Risk of central line-associated bloodstream infections during COVID-19 pandemic in intensive care patients in a tertiary care centre in Saudi Arabia.

This retrospective study compared central line-associated bloodstream infection (CLABSI) rates per 1 000 central line days, and overall mortality before and during the COVID-19 pandemic in adult, paediatric, and neonatal ICU patients at King Abdul-Aziz Medical City-Riyadh who had a central line and were diagnosed with CLABSI according to the National Healthcare Safety Network standard definition. The study spanned between January 2018 and December 2019 (pre-pandemic), and January 2020 and December 2021 (pandemic). SARS-CoV-2 was confirmed by positive RT-PCR testing. The study included 156 CLABSI events and 46 406 central line days; 52 and 22 447 (respectively) in pre-pandemic, and 104 and 23 959 (respectively) during the pandemic. CLABSI rates increased by 2.02 per 1 000 central line days during the pandemic period (from 2.32 to 4.34, p < 0.001). Likewise, overall mortality rates increased by 0.86 per 1 000 patient days (from 0.93 to 1.79, p = 0.003). Both CLABSI rates (6.18 vs. 3.7, p = 0.006) and overall mortality (2.72 vs. 1.47, p = 0.014) were higher among COVID-19 patients compared to non-COVID-19 patients. The pandemic was associated with a substantial increase in CLABSI-associated morbidity and mortality.

Competency level and determinants among infection prevention and control staff in the Middle East and North Africa region.

BACKGROUND: Competency of the staff working in infection prevention and control (IPC) is the cornerstone of successful IPC programs. The objective was to assess competency level and associated factors among IPC staff working in the Middle East and North Africa (MENA) region. METHODS: A cross-sectional study was carried out in 2019 among active IPC staff who were members of the Arab Countries Infection Control Network. The questionnaire covered demographic and professional characteristics of IPC staff and characteristics of work facilities and IPC programs. A competency score was created from self-perceived responses to 8 competency domains. The competency score was then transformed into 100-scale and categorized into two groups (≥ median and < median). RESULTS: A total of 176 participants completed the survey. Participants were mostly female (65.7%), and the mean age was 40.2 ± 8.3 years. The mean competency score was 61.4%. It was slightly variable between domains, being highest with preventing transmission of infection (65%) and lowest with sterilization and disinfection (59%). Higher (≥ median) competency score was associated with having CBIC certification (p < 0.001). It was also associated with facilities having IPC plan (p = 0.005), IPC committee (p = 0.049), regular meetings of IPC committee (p < 0.001), and IPC plan included communications with healthcare workers (p < 0.001). Domain-specific competency scores were significantly associated with receiving same domain-specific training (p < 0.05 for all). CONCLUSIONS: The competency levels of IPC staff in the MENA region is still suboptimal. The current finding calls for more regional and national investment in IPC staff by providing up-to-date customized educational and training opportunities.

Isotope Labeling and Biochemical Assessment of Liver-Triacylglycerol in Patients with Different Levels of Histologically-Graded Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) prevalence is rapidly growing, and fatty liver has been found in a quarter of the US population. Increased liver lipids, particularly those derived from the pathway of de novo lipogenesis (DNL), have been identified as a hallmark feature in individuals with high liver fat. This has led to much activity in basic science and drug development in this area. No studies to date have investigated the contribution of DNL across a spectrum of disease, although it is clear that inhibition of DNL has been shown to reduce liver fat. OBJECTIVES: The purpose of this study was to determine whether liver lipid synthesis increases across the continuum of liver injury. METHODS: Individuals (n = 49) consumed deuterated water for 10 d before their scheduled bariatric surgeries to label DNL; blood and liver tissue samples were obtained on the day of the surgery. Liver lipid concentrations were quantitated, and levels of protein and gene expression assessed. RESULTS: Increased liver DNL, measured isotopically, was significantly associated with liver fatty acid synthase protein content (R = 0.470, P = 0.003), total steatosis assessed by histology (R = 0.526, P = 0.0008), and the fraction of DNL fatty acids in plasma very low-density lipoprotein-triacylglycerol (R = 0.747, P < 0.001). Regression analysis revealed a parabolic relationship between fractional liver DNL (percent) and NAFLD activity score (R = 0.538, P = 0.0004). CONCLUSION: These data demonstrate that higher DNL is associated with early to mid stages of liver disease, and this pathway may be an effective target for the treatment of NAFLD and nonalcoholic steatohepatitis. This study was registered at clinicaltrials.gov as NCT03683589.

