Analysis of signaling cascades from myeloma cells treated with pristimerin.

Multiple myeloma (MM) is the 2nd most frequently diagnosed blood cancer after non-Hodgkin's lymphoma. The present study aimed to identify the differentially expressed genes (DEGs) between the control and pristimerin-treated MM cell lines. We examined the GSE14011 microarray dataset and screened DEGs with GEO2R statistical tool using the inbuilt limma package. We used a bioinformatics pipeline to identify the differential networks, signaling cascades, and the survival of the hub genes. We implemented two different enrichment analysis including ClueGO and Metacore™, to get accurate annotation for most significant DEGs. We screened the most significant 408 DEGs from the dataset based on p-values and logFC values. Using protein network analysis, we found the genes UBC, HSP90AB1, HSPH1, HSPA1B, HSPA1L, HSPA6, HSPD1, DNAJB1, HSPE1, DNAJC10, BAG3, and DNAJC7 had higher node degree distribution. In contrast, the functional annotation provided that the DEGs were predominantly enriched in B-cell receptor signaling, unfolded protein response, positive regulation of phagocytosis, HSP70, and HSP40-dependent folding, and ubiquitin-proteasomal proteolysis. Using network algorithms, and comparing enrichment analysis, we found the hub genes enriched were INHBE, UBC, HSPA1A, HSP90AB1, IKBKB, and BAG3. These DEGs were further validated with overall survival and gene expression analysis between the tumor and control groups. Finally, pristimerin effects were validated independently in a cell line model consisting of IM9 and U266 MM cells. Pristimerin induced in vitro cytotoxicity in MM cells in a dose-dependent manner. Pristimerin inhibited NF-κB, induced accumulation of ubiquitinated proteins and inhibited HSP60 in the validation of bioinformatics findings, while pristimerin-induced caspase-3 and PARP cleavage confirmed cell death. Taken together, we found that the identified DEGs were strongly associated with the apoptosis induced in MM cell lines due to pristimerin treatment, and combinatorial therapy derived from pristimerin could act as novel anti-myeloma multifunctional agents.

Clinical Practicum Assessment for Biomedical Science Program from Graduates' Perspective.

The clinical practicum for biomedical science students aims to provide graduates with the knowledge and skills required to work in diagnostic laboratory settings. This study examines graduates' perspectives on content, teachers and clinical training and their satisfaction rates based on the skills gained during training. The study was conducted on females who graduated from Qatar University between 2015 and 2020. We used a previously validated questionnaire called CPAT-QU. Telephonic interviews were conducted and were analyzed using SPSS. The results showed a high satisfaction rate, of 80%, for the content and organization of the clinical training. The participants' main concerns included the evaluation criteria, as 8.7% were not satisfied. The students suggested increasing the length of the training in order to obtain experience that was more practical. The students' satisfaction with the teachers was 70% in terms of their attitude, command of knowledge and ability to convey knowledge. In total, 69.5% of the graduates claimed that their instructors were interested in teaching and 4.4% claimed their instructors conveyed disinterest in teaching. The Qatar University graduates were satisfied with the content of their clinical training. However, they reported some gaps in this training. Identifying these gaps will help in restructuring clinical training to improve student experience.

Genetic epidemiology of male infertility (MI) in Arabs: a systematic review.

Although Male Infertility (MI) in Arabs is fairly common, there is a dearth in published reports of genetic epidemiology of MI among Arabs. This study aimed to review the existing literature reporting the variants that are associated with MI in the 22 Arab countries. We searched four literature databases (PubMed, Science Direct, Scopus, and Web of Science) from the time of inception until April 2021 using broad search terms to capture all reported genetic data related to Arab patients with MI. Our search strategy identified 3488 articles, of these 34 were eligible for this systemic review. We retrieved data from nine Arab Countries (Tunisia, Algeria, Morocco, Syria, Jordan, Yemen, Iraq, Egypt and Lebanon). Only 2597 patients and 10 families with MI were identified and compared to 3721 controls. Our search strategy identified 25 genes, including 89 variants: 52.7% are shared with other ethnic groups, 41.7% are unique to Arab patients, and 5.6% are common among Arabs. Azoospermia (41.18%) was the most frequently reported phenotype. This is the first systematic review to capture reported variants associated with MI among the Arab populations. Although Arabs seem to share genetic profiles with other ethnicities, they have distinctive genotype-phenotype correlations for some of genetic variants.

Development and Validation of a Clinical Practicum Assessment Tool for the NAACLS-Accredited Biomedical Science Program.

