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Objective: Multidrug-resistant bacteria, including carbapenem-resistant Acinetobacter baumannii (CRAB), are considered a major public health threat, particularly those which are responsible for nosocomial infections. This study aimed to investigate the molecular mechanism of carbapenem resistance and the clonal relationship of CRAB isolates of a probable outbreak in the intensive care unit (ICU) of Saydet Zgharta University Medical Center, in north Lebanon. Methods: Thirty-two non-duplicate CRAB isolates were collected from patients hospitalised in the ICU. Antibiotic susceptibility testing was carried out using the disk diffusion method and carbapenemase-encoding genes were searched for using standard polymerase chain reaction. Epidemiological relatedness was studied using multilocus sequence typing. Results: Polymerase chain reaction and multilocus sequence typing results suggested the presence of two different periods: period 1 (November 2018 to February 2019), where 15 CRAB isolates were collected harbouring the blaOXA-23 and blaOXA-24 genes mainly and belonging to several clones; and period 2 (March to May 2019), considered an outbreak period where 17 carbapenem-resistant isolates were isolated, harbouring mostly the blaNDM-2 gene, never previously described in Lebanon and belonging to ST103. Infection control measures implemented in Saydet Zgharta University Medical Center successfully eradicated the NDM-2-producing CRAB ST103 clone, thus putting an end to this outbreak in the ICU department. Conclusions: This study showed that infection control measures and adequate identification of NDM-producing A. baumannii remain a powerful tool to limit the spread of such resistant micro-organisms.

Abstract Background Previous studies have reported a protective effect of type 2 diabetes on the incidence and progression of aortic aneurysms. We investigated whether this protective effect extends to aortic dissections. Methods Data from the US Nationwide Readmission Database (2016–2019) were analyzed. Patients admitted for open surgery repair of acute type A aortic dissection (TAAD) were initially analyzed (index group). Those discharged alive were followed for up to 30 days (readmission group). The co-primary outcomes were in-hospital and 30-day mortality. Results Between 2016 and 2019, 7,324 patients were admitted for open surgical repair of acute TAAD, of whom 965 (13.2%) had diabetes. Patients with diabetes were older and had a higher prevalence of obesity, hypertension, smoking, dyslipidemia, and chronic kidney disease (CKD). 15.2% of patients with diabetes and 14.6% without diabetes died; hence, diabetes did not have a significant impact on in-hospital mortality (adjusted odd ratio [aOR] = 1.02 [0.84–1.24]). Similarly, diabetes was not associated with a higher adjusted risk of atrial fibrillation (aOR = 1.03 [0.89–1.20]), stroke (aOR = 0.83 [0.55–1.26]), cardiogenic shock (aOR = 1.18 [0.98–1.42]), but increased the risk of acute renal failure (aOR = 1.20 [1.04–1.39]). Within 30 days of discharge, 154 (15.9%) patients with diabetes and 952 (15%) from the non-diabetes group were readmitted. Readmitted patients with diabetes were older and had a higher prevalence of cardiovascular comorbidities. We didn’t observe any significant difference in the adjusted risk of 30-day mortality between the diabetes and non-diabetes groups (adjusted hazard ratio [aHR] = 0.81 [0.41–1.60]). However, diabetes was associated with a lower risk of readmission (aHR = 0.81 [0.68–0.97]). Age was the most significant predictor of all outcomes. CKD was the most significant predictor of 30-day mortality, with the risk increasing five-fold in patients with diabetes (HR = 5.58 [2.58–6.62]. Cardiovascular-related conditions were the most common causes of readmission in both groups. However, respiratory-related conditions were more prevalent in the diabetes group compared to the non-diabetes group (19.5% vs. 13%, respectively, p = 0.032). Conclusions Diabetes does not increase in-hospital or short-term mortality in patients undergoing surgical repair for Type A aortic dissection. Graphical abstract

