Clinical presentation and angiographic findings of acute myocardial infarction in young adults in Jazan region.

BACKGROUND: There is a paucity of information about the clinical features and angiographic findings in young patients with acute myocardial infarction (MI), especially in the Arab Peninsula countries. OBJECTIVE: The aim of this study was to assess the proposed risk factors, clinical presentation, and angiographic findings of acute myocardial infarction in young adults. METHODS: This prospective study included young (range, 18 to 45 years) patients who presented with acute MI based on clinical evaluation, laboratory investigation, and electrocardiogram, and they underwent a coronary angiography procedure. KEY FINDINGS: Data of 109 patients with a diagnosis of acute MI were collected. Patients' mean age was 39.98 ± 7.52 years (range, 31 to 45 years), and 92.7% (101) were male. Smoking was the highest risk factor in 67% of patients, obesity and overweight in 66%, sedentary lifestyle in 64%, dyslipidaemia in 33%, and hypertension in 28%. Smoking was the most common risk factor for acute MI in males (p = 0.009), whereas sedentary lifestyle was the most common risk factor in females (p = 0.028). Chest pain typical of acute MI was the most common presenting symptom in 96% of patients (p < 0.001). On admission, 96% of patients were conscious, and 95% were oriented. On angiography, the left anterior descending artery (LAD) was affected in 57%, the right coronary artery (RCA) was affected in 42%, and the left circumflex artery (LCX) was affected in 32% of patients. The LAD was severely affected in 44%, the RCA was severely affected in 25.7%, and the LCX was severely affected in 19.26% of patients (p < 0.001). CONCLUSION: Smoking, obesity, sedentary lifestyle, dyslipidaemia, and hypertension were the most common risk factors for acute MI. Smoking was the most common risk factor in males and sedentary lifestyle in females. The LAD was the most commonly affected coronary artery, followed by the RCA and LCX arteries, with the same order for severity of stenosis.

LC-MS/MS and GC-MS based phytochemical perspectives and antimicrobial effects of endophytic fungus Chaetomium ovatoascomatis isolated from Euphorbia milii.

The antimicrobial activity of endophytic fungi isolated from Euphorbia milii was evaluated against Gram-positive, Gram-negative bacteria, unicellular yeast, and filamentous fungi. Chaetomium ovatoascomatis NRC was identified morphologically and genetically as the most active strain. The total ethyl acetate extract of C. ovatoascomatis NRC demonstrated significant antimicrobial activity against Gram-negative; Escherichia coli, Salmonella enteric, and fungi; Aspergillus niger with MIC of 62.5 ug/ml. Whereas n-hexane fraction demonstrated broader activity against Gram-positive; Bacillus subtilis, Lactobacillus cereus, Gram-negative; Escherichia coli and Salmonella enteric, fungi; Candida albicans and F. solani. LC-MS/MS analysis of ethyl acetate strain extract and GC-MS analysis of the n-hexane fraction were used to identify the metabolites of the strain extract. LC-MS/MS determined three major metabolites with potential antimicrobial activities including grevilline B, aflatoxin G2 and apigenin. GC-MS analysis of n-hexane fraction tentatively identified 30 compounds, where 9,12-octadecadienoic acid methyl ester was the major compound.

Incidentally discovered Kawasaki disease in an adult man.

Kawasaki disease (KD) is a systemic vasculitis of unknown cause which usually diagnosed in small children. However, KD can be present as coronary disease in adults even with no history of the disease in childhood. Here, we describe a case of KD in a 42-year-old male patient presented with severe retrosternal chest pain radiating to the left arm and provisionally diagnosed as acute coronary disease. Coronary artery ectasia and multiple aneurysms have been confirmed by coronary angiography that led to the diagnosis of KD. The patient was treated with Aspirin 81 mg orally once daily, Apixapan 5 mg orally twice daily, Rosuvastatin 40 mg orally once daily, Bisoprolol 5 mg orally once daily, and omeprazole 20 mg orally once daily. The patient was improved and discharged with anticoagulant drugs for life. Physicians should be aware that KD can be present as coronary disease in adults even with no history of the disease in childhood and has a limited treatment options due to unfavorable coronary anatomy.

Association between liver fibrosis and cognition in a nationally representative sample of older adults.

