Delanzomib, a Novel Proteasome Inhibitor, Combined With Adalimumab Drastically Ameliorates Collagen-Induced Arthritis in Rats by Improving and Prolonging the Anti-TNF-α Effect of Adalimumab

Delanzomib is a novel proteasome inhibitor initially developed for treating multiple myeloma. It was found to inhibit the expression of tumor necrosis factor alpha (TNF-α). This study aimed to investigate the ameliorating effect of delanzomib on collagen-induced arthritis (CIA) and to explore the pharmacodynamics and pharmacokinetics (PK) interactions between delanzomib and adalimumab. Rats with CIA were randomly assigned to receive the treatment with delanzomib, adalimumab, delanzomib combined with adalimumab, or placebo. Visual inspection and biochemical examinations including TNF-α, interleukin 6, and C-reactive protein were performed to assess arthritis severity during the treatment. The adalimumab concentration in rats was determined to evaluate the PK interaction between delanzomib and adalimumab. Also, the levels of neonatal Fc receptor (FcRn) and FcRn mRNA were measured to explore the role of FcRn in the PK interaction between delanzomib and adalimumab. As a result, delanzomib combined with adalimumab exhibited stronger anti-arthritis activity than a single drug because both drugs synergistically reduced TNF-α level in vivo. Delanzomib also decreased adalimumab elimination in rats by increasing the level of FcRn. The slower elimination of adalimumab in rats further prolonged the anti-TNF-α effect of adalimumab. Moreover, FcRn level was increased by delanzomib via suppressing FcRn degradation rather than promoting FcRn production. In conclusion, delanzomib combined with adalimumab may be a potential therapeutic approach for treating rheumatoid arthritis. The initial finding that the PK interaction occurred between delanzomib and adalimumab may have clinical relevance for patients who simultaneously take proteasome inhibitors and anti-TNF-α therapeutic proteins.

Terc Gene Cluster Variants Predict Liver Telomere Length in Mice

Variants in a gene cluster upstream-adjacent to TERC on human chromosome 3, which includes genes APRM, LRRC31, LRRC34 and MYNN, have been associated with telomere length in several human populations. Currently, the mechanism by which variants in the TERC gene cluster influence telomere length in humans is unknown. Given the proximity between the TERC gene cluster and TERC (~0.05 Mb) in humans, it is speculated that cluster variants are in linkage disequilibrium with a TERC causal variant. In mice, the Terc gene/Terc gene cluster are also located on chromosome 3; however, the Terc gene cluster is located distantly downstream of Terc (~60 Mb). Here, we initially aim to investigate the interactions between genotype and nicotine exposure on absolute liver telomere length (aTL) in a panel of eight inbred mouse strains. Although we found no significant impact of nicotine on liver aTL, this first experiment identified candidate single nucleotide polymorphisms (SNPs) in the murine Terc gene cluster (within genes Lrrc31, Lrriq4 and Mynn) co-varying with aTL in our panel. In a second experiment, we tested the association of these Terc gene cluster variants with liver aTL in an independent panel of eight inbred mice selected based on candidate SNP genotype. This supported our initial finding that Terc gene cluster polymorphisms impact aTL in mice, consistent with data in human populations. This provides support for mice as a model for telomere dynamics, especially for studying mechanisms underlying the association between Terc cluster variants and telomere length. Finally, these data suggest that mechanisms independent of linkage disequilibrium between the Terc/TERC gene cluster and the Terc/TERC gene mediate the cluster’s regulation of telomere length.

Life Experience of Ethnic Minorities in Urban of Vietnam: An Analysis of the Social Relationship and Social Networks

This article is a part of a research project supported by Vietnam National University-Hanoi about the social welfare of ethnic people in the urban and industrial zones, aims at identifying and describing the life experiences of these groups in the urbanization process. Shreds of evidence from analysing the social network, social connection, social interaction of research participants in their living and working places, it is found that the ethnic minorities face difficulties in setting their life in the new context. However, they tend to build the social cohesion and to be satisfied with the new life conditions to meet the objectives of having a better life and a job in the new context. The findings from this analysis also show that there is a difference among the living place, age group, gender correlated to the social network, social relation and life experiences in the new context. It is the initial finding from the survey of 600 ethnic people in urban of three provinces of Daklak, Lang Son and Binh Duong of Vietnam. Received: 22 June 2021 / Accepted: 05 August 2021 / Published: 5 September 2021

Left Supraclavicular (Virchow’s) Node Metastasis Detected Before Diagnosis of the Primary Infradiaphragmatic Tumor