Objective: Antimicrobial resistance (AMR), together with multidrug resistance (MDR), mainly among Gram-negative bacteria, has been on the rise. Colistin (polymyxin E) remains one of the primary available last resorts to treat infections caused by MDR bacteria during the rapid emergence of global resistance. As the exact mechanism of bacterial resistance to colistin remains undetermined, this study warranted elucidation of the underlying mechanisms of colistin resistance and heteroresistance among carbapenem-resistant Klebsiella pneumoniae isolates. Methods: Molecular analysis was carried out on the resistant isolates using a genome-wide characterisation approach, as well as MALDI-TOF mass spectrometry, to identify lipid A. Results: Among the 32 carbapenem-resistant K. pneumoniae isolates, several isolates showed resistance and intermediate resistance to colistin. The seven isolates with intermediate resistance exhibited the “skip-well” phenomenon, attributed to the presence of resistant subpopulations. The three isolates with full resistance to colistin showed ions using MALDI-TOF mass spectrometry at m/z of 1840 and 1824 representing bisphosphorylated and hexa-acylated lipid A, respectively, with or without hydroxylation at position C’-2 of the fatty acyl chain. Studying the genetic environment of mgrB locus revealed the presence of two insertion sequences that disrupted the mgrB locus in the three colistin-resistant isolates: IS1R and IS903B. Conclusions: Our findings show that colistin resistance/heteroresistance was inducible with mutations in chromosomal regulatory networks controlling the lipid A moiety and insertion sequences disrupting the mgrB gene, leading to elevated minimum inhibitory concentration values and treatment failure. Different treatment strategies should be employed to avoid colistin heteroresistance-linked treatment failures, mainly through combination therapy using colistin with carbapenems, aminoglycosides, or tigecycline.

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disorder, particularly present in the Mediterranean populations, and associated with pathogenic variants in the MEFV gene. This study aims to investigate the distribution of MEFV variants in a large cohort of Lebanese patients, and to explore the genotype-phenotype correlation among affected individuals. A retrospective analysis was conducted on 3,167 patients referred for MEFV sequencing at the Medical Genetics and Genomics Center(CGGM) at Saint-Joseph University of Beirut-Lebanon, from 2006 to 2023. Sanger sequencing was used to detect MEFV variants, focusing initially on hot-spot exons. Among the 3,167 patients, 46.73% (N = 1,480) carried at least one MEFV variant. The most common variants detected were M694V and V726A, both found in 28.98% of cases, followed by E148Q(27.83%) and M694I(13.98%). Moreover, Shiites and Sunni Muslims, and individuals from South and North Lebanon exhibited the highest frequency of variants. Interestingly, family history was found to be significantly higher in patients having two MEFV variants than those with one variant (p = 0.0026). The most commonly reported symptoms were fever(78%), abdominal pain(88%), joint pain(65%), and thoracic pain(46%). The genotype-phenotype correlation analysis revealed a more severe phenotype in patients carrying the M694V or V726A mutations compared to those with the homozygous E148Q genotype. This study, the largest in Lebanon, highlights the high prevalence of MEFV variants, particularly M694V and V726A, in FMF patients. Our data provide valuable insights into the genetic landscape of FMF in Lebanon and emphasize the importance of early genetic screening for a better disease management and genetic counselling.

Background Transcatheter aortic valve replacement (TAVR) is increasingly used for aortic valve replacement instead of surgical aortic valve replacement (sAVR). We aimed to examine the impact of diabetes on 30-day mortality, 30-day readmission and compare outcomes between TAVR and sAVR.Methods Data were extracted from the Nationwide Readmissions Database from 2012 to 2017. The primary outcome was 30-day mortality, and the secondary outcome was 30-day readmission.Results The study included 110 135 patients who underwent aortic valve replacement. Of these, 59 466 (54.0%) were hospitalised for TAVR, and 50 669 (46.0%) underwent sAVR. Diabetes was present in 36.4% of TAVR patients and 29.1% of sAVR patients. In TAVR patients, the adjusted risk of 30-day readmission and mortality was similar regardless of diabetes status (aHR=0.94 (0.86–1.03); 0.97 (0.84–1.12); respectively). However, sAVR patients with diabetes had a higher adjusted risk of 30-day mortality (aHR=1.13 (1.01–1.25)) but not readmission (aHR=0.92 (0.84–1.01)). When comparing outcomes between TAVR and sAVR in patients with diabetes, TAVR patients were older and had a higher prevalence of chronic kidney disease (CKD). Nevertheless, 30-day readmission and mortality were lower in patients who underwent TAVR (aHR=0.59 (0.53–0.67), aHR=0.29 (0.25–0.34), respectively) compared with sAVR. Coronary artery disease was the most significant predictor of readmission in patients with diabetes. CKD increased the risk of mortality by almost twofold in both techniques.Conclusion Diabetes increases the risk of short-term mortality in sAVR but not TAVR. Moreover, the incidence of 30-day mortality and readmission is lower in TAVR compared with TAVR among patients with diabetes.

