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Background and Aims: Liver transplantation is a life-saving procedure for end-stage liver disease. However, post-transplant medication regimens are complex and non-adherence is common. Post-transplant medication non-adherence is associated with graft rejection, which can have long-term adverse consequences. Transplant centres are equipped with clinical staff that monitor patients post-transplant; however, digital health tools and proactive immunosuppression adherence monitoring has potential to improve outcomes., Methods and Analysis: This is a patient-randomised prospective clinical trial at three transplant centres in the Northeast, Midwest and South to investigate the effects of a remotely administered adherence programme compared with usual care. The programme monitors potential non-adherence largely levering text message prompts and phenotypes the nature of the non-adhere as cognitive, psychological, medical, social or economic. Additional reminders for medications, clinical appointments and routine self-management support are incorporated to promote adherence to the entire medical regimen. The primary study outcome is medication adherence via 24-hour recall; secondary outcomes include additional medication adherence (ASK-12 self-reported scale, regimen knowledge scales, tacrolimus values), quality of life, functional health status and clinical outcomes (eg, days hospitalised). Study implementation, acceptability, feasibility, costs and potential cost-effectiveness will also be evaluated., Ethics and Dissemination: The University of Pennsylvania Review Board has approved the study as the single IRB of record (protocol # 849575, V.1.4). Results will be published in peer-reviewed journals and summaries will be provided to study funders., Trial Registration Number: NCT05260268., Competing Interests: Competing interests: MS reports additional grants from NIH/NIDDK/NIAAA, PCORI, and Grifols, SA., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

COVID-19 has caused many deaths since the first outbreak in 2019. The burden on healthcare systems around the world has been reduced by the success of vaccines. However, population adherence and the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are still challenging tasks to be affronted. In addition, the newly approved drug presents some limitations in terms of side effects and drug interference, highlighting the importance of searching for new antiviral agents against SARS-CoV-2. The SARS-CoV-2 main protease (M pr o ) represents a versatile target to search for new drug candidates due to its essential role in proteolytic activities responsible for the virus replication. In this work, a series of 190 compounds, composed of 27 natural ones and 163 synthetic compounds, were screened in vitro for their inhibitory effects against SARS-CoV-2 M pro . Twenty-five compounds inhibited M pro with inhibitory constant values (K i ) between 23.2 and 241 µM. Among them, a thiosemicarbazone derivative was the most active compound. Molecular docking studies using Protein Data Bank ID 5RG1, 5RG2, and 5RG3 crystal structures of M pro revealed important interactions identified as hydrophobic, hydrogen bonding and steric interactions with amino acid residues in the active site cavity. Overall, our findings indicate the described thiosemicarbazones as good candidates to be further explored to develop antiviral leads against SARS-CoV-2. Moreover, the studies showed the importance of careful evaluation of test results to detect and exclude false-positive findings., (© 2023 Deutsche Pharmazeutische Gesellschaft.)

The inflammatory response is a common feature of many pathological conditions, and there is urgent necessity for new substances that minimize the harmful effects of inflammation. Chromenes represent a class of compounds with multiple pharmacological actions that have already been described and may be potential candidates for studies of therapeutic action. This study aimed to test novel 4-aryl-4H-chromene-derived molecules in an in vitro model of inflammation using lipopolysaccharide (LPS)-induced Raw 264.7 cells. Seven compounds derived from 4-aryl-4H-chromene were tested on Raw 264.7 cells to evaluate their cytotoxic effects. Next, the effect of the selected compounds on the pro-inflammatory mediators (tumor necrosis factor-alpha [TNF-α], monocyte chemoattractant protein-1 [MCP-1], interleukin [IL]-6) and on the anti-inflammatory mediators (IL-10 and IL-13) was analyzed, and finally, the effect of the compounds on macrophage apoptosis and expression of surface receptors (toll-like receptor 4 [TLR-4] and mannose) was evaluated. The results of this study demonstrated that changes in the molecular structure of 4-aryl-4H-chromene altered its cytotoxic profile. Therefore, derivatives that showed safe results were selected for further analyses (named compounds: 4-6). In these experiments, the compounds were able to decrease nitric oxide (NO) levels and production of MCP-1, IL-6, IL-10, and IL-13. Furthermore, these derivatives were effective in reducing macrophage apoptosis and the expression of surface receptors, as TLR-4/CD284. Moreover, compounds 5 and 6 also were effective in increasing mannose receptor (CD206) expression. The results indicate, for the first time to our knowledge, that the anti-inflammatory effect produced by chromenes is linked to macrophage repolarization (M1 to M2)., (© 2022 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)