Student perspectives on their final year clinical placements in biomedical sciences at Qatar University are assessed using the clinical practicum assessment tool (CPAT), which was developed in-house following accreditation body requirements. The tool, which we call the CPAT-Qatar University (CPAT-QU), covers the three clinical practicum domains: practicum content, preceptors, and competencies. Here, we validate this tool. The CPAT-QU has 27 Likert-scale questions and free-text open questions. CPAT-QU readability was calculated using the Flesch-Kincaid Reading Ease (FKRE) instrument. Content validity was assessed using the average and universal average scale-level content validity indices (S-CVI/Average and S-CVI/UA). For construct validity, 50 employed graduates who had completed the practicum were consented for study participation, and the validity was calculated by a principal component analysis (PCA). Reliability was analyzed by Cronbach's alpha. The S-CVI/Average and S-CVI/UA were 0.90 and 0.59, respectively, indicating that an adequate proportion of the content was relevant. The PCA extracted two core components, which explained 63% of the variance in the CPAT-QU. Cronbach's alpha values for the items were within the acceptable range of 0.60-1.00, showing that internal consistency has a good level. CPAT-QU appears to be a useful tool for assessing student perspectives on their clinical placements; however, construct validity needs continuous improvement.

Fasting Ramadan During COVID-19 Pandemic: Immunomodulatory Effect.

As of April 24, 2020, more than 1. 6 billion Muslims observe the holy fasting month of Ramadan worldwide. The safety of fasting of healthy adult Muslims during the COVID-19 era is debatable. In this perspective, we discuss the available scientific evidence of the advantages of fasting against COVID-19.

Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity.

(1) Aims: Diabesity, defined as diabetes occurring in the context of obesity, is a serious health problem that is associated with an increased risk of premature heart attack, stroke, and death. To date, a key challenge has been to understand the molecular pathways that play significant roles in diabesity. In this study, we aimed to investigate the genetic links between diabetes and obesity in diabetic individuals and highlight the role(s) of shared genes in individuals with diabesity. (2) Methods: The interactions between the genes were analyzed using the Search Tool for the Retrieval of Interacting Genes (STRING) tool after the compilation of obesity genes associated with type 1 diabetes (T1D), type 2 diabetes (T2D), and maturity-onset diabetes of the young (MODY). Cytoscape plugins were utilized for enrichment analysis. (3) Results: We identified 546 obesity genes that are associated with T1D, T2D, and MODY. The network backbone of the identified genes comprised 514 nodes and 4126 edges with an estimated clustering coefficient of 0.242. The Molecular Complex Detection (MCODE) generated three clusters with a score of 33.61, 16.788, and 6.783, each. The highest-scoring nodes of the clusters were AGT, FGB, and LDLR genes. The genes from cluster 1 were enriched in FOXO-mediated transcription of oxidative stress, renin secretion, and regulation of lipolysis in adipocytes. The cluster 2 genes enriched in Src homology 2 domain-containing (SHC)-related events triggered by IGF1R, regulation of lipolysis in adipocytes, and GRB2: SOS produce a link to mitogen-activated protein kinase (MAPK) signaling for integrins. The cluster 3 genes ere enriched in IGF1R signaling cascade and insulin signaling pathway. (4) Conclusion: This study presents a platform to discover potential targets for diabesity treatment and helps in understanding the molecular mechanism.

Investigating the structural impacts of a novel missense variant identified with whole exome sequencing in an Egyptian patient with propionic acidemia.

Propionic Acidemia (PA) is an inborn error of metabolism caused by variants in the PCCA or PCCB genes, leading to mitochondrial accumulation of propionyl-CoA and its by-products. Here, we report a 2 year-old Egyptian boy with PA who was born to consanguineous parents. Biochemical analysis was performed using tandem mass spectrometry (MS/MS) on the patient's dried blood spots (DBS) followed by urine examination of amino acids using gas chromatography/mass spectrometry (GC/MS). Molecular genetic analysis was carried out using whole-exome sequencing (WES). The PCCA gene sequencing revealed a novel homozygous missense variant affecting the locus (chr13:100962160) of exon 16 of the PCCA gene, resulting in the substitution of the amino acid arginine with proline at site 476 (p.Arg476Pro). Computational analysis revealed that the novel variant might be pathogenic and attributed to decrease the stability and also has an effect on the biotin carboxylase c-terminal domain of the propionyl carboxylase enzyme. The physicochemical properties analysis using NCBI amino acid explorer study revealed restrictions in the side chain and loss of hydrogen bonds due to the variant. On the structural level, the loss of beta-sheet was observed due to the variant proline, which has further led to the loss of surrounding interactions. This loss of beta-sheet and the surrounding interactions might serve the purpose of the structural stability changes. The current study demonstrates that a combination of whole-exome sequencing (WES) and computational analysis are potent tools for validation of diagnosis and classification of disease-causing variants.