Symptomatic MERS-CoV infection reduces the risk of future COVID-19 disease; a retrospective cohort study.

BACKGROUND: The general human immune responses similarity against different coronaviruses may reflect some degree of cross-immunity, whereby exposure to one coronavirus may confer partial immunity to another. The aim was to determine whether previous MERS-CoV infection was associated with a lower risk of subsequent COVID-19 disease and its related outcomes. METHODS: We conducted a retrospective cohort study among all patients screened for MERS-CoV at a tertiary care hospital in Saudi Arabia between 2012 and early 2020. Both MERS-CoV positive and negative patients were followed up from early 2020 to September 2021 for developing COVID-19 infection confirmed by RT-PCR testing. RESULTS: A total of 397 participants followed for an average 15 months during COVID-19 pandemic (4.9 years from MERS-CoV infection). Of the 397 participants, 93 (23.4%) were positive for MERS-CoV at baseline; 61 (65.6%) of the positive cases were symptomatic. Out of 397, 48 (12.1%) participants developed COVID-19 by the end of the follow-up period. Cox regression analysis adjusted for age, gender, and major comorbidity showed a marginally significant lower risk of COVID-19 disease (hazard ratio = 0.533, p = 0.085) and hospital admission (hazard ratio = 0.411, p = 0.061) in patients with positive MERS-CoV. Additionally, the risk of COVID-19 disease was further reduced and became significant in patients with symptomatic MERS-CoV infection (hazard ratio = 0.324, p = 0.034) and hospital admission (hazard ratio = 0.317, p = 0.042). CONCLUSIONS: The current findings may indicate a partial cross-immunity, where patients with symptomatic MERS-CoV have a lower risk of future COVID-19 infection and related hospitalization. The present results may need further examination nationally using immunity markers.

Lymphatics - not just a chylomicron conduit.

PURPOSE OF REVIEW: Lymphatics are known to have active, regulated pumping by smooth muscle cells that enhance lymph flow, but whether active regulation of lymphatic pumping contributes significantly to the rate of appearance of chylomicrons (CMs) in the blood circulation (i.e., CM production rate) is not currently known. In this review, we highlight some of the potential mechanisms by which lymphatics may regulate CM production. RECENT FINDINGS: Recent data from our lab and others are beginning to provide clues that suggest a more active role of lymphatics in regulating CM appearance in the circulation through various mechanisms. Potential contributors include apolipoproteins, glucose, glucagon-like peptide-2, and vascular endothelial growth factor-C, but there are likely to be many more. SUMMARY: The digested products of dietary fats absorbed by the small intestine are re-esterified and packaged by enterocytes into large, triglyceride-rich CM particles or stored temporarily in intracellular cytoplasmic lipid droplets. Secreted CMs traverse the lamina propria and are transported via lymphatics and then the blood circulation to liver and extrahepatic tissues, where they are stored or metabolized as a rich energy source. Although indirect data suggest a relationship between lymphatic pumping and CM production, this concept requires more experimental evidence before we can be sure that lymphatic pumping contributes significantly to the rate of CM appearance in the blood circulation.

Lactation alters the relationship between liver lipid synthesis and hepatic fat stores in the postpartum period.