BACKGROUND AND PURPOSE: Liver fibrosis, a common yet often subclinical manifestation of chronic liver disease, may have an unrecognized role in cognitive impairment. We evaluated the association between a validated liver fibrosis index and cognitive measures among older adults. METHODS: We examined the association between liver fibrosis and cognitive performance among participants aged 60 years and older in the US National Health and Nutrition Examination Survey. Liver fibrosis was measured with the validated Fibrosis-4 (FIB-4) liver fibrosis score. The outcomes were performance on four standardized cognitive tests of immediate and delayed verbal learning, verbal fluency, and attention/concentration. We used linear regression to evaluate the association between FIB-4 score and performance on cognitive tests while adjusting for potential confounders. In sensitivity analyses, we examined this association in participants without known liver disease. RESULTS: Among 3217 adult participants, the mean age was 69 years, and 54% were women. Standard liver chemistries were largely in the normal range. However, 5.0% [95% confidence interval (CI) 4.0-6.0] had liver fibrosis based on a validated cut-off. In adjusted linear regression models, higher liver fibrosis scores were associated with worse immediate recall (ß -0.39; 95% CI -0.58, -0.21), language fluency (ß -0.46; 95% CI -0.72, -0.21), and attention/concentration (ß -1.34; 95% CI -2.25, -0.43), but not delayed recall (ß -0.10; 95% CI -0.20, 0.01). Results were similar when limiting the study population to participants without known clinical liver disease. CONCLUSION: Liver fibrosis, including subclinical liver fibrosis, may be an independent risk factor for cognitive impairment among older adults.

The Future of Neurocritical Care Research: Proceedings and Recommendations from the Fifth Neurocritical Care Research Network Conference.

The Fifth Neurocritical Care Research Network (NCRN) Conference held in Boca Raton, Florida, in September of 2018 was devoted to challenging the current status quo and examining the role of the Neurocritical Care Society (NCS) in driving the science and research of neurocritical care. The aim of this in-person meeting was to set the agenda for the NCS's Neurocritical Care Research Central, which is the overall research arm of the society. Prior to the meeting, all 103 participants received educational content (book and seminar) on the 'Blue Ocean Strategy®,' a concept from the business world which aims to identify undiscovered and uncontested market space, and to brainstorm innovative ideas and methods with which to address current challenges in neurocritical care research. Three five-member working groups met at least four times by teleconference prior to the in-person meeting to prepare answers to a set of questions using the Blue Ocean Strategy concept as a platform. At the Fifth NCRN Conference, these groups presented to a five-member jury and all attendees for open discussion. The jury then developed a set of recommendations for NCS to consider in order to move neurocritical care research forward. We have summarized the topics discussed at the conference and put forward recommendations for the future direction of the NCRN and neurocritical care research in general.

Homozygous nonsense mutation in SCHIP1/IQCJ-SCHIP1 causes a neurodevelopmental brain malformation syndrome.

We report a consanguineous Arab family with 3 affected siblings who display a disorder of global developmental delay, learning difficulties, facial dysmorphism, hearing impairments, and cataract. The clinical phenotype was associated with characteristic brain magnetic resonance imaging (MRI) features of axonal guidance defects involving anterior commissure agenesis as well as scattered areas of polymicrogyria-cobblestone complex. Whole genome sequencing revealed a novel nonsense mutation (159609921C>T) that segregated in the family consistent in an autosomal recessive pattern. This mutation located in the C-terminal region shared by the Schwanomin-Interacting Protein1 (SCHIP1) isoforms including the IQCJ-SCHIP1. The in vitro expression of SCHIP1 and IQCJ-SCHIP1 truncated mutant isoforms (NM_001197109.1; p.R209* and NM_001197114.1; p.R501*, respectively) were markedly reduced as compared to their full-length versions suggesting protein stability/folding impairment. The pathogenic nature of this mutation is supported by a previously reported mouse knockout of Schip1 isoforms, which phenocopied the human axon guidance abnormality. This is the first report of a SCHIP1/IQCJ-SCHIP1 point mutation in humans associated with a neurological-developmental phenotype.

Comparative Correlation Between Chemical Composition and Cytotoxic Potential of the Coral-Associated Fungus Aspergillus sp. 2C1-EGY Against Human Colon Cancer Cells.