Despite a significant increase in the total number of liver transplants (LTs) performed over the last 3 decades, primary biliary cholangitis (PBC) has become an uncommon indication for LT, which likely reflects the benefits of earlier diagnosis and available treatment, such as ursodeoxycholic acid (UDCA). Nonetheless, LT remains the only cure for patients with progressive PBC despite medical therapy with survival rates that are among the highest of all indications for LT. Post-LT PBC patients, however, are at increased risk of rejection and disease recurrence., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background & Aims: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival., Methods: We included 736 patients (77% female, mean age 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis., Results: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p = 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p = 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p = 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p = 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p = 0.001)., Conclusion: Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH., Lay Summary: Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition., Competing Interests: Conflicts of interest These authors disclose the following: A.J. Montano-Loza has served on advisory boards for Intercept Pharmaceuticals. B.E. Hansen reports grants from Intercept Pharmaceuticals and Zambon Nederland B.V. and consulting work for Intercept Pharmaceuticals and Novartis. A.E. Kremer reports consulting work for CymaBay, GSK, Intercept Pharmaceuticals, and Mirum and grants from Intercept Pharmaceuticals. A. Parés consults for Intercept and Novartis. A. Floreani reports consulting activities for Intercept Pharmaceuticals. A. Mason consults for, is on the speakers' bureau of, and received grants from Intercept. He received grants from Merk. The remaining authors disclose no conflicts. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Cerebral palsy is a developmental motor disorder which has far-reaching impacts on oral health. This scoping review examined the extent of research undertaken regarding the risk factors affecting dental caries experience in children and adolescents with cerebral palsy. Data were obtained from the electronic databases Web of Science and PubMed, using 10 search strings, for studies published between 1983 and 2018. Eligible studies were required to have investigated caries in children under 18 with cerebral palsy, as well as be written in English. 30 papers published were identified for inclusion in the review. These included 23 cross-sectional, 6 case-control, and 1 longitudinal study. Studies were categorized into six domains of risk factors: socioeconomic status (SE); cerebral palsy subtype (CPS); demographics (D); condition of oral cavity (OC); dental habits (DH); nutrition and diet (ND). This review was conducted and reported in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. The most significant risk factors were caregiver-related education levels, oral health literacy, and sugar intake; this underlines the important role of special education and dental awareness in reducing dental caries incidence in CP children. Other factors showed divergent findings, highlighting the need for standardization and culturally specific studies in future literature.

Background: The Coronavirus disease 2019(COVID-19) pandemic has negatively impacted worldwide organ transplantation. However, there is limited information on recipients transplanted after SARS-CoV-2 infection. A full understanding of this scenario is required, as transplantation is a life-saving procedure and COVID-19 remains an ongoing threat., Methods: Abdominal organ transplant recipients diagnosed with COVID-19 prior to transplantation were identified by chart review and clinical data were collected. The primary outcome was the transplant outcome including graft loss, rejection and death, and reactivation of infection post-transplant., Results: We identified 14 patients who received abdominal organ transplants after symptomatic PCR confirmed SARS-CoV-2 infection; four patients had a positive PCR at the time of admission for transplantation. The median time of follow-up was 79 (22-190) days. One recipient with negative PCR before transplant tested positive 9 days after transplant. One of 14 transplanted patients developed disseminated mold infection and died 86 days after transplant. During the follow-up, only one patient developed rejection; thirteen patients had favorable graft outcomes., Conclusions: We were able to perform abdominal transplantation for patients with COVID-19 before transplant, even with positive PCR at the time of transplant. Larger studies are needed to determine the time to safe transplant after SARS-CoV-2 infection., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Despite record-breaking numbers of liver transplants (LTs) performed in the United States in each of the last 7 years, many patients remain on the wait list as the demand for LT continues to exceed the supply of available donors. The emergence of highly effective and well-tolerated direct-acting antiviral therapy has transformed the clinical course and management of hepatitis C virus (HCV) in both the pretransplant and posttransplant setting. Historically, donor livers infected with HCV were either transplanted into patients already infected with HCV or discarded., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Drug-resistant tuberculosis threatens to undermine global control programs by limiting treatment options. New antimicrobial drugs are required, derived from new chemical classes. Natural products offer extensive chemical diversity and inspiration for synthetic chemistry. Here, we isolate, synthesize and test a library of 52 natural and synthetic compounds for activity against Mycobacterium tuberculosis . We identify seven compounds as antimycobacterial, including the natural products isobavachalcone and isoneorautenol, and a synthetic chromene. The plant-derived secondary metabolite damnacanthal was the most active compound with the lowest minimum inhibitory concentration of 13.07 μg/mL and a favorable selectivity index value. Three synthetic polyacetylene compounds demonstrated antimycobacterial activity, with the lowest MIC of 17.88 μg/mL. These results suggest new avenues for drug discovery, expanding antimicrobial compound chemistries to novel anthraquinone and polyacetylene scaffolds in the search for new drugs to treat drug-resistant bacterial diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pollo, Martin, Machado, Cantillon, Wildner, Bazzo, Waddell, Biavatti and Sandjo.)