In mothers who are nursing their infants, increased clearance of plasma metabolites into the mammary gland may reduce ectopic lipid in the liver. No study to date has investigated the role of lactation on liver lipid synthesis in humans, and we hypothesized that lactation would modify fatty acid and glucose handling to support liver metabolism in a manner synchronized with the demands of milk production. Lactating (n = 18) and formula-feeding women (n = 10) underwent metabolic testing at 6-week postpartum to determine whether lactation modified intrahepatic triacylglycerols (IHTGs), measured by proton magnetic resonance spectroscopy. Subjects ingested oral deuterated water to measure fractional de novo lipogenesis (DNL) in VLDL-TG during fasting and during an isotope-labeled clamp at an insulin infusion rate of 10 mU/m2/min. Compared with formula-feeding women, we found that lactating women exhibited lower plasma VLDL-TG concentrations, similar IHTG content and similar contribution of DNL to total VLDL-TG production. These findings suggest that lactation lowers plasma VLDL-TG concentrations for reasons that are unrelated to IHTG and DNL. Surprisingly, we determined that the rate of appearance of nonesterified fatty acids was not related to IHTG in either group, and the expected positive association between DNL and IHTG was only significant in formula-feeding women. Further, in lactating women only, the higher the prolactin concentration, the lower the IHTG, while greater DNL strongly associated with elevations in VLDL-TG. In conclusion, we suggest that future studies should investigate the role of lactation and prolactin in liver lipid secretion and metabolism.

Layered double hydroxides as heterogeneous catalyst systems in the cross-coupling reactions: an overview.

Layered double hydroxides (LDHs) are recognized as two-dimensional (2D) clay materials, which comprise the interlayer anions and host layers with a positive charge (brucite-like M(OH)6 octahedral). They have been used as effective and eco-friendly heterogeneous catalytic systems in cross-coupling reactions. In this review, we try to underscore the applications of (LDHs) as an efficient and green catalyst in some important name reactions, namely Suzuki, Heck, Sonogashira, and Ullmann cross-coupling reactions leading to carbon-carbon bond formations.

Fatty Acid Synthase Inhibitor TVB-2640 Reduces Hepatic de Novo Lipogenesis in Males With Metabolic Abnormalities.

BACKGROUND AND AIMS: Elevated hepatic de novo lipogenesis (DNL) is a key distinguishing characteristic of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis. In rodent models of NAFLD, treatment with a surrogate of TVB-2640, a pharmacological fatty acid synthase inhibitor, has been shown to reduce hepatic fat and other biomarkers of DNL. The purpose of this phase I clinical study was to test the effect of the TVB-2640 in obese men with certain metabolic abnormalities that put them at risk for NAFLD. APPROACH AND RESULTS: Twelve subjects (mean ± SEM, 42 ± 2 years, body mass index 37.4 ± 1.2 kg/m2 , glucose 103 ± 2 mg/dL, triacylglycerols 196 ± 27 mg/dL, and elevated liver enzymes) underwent 10 days of treatment with TVB-2640 at doses ranging from 50-150 mg/day. Food intake was controlled throughout the study. Hepatic DNL was measured before and after an oral fructose/glucose bolus using isotopic labeling with 1-13 C1 -acetate intravenous infusion, followed by measurement of labeled very low-density lipoprotein palmitate via gas chromatography mass spectometry. Substrate oxidation was measured by indirect calorimetry. Across the range of doses, fasting DNL was reduced by up to 90% (P = 0.003). Increasing plasma concentrations of TVB-2640 were associated with progressive reductions in the percent of fructose-stimulated peak fractional DNL (R2  = -0.749, P = 0.0003) and absolute DNL area under the curve 6 hours following fructose/glucose bolus (R2  = -0.554, P = 0.005). For all subjects combined, alanine aminotransferase was reduced by 15.8 ± 8.4% (P = 0.05). Substrate oxidation was unchanged, and safety monitoring revealed that the drug was well tolerated, without an increase in plasma triglycerides. Alopecia occurred in 2 subjects (reversed after stopping the drug), but otherwise no changes were observed in fasting glucose, insulin, ketones, and renal function. CONCLUSION: These data support the therapeutic potential of a fatty acid synthase inhibitor, TVB-2640 in particular, in patients with NAFLD and nonalcoholic steatohepatitis.

Applications of Transition-Metal-Catalyzed Asymmetric Allylic Substitution in Total Synthesis of Natural Products: An Update.

