An aniline-substituted bile salt analog protects both mice and hamsters from multiple Clostridioides difficile strains

Clostridioides difficile infection (CDI) is the major identifiable cause of antibiotic-associated diarrhea. The emergence of hypervirulent C. difficile strains has led to increases in both hospital- and community-acquired CDI. Furthermore, CDI relapse from hypervirulent strains can reach up to 25%. Thus, standard treatments are rendered less effective, making new methods of prevention and treatment more critical. Previously, the bile salt analog CamSA was shown to inhibit spore germination in vitro and protect mice and hamsters from C. difficile strain 630. Here, we show that CamSA was less active at preventing spore germination of other C. difficile ribotypes, including the hypervirulent strain R20291. Strain-specific in vitro germination activity of CamSA correlated with its ability to prevent CDI in mice. Additional bile salt analogs were screened for in vitro germination inhibition activity against strain R20291, and the most active compounds were tested against other strains. An aniline-substituted bile salt analog, (CaPA), was found to be a better anti-germinant than CamSA against eight different C. difficile strains. In addition, CaPA was capable of reducing, delaying, or preventing murine CDI signs in all strains tested. CaPA-treated mice showed no obvious toxicity and showed minor effects on their gut microbiome. CaPA’s efficacy was further confirmed by its ability to prevent CDI in hamsters infected with strain 630. These data suggest that C. difficile spores respond to germination inhibitors in a strain-dependent manner. However, careful screening can identify anti-germinants with broad CDI prophylaxis activity.

Detection of Cacao Mild Mosaic Virus (CaMMV) Using Nested PCR and Evidence of Uneven Distribution in Leaf Tissue

Distribution of improved germplasm of Theobroma cacao is essential for meeting the increased demand for cocoa beans. In cacao, the introduction of new diseases is prevented by exchanging material through a national and international quarantine system. In 2020, virus symptoms were observed on plants in a quarantine greenhouse, and Cacao mild mosaic virus (CaMMV) was detected in one plant using published diagnostic primers. However, no virus was detected in other symptomatic plants. To address high pathogen diversity and low virus titer in recently infected plants, a nested PCR test was developed based on 15 CaMMV sequences from Trinidad and Puerto Rico. The test was validated on a subset (n = 30) of plants in the greenhouse, of which 29 tested positive. Most infections are thought to have occurred during the later stage of the quarantine period, possibly due to spread by mealybugs. However, phylogenetic analysis revealed the presence of three strains, suggesting that it was introduced on scionwood from multiple sources. Results of PCR assays on different leaf tissues indicate that the virus is unevenly distributed and that petiole tissue should be used in molecular diagnostics. The movement of infected scionwood is a major dissemination pathway for CaMMV but can be managed through careful screening.

Exposure to cadmium and head and neck cancers: a meta-analysis of observational studies

Cadmium (Cd) is a widespread environmental pollutant. A number of observational studies have reported that Cd might be a cause of nasopharyngeal (NPC), pharyngeal (PC), or laryngeal cancers (LC). In this study evidence about the relation of Cd and NPC, PC, and LC has been summarized. A literature review was conducted until 20 June 2020 in PubMed, Ovid, Scopus, Web of Science and Google scholar databases to investigate the epidemiologic evidence for the relation between cadmium exposure and cancers of the nasopharynx, pharynx, and larynx. Ten articles were selected after careful screening of retrieved studies. All of these studies obtained a Newcastle-Ottawa Scale (NOS) quality score from 6 to 8. Due to high heterogeneity, in all analyses, random effect was used. The pooled results showed that cadmium levels in NPC (standard mean difference (SMD=0.55; 95% CI=0.20, 0.89; p=0.002) and PC (SMD=9.79; 95% CI=0.62, 18.96; p=0.036) patients/tissues were significantly higher than their controls. But cadmium levels were not significantly different between LC cases/tissues and their controls. (SMD=−0.05; 95% CI=−0.99, 0.89; p=0.921). Exposure to cadmium is likely to cause nasopharyngeal and pharyngeal cancer.