Background: The aging of liver transplant (LT) recipients, the weighting of the model for end-stage liver disease score, and the increased prevalence of nonalcoholic steatohepatitis has led to an increased number of older LT recipients with pre-LT chronic kidney disease (CKD). There are limited data on the impact of increased recipient age on post-simultaneous liver-kidney (SLK) transplant outcomes among patients with CKD, leading some centers to employ subjective age cutoffs for potential SLK recipients., Methods: We evaluated United Network for Organ Sharing data of adult SLK recipients from February 27, 2002, to December 31, 2018, restricted to recipients with ≥90 days of waiting time and CKD (estimated glomerular filtration rate persistently <60 mL/min/1.73 m2 for ≥90 d using the modification of diet in renal disease-4 equation). We fit mixed-effects Cox regression models (center as random effect) to evaluate the association of recipient age and patient survival., Results: Among 3146 SLK recipients with CKD, nearly two-thirds were 50-64 years of age, while 465 (14.8%) and 93 (3.0%) were 65-69 years and ≥70 years, respectively. Compared with nondiabetic SLK recipients aged 50-59 years, SLK recipients ≥70 years of age without diabetes (hazard ratio, 1.97; 95% CI, 1.20-3.23; P = 0.007) and with diabetes (hazard ratio, 1.90; 95% CI, 1.16-3.09; P = 0.01) had higher mortality compared with the reference group. In absolute terms, SLK recipients ≥70 years of age had 25% lower patient survival at 5 years compared to recipients aged 40-49 years., Conclusions: Although careful selection is required of any SLK recipient, especially those with increased comorbidities, there are no objective data to justify a specific age cutoff <70 years among potential SLK recipients with CKD.

Background: Children with complex neurodevelopmental disabilities such as cerebral palsy (CP), have a higher risk of dental disease related at least in part to greater difficulties in performing and maintaining effective oral hygiene and oral care practices. However, to date, there are very few studies that have considered the impact of dental disease on the Oral Health-Related Quality of Life (OHRQoL) of children and adolescents with cerebral palsy. This study aimed to investigate the association between dental caries experience and oral health related quality of life (OHRQoL) among children and adolescents with cerebral palsy in a low-resource setting (Bangladesh)., Methods: A total of 90 children and adolescents with CP, 2-17 years old (median age 10 years; 37.8% female and 62.2% male) were randomly selected from the Bangladesh Cerebral Palsy Register (BCPR) The decayed, missing and filled teeth (dmft/DMFT) index was used to measure caries experience. Child Perceptions Questionnaire (CPQ) and Family Impact Scale (FIS) were used to assess oral health-related quality of life (OHRQoL). Binary logistic regression was used to investigate factors that may contribute to dental caries experience., Results: Dental caries were observed among 55.6% of the participants. After adjusting for age and gender, binary logistic regression analysis showed that dental caries experience was significantly associated with those who had teeth/mouth pain (rate ratio 7.3; P = 0.02), food caught between teeth (rate ratio: 6.4; P = 0.02), difficulty in eating and drinking (rate ratio 5.9; p = 0.02) and those who felt frequently upset (rate ratio: 54.7; P = 0.02)., Conclusion: In this study, we found that children and adolescents with CP in a low-resource setting had high dental caries experience and that dental caries had a negative impact on OHRQoL amongst these participants and their parents/caregivers. Health care professionals should be aware of the importance of dental health and oral hygiene in this population. These findings highlight the need for oral health promotion programs for children and adolescents with CP in these settings to reduce pain and to improve quality of life.