Cancer is a leading cause of death in several countries. In the search for new anticancer drugs, marine organisms have played an important role in the discovery of lead compounds and the development of new pharmaceuticals for their wide diversity of chemical structures and biological activities. In the present study, the cytotoxicity on colorectal cancer cells HCT116 exerted by marine fungus Aspergillus sp. 2C1-EGY extracts associated with the soft coral Sinularia sp. was investigated; the sub-fractions Fr 2c and Fr 2d had significantly high cytotoxic activity (88 and 85%, respectively). Moreover, the major hexadecanoic, octadecanoic, and octadecenoic acids as well as their methyl esters were isolated. GC/MS analysis revealed the identification of 46 major and minor compounds, from which 19 saturated and unsaturated fatty acids and eight fatty acid esters were identified.

Non-truncating LIFR mutation: causal for prominent congenital pain insensitivity phenotype with progressive vertebral destruction?

We present a Qatari family with two children who displayed a characteristic phenotype of congenital marked pain insensitivity with hypohidrosis and progressive aseptic destruction of joints and vertebrae resembling that of hereditary sensory and autonomic neuropathies (HSANs). The patients, aged 10 and 14, remained of uncertain genetic diagnosis until whole genome sequencing was pursued. Genome sequencing identified a novel homozygous C65S mutation in the LIFR gene that is predicted to markedly destabilize and alter the structure of a particular domain and consequently to affect the functionality of the whole multi-domain LIFR protein. The C65S mutant LIFR showed altered glycosylation and an elevated expression level that might be attributed to a slow turnover of the mutant form. LIFR mutations have been reported in Stüve-Wiedemann syndrome (SWS), a severe autosomal recessive skeletal dysplasia often resulting in early death. Our patients share some clinical features of rare cases of SWS long-term survivors; however, they also phenocopy HSAN due to the marked pain insensitivity phenotype and progressive bone destruction. Screening for LIFR mutations might be warranted in genetically unresolved HSAN phenotypes.

Trypanosoma cruzi screening in Texas blood donors, 2008-2012.

Chagas disease is an important emerging disease in Texas that results in cardiomyopathy in about 30% of those infected with the parasite Trypanosoma cruzi. Between the years 2008 and 2012, about 1/6500 blood donors were T. cruzi antibody-confirmed positive. We found older persons and minority populations, particularly Hispanic, at highest risk for screening positive for T. cruzi antibodies during routine blood donation. Zip code analysis determined that T. cruzi is associated with poverty. Chagas disease has a significant disease burden and is a cause of substantial economic losses in Texas.

Impact of increasing sample volume from 4 ml to 8 ml on bacterial detection rates in apheresis platelets: a meta-analysis.

Some blood centres have increased sample volume of in-process cultures to improve detection of bacterial contamination when screening apheresis platelet units. We performed a meta-analysis to evaluate extant published North American data comparing apheresis platelet bacterial contamination rates from 4 ml and 8 ml sample volume. Pooled results indicate an 8 ml sample volume yields higher true-positive rates than 4 ml resulting in a significant increase in the detection rate and interdiction of contaminated units, which should contribute to reduced risk of adverse transfusion outcomes.

Indole Alkaloids from the Sea Anemone Heteractis aurora and Homarine from Octopus cyanea.

The two new indole alkaloids 2-amino-1,5-dihydro-5-(1H-indol-3-ylmethyl)-4H-imidazol-4-one (1), 2-amino-5-[(6-bromo-1H-indol-3-yl)methyl]-3,5-dihydro-3-methyl-4H-imidazol-4-one (2), and auramine (3) have been isolated from the sea anemone Heteractis aurora. Both indole alkaloids were synthesized for the confirmation of the structures. Homarine (4), along with uracil (5), hypoxanthine (6), and inosine (7) have been obtained from Octopus cyanea.

Flavone composition and antihypercholesterolemic and antihyperglycemic activities of Chrysanthemum coronarium L.