Mortality in chronic kidney disease patients with COVID-19: a systematic review and meta-analysis

At the beginning of 2020, the outbreak of coronavirus disease 2019 (COVID-19) led to a worldwide pandemic and mass panic. The number of infected people has been increasing exponentially since, and the mortality rate has also been concomitantly increasing. At present, no study has summarized the mortality risk of COVID-19 in patients with chronic kidney disease (CKD). Therefore, the aim of the present study was to conduct a literature review and meta-analysis to understand the frequency of mortality among CKD patients infected with COVID-19. A comprehensive systematic search was conducted on the PubMed, Embase, and Cochrane databases to find articles published until May 15, 2020. Study quality was assessed using a modified version of the Newcastle–Ottawa Scale. After careful screening based on the inclusion and exclusion criteria, 3,867,367 patients from 12 studies were included. The mortality rate was significantly higher among CKD patients with COVID-19 infection than among CKD patients without COVID-19 infection, as indicated by a pooled OR of 5.81 (95% CI 3.78–8.94, P < 0.00001, I2 = 30%). The patients were then stratified into ≥ 70 and < 70 years, and subgroup analysis revealed that among CKD patients with COVID-19 infection, the mortality rate was higher in the < 70 years group (OR 8.69, 95% CI 7.56–9.97, P < 0.0001) than in the ≥ 70 years group (OR 2.44, 95% CI 0.75–6.63, P = 0.15). Thus, COVID-19 patients with CKD have a high mortality risk and require a comprehensive multidisciplinary management strategy.

IDENTIFYING BEST-PRACTICE STRATEGIES FOR MANAGING RESIDENTIAL CAREGIVERS WORKING WITH CHILDREN AT RISK

Residential caregivers are the central figures responsible for the children in their charge. Their work is physically and emotionally taxing, and carried out under pressure: they are prone to burnout. In addition, their status is lower than that of other staff. This study aimed to identify the strategies to improve caregiver functioning that have been adopted in Israel’s residential social-service facilities, and to examine the extent of their implementation. A two-stage, mixed-methods study design was employed. In the qualitative stage, six successful care facilities were identified; their directors were interviewed in depth using the Learning from Success method. In the quantitative stage, a survey was administered to 95 directors, using open and closed questions. Six best-practice strategies for working with caregivers were identified: careful screening, training, ongoing supervision, personal and professional support mechanisms, flexible schedules, and a clear work plan and procedures. While these strategies were applied to some extent in most facilities, they varied in scope and implementation. Using a regression model, we found a connection between the implementation of these strategies and the directors’ satisfaction with the caregivers’ work. We discuss recommendations that can help directors incorporate the six strategies in residential homes and meet the challenges directors face in their work with caregivers.

Systematic Review on the Functional Status of Elderly Hip Fracture Patients using Katz Index of Activity of Daily Living (Katz ADL) Score

Hip fractures cases are common in elderly population. After a hip fracture, around 80% of patients were unable to carry out at least one independent activity of daily living (ADL). This review attempted to provide an evidence-based literature on ADL of elderly hip fracture patients. A computerised literature search using Medline (OVID) and Scopus databases were conducted to identify relevant studies on ADL of elderly hip fracture patients that was assessed with Katz ADL score. Only articles that fulfilled the inclusion criteria were included in this review. Initial search identified 314 potentially relevant articles but after careful screening, only 5 full-text articles were selected for the present review. Three studies showed an increase dependent level of the patients’ ADL after hip fractures. Two studies showed not more than half of the patients were unable to regain their pre-fracture ADL level after one year of hip fracture incidence. Feeding/eating showed the highest independent activity while bathing was the lowest independent activity among patients. In conclusion, elderly hip fracture patients have declined ADL with the risk that they may never regain their pre-fracture ADL level.

Liver Function Changes in Patients with Hepatocellular Carcinoma Treated with Lenvatinib: Predictive Factors of Progression to Child-Pugh Class B, the Formation of Ascites and the Candidates for the Post-Progression Treatment