Background and Purpose: Malignant infradiaphragmatic tumors that metastasize to the left supraclavicular (Virchow’s) node are relatively rare. Since Virchow's time, the survival rates of cancer patients have improved because of dramatic research advances in the epidemiology of cancer and the development of screening technologies and treatment methods. However, when metastasis is detected in the left supraclavicular node in patients with head and neck carcinoma, locating the primary cancer remains a difficult and time-consuming challenge. We report three cases of malignant infradiaphragmatic tumors diagnosed following the initial finding of left supraclavicular node (LSN) metastasis after surgery for tongue squamous cell carcinoma (follow-up period, range 18–62 months).Methods: In these cases, adenocarcinoma was diagnosed based on LSN biopsies, and a second primary tumor was found, including cholangiocarcinoma, bladder carcinoma, and prostate carcinoma.Results: CA19-9 and alpha-fetoprotein levels helped to diagnose cholangiocarcinoma. In the bladder carcinoma case, immunopathological examination of the metastatic LSN and bladder lesion showed GATA 3(+), and the tongue squamous cell carcinoma showed GATA 3(-). GATA 3 staining aided in the diagnosis of urothelial bladder cancer with LSN metastasis. In the prostate carcinoma case, PSA levels and weak FDG-PET/CT uptake aided the diagnosis process. This patient underwent bilateral orchiectomy and adjuvant hormonal therapy and survived for 47 months after the diagnosis of LSN metastasis. The other patients died within 1 year.Discussion and Conclusions: These cases suggest that the prognosis of malignant infradiaphragmatic tumors after LSN metastasis depends on the tumor characteristics and that rapid diagnosis is important for providing appropriate treatment.

Social Media Conversations About High Engagement Sports Team Brands

This study conducts an analysis of social media discussions related to high engagement sports brands. More specifically, our study examined the English Premier League (EPL); it sought to retrieve data systematically over the same day, weekly, for a period of five months. After this process, we had built 20 datasets and NodeXL was utilized to analyse the data. After we had this data, we were able to use qualitative observations to identify key users and conversations that formed around the EPL as well as the connections between the conversations that arose from the brand’s posts and the people involved in them. We also analyzed the quantitative data underpinning our network visualisations to provide further insights. The most obvious initial finding was that when the EPL tweets, it prompts a large volume of conversations directly related to these tweets. However, we also noted that EPL tweets also help instigate further, sometimes unrelated, tweets and conversations. More specifically, we identified that the visualized network of conversations was of a broadcast form, which is characterized by messages being generated by a central account (the EPL) and shared by a number of decentralized users. Based on our analysis, we propose guidance around (S)ocial media presence, (C)rafting the message, Planned (i)ntervention, (S)pontaneous follow-up, and (M)essage mortality to form the SCISM framework. This framework is likely to be of interest to brands that wish to promote, sustain and benefit from their instigation of social media.

An update on the distribution, bionomics, and insecticide susceptibility of Anopheles stephensi in Ethiopia, 2018–2020

Background Anopheles stephensi, an invasive malaria vector, was first detected in Africa nearly 10 years ago. After the initial finding in Djibouti, it has subsequently been found in Ethiopia, Sudan and Somalia. To better inform policies and vector control decisions, it is important to understand the distribution, bionomics, insecticide susceptibility, and transmission potential of An. stephensi. These aspects were studied as part of routine entomological monitoring in Ethiopia between 2018 and 2020. Methods Adult mosquitoes were collected using human landing collections, pyrethrum spray catches, CDC light traps, animal-baited tent traps, resting boxes, and manual aspiration from animal shelters. Larvae were collected using hand-held dippers. The source of blood in blood-fed mosquitoes and the presence of sporozoites was assessed through enzyme-linked immunosorbent assays (ELISA). Insecticide susceptibility was assessed for pyrethroids, organophosphates and carbamates. Results Adult An. stephensi were collected with aspiration, black resting boxes, and animal-baited traps collecting the highest numbers of mosquitoes. Although sampling efforts were geographically widespread, An. stephensi larvae were collected in urban and rural sites in eastern Ethiopia, but An. stephensi larvae were not found in western Ethiopian sites. Blood-meal analysis revealed a high proportion of blood meals that were taken from goats, and only a small proportion from humans. Plasmodium vivax was detected in wild-collected An. stephensi. High levels of insecticide resistance were detected to pyrethroids, carbamates and organophosphates. Pre-exposure to piperonyl butoxide increased susceptibility to pyrethroids. Larvae were found to be susceptible to temephos. Conclusions Understanding the bionomics, insecticide susceptibility and distribution of An. stephensi will improve the quality of a national response in Ethiopia and provide additional information on populations of this invasive species in Africa. Further work is needed to understand the role that An. stephensi will have in Plasmodium transmission and malaria case incidence. While additional data are being collected, national programmes can use the available data to formulate and operationalize national strategies against the threat of An. stephensi.

