. Our results suggest that the commensal-specific T-cell responses observed in IBD exacerbate rather than initiate disease.

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Cryptosporidium is a leading cause of diarrheal-related deaths in children, especially in resource-poor settings. It also targets the immunocompromised, chronically infecting people living with HIV and primary immunodeficiencies. There is no vaccine or effective treatment. Although it is known from human cases and animal models that CD4+ T cells play a role in curbing Cryptosporidium, the role of CD8+ T cells remains to be defined. Using a Cryptosporidium tyzzeri mouse model, we show that gut-resident CD8+ intraepithelial lymphocytes (IELs) confer resistance to parasite growth. CD8+ IELs express and depend on the ligand-dependent transcription factor aryl hydrocarbon receptor (AHR). AHR deficiency reduces CD8+ IELs, decreases their cytotoxicity, and worsens infection. Transfer of CD8+ IELs rescues severely immunodeficient mice from death following Cryptosporidium challenge. Finally, dietary supplementation of the AHR pro-ligand indole-3-carbinol in newborn mice promotes resistance to infection. Therefore, common dietary metabolites augment the host immune response to cryptosporidiosis, protecting against disease.

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BACKGROUND: Sahaja Yoga Meditation draws on many religious traditions and uses a variety of techniques including Christian prayer to reach a state known as thoughtless awareness, or mental silence. While there are many studies on the neural correlates of meditation, few studies have focused on the neural correlates of praying. Thus, the aim of our research was to study the neural activity associated with the prayer practices in Sahaja Yoga Mediation, which have not been studied before, to explore effects beyond repetitive speech or "mantra effects". Sixteen experienced Sahaja Yoga Meditation practitioners were scanned using task based functional Magnetic Resonance Imaging while performing formalised and improvised forms of praying and their equivalent secular tasks. RESULTS: Our results showed the deactivation of bilateral thalamus during both prayers compared to secular conditions and the activation in the medial prefrontal cortex that was reduced by religious and formalised secular speech conditions but increased during improvised secular speech; similarly, frontal regions were deactivated when comparing prayers to their secular equivalents. DISCUSSION: These results seem to depict two important factors related with praying in Sahaja Yoga Meditation merging inner concentration and social cognition. First, the perception of the surroundings mediated by the thalamus may be decreased during these prayers probably due to the establishment of inner concentration and, second, frontal deactivation effects could be related to reduced social judgement and 'mentalizing', particularly in the medial prefrontal cortex. Our findings suggest that praying by Sahaja Yoga Meditation practitioners is neurophenomenologically different from the social cognitive attempt of praying within Christian praying practices.

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The close association between rheumatoid arthritis (RA), sex, reproductive state, and stress has long linked prolactin (PRL) to disease progression. PRL has both proinflammatory and anti-inflammatory outcomes in RA, but responsible mechanisms are not understood. Here, we show that PRL modifies in an opposite manner the proinflammatory actions of IL-1ß and TNF-α in mouse synovial fibroblasts in culture. Both IL-1ß and TNF-α upregulated the metabolic activity and the expression of proinflammatory factors (Il1b, Inos, and Il6) via the activation of the nuclear factor-κB (NF-κB) signaling pathway. However, IL-1ß increased and TNF-α decreased the levels of the long PRL receptor isoform in association with dual actions of PRL on synovial fibroblast inflammatory response. PRL reduced the proinflammatory effect and activation of NF-κB by IL-1ß but increased TNF-α-induced inflammation and NF-κB signaling. The double-faceted role of PRL against the 2 cytokines manifested also in vivo. IL-1ß or TNF-α with or without PRL were injected into the knee joints of healthy mice, and joint inflammation was monitored after 24 hours. IL-1ß and TNF-α increased the joint expression of proinflammatory factors and the infiltration of immune cells. PRL prevented the actions of IL-1ß but was either inactive or further increased the proinflammatory effect of TNF-α. We conclude that PRL exerts opposite actions on joint inflammation in males and females that depend on specific proinflammatory cytokines, the level of the PRL receptor, and the activation of NF-κB signaling. Dual actions of PRL may help balance joint inflammation in RA and provide insights for development of new treatments.