Abstract Background Monocytes play a central role in the pathophysiology of cardiovascular complications in type 2 diabetes (T2D) patients through different mechanisms. We investigated diabetes-induced changes in lncRNA genes from T2D patients with cardiovascular disease (CVD), long-duration diabetes, and poor glycemic control. Methods We performed paired-end RNA sequencing of monocytes from 37 non-diabetes controls and 120 patients with T2D, of whom 86 had either macro or microvascular disease or both. Monocytes were sorted from peripheral blood using flow cytometry; their RNA was purified and sequenced. Alignments and gene counts were obtained with STAR to reference GRCh38 using Gencode (v41) annotations followed by batch correction with CombatSeq. Differential expression analysis was performed with EdgeR and pathway analysis with IPA software focusing on differentially expressed genes (DEGs) with a p-value

Conventional cytogenetic analysis is an important tool for the diagnosis of many hematologic disorders (HD). A karyotype is designed as « complex » when several alterations are detected. However, there is no clear consensus on the exact definition of a complex karyotype (CK), and there is a lack of studies that exclusively analyze CK in the literature. Complex karyotypes were analyzed over a period of 12 years at the Jacques Loiselet Center for Medical Genetics and Genomics (CGGM) at Saint Joseph University in Beirut (USJ) in Lebanon. 255 CK were analyzed with their associated chromosomal abnormalities (CA) detected. Out of 255 patients, 59.22% were males with a mean age of 59 years. The most common anomaly associated with CK was hyperdiploidy with a prevalence of 22.41%, which is different from a previously published study. To our knowledge, this represents the largest series of CK, particularly within the Middle East region. This study underscores the critical role of conventional cytogenetics in detecting CK, ultimately contributing to improved management of HD. Further investigations focusing on CK are needed.

In this paper we compute the overlaps of the ground states for the open spin chains after a change of one of the boundary magnetic fields. It can be considered as the first step toward the study of the boundary quench problem: behaviour of an open spin chain after an abrupt change of one boundary magnetic field.

Abstract Background Aging has been reported as a major risk factor for severe symptoms and higher mortality rates in COVID-19 patients. Molecular hallmarks such as epigenetic alterations and telomere attenuation reflect the biological process of aging. Epigenetic clocks have been shown to be valuable tools for measuring biological age in various tissues and samples. As such, these epigenetic clocks can determine accelerated biological aging and time-to-mortality across various tissues. Previous reports have shown accelerated biological aging and telomere attrition acceleration following SARS-CoV-2 infection. However, the effect of accelerated epigenetic aging on outcome (death/recovery) in COVID-19 patients with acute respiratory distress syndrome (ARDS) has not been well investigated. Results In this study, we measured DNA methylation age and telomere attrition in 87 severe COVID-19 cases with ARDS under mechanical ventilation. Furthermore, we compared dynamic changes in epigenetic aging across multiple time points until recovery or death. Epigenetic age was measured using the Horvath, Hannum, DNAm skin and blood, GrimAge, and PhenoAge clocks, whereas telomere length was calculated using the surrogate marker DNAmTL. Our analysis revealed significant accelerated epigenetic aging but no telomere attrition acceleration in severe COVID-19 cases. In addition, we observed epigenetic age deceleration at inclusion versus end of follow-up in recovered but not in deceased COVID-19 cases using certain clocks. When comparing dynamic changes in epigenetic age acceleration (EAA), we detected higher EAA using both the Horvath and PhenoAge clocks in deceased versus recovered patients. The DNAmTL measurements revealed telomere attrition acceleration in deceased COVID-19 patients between inclusion and end of follow-up and a significant change in dynamic telomere attrition acceleration when comparing patients who recovered versus those who died. Conclusions EAA and telomere attrition acceleration were associated with treatment outcomes in hospitalized COVID-19 patients with ARDS. A better understanding of the long-term effects of EAA in COVID-19 patients and how they might contribute to long COVID symptoms in recovered individuals is urgently needed.