An Update on the Distribution, Bionomics, and Insecticide Susceptibility of Anopheles Stephensi in Ethiopia, 2018-2020

BackgroundAnopheles stephensi, an invasive malaria vector, was first detected in Africa nearly 10 years ago. After the initial finding in Djibouti, it has subsequently been found in Ethiopia, Sudan, and Somalia. To better inform policies and vector control decisions, it is important to understand the distribution, bionomics, insecticide susceptibility, and transmission potential of An. stephensi. These aspects were studied as part of routine entomological monitoring in Ethiopia between 2018 and 2020.MethodsAdult mosquitoes were collected using human landing collections, pyrethrum spray catches, CDC light traps, animal-baited tent traps, resting boxes, and manual aspiration from animal shelters. Larvae were collected using handheld dippers. The source of blood in bloodfed mosquitoes and the presence of sporozoites was assessed through enzyme linked immunosorbent assays (ELISA). Insecticide susceptibility was assessed for pyrethroids, organophosphates, and carbamates.ResultsAdult An. stephensi were collected with aspiration, black resting boxes, and animal-baited traps collecting the highest numbers of mosquitoes. Although sampling efforts were geographically widespread, An. stephensi larvae were collected in urban and rural sites in eastern Ethiopia, but An. stephensi larvae were not found in western Ethiopian sites. Blood meal analysis revealed a high proportion of blood meals that were taken from goats, and only a small proportion from humans. Plasmodium vivax was detected in wild collected An. stephensi. High levels of insecticide resistance were detected to pyrethroids, carbamates, and organophosphates. Pre-exposure to piperonyl butoxide increased susceptibility to pyrethroids. Larvae were found to be susceptible to temephos.ConclusionsUnderstanding the bionomics, insecticide susceptibility, and distribution of An. stephensi will improve the quality of a national response in Ethiopia and provide additional information on populations of this invasive species in Africa. Further work is needed to understand the role that An. stephensi will have in Plasmodium transmission and malaria case incidence. While additional data are being collected, national programs can use the available data to formulate and operationalize national strategies against the threat of An. stephensi.

Core values measurement

Indonesia's state-owned enterprises are now on the verge of adopting a new management system called values-based management (VBM) or management by values (MBV) initiated by the Ministry of State-Owned Enterprises (SoE) by introducing a set of core values, namely AKHLAK (abbreviation from Bahasa Indonesia's words: Amanah / Trustworthy, Kompeten / Competent, Harmonis / Harmonious, Loyal, Adaptif / Adaptive, and Kolaboratif / Collaborative). This study uses an inductive/qualitative approach to understand how these core values are measured. The implication of this study will help SoEs to decide whether to use indirect or direct measurement methods in their effort to translate core values into values-based management. The initial finding shows the sample SoEs do not have a solid understanding of the differences between direct and indirect values assessments yet utilize the method of choice quite exclusively and extensively.

Can COVID-19 Cause Peripheral Facial Nerve Palsy?

Background/Objective: The aim of our study is to evaluate the relationship between peripheral facial paralysis and the patients who had a contact with a Coronavirus Disease 2019 (COVID-19) patient or had COVID-19.Methods: Patients with a history of contact with a COVID-19 patient or having COVID-19 disease, who were admitted to the emergency department for peripheral facial paralysis in the last 6 months were included in the study. Facial paralysis grade at first presentation, treatment modality, treatment duration, post-treatment facial paralysis grade, and additional findings were analyzed.Results: A total of 34 patients, 20 females and 14 males, were included into the study. Nasal-oropharyngeal Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) test taken from patients with a history of contact, and patients having COVID-19 disease were determined as positive in 5 and 3 patients, respectively. Peripheral facial paralysis was detected as an initial finding in 5 of these 8 patients, and paralysis developed in 7 to 12 days after the diagnosis of the COVID-19 disease in the remaining 3 patients. The grade of first admission paralysis did not change in one patient in the (+) group, while improvement was observed in all patients in the (-) group.Conclusion: Neuroinvasive potential of COVID-19 in central and peripheral nervous system was reported in current literature. Our study indicates peripheral facial palsy can also be encountered during the clinical course of COVID-19 and should be considered as a finding of this disease.