Elements of the rat tropoelastin gene associated with alternative splicing

Multiple isoforms of tropoelastin, the soluble precursor of elastin, are the products of translation of splice-variant mRNAs derived from the single-copy tropoelastin gene. Previous data had demonstrated DNA sequence heterogeneity in three domains of rat tropoelastin mRNA, indicating alternative splicing of several exons of the rat tropoelastin gene. Rat tropoelastin genomic clones encompassing the sites of alternative splicing were isolated and sequenced. Two sites of alternative splicing identified in rat tropoelastin mRNA sequences corresponded to exons 13-15 and exon 33 of the rat tropoelastin gene. Furthermore, the variable inclusion of an alanine codon in exon 16 resulted from two functional acceptor sites separated by three nucleotides. DNA sequences flanking exons subject to alternative splicing were analyzed. These exons contained splicing signals that differed from consensus sequences and from splicing signals of constitutively spliced exons. Introns immediately 5' of exons 14 and 33, for example, lacked typical polypyrimidine tracts and had weak, overlapping branch point sequences. Further, a region of secondary structure encompassing the acceptor site of exon 13 may influence alternative splicing of this exon. These results demonstrate that multiple cis-acting sequence elements may contribute to alternative splicing of rat tropoelastin pre-mRNA.     

Development of unit cost for the health services offered at King FAHD Central hospital Jazan,Saudi Arabia

BackgroundEfficiency remains one of the most important drivers of decision making in health care system. Fund allocators need to receive structured information about the cost healthcare services from hospitals for better decisions related to resource allocation and budgeting. The objective of the study was to estimate the unit cost for health services offered to inpatients in King Fahd Central hospital (KFCH) Jazan during the financial year 2018.MethodsWe applied a retrospective approach using a top-down costing method to estimate the cost of health care services. Clinical and Administrative departments divided into cost centres, and the unit cost was calculated by dividing the total cost of final care cost centres into the total number of patients discharged in one year. The average cost of inpatient services was calculated based on the average cost of each ward and the number of patients treated.ResultsThe average cost per patient stayed in KFCH was SAR 19,034, with the highest cost of SAR 108,561 for patients in the Orthopedic ward. The average cost of the patient in the Surgery ward, Plastic surgery, Neurosurgery, Medical ward, Pediatric ward and Gynecology ward was SAR 33,033, SAR 29,425, SAR 23,444, SAR 20,450, SAR 9579 and SAR 8636 respectively.ConclusionThis study provides necessary information about the cost of health care services in a tertiary care setting. This information can be used as a primary tool and reference for further studies in other regions of the country. Hence, this data can help to provide a better understanding of tertiary hospital costing in the region to achieve the privatization objective.     

Synthesis,antitumor and antimicrobial activity of some new 6-methyl-3-phenyl-4(3H)-quinazolinone analogues: in silico studies

Some new derivatives of substituted-4(3H)-quinazolinones were synthesized and evaluated for their in vitro antitumor and antimicrobial activities. The results of this study demonstrated that compound 5 yielded selective activities toward NSC Lung Cancer EKVX cell line, Colon Cancer HCT-15 cell line and Breast Cancer MDA-MB-231/ATCC cell line, while NSC Lung Cancer EKVX cell line and CNS Cancer SF-295 cell line were sensitive to compound 8. Additionally, compounds 12 and 13 showed moderate effectiveness toward numerous cell lines belonging to different tumor subpanels. On the other hand, the results of antimicrobial screening revealed that compounds 1, 9 and 14 are the most active against Staphylococcus aureus ATCC 29213 with minimum inhibitory concentration (MIC) of 16, 32 and 32?μg/mL respectively, while compound 14 possessed antimicrobial activities against all tested strains with the lowest MIC compared with other tested compounds. In silico study, ADME-Tox prediction and molecular docking methodology were used to study the antitumor activity and to identify the structural features required for antitumor activity.     

Combined Medical and Surgical Management of Hepatic Mucormycosis in an Adult with Acute Myeloid Leukemia: Case Report and Review of the Literature

Mycopathologia - Hepatic mucormycosis is a disease caused by a ubiquitous fungus which is especially important in patients with hematologic malignancies. We present a case of an adult patient with...     