The chaperone system (CS) is emerging as a key multistage participant in carcinogenesis. The CS chief components are the molecular chaperones (some of which are named heat shock proteins or Hsp), which are typically cytoprotective but if abnormal in structure, location, or quantity, can become etiopathogenic and cause diseases, known as chaperonopathies, including some cancers. For example, abnormal Hsp90 expression is associated with tumorigenesis and poor prognosis. Hsp90 is positioned at the center of several key oncogenic pathways by stabilizing and activating oncogenic kinases responsible for driving cell proliferation and survival. Consequently, inhibition of Hsp90 is being investigated as a possible anti-cancer strategy and some results are encouraging. However, the 5-year survival rate for patients suffering from salivary gland carcinomas is still unsatisfactory. Because of the rarity of these malignancies, they may have been overlooked and understudied and, thus, novel therapies (e.g., inhibition of CS components like Hsp90 and others) are urgently needed. In this review, we also summarize the histopathological quantitative patterns and the intra- and extra-cellular location characteristics of Hsp90 in tumors of salivary glands, pointing to their potential for differential diagnosis, prognostication, and patient monitoring.

Abstract Pervasive transcription of the human genome generates an abundance of RNAs that must be processed and degraded. The nuclear RNA exosome is the main RNA degradation machinery in the nucleus. However, nuclear exosome must be recruited to its substrates by targeting complexes, such as NEXT or PAXT. By proteomic analysis, we identify additional subunits of PAXT, including many orthologs of MTREC found in S. pombe. In particular, we show that polyA polymerase gamma (PAPγ) associates with PAXT. Genome-wide mapping of the binding sites of ZFC3H1, RBM27 and PAPγ shows that PAXT is recruited to the TSS of hundreds of genes. Loss of ZFC3H1 abolishes recruitment of PAXT subunits including PAPγ to TSSs and concomitantly increases the abundance of PROMPTs at the same sites. Moreover, PAPγ, as well as MTR4 and ZFC3H1, is implicated in the polyadenylation of PROMPTs. Our results thus provide key insights into the direct targeting of PROMPT ncRNAs by PAXT at their genomic sites.

Background: Anatomical variations and, in particular, arterial variations constitute an important chapter in the learning of Clinical Anatomy. Purpose: The purpose of this report is to describe a rare bilateral anatomical variation in the internal thoracic artery (ITA) in a 60-year-old corpse and to depict its extreme clinical importance in coronary artery bypass surgery. Methods: The rare bilateral aberrant branches of the internal thoracic artery and their course in the thorax were incidentally discovered during routine anatomy dissection of the thorax at the Faculty of Medicine and Medical Sciences of the University of Balamand. The findings were thoroughly documented using digital photography, and the dissection followed the instructions from the “16th Edition of Grant’s Dissector”. Results: In the observed case, the left aberrant branch of ITA descends laterally and gives medial and lateral anterior intercostal branches at the first six intercostal spaces. Conversely, the right aberrant artery, which branches from the ITA, descends laterally and gives medial and lateral branches to every intercostal space in the first five intercostal spaces. Conclusion: This report emphasizes that any unexpected variations in the lateral aberrant branches of the internal thoracic artery may complicate the surgical procedure. Bilateral aberrant lateral branches of the internal thoracic artery constitute rare anatomical variations of the internal thoracic artery and have been rarely reported in the literature. Such a course for aberrant lateral branches in the thorax poses possible lethal complications during several procedures involving the thorax, including basic coronary artery bypass graft, thoracocentesis and intercostal paracentesis and breast reconstruction.