Supervised practice program guided by the Accreditation Council for Education in Nutrition and Dietetics standards improves potential employability of nutrition/dietetics graduates: perspective of employers and preceptors.

BACKGROUND: This study investigated employers' perspectives on the impact of a supervised practice program (SPP), guided by international accreditation standards on the skill development and potential employability of dietetics students. MAIN BODY: This study was based on qualitative research. Fifteen potential employers, who also served as SPP preceptors, participated in this study. Participants were interviewed using semi-structured questionnaire. All interviews were conducted face-to-face by a trained interviewer. Participates were invited to discuss their own experiences in the current SPP, their perceptions of the impact of SPP on skills and attributes of graduates, and their overall ideas of how SPP may contribute to the employability of graduates. This study found that the SPP program guided by international accreditation standards shaped the duties and responsibilities of preceptors/supervisors and promoted a beneficial relationship between preceptors and SPP students. The benefits to graduates include bridging the gap between classroom didactic knowledge and practice; improving workplace self-confidence; developing competencies such as critical-thinking, communication, interviewing, and counselling skills in various multidisciplinary and multicultural settings. In addition, the preceptors suggested that accreditation-guided SPP contributes to the employability of graduates. Also, they opined that it reduced the need for orientation and shortened the probation time because students were familiar with the work environment and work flow. This lead to the improved preparedness for work. CONCLUSION: SPP based on set of competencies guided by international accreditation standards provides an up-to-date curriculum, improves the quality of the nutrition and dietetics services, and increases the potential employability of the graduates.

Spectrum of mutations of cystic fibrosis in the 22 Arab countries: A systematic review.

Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene, with various clinical manifestations that affect pulmonary, digestive, exocrine and male reproductive functions as well as the bones and kidneys. This study aimed to reveal the spectrum of CFTR gene mutations in Arab CF patients and their corresponding clinical phenotypes among the 22 Arab countries. We searched four literature databases (PubMed, Science Direct, Web of Science and Scopus) from their times of inception to January 2018. All possible search terms were used to encompass the different clinical phenotypes, disease incidences, CFTR mutations, ages and consanguinity rates of CF patients in the 22 Arab countries. Our search strategy identified 678 articles; of these, 72 were eligible for this systematic review. We retrieved data from 18 Arab countries; only 1766 Arab patients with CF were identified, even after additional searches using Google and Google Scholar. The search uncovered a wide spectrum of mutations, some of which are shared with other ethnic groups and some unique to Arab patients. Although the clinical phenotypes of Arab patients were typical of CF, several distinct phenotypes were reported. Despite the rarity of genetic epidemiological studies of CF patients among the 22 Arab nations, the disease is frequently reported in Arab countries where consanguineous marriage is common. Therefore, significant attention should be paid to this problem by implementing carrier and premarital screening, newborn screening and genetic counselling.

Anaphylaxis triggers in a large tertiary care hospital in Qatar: a retrospective study.

BACKGROUND: Anaphylaxis is a serious allergic disease that may lead to death if not immediately recognized and treated. Triggers of anaphylaxis including food, drugs, and insect stings can vary widely. The incidence of anaphylaxis seems to be affected by age, sex, atopy, and geographic location. This study aims to examine the common triggers of anaphylaxis in Qatar. METHODS: A total of 1068 electronic medical records were audited using power chart system: 446 from the medical coding system of anaphylaxis and 622 from the epinephrine auto-injectors (EAIs) dispensed during January 2012-December 2017. RESULTS: Of 1068 patients, 574 (53.5%) had anaphylaxis; male to female ratio was 1.2, and 300 patients (77.9%) were less than 10 years old. The common triggers were food (n = 316, 55.0%), insect stings (n = 161, 28.0%), and drugs (n = 103, 17.9%). Common anaphylaxis food triggers were nuts (n = 173, 30.1%), eggs (n = 89, 15.5%), and seafood (n = 72, 12.5%), and common anaphylaxis medication triggers were antibiotics (n = 49, 8.5%) and nonsteroidal anti-inflammatory drugs (n = 30, 5.2%). Interestingly, 135 anaphylactic patients (23.5%) were due to black ant stings. The anaphylaxis triggers varied significantly between children and adults. Among children (less than 10 years), three quarters of the events were triggered by food (223, 74.3%) while among adults (20-55 years), insect stings (n = 59, 43.0%) and drugs (n = 44, 32.0%) were dominant. DISCUSSION: This is the first national study stratifying anaphylaxis triggers among different age groups in Qatar. This study will serve as a guide for clinical practice in allergy clinics in Qatar and will help to assess future trends of anaphylaxis in Qatar.