Five flavones were isolated from Chrysanthemum coronarium L., four of which were isolated for the first time from the genus Chrysanthemum. Two were the flavonoid aglycones 5,7-dihydroxy-3,6,4'-trimethoxyflavone (1) and scutellarin-6,7-dimethyl ether (2). A new flavonoid glycoside, apigenin-7-O-[2"(6'''-O-beta-D-acetylglucopyranosyl)]-6"-O-acetylglucopyranoside (3), along with two known ones, i. e. apigenin-7-O-(2"-O-beta-D-glucopyranosyl)-beta-D-glucopyranoside (4) and 6-methoxy quercetin-7-O-beta-D-glucopyranoside (5), were identified. Structures were elucidated by NMR and MS. The therapeutic value of petroleum ether, ethyl acetate, and methanol extracts, respectively, in rats suffering from hypercholesterolemia--as a consequence of high-fat diet-and hyperglycemia--as a consequence of hypercholesterolemia and low doses of streptozotocin--was investigated through determination of biochemical markers and histopathology. The ethyl acetate and methanol extracts showed remarkable results, followed by the petroleum ether extract.

Beetles do it differently: two stereodivergent cyclisation modes in iridoid-producing leaf-beetle larvae.

Larvae of the Chrysomelina species Phaedon cochleariae, Hydrothassa marginella, Phratora vulgatissima, Gastrophysa viridula, Gastrophysa atrocyanea, Gastrophysa cyanea and Gastrophysa polygoni produce the iridoid chrysomelidial (1) to defend themselves against predators. Feeding experiments with a deuterated precursor ([(2)H(5)]8-hydroxygeraniol 9) and in vitro isotope exchange experiments with defensive secretion in (2)H(2)O revealed differences in the cyclisation of the ultimate precursor 8-oxogeranial (8) to 1, between members of the genus Gastrophysa and all other species. In P. cochleariae, H. marginella and P. vulgatissima 1 is most likely produced by a Rauhut-Currier-type cyclisation via a "transoid dienamine", with loss of a single deuterium atom from C(4) of the precursor. In contrast, members of the genus Gastrophysa cyclise 8 via a "cisoid dienamine" intermediate, with exchange of all three deuterium atoms from the methyl group at C(3). To study whether the different cyclisation modes influence the stereochemistry of 1, the absolute configuration of 1 of the larvae was determined by GC-MS on a chiral column. In accordance with literature (J. Meinwald, T. H. Jones, J. Am. Chem. Soc. 1978, 100, 1883 and N. Shimizu, R. Yakumaru, T. Sakata, S. Shimano, Y. Kuwahara, J. Chem. Ecol. 2012, 38, 29), we found (5S,8S)-chrysomelidial (1) in H. marginella and P. vulgatissima, but P. cochleariae and all investigated members of the genus Gastrophysa synthesise (5R,8R)-chrysomelidial (1).

Defining a positive circumferential resection margin in oesophageal cancer and its implications for adjuvant treatment.

BACKGROUND: A positive circumferential resection margin (CRM) has been associated with a poorer prognosis in oesophageal and oesophagogastric junctional (OGJ) cancer. The College of American Pathologists defines the CRM as positive if tumour cells are present at the margin, whereas the Royal College of Pathologists also include tumour cells within 1 mm of this margin. The relevance of these differences is not clear and no study has investigated the impact of adjuvant therapy. The aim was to identify the optimal definition of an involved CRM in patients undergoing resection for oesophageal or OGJ cancer, and to determine whether adjuvant radiotherapy improved survival in patients with an involved CRM. METHODS: This was a single-centre retrospective study of patients who had undergone attempted curative resection for a pathological T3 oesophageal or OGJ cancer. Clinicopathological variables and distance from the tumour to the CRM, measured to ± 0.1 mm, were correlated with survival. RESULTS: A total of 226 patients were included. Sex (P = 0·018), tumour differentiation (P = 0·019), lymph node status (P < 0·001), number of positive nodes (P < 0·001), and CRM distance (P = 0·042) were independently predictive of prognosis. No significant survival difference was observed between positive CRM 0-mm and 0·1-0·9-mm groups after controlling for other prognostic variables. Both groups had poorer survival than matched patients with a CRM at least 1 mm clear of tumour cells. Among patients with a positive CRM of less than 1 mm, those undergoing observation alone had a median survival of 18·6 months, whereas survival was a median of 10 months longer in patients undergoing adjuvant radiotherapy, but otherwise matched for prognostic variables (P = 0·009). CONCLUSION: A positive CRM of 1 mm or less should be regarded as involved. Adjuvant radiotherapy confers a significant survival benefit in selected patients with an involved CRM.