Abstract Background The murine leukemia virus (MLV) has been a powerful model of pathogenesis for the discovery of genes involved in cancer. Its splice donor (SD’)-associated retroelement (SDARE) is important for infectivity and tumorigenesis, but the mechanism remains poorly characterized. Here, we show for the first time that P50 protein, which is produced from SDARE, acts as an accessory protein that transregulates transcription and induces cell transformation. Results By infecting cells with MLV particles containing SDARE transcript alone (lacking genomic RNA), we show that SDARE can spread to neighbouring cells as shown by the presence of P50 in infected cells. Furthermore, a role for P50 in cell transformation was demonstrated by CCK8, TUNEL and anchorage-independent growth assays. We identified the integrase domain of P50 as being responsible for transregulation of the MLV promoter using luciferase assay and RTqPCR with P50 deleted mutants. Transcriptomic analysis furthermore revealed that the expression of hundreds of cellular RNAs involved in cancerogenesis were deregulated in the presence of P50, suggesting that P50 induces carcinogenic processes via its transcriptional regulatory function. Conclusion We propose a novel SDARE-mediated mode of propagation of the P50 accessory protein in surrounding cells. Moreover, due to its transforming properties, P50 expression could lead to a cellular and tissue microenvironment that is conducive to cancer development.

Abstract Nuclear spin hyperpolarization is a quantum effect that enhances the nuclear magnetic resonance signal by several orders of magnitude and has enabled real-time metabolic imaging in humans. However, the translation of hyperpolarization technology into routine use in laboratories and medical centers is hampered by the lack of portable, cost-effective polarizers that are not commercially available. Here, we present a portable, automated polarizer based on parahydrogen-induced hyperpolarization (PHIP) at an intermediate magnetic field of 0.5 T (achieved by permanent magnets). With a footprint of 1 m2, we demonstrate semi-continuous, fully automated 1H hyperpolarization of ethyl acetate-d6 and ethyl pyruvate-d6 to P = 14.4% and 16.2%, respectively, and a 13C polarization of 1-13C-ethyl pyruvate-d6 of P = 7%. The duty cycle for preparing a dose is no more than 1 min. To reveal the full potential of 1H hyperpolarization in an inhomogeneous magnetic field, we convert the anti-phase PHIP signals into in-phase peaks, thereby increasing the SNR by a factor of 5. Using a spin-echo approach allowed us to observe the evolution of spin order distribution in real time while conserving the expensive reagents for reaction monitoring, imaging and potential in vivo usage. This compact polarizer will allow us to pursue the translation of hyperpolarized MRI towards in vivo applications further.

Greater Cairo, the largest megacity of the Middle East North Africa (MENA) region, is currently suffering from major aerosol pollution, posing a significant threat to public health. However, the main sources of pollution remain insufficiently characterized due to limited atmospheric observations. To bridge this knowledge gap, we conducted a continuous 2-month field study during the winter of 2019–2020 at an urban background site, documenting for the first time the chemical and physical properties of submicron (PM1) aerosols. Crustal material from both desert dust and road traffic dust resuspension contributed as much as 24 % of the total PM1 mass (rising to 66 % during desert dust events), a figure not commonly observed in urban environments. Our observations showed significant decreases in black carbon concentrations and ammonium sulfate compared to data from 15 years ago, indicating an important reduction in both local and regional emissions as a result of effective mitigation measures. The diurnal variability of carbonaceous aerosols was attributed to emissions emanating from local traffic at rush hours and nighttime open biomass burning. Surprisingly, semi-volatile ammonium chloride (NH4Cl) originating from local open biomass and waste burning was found to be the main chemical species in PM1 over Cairo. Its nighttime formation contributed to aerosol water uptake during morning hours, thereby playing a major role in the build-up of urban haze. While our results confirm the persistence of a significant dust reservoir over Cairo, they also unveil an additional source of highly hygroscopic (semi-volatile) inorganic salts, leading to a unique type of urban haze. This haze, with dominant contributors present in both submicron (primarily as NH4Cl) and supermicron (largely as dust) modes, underscores the potential implications of heterogeneous chemical transformation of air pollutants in urban environments.