Different studies reported that genetic predisposition or metabolic dysfunction are the risk factors for cancer. Infectious parasitic diseases were listed among factors that predispose to cancer. Because of the resemblance between the life cycle of cancer cells and some parasites, this study aimed to prepare pyran derivatives with cytotoxic and antiprotozoal potencies. Therefore, 7 chromenes, 10 pyranocoumarins, and an unexpected intermediate were obtained from a multi-reagent one-pot reaction. These compounds were evaluated for their cytotoxicity on sensitive and resistant leukemia cancer cells lines and against two protozoan parasites, namely Trypanosoma cruzi and Leishmania amazonensis amastigote. Promising cytotoxicity (IC 50 values of less than 1 µM) was obtained for two of the synthetic products (12 and 15). Compound 12 induced apoptosis and cell cycle arrest in CCRF-CEM leukemia cells in G0/G1 while compound 15 and doxorubicin induced apoptosis and arrest in the S and G2/M phases. Ten of these products showed trypanocidal activity, while only five of them were weakly active on L. amazonensis. Three of the obtained pyrans showed significant cytotoxicity and antitrypanocidal activity, simultaneously. Nevertheless, all antiparasitic compounds revealed potency with low selectivity toward THP-1 cells used as host., (© 2018 Deutsche Pharmazeutische Gesellschaft.)

Primary sclerosing cholangitis (PSC) is a chronic, immune-mediated cholestatic liver disease that often progresses to secondary biliary cirrhosis and end-stage liver disease. Short of liver transplantation (LT), there is no effective treatment for PSC. PSC accounts for approximately 5% of total adult LTs in the US and is currently the fifth most common indication for LT. Patient and graft survival for PSC is among the highest for all indications for LT. The main factors that impact outcomes after LT for PSC include biliary strictures, rejection, and recurrence of PSC. Recurrent PSC (rPSC) develops in 20% of LT recipients within 5 years of LT and is associated with negative patient and graft survival. LT is a viable option for recipients who develop rPSC and progress to graft failure., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Early vision care is critical for all children. If undetected, eye disorders such as amblyopia and strabismus may result in permanent vision loss. Vision exams should include a careful history and physical including fix and follow, red reflex, and cover/uncover testing. Photo screening and visual acuity exams should be administered whenever possible.

Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are the most common cholestatic liver diseases (CLD) in adults. Liver transplant (LT) is desirable for those who progress to end-stage liver disease. CLD have become an uncommon indication for LT. PSC and PBC accounted for 7.1% of all adult LT in 2015. CLD have the best post-LT outcomes compared with other indications for LT. Disease recurrence of PSC and PBC after LT is reported in up to 37% and 43% of LT recipients, respectively. Although recurrent PBC does not affect post-LT outcomes, recurrent PSC is associated with worse post-LT survival., (Published by Elsevier Inc.)

Aim: To describe the oral health status and investigate factors affecting dental caries experience among children with cerebral palsy (CP) in rural Bangladesh., Method: A cross-sectional study was conducted among children with CP who are part of the Bangladesh Cerebral Palsy Register (BCPR) study. Caries experience was measured by identifying decayed, missing, and filled teeth for deciduous and permanent teeth (dmft/DMFT). Clinical periodontal index, body mass index, oral hygiene behaviour, masticatory ability, and dietary habits were recorded. CP motor types and severity of functional mobility (Gross Motor Function Classification System [GMFCS]) were assessed., Results: Of 90 children with CP (mean age 9y 7mo, range 2-17y, 37.8% female and 62.2% male), 35% of 2 to 6 year olds, and 70% of 7 to 11 year olds (p=0.014) experienced caries (dmft+DMFT>0). The mean values (standard deviation [SD]) of dmft and DMFT were 2.46 (3.75) and 0.72 (1.79) respectively. After adjusting for age and sex, binary logistic regression analysis showed a significant relationship with dental caries for children who had quadriplegia (odds ratio [OR] 5.56, p=0.035), tooth cleaning less than one time/day (OR 0.08, p=0.016), using toothpowder or charcoal for cleaning (OR 7.63, p=0.015), and snacking between meals more than one time/day (OR 6.93, p=0.012)., Interpretation: Early oral health preventive care is required for children with CP because dental caries is highly prevalent in these children., (© 2016 Mac Keith Press.)