Metal-catalyzed asymmetric allylic substitution (AAS) reaction is one of the most synthetically useful reactions catalyzed by metal complexes for the formation of carbon-carbon and carbon-heteroatom bonds. It comprises the substitution of allylic substrates with a wide range of nucleophiles or SN 2'-type allylic substitution, which results in the formation of the above-mentioned bonds with high levels of enantioselective induction. AAS reaction tolerates a broad range of functional groups, thus has been successfully applied in the asymmetric synthesis of a wide range of optically pure compounds. This reaction has been extensively used in the total synthesis of several complex molecules, especially natural products. In this review, we try to highlight the applications of metal (Pd, Ir, Mo, or Cu)-catalyzed AAS reaction in the total synthesis of the biologically active natural products, as a key step, updating the subject from 2003 till date.

Recent Advances on Heteroatom-Doped Porous Carbon/Metal Materials: Fascinating Heterogeneous Catalysts for Organic Transformations.

Design and preparation of low-cost, effective, and novel catalysts are important topics in the field of heterogeneous catalysis from academic and industrial perspectives. Recently, heteroatom-doped porous carbon/metal materials have received significant attention as promising catalysts in divergent organic reactions. Incorporation of heteroatom into the carbon framework can tailor the properties of carbon, providing suitable interaction between support and metal, resulting in superior catalytic performance compared with those of traditional pure carbon/metal catalytic systems. In this review, we try to underscore the recent advances in the design, preparation, and application of heteroatom-doped porous carbon/metal catalysts towards various organic transformations.

Electrochemically Induced Diels-Alder Reaction: An Overview.

One of the most important name reactions in organic chemistry, is the Diels-Alder cycloaddition reaction. It is a chemical reaction between a conjugated diene and a substituted alkene, commonly termed the dienophile to construct a substituted cyclohexene derivative. It is the stereotypical example of a pericyclic reaction with a concerted mechanism. In synthesis, the use of electricity instead of stoichiometric amounts of oxidant or reducing agents is definitely appealing for economic, ecological and selective, reasons. In this review, we try to underscore the combination of the electrosynthesis with Diels-Alder cycloaddition reaction to establish of a powerful synthetic tool which may encourage synthetic organic chemists to use it in the future.

High contribution and impact of resistant gram negative pathogens causing surgical site infections at a multi-hospital healthcare system in Saudi Arabia, 2007-2016.

BACKGROUND: Despite being largely preventable, surgical site infections (SSIs) are still one of the most frequent healthcare-associated infections. The presence of resistant pathogens can further augment their clinical and economic impacts. The objective was to estimate the distribution and resistance in SSI pathogens in Saudi Arabia and to compare them to the US National Healthcare Safety Network (NHSN) hospitals. METHODS: Targeted SSI surveillance was prospectively conducted on several surgical procedures done between 2007 and 2016 in four hospitals of Ministry of National Guard Health Affairs. Definitions and methodology of SSI and bacterial resistance were based on NHSN. RESULTS: A total 492 pathogens causing 403 SSI events were included. The most frequent pathogens were Staphylococcus aureus (22.8%), Pseudomonas aeruginosa (20.1%), Klebsiella spp. (12.2%), and Escherichia coli (12.2%), with marked variability between surgeries. Approximately 30.3% of Staphylococcus aureus was methicillin-resistant (MRSA), 13.0% of Enterococcus spp. was vancomycin-resistant (VRE), and 5.5% of Enterobacteriaceae were carbapenem resistant (CRE). The highest multidrug-resistant (MDR) GNPs were Acinetobacter spp. (58.3%), Klebsiella spp. (20.4%) and Escherichia coli (16.3%). MRSA was significantly less frequent while cephalosporin-resistant Klebsiella spp., MDR Klebsiella spp., and MDR Escherichia coli were significantly more frequent in our hospitals compared with NHSN hospitals. CONCLUSION: GNPs in a tertiary care setting in Saudi Arabia are responsible for more than 60% of SSI with more resistant patterns than Western countries. This information may be critical to secure resources and ensure support for caregivers and healthcare leaders in implementing antimicrobial stewardship programs and evidence-based SSI preventive practices.

Synthesis of N-heterocycles containing 1,5-disubstituted-1H-tetrazole via post-Ugi-azide reaction.