One of the most challenging issues scientists face is finding a suitable non-invasive treatment for cancer, as it is widespread around the world. The efficacy of phytochemicals that target oncogenic pathways appears to be quite promising and has gained attention over the past few years. We investigated the effect of docking phytochemicals isolated from the rhizomes of the Cimicifuga foetida plant on different domains of the IκB kinase alpha (IKK1/alpha) protein. The Cimicifugoside H-2 phytochemical registered a high docking score on the activation loop of IKK1/alpha amongst the other phytochemicals compared to the positive control. The interaction of the protein with Cimicifugoside H-2 was mostly stabilized by hydrogen bonds and hydrophobic interactions. A dynamic simulation was then performed with the Cimicifugoside H-2 phytochemical on the activation loop of IKK1/alpha, revealing that Cimicifugoside H-2 is a possible inhibitor of this protein. The pharmacokinetic properties of the drug were also examined to assess the safety of administering the drug. Therefore, in this in silico study, we discovered that the Cimicifugoside H-2 phytochemical inhibits the actively mutated conformation of IKK1/alpha, potentially suppressing the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) pathway.

Background: Early SARS-CoV-2 variant detection relies on testing and genomic surveillance. The Omicron variant (B.1.1.529) has quickly become the dominant type among the previous circulating variants worldwide. Several subvariants have emerged exhibiting greater infectivity and immune evasion. In this study we aimed at studying the prevalence of the Omicron subvariants during the flu season and beyond in Lebanon through genomic screening and at determining the overall standing and trajectory of the pandemic in the country. Methods: A total of 155 SARS-CoV-2 RNA samples were sequenced, using Nanopore sequencing technology. Results: Nanopore sequencing of 155 genomes revealed their distribution over 39 Omicron variants. XBB.1.5 (23.29 %) was the most common, followed by XBB.1.9.1 (10.96 %) and XBB.1.42 (7.5 %). The first batch collected between September and November 2022, included the BA.2.75.2, BA.5.2, BA.5.2.20, BA.5.2.25 and BQ.1.1.5 lineages. Between December 2022 and January 2023, those lineages were replaced by BA.2.75.5, BN.1, BN.1.4, BQ.1, BQ.1.1, BQ.1.1.23, CH.1.1, CM.4 and XBK. Starting February 2023, we observed a gradual emergence and dominance of the recombinant XBB and its sub-lineages (XBB.1, XBB.1.5, XBB.1.5.2, XBB.1.5.3, XBB.1.9, XBB.1.9.1, XBB.1.9.2, XBB.1.16, XBB.1.22 and XBB.1.42). Conclusions: The timely detection and characterization of SARS-CoV-2 variants is important to reduce transmission through established disease control measures and to avoid introductions into animal populations that could lead to serious public health implications.

Introduction Subarachnoid Hemorrhage (SAH) is the leading cause of morbidity and mortality in stroke patients, associated with severe neurological, infectious, and thromboembolic complications. Identifying clinical predictors linked to hospital readmissions after a SAH allows for the determination of patients with higher risks of complications, opening an avenue for prevention and improved quality of care. Methods The Nationwide Readmission Database (NRD) was used to extract patients with SAH (ICD‐10 code: I60.x) from 2016‐2019. The difference in days between the index admission and the readmission was used to identify patients who were readmitted within 30 and 90 days. The primary diagnosis of the readmission was used to identify the etiology of readmission. Data was weighted to allow for representative nationwide estimates. Results We identified 68,726 patients with SAH, with a mean age of 60.47 years, and 57.86% being female. Overall, 7.79% (n=5354) were readmitted within 30 days and 12.04% (n=8525) were readmitted within 90 days. The rate of 30‐day readmission was overall stable (7.34% in 2016 and 7.70% in 2019; p=0.42), but the 90‐day readmission rate slightly increased from 11.69% in 2016 to 12.47% in 2019 (p=0.04). Around 62% of 90‐day readmissions occurred within the first 30 days. Patients readmitted within 30 days were more likely to be older (mean age = 61.92 vs 60.99 years; p