The aim of this multicenter retrospective study was to assess the change in liver function in patients with hepatocellular carcinoma treated with lenvatinib. Among 139 consecutive patients receiving lenvatinib treatment between March 2018 and July 2019, 28 patients with Child-Pugh class B and one patient with inadequate patient information were excluded. Remaining 110 patients with Child-Pugh class A were analyzed. The median age of 110 patients was 73 years (IQR 66.7–80) and 88 patients (80.0%) were men. Child-Pugh score was 5 (CP5A) and 6 (CP6A) in 58 (52.7%) and 52 patients (47.3%), and ALBI grade was 1 and 2 in 38 (34.5%) and 72 patients (65.5%), respectively. The deterioration to Child-Pugh class B was found in 43 patients (39.1%) during the lenvatinib treatment. The favorable factors related to preserving liver function were significantly shown to be male, ALBI grade 1, CP5A and BCLC early or intermediate stage in the multivariate analysis. The formation of ascites was found in 32 patients (28.6%). The significant unfavorable factors associated with the formation of ascites were found to be low platelet count and CP6A. Among the 79 patients, there were 36 (45.6%) and 11 patients (13.9%) who fulfilled the criteria for candidate for the post-progression treatment and ramucirumab treatment, respectively. The predictive factors of the post-progression treatment were shown to be ALBI grade 1 and CP5A in multivariate analysis. In conclusion, male, ALBI grade 1, CP5A and BCLC early or intermediate stage were favorable factors related to sustaining liver function and the patients with ALBI grade 1 and CP5A were eligible for the post-progression treatment. Careful screening for ascites was needed in patients with low platelet count and CP6A.

The Concept of Justice in Stakeholder Theory: A Systematic Literature Review

In strategic management, the Stakeholder Theory proclaims that in order to achieve better performance and sustainable competitive advantage, the organization has to treat each of its stakeholders fairly. Hence, the concept of justice becomes relevant in assessing the effectiveness of managerial decisions and is ingrained in the Stakeholder Theory literature. This paper aims to examine how the notion of justice is conceptualized and applied in the Stakeholder Theory literature; and to propose new avenues of research regarding the interconnections between these two subjects. We present a systematic literature review to synthesize the research in the area. A careful screening held in April 2019, resulted in 75 papers published in 35 journals from 1999 to 2019. The results were presented in two phases. First, in the form of a descriptive and bibliometric analysis of the selected papers. Second, by reviewing those papers, we offer a framework of how the notion of justice has been conceptualized and applied in the Stakeholder Theory literature. Finally, we propose an agenda for future research regarding the interconnection between justice and Stakeholder Theory.

Fatal intracranial hemorrhage after carotid artery stenting: Three case reports and a literature review

Introduction We herein describe three patients who developed fatal intracranial hemorrhage (ICH) after carotid artery stenting (CAS). Case Presentation: We retrospectively reviewed 126 patients who underwent CAS from January 2016 to December 2018 and identified 3 patients (2.4%) (all male, mean age of 59 years) who developed ICH after CAS. Two of them developed left basal ganglia hemorrhage with extension into the ventricle and subarachnoid space, and the third patient developed primary ventricular bleeding. One hemorrhage occurred immediately after CAS, whereas the other two occurred 3 hours and 8 hours after the procedure, respectively. The mean stenosis of the treated carotid arteries was 91%. All three hemorrhages were fatal, and the mean time from hemorrhage to death was 50 hours. Conclusion ICH is a potentially fatal complication of CAS and often occurs several hours after the procedure. Headache, vomiting, and consciousness disorders are the most common symptoms of ICH. Careful screening to identify high-risk patients and strict management of perioperative blood pressure are important to prevent this complication.

Sweetness Enhancement by Aromas: Measured by Descriptive Sensory Analysis and Relative to Reference Scaling

Sweetness enhancement by aromas has been suggested as a strategy to mitigate sugar reduction in food products, but enhancement is dependent on type of aroma and sugar level. A careful screening of aromas across sugar levels is thus required. Screening results might, however, depend on the method employed. Both descriptive sensory analysis and relative to reference scaling were therefore used to screen 5 aromas across 3 sucrose concentrations for their sweetness-enhancing effects in aqueous solutions. In the descriptive analysis, samples with added vanilla, honey, and banana aroma were rated as significantly sweeter than samples with added elderflower or raspberry aroma at all sucrose concentrations. In relative to reference scaling, honey aroma significantly increased the sweet taste compared with samples with added elderflower or no aroma at low and medium sucrose concentrations. Banana and raspberry aromas also increased the sweet taste significantly compared with the sample with added elderflower aroma at medium sucrose concentration in the relative to reference scaling. This demonstrates that the cross-modal effects observed by the 2 methods were different. In terms of the methods applied, relative to reference scaling was generally found to result in a decrease in the measured sweetness enhancement by aromas. In the descriptive analysis, the cross-modal effect of aromas on sweet taste perception was found to be significantly higher at 2.5% and 5.0% w/w sucrose compared with 7.5% w/w sucrose. These results highlight the importance of considering how references are employed in sensory analysis and how they affect cross-modal interactions.