Ugi-azide four-component reaction (UA-4CR) as development on Ugi four-component reaction (U-4CR) is the condensation reaction involving an aldehyde, an amine, an isocyanide, and an azide source. Nowadays, UA-4CR has been employed for the efficient and facile production of 1,5-disubstituted-1H-tetrazoles (1,5-DS-1H-Ts). Interestingly, the combination of 1,5-DS-1H-Ts with suitable post-transformations in a tandem manner results in the construction of various classes of heterocyclic compounds bearing 1,5-DS-1H-T moiety. This review aims to provide the application of diverse post-Ugi-azide reaction in the preparation of different N-heterocyclic compounds bearing 1,5-DS-1H-T such as substituted and fused 1,5-DS-1H-Ts.

Cascade process for direct synthesis of indeno[1,2-b]furans and indeno[1,2-b]pyrroles from diketene and ninhydrin.

Novel and efficient multicomponent reactions (MCRs) involving diketene, ninhydrin (indane-1,2,3-trione) and one primary amine (3CR) or two different primary amines (4CR) were achieved for the successful synthesis of dihydro-4H-indeno[1,2-b]furan-3-carboxamides or tetrahydroindeno[1,2-b]pyrrole-3-carboxamides, respectively. The merits of this method are highlighted by using either commercially available or easily accessible starting materials, operational simplicity, facile workup procedure, efficient usage of all the reactants, tolerance of a variety of functional groups and ability to conduct under un-catalyzed reaction condition. The products were also isolated by just decantation of the solvent, and for the purification column chromatography was non-required.

Response of the public and restaurant owners to the mandatory menu energy-labelling implementation in restaurants in Saudi Arabia.

OBJECTIVE: Mandatory menu energy-labelling policy in restaurants has received increasing attention worldwide as a useful tool for promoting balanced energy intake and encouraging healthier food selection to reduce obesity prevalence. Therefore, we aimed to evaluate the knowledge, views and observations of the public and restaurant owners towards the mandatory menu energy-labelling policy (introduced in August 2018) in restaurants in Saudi Arabia. DESIGN: In February 2019, we conducted a cross-sectional study using an electronic questionnaire. SETTING: Saudi Arabia. PARTICIPANTS: Saudi individuals (n 1228) aged 18-80 years and forty-one restaurant owners. RESULTS: Most participants identified the correct daily energetic requirements for moderately active men (51 %) and women (69 %), but not for inactive adults (36 %). Although 40 % reported adequate knowledge to select low-energetic meals and 55 % perceived the policy as useful, 51 % reported they would be less likely to eat at restaurants displaying energy. Most participants (76 %) mentioned they would choose lower-energetic meals, and 79 % would feel guilty after consuming high-energetic meals. Moreover, 62 % of participants reported that the new labelling policy affected their food selections, prompting them to order different food items, eat less, change restaurants or eat at restaurants less frequently. Among restaurant owners, half were aware of the reason for the implementation of this policy and supported this measure. However, they did not consider modifying recipes to reduce energy. Sales of low- and high-energetic meals increased and decreased in 44 % and 39 % of restaurants, respectively. CONCLUSIONS: This policy may be an effective public health tool for promoting balanced energy intake and encouraging healthier food selection in Saudi Arabia.

Ag Nanoparticles Stabilized on Cyclodextrin Polymer Decorated with Multi-Nitrogen Atom Containing Polymer: An Efficient Catalyst for the Synthesis of Xanthenes.

In attempt to broaden the use of cyclodextrin polymer for catalytic purposes, a novel covalent hybrid system was prepared through growth of multi-nitrogen atom containing polymer (PMelamine) derived from reaction of ethylenediamine and 2,4,6-trichloro-1,3,5-triazine on the functionalized cyclodextrin polymer (CDNS). The resulting hybrid system was then utilized as a catalyst support for the immobilization of silver nanoparticles through using Cuscuta epithymum extract as a naturally-derived reducing agent. The catalytic activity of the catalyst, Ag@CDNS-N/PMelamine, for the synthesis of xanthenes through reaction of aldehydes and dimedone in aqueous media was examined. The results showed high catalytic activity and recyclability of the catalyst. It was believed that cyclodextrin in the backbone of the catalyst could act both as a capping agent for Ag nanoparticles and phase transfer agent to bring the hydrophobic substrates in the vicinity of the catalytic active sites and accelerate the reaction rate. Multi-nitrogen atoms on the polymer, on the other hand, could improve the Ag NPs anchoring and suppress their leaching.