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Background: Adequate methods reporting in observational and trial literature is critical to interpretation and implementation. Objective: Evaluate methodology reporting adherence in the dermatology literature and compare this to internal medicine (IM) literature. Methods: We performed a cross-sectional review of randomly-selected dermatology and IM manuscripts published between 2014-2018. Observational and trial articles were retrieved from PubMed. The primary outcome was percent adherence to STROBE or CONSORT methods-related checklist items (methods reporting score, MRS). Secondary outcomes included the relationship between methods section length (MSL) and MRS. We additionally compared these with IM literature. MRS and MSL were compared by overall article length, checklist type, field, journal, study topic, and funding source. Comparisons were assessed using univariable and multivariable linear regression. Results: We identified 389 articles (172 dermatology and 217 IM). Within dermatology, we identified 83 clinical trials and 89 observational studies. Mean MRS was 61.4 percent. A one word increase in MSL corresponded to a 0.02 percent increase MRS (ß=0.02, 95% CI 0.01-0.03). Mean MRS was 12.8 percent lower in the dermatology literature compared with IM (ß=-12.8%, -15.6-[-9.91]). Mean dermatology MSL was 345 words shorter (ß=-345, -413-[-277]). Studies from JAMA Dermatology, Journal of Investigative Dermatology, and British Journal of Dermatology, with government funding, and having supplemental methods had higher mean MRS's. Conclusion: Methods reporting quality was low in dermatology. A weak relationship between MRS and MSL was observed. These data support enhancing researcher emphasis on methods reporting, editorial staff, and peer reviewers that more strictly enforce checklist reporting.

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Recipient vessel selection is vital for successful autologous free-flap breast reconstruction. Internal mammary artery perforators have gained interest as a recipient vessel option. However, previous studies on their microsurgical safety and efficacy are limited and inconsistent. Thus, we conducted a systematic review and meta-analysis to assess the safety and effectiveness of using internal mammary artery perforators as recipient vessels in breast reconstruction. Methods: The protocol has been previously published in PROSPERO (CRD42020190020). The PubMed, Scopus, Web of Science, and PROSPERO databases were searched. Two independent reviewers evaluated the articles for inclusion in the study. Study quality was assessed using the Newcastle-Ottawa Scale and the MINORS instrument (Methodological Index for Non-Randomized Studies). Results: Of the 361 articles screened, 13 studies were included (313 patients with 318 flaps; 223 unilateral, 31 bilateral, mean average age 51.2 and mean BMI 27.8 ± 1.9). The mean overall success rate was 99.8%, the pooled surgical success rate was 100% [95% confidence interval (CI): 97%-100%], and the overall rate of complications was 11% (95% CI: 7%-18%). The most common complication was vascular-related to microanastomoses, with an incidence of 5% (95% CI: 2%-10%). The fat necrosis rate was 3% (95% CI: 2%-6%). Conclusions: This study verified that internal mammary artery perforator vessels are reliable in breast reconstruction, with a high success rate and a relatively low complication rate. Moreover, in selected microsurgical breast reconstruction patients, internal mammary artery perforators may be the primary recipient vessel choice over the internal mammary artery or thoracodorsal vessels.

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Burnout has earned notoriety in medicine. It affects medical students, residents and surgeons, causing a decrease in career satisfaction, quality of life, and increased risk of depression and suicide. The effect of resilience against burnout is yet unknown in plastic surgery trainees. Methods: A survey was sent via email to the members of plastic surgery societies (ICOPLAST) and the trainees from (ASPS) Resident Council from November 2021 through January 2022. The data included: demographics, training program characteristics, physician wellness resources, and single item Maslach-Burnout Inventory and Connor-Davidson Resilience Scale questionnaire. Results: One-hundred seventy-five plastic surgery trainees responded to the survey. Of these, 119 (68%) trainees from 24 countries completed the full survey. Most respondents 110 (92%) had heard of physician burnout, and almost half of respondents (45%) had burnout. The average Connor-Davidson Resilience Scale score varied significantly amongst trainees self-reporting burnout and those who did not (28.6 versus 31.3, P = 0.008). Multivariate logistic regression demonstrated that increased work hours per week were associated with an increased risk of burnout (OR = 1.03, P = 0.04). Higher resilience score (OR = 0.92; P = 0.04) and access to wellness programs (OR = 0.60, P = 0.0004) were associated with lower risk of burnout. Conclusions: Burnout is prevalent across plastic surgery trainees from diverse countries. Increased work hours were associated with burnout, whereas access to wellness programs and higher resilience scores were "protective." Our data suggest that efforts to build resilience may mitigate burnout in plastic surgery trainees.