Study of the gut microbiome in Egyptian patients with type 1 diabetes mellitus.

Introduction: Type 1 diabetes mellitus (T1DM) is an autoimmune disease. The gut microbiota has been proposed as a key actor in the pathogenesis of T1DM. Aim: To identify the gut microbiome that are likely to be related to T1DM. This may have an impact on the future understanding of the pathogenesis of T1DM and possible approaches to prevent and treat it. Material and methods: The study included 40 T1DM patients and a cross-matching control group of 20 healthy subjects of matched age and sex; stool specimens were taken from each group. Quantitative SYBR Green Real-Time PCR technique targeting 16S rRNA was done for the identification and quantitation of Bacteroides, Prevotella, Ruminococcus, Lactobacillus johnsonii, Lactobacillus reuteri, and Veillonella. Results: T1DM patients showed significantly higher Bacteroides (p < 0.001) and Lactobacillus johnsonii (p = 0.003), but lower Veillonella (p = 0.013) than the control group. However, there was no statistical difference between T1DM and control cases as regards Prevotella (p = 0.204), Ruminococcus (p = 0.598), Lactobacilli (p = 0.901), and Lactobacillus reuteri (p = 0.332). Conclusions: Egyptian patients showed dysbiosis of the gut microbiome that can be related to the pathogenesis of T1DM. This hopefully points to the potential therapeutic benefits of manipulating the composition of the gut microbiome in the management of, or even protection from, T1DM.

In vitro acetylcholinesterase, tyrosinase inhibitory potentials of secondary metabolites from Euphorbia schimperiana and Euphorbia balsamifera.

Acetylcholinesterase, tyrosinase, and α-glucosidase inhibition activities of Euphorbia schimperiana and Euphorbia balsamifera extracts, fractions, and available pure compounds were evaluated for the first time. Acetylcholinesterase assay revealed a significant inhibitory activity of E. balsamifera total extract and n-hexane fraction with 47.7% and 43.3%, respectively, compared to the reference drug, which was 75%. The n-butanol fraction demonstrated tyrosinase inhibitory activity for E. balsamifera and E. schimperiana with 36.7% and 29.7%, respectively, compared to 60% for the reference drug. Quercetin-3-O-α-glucuronide, quercetin-3-O-ß-D-glucuronide-methyl ester, quercetin-3-O-α-L-rhamnoside, 3,3'-di-O-methyl ellagic acid, 3,3'-di-O-methyl-ellagic acid-4-ß-D-xylopyranoside, and 4-O-ethyl gallic acid were identified from E. schimperiana while quercetin-3-O-glucopyranoside and isoorientin were determined from E. balsamifera. The AChE inhibitory effect of pure compounds exhibited promising activity, where 4-O-ethylgallic acid demonstrated 51.1%, while the highest tyrosinase inhibition was demonstrated by isoorientin with 50.6% compared to the reference drug (60%). Finally, a molecular docking study was performed for the most promising AChE and tyrosinase inhibitors. The extracts, fractions, and isolated compounds showed no α-glucosidase inhibitory activity.

ACE2 and TMPRSS2 SNPs as Determinants of Susceptibility to, and Severity of, a COVID-19 Infection.

Background: Genetic risk factors may be related to the infectivity and severity of SARS-CoV-2 infection. Angiotensin-converting enzyme 2 (ACE2) and host transmembrane serine protease (TMPRSS2) have key role in viral cell entrance and priming. Methods: This case-control study on 147 healthy controls and 299 COVID-19 patients identified potential determinants and risk factors, including gene polymorphism involved in the severity (mild, moderate, severe) of COVID-19 disease defined by CORAD radiological criteria. Results: The ACE2 s2285666 and TMPRSS2 rs12329760 SNPs were significantly linked with COVID-19 disease severity, as were certain co-morbidities (hypertension, heart disease) and laboratory parameters. Both SNPs were amongst the highest predictors of disease severity: TMPRSS2 rs12329760 CT + TT [odds ratio (95% CI) 17.6 (5.1-61.10), ACE2 rs2285666 CT + TT 9.9 (3.2-30.9), both p < 0.001]. There was an increase in the expression of genotype frequencies of ACE2 rs2285666 and TMPRSS2 rs1232976 (TT), (CT + TT), and (T) allele in severe COVID-19 group compared to control and mild groups. Disease severity was also linked to elevated CRP, ferritin and D-dimer, and lower lymphocytes and platelet count (all p < 0.001). Conclusion: ACE2 rs2285666 and TMPRSS2 rs12329760 SNPs, in addition to lymphocyte count, CRP, D-dimers, ferritin, and hypertension, are predictors of COVID-19 disease severity.