Applications of Dainshefsky's Dienes in the Asymmetric synthesis of Aza-Diels-Alder Reaction.

Asymmetric hetero-Diels-Alder (AHDA) reactions provide a multitude of opportunities for the highly efficient, regio- and stereoselective construction of various heterocycles in enantiomerically pure form. The asymmetric aza-Diels-Alder (A-aza-DA) reaction using diversely hetero-dienophiles and hetero-dienes have been increasingly developed as a valuable method for the synthesis of functionalized nitrogen ring systems. The purpose of this review is to give a detailed discussion of the A-aza-DA reaction particularly, the stereoselective reactions of imines as dienophiles with Dainshefsky dienes to obtain optically pure aza-Diels-Alder products. The development of stereoselective variants of the reaction make use of imines as the dienophile and Dainshefsky dienes is at the forefront of these studies. This review updates the A-aza-DA reactions covering the literature from 1972 till date.

Attenuation of the association between sugar-sweetened beverages and diabetes risk by adiposity adjustment: a secondary analysis of national health survey data.

PURPOSE: While weight gain and obesity are the dominant factors, dietary sugar and specifically sugar-sweetened beverages (SSB) has been implicated in causing type 2 diabetes (T2DM). We assessed how much of the apparent effect of SSB is explained by adiposity, but not captured by adjustment for BMI, which is a poor index of body fat. METHODS: We examined data from 5187 adults (mean age 50.8 years, SD = 16.4, 172 (3.3%) T2DM), from the Scottish Health Survey 2003 and 2008-2010 databases. Logistic regression was used to assess the association between SSB consumption and T2DM (non-insulin treated) and its attenuation (reduction in odds ratios, ORs), after entering published anthropometric indices of adiposity into the regression model, adjusted for age, sex, social class, education, smoking, alcohol consumption and physical activity. RESULTS: Compared with low SSB categories ("less often/never", once/week or 1-3 times/month), the OR without adiposity adjustment for having T2DM in high SSB consumers (2-3, 4-5, ≥ 6/day) was 2.56 (95% CI 1.12-5.83; p = 0.026). That OR was marginally changed by adjusting for BMI (+ 4.3%), WC (+ 5.5%) or total body fat (- 4.3%), but greatly attenuated by adjusting for estimated %body fat (- 23.4%). These indices had similar influences on the associations between SSB and T2DM combining known T2DM patients with unknown HbA1c > 6.5%, > 48 mmol/mol. CONCLUSIONS: Associations between SSB and T2DM are attenuated more markedly by adjustment with estimated %body fat than with BMI, indicating an adiposity effect not captured using BMI. Future research should employ best available estimates of adiposity.

Electrochemically Induced Michael Addition Reaction: An Overview.

Due to its high potential for the formation of carbon-carbon bonds, Michael addition reaction is one of the closest reactions to the heart of synthetic organic chemists. Electrochemistry presents a very stimulating and divergent resource for selective oxidation and reduction in organic chemistry, generating activated species, for example radical anions or radical cations. In this review, we try to underscore usefulness of electrogenerated Michael addition reaction with the hope of encouraging synthetic organic chemists to contemplate it, as an efficient and green strategy when it is required in their designed multi-step reaction pathways.

Current progress in asymmetric Biginelli reaction: an update.

The Biginelli reaction, involving a three-component reaction of an aromatic aldehyde, urea and ethyl acetoacetate, has emerged as an extremely useful synthetic tool to organic chemists for the synthesis of 3,4-dihydropyrimidine-2-(1H)-ones and related heterocyclic compounds. In the past decades, the asymmetric variants of this reaction have been at the forefront of investigations in several research groups. In 2013, we highlighted the developments occurred in the asymmetric version of the Biginelli reaction. This review article focuses on the recent developments of asymmetric Biginelli reaction covers the literature going back to 2012.