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Background: One of the main lessons of the COVID-19 pandemic is that we must prepare to face another pandemic like it. Consequently, this article aims to develop a general framework consisting of epidemiological modeling and a practical identifiability approach to assess combined vaccination and non-pharmaceutical intervention (NPI) strategies for the dynamics of any transmissible disease. Materials and methods: Epidemiological modeling of the present work relies on delay differential equations describing time variation and transitions between suitable compartments. The practical identifiability approach relies on parameter optimization, a parametric bootstrap technique, and data processing. We implemented a careful parameter optimization algorithm by searching for suitable initialization according to each processed dataset. In addition, we implemented a parametric bootstrap technique to accurately predict the ICU curve trend in the medium term and assess vaccination. Results: We show the framework's calibration capabilities for several processed COVID-19 datasets of different regions of Chile. We found a unique range of parameters that works well for every dataset and provides overall numerical stability and convergence for parameter optimization. Consequently, the framework produces outstanding results concerning quantitative tracking of COVID-19 dynamics. In addition, it allows us to accurately predict the ICU curve trend in the medium term and assess vaccination. Finally, it is reproducible since we provide open-source codes that consider parameter initialization standardized for every dataset. Conclusion: This work attempts to implement a holistic and general modeling framework for quantitative tracking of the dynamics of any transmissible disease, focusing on accurately predicting the ICU curve trend in the medium term and assessing vaccination. The scientific community could adapt it to evaluate the impact of combined vaccination and NPIs strategies for COVID-19 or any transmissible disease in any country and help visualize the potential effects of implemented plans by policymakers. In future work, we want to improve the computational cost of the parametric bootstrap technique or use another more efficient technique. The aim would be to reconstruct epidemiological curves to predict the combined NPIs and vaccination policies' impact on the ICU curve trend in real-time, providing scientific evidence to help anticipate policymakers' decisions.

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SARS-CoV-2, responsible for the COVID-19 pandemic, is a highly infectious virus that quickly became and continues to be a public health emergency, given the severe international implications. Immunocompromised patients, such as those undergoing kidney transplantation, are at an increased risk for severe illness from COVID-19 and require hospitalization for more aggressive treatment to ensure survival. COVID-19 has been infecting kidney transplant recipients (KTRs), affecting their treatment protocols, and threatening their survival. The objective of this scoping review was to summarize the published literature regarding the impact of COVID-19 on KTRs in the United States in terms of prevention, various treatment protocols, COVID-19 vaccination, and risk factors. The databases such as PubMed, MEDLINE/Ebsco, and Embase were used to search for peer-reviewed literature. The search was restricted to articles that were published on KTRs in the United States from January 1, 2019, to March 2022. The initial search yielded 1,023 articles after removing duplicates, leading to a final selection of 16 articles after screening with inclusion and exclusion criteria. Four domains emerged from the review: (1) impacts of COVID-19 on performing kidney transplants, (2) impacts of COVID-19 vaccinations on KTRs, (3) outcomes of treatment regiments for KTRs with COVID-19, and (4) risk factors associated with an increased mortality rate of COVID-19 in KTRs. Waitlisted patients for kidney transplants had a higher risk of mortality compared to nontransplant patients. COVID-19 vaccinations in KTRs are found to be safe, and the immune response can be improved by placing patients on a low dose of mycophenolate before vaccination. Withdrawal of immunosuppressants showed a mortality rate of 20% without increasing the rate of acute kidney injury (AKI). There is evidence to support that kidney transplantation with the accompanying immunosuppressant regimen can provide KTRs with better COVID-19 infection outcomes compared to waitlisted patients. Hospitalization, graft dysfunction, AKI, and respiratory failure were the most common risk factors that increased the risk of mortality in COVID-19-positive KTRs. Withdrawing KTRs from immunosuppressive drugs increased the mortality rate. Further studies are needed to investigate the effects of specific drugs and dosages on the severity and mortality rate of COVID-19 in KTRs.

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Electrophotonic (EPh) circuits are novel systems where photons and electrons can be controlled simultaneously in the same integrated circuit, attaining the development of innovative sensors for different applications. In this work, we present a complementary metal-oxide-semiconductor (CMOS)-compatible EPh circuit for biotin sensing, in which a silicon-based light source is monolithically integrated. The device is composed of an integrated light source, a waveguide, and a p-n photodiode, which are all fabricated in the same chip. The functionalization of the waveguide's surface was investigated to biotinylate the EPh system for potential biosensing applications. The modified surfaces were characterized by AFM, optical microscopy, and Raman spectroscopy, as well as by photoluminescence measurements. The changes on the waveguide's surface due to functionalization and biotinylation translated into different photocurrent intensities detected in the photodiode, demonstrating the potential uses of the EPh circuit as a biosensor.

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Allosteric modulators are of prime interest in drug discovery. These drugs regulate the binding and function of endogenous ligands, with some advantages over orthosteric ligands. A typical pharmacological parameter in allosteric modulation is binding cooperativity. This property can yield unexpected but illuminating results when decomposed into its kinetic parameters. Using two reference models (the allosteric ternary complex receptor model and a heterodimer receptor model), a relationship has been derived for the cooperativity rate constant parameters. This relationship allows many combinations of the cooperativity kinetic parameters for a single binding cooperativity value obtained under equilibrium conditions. This assessment may help understand striking experimental results involving allosteric modulation and suggest further investigations in the field.

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