Factors associated with fainting: before, during and after whole blood donation.

BACKGROUND Whole blood (WB) donation encompasses several periods during which some donors faint. Identification of factors associated with fainting during each period should guide intervention strategies. Reducing faint reactions may reduce donor injuries and disability. METHODS Blood donation was divided into three periods: Period 1 - registration; Period 2 - phlebotomy; and Period 3 - post-phlebotomy. Period 3 consists of two sub-periods (3A - on-site and 3B - off-site). For each Period, stratified rates of fainting in relation to various donor and donation characteristics were calculated and multivariable logistic regression analyses to identify factors associated with fainting were conducted. Donor injuries in each period were also analysed. RESULTS Of the 956 766 donors registered in 2007, 554 534 (58%) donated WB. There were 43 fainting episodes and two injuries in Period 1 and 1520 faints and 73 injuries in Periods 2 and 3. Regression analyses showed that youth and donor first-time status are associated with fainting in all periods; but most significantly in Period 1. Small estimated blood volume is notably not a factor in Period 1 but is significant in Periods 2 and 3. The highest injury rate is seen in Period 3A (0·07 and 0·09/1000 donations) for male and female donors, respectively. CONCLUSIONS Variability in factors associated with fainting across defined periods of the donation process suggest differing underlying mechanisms and the possibility that interventions for the reactions most associated with injury during each time period can be designed. The highest rate of injury per donation occurred in ambulating donors.

Isolation of diverse bioactive compounds from Euphorbia balsamifera: Cytotoxicity and antibacterial activity studies.

Antibacterial and cytotoxic activities of Euphorbia balsamifera, fractions and pure compounds were evaluated. The cytotoxic assays for HCT116, HePG2 and MCF7 showed a significant IC50: 54.7 and 76.2 µg/mL of non-polar fraction "n-hexane" against HCT116 and HePG2, respectively. Antibacterial results revealed that plant fractions exhibited significant potential against the tested pathogens than the total extract where n-butanol and ethyl acetate fractions showed significant antibacterial activity (P < 0.05) against tested bacterial strains. Isolation and structure determination of compounds from n-hexane and n-butanol fractions were performed. From n-hexane fraction, 29-nor-cycloartanol (1), lanost-8-en-3-ol (2a), cycloartanol (2b) and kampferol-3,4'-dimethyl ether (3) were isolated and structurally identified, along with 24 compounds were tentatively identified by GC-MS. From the polar n-butanol fraction, 4-O-ß-D-glucopyranosyl-2-hydroxy-6-methoxyacetophenone (4), 4-O-α-L-rhamnosyl-(1 â†’ 6)-ß-D-glucopyranosyl-2-hydroxy-6methoxy-acetophenone (5), quercetin-3-O-glucopyranoside (6) and isoorientin (7) were assigned. Structures of the obtained compounds were determined by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. Except compounds 1 and 5, all reported compounds announced antibacterial efficiency. Compound 2 showed selectively the highest activity against Enterococcus faecalis (22 ± 0.13 mm), meanwhile 4-O-ß-D-glucopyranosyl-2-hydroxy-6-methoxyacetophenone (4) showed broadly the highest antibacterial activity with MIC of 1.15-1.88 mg/mL against the test Gram-positive and Gram-negative bacteria. Cytotoxic assays indicated that kampferol-3,4'-dimethyl ether (3) exhibited the highest activity with matching IC50 values to doxorubicin; 111.46, 42.67 and 44.90 µM against HCT116, HePG2 and MCF7, respectively, however, it is toxic on retina normal cell line RPE1.