Discovery of new VEGFR-2 inhibitors based on bis([1, 2, 4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives as anticancer agents and apoptosis inducers

Herein, a new wave of bis([1, 2, 4]triazolo)[4,3-a:3'',4''-c]quinoxaline derivatives have been successfully designed and synthesised. The synthesised derivatives were biologically investigated for their cytotoxic activities against HepG2 and MCF-7. Also, the tested compounds were further examined in vitro for their VEGFR-2 inhibitory activity. The most promising derivative 23j was further investigated for its apoptotic behaviour in HepG2 cell lines using flow cytometric and western-plot analyses. Additional in-silico studies were performed to predict how the synthesised compounds can bind to VEGFR-2 and to determine the drug-likeness profiling of these derivatives. The results revealed that compounds 23a, 23i, 23j, 23l, and 23n displayed the highest antiproliferative activities against the two cell lines with IC₅₀ values ranging from 6.4 to 19.4 µM. Furthermore, compounds 23a, 23d, 23h, 23i, 23j, 23l, 23 m, and 23n showed the highest VEGFR-2 inhibitory activities with IC₅₀ values ranging from 3.7 to 11.8 nM, comparing to sorafenib (IC₅₀ = 3.12 nM). Moreover, compound 23j arrested the HepG2 cell growth at the G2/M phase and induced apoptosis by 40.12% compared to the control cells (7.07%). As well, such compound showed a significant increase in the level of caspase-3 (1.36-fold), caspase-9 (2.80-fold), and BAX (1.65-fold), and exhibited a significant decrease in Bcl-2 level (2.63-fold).     

Dietary intake of artificial food color additives containing food products by school-going children

Nutritional risk in children is associated with food safety. This is the first study to identify the food type consumed by 6–17-year-old school-going children in Saudi Arabia. Eight permitted artificial food color additives, including Tartrazine (E102), Sunset Yellow (E110), Carmoisine (E122), Allura Red (E129), Indigo Carmine (E132), Brilliant Blue (E133), Fast Green (E143), and Black PN (E151), and two non-permitted ones, Erythrosine (E127) and Red 2G (E128), were determined using 24-h dietary recall questionnaires. Artificial color additives in 839 food products were divided into nine categories, including biscuits, cakes, chocolates, chips, ice cream, juices and drinks, candy, jelly, and chewing gum, are determined using high performance liquid chromatography and diode array detector. The results indicated a high intake of juices and drinks, ice cream, and cakes, but low consumption of chewing gum among school-going children. Among the permitted artificial food color additives, Brilliant Blue (E133) (54.1%) and Tartrazine (E102) (42.3%) were the most commonly used. Sunset Yellow (E110) in one chocolate sample, Tartrazine (E102) and Sunset Yellow (E110) in one and two juice and drink samples, respectively, and Brilliant Blue (E133) in two candy samples exceeded the permitted level. Therefore, further investigations are needed to provide insights into the possible adverse health effects of high intake of these additives in artificial food coloring on the test population are warranted.     

Associations of Spexin and cardiometabolic parameters among women with and without gestational diabetes mellitus

Spexin (SPX) is a novel biomarker abundantly expressed in several animal and human tissues implicated in food intake and glucose control, respectively. As new roles for SPX are emerging, the present study explored for the first time, the associations of SPX to several cardiometabolic indices and inflammatory markers in pregnant women, a demographic not yet investigated with respect to SPX. A total of 117 Saudi women subdivided to those with gestational diabetes mellitus (GDM) (N?=?63) and those without (N?=?54) were included in this cross-sectional study. Anthropometry, glycemic, lipid, vitamin D, adipocytokines and inflammatory markers were measured consecutively at baseline and after the 2nd and 3rd trimesters. Age- and BMI adjusted comparisons revealed that levels of SPX were not significantly different in pregnant women with and without GDM. In all subjects, circulating levels of SPX showed modest associations with glucose (R?=?0.18; p?=?.08) and HOMA β (R?=??0.19; p?=?.09) as well as significant positive associations with total cholesterol (R?=?0.25; p?=?.02), LDL-cholesterol (R?=?0.25; p?=?.02), 25(OH)D (R?=?0.22; p?=?.04), albumin (R?=?0.30; p?<?.01) and IL1β (R?=?0.41; p?<?.01). Stepwise regression analysis also suggested that IL1β, leptin and albumin were the significant predictors of SPX. In summary, SPX levels modestly affect glucose and insulin sensitivity in pregnant women but is not associated with GDM and obesity. The significant association of SPX to ILβ warrants further investigation as to the role of SPX in immune modulation.     

The role of infectious agents in sudden infant death syndrome

Abstract Epidemiological factors associated with susceptibility to respiratory infections are similar to those associated with Sudden Infant Death Syndrome. Here we review the evidence that respiratory pathogens might be involved in some cases of Sudden Infact Death Syndrome in the context of factors identified in epidemiological studies of cot deaths: the age range affected; mother's smoking; respiratory viral infections; immunisation status. Both laboratory and epidimiological evidence suggests that vulnerability of infants to infectious agents depends on interactions between genetic, developmental and environmental factors that contribute to colonisation by microorganisms, the inflammatory and specific immune responses and the infants' physiological responses to inflammatory mediators. A model is proposed to explain how microorganisms might trigger a series of events resulting in some of these unexpected deaths and discusses how the present recommendations regarding child care practices might help reduce the numbers of Sudden Infant Death Syndrome cases associated with infectious agents.