Background: Schools of nursing have moved to multiple choice test questions to help prepare students for licensure and practice. However, students can buy test banks to help them "get through" nursing school. Accurate assessment of nursing students' knowledge and judgment comprises access to test banks., Method: The purpose of this exploratory study was to gain an understanding about nursing faculty's knowledge concerning test bank security issues, to assess whether publishers were aware of this issue, and vendor's reasons for supplying test banks to students., Results: Overall, the results indicated that the majority of faculty were unaware of student access to test banks, and although most do not use test banks verbatim, general consensus existed that test bank security is a concern., Conclusion: Implications include increasing faculty awareness of test bank access by students, supporting educators to develop their own test bank items, and promoting security of all examinations. [J Nurs Educ. 2017;56(5):292-294.]., (Copyright 2017, SLACK Incorporated.)

Recipients of solitary liver and kidney transplants are living longer, and this increases their risk of long-term complications such as recurrent hepatitis C virus (HCV) and drug-induced nephrotoxicity. These complications may require retransplantation. Since the adoption of the Model for End-Stage Liver Disease, the number of simultaneous liver-kidney transplantation (SLK) procedures has increased. However, there are no standardized criteria for organ allocation to SLK candidates. The aims of this study were to retrospectively compare recipient and graft survival with liver transplantation alone (LTA), SLK, kidney after liver transplantation (KALT), and liver after kidney transplantation (LAKT) and to identify independent risk factors affecting recipient and graft survival. The United Network for Organ Sharing/Organ Procurement and Transplantation Network database (1988-2007) was queried for adult LTA (66,026), SLK (2327), KALT (1738), and LAKT procedures (242). After adjustments for potential confounding demographic and clinical variables, there was no difference in recipient mortality rates with LTA and SLK (P = 0.02). However, there was a 15% decreased risk of graft loss with SLK versus LTA (hazard ratio = 0.85, P < 0.001). The recipient and graft survival rates with SLK were higher than the rates with both KALT (P <0.001 and P <0.001) and LAKT (P = 0.003 and P < 0.001). The following were all identified as independent negative predictors of recipient mortality and graft loss: recipient age ≥ 65 years, male sex, black race, HCV/diabetes mellitus status, donor age ≥ 60 years, serum creatinine level ≥2.0 mg/dL, cold ischemia time > 12 hours, and warm ischemia time > 60 minutes. Although the recent increase in the number of SLK procedures performed each year has effectively decreased the number of potential donor kidneys available to patients with end-stage renal disease (ESRD) awaiting kidney transplantation, SLK in patients with end-stage liver disease and ESRD is justified because of the lower risk of graft loss with SLK versus LTA as well as the superior recipient and graft survival with SLK versus serial liver-kidney transplantation., (Copyright © 2012 American Association for the Study of Liver Diseases.)

Micellar suspensions of acrylic diblock copolymers are excellent model materials for studying the adhesive transfer of viscoelastic solids. The micellar structure is maintained in films with a variety of thicknesses, giving films with a well-defined structure and viscoelastic character. Thin films were cast onto elastomeric silicone substrates from micellar suspensions in butanol, and the adhesive interactions between these coated elastomeric substrates and a rigid indenter were quantified. By controlling the adhesive properties of the film/indenter and film/substrate interfaces we were able to obtain very clean transfer of the film from the substrate to the portion of the glass indenter with which the film was in contact. Adhesive failure at the film/substrate interface occurs when the film/indenter interface is able to support an applied energy release rate that is sufficient to result in cavity nucleation at the film/substrate interface. Cavity formation is rapidly followed by delamination of the entire region under the indenter. The final stage in the transfer process involves the failure of the film that bridges the indenter and the elastomeric substrate. This film is remarkably robust and is extended to three times its original width prior to failure. Failure of this film occurs at the periphery of the indenter, giving a transferred film that conforms to the original contact area between the indenter and the coated substrate.