Introduction Nontraumatic Intracerebral Hemorrhage (ICH) is the second most prevalent type of stroke worldwide and is strongly linked with severe disability and mortality. Survivors of ICH have a high risk of all‐cause readmission. Understanding characteristics of readmitted patients and etiologies of readmission may provide a framework for risk stratification and readmission prevention. Methods We identified patients with a primary diagnosis of ICH (ICD‐10 code: I61.x) from 2016‐2019 using the Nationwide Readmission Database (NRD). The difference in days between the index admission and the readmission was used to identify patients who were readmitted within 30 and 90 days. The primary diagnosis of the readmission was used to identify the etiology of readmission. Data was weighted to allow for representative nationwide estimates. Results A total of 260,854 patients were admitted with a primary diagnosis of ICH between 2016‐2019. The mean age of the cohort was 68.49 years, with 52.6% being male. The 30‐day readmission rate was 7.68% while the 90‐day readmission rate was 12.73%. There was a small but significant increase in 90‐day readmission rates from 2016 to 2019 (12.61% vs 12.93%, p=0.05), but no significant increase in 30‐day readmission rates (7.10% vs 7.72%, p=0.870). Around 60% of 90‐day readmissions occurred within the first 30 days. Patients readmitted within 30 days and within 90 days, compared to those not requiring readmission, were more likely to be younger (68 and 68.1 vs 68.53 years) and male (54.87% and 53.92% vs 52.41) (p

Introduction Transient Ischemic Attack (TIA) is a common neurologic condition characterized by temporary, focal cerebral ischemia that results in reversible neurological deficits without tissue infarction. Type 2 Diabetes Mellitus (T2DM) is a rapidly growing global health problem with increasing prevalence. Currently, data are lacking regarding the trends of 90‐day readmission rates and etiologies among diabetic patients with TIA. Methods We used the Nationwide Readmission Database (NRD) to identify patients with a primary diagnosis of TIA (ICD‐10 code: G45.9) from 2016‐2019 and secondary diagnosis of T2DM. The difference in days between the index admission and the readmission was used to identify patients who were readmitted within 90 days. The primary diagnosis of the readmission was used to identify the etiology of readmission. Data was weighted to allow for representative nationwide estimates. Results We identified 426,549 patients who were admitted with a primary diagnosis of TIA between 2016 and 2019. Of those patients, 35.43% (n=273,993) were diabetic and 64.57% (n=151,112) were non‐diabetic. Diabetics were more likely to be younger (70.43 vs 70.71 years, p

Introduction Primary Angiitis of the Central Nervous System (PACNS) is a rare, relapsing inflammatory disorder of blood vessels in the brain and spinal cord presenting clinically with a spectrum of manifestations including strokes, seizures, and neurologic deficits. Limited data are available on the modifiable and nonmodifiable predictors of readmissions for patients diagnosed with PACNS, which hinders the ability of healthcare systems to risk‐stratify patients based on their specific demographics, comorbidities, and hospital status. Methods We identified patients with PACNS (ICD‐10 code: I67.7) admitted from 2016‐2019 using the Nationwide Readmission Database (NRD). The difference in days between the index admission and the readmission was used to identify patients who were readmitted within 30 and 90 days. The primary diagnosis of the readmission was used to identify the etiology of readmission. Data was weighted to allow for representative nationwide estimates. Results We identified 1,398 patients admitted with a primary diagnosis of PACNS between 2016 and 2019. The mean age was 52.81 years, with 59.20% (n=828) being female. The 30‐day readmission rate was 10.52% (n=147) and the 90‐day readmission rate was 19.60% (n=274). Nearly half of 90‐day readmissions occurred within the first 30 days. Annual variations in readmission rates were insignificant. Age and sex distribution were not statistically different between patients not requiring readmission, those readmitted within 30 days, and those readmitted within 90 days. Compared to those not requiring readmission, patients readmitted within 30 days had a higher prevalence of diabetes (38.07% vs 29.06%; p=0.023) and hypertension (65.66% vs 56.88%; p=0.035), while those readmitted within 90 days had a higher prevalence of diabetes (41.56% vs 27.19%, p

The applications and services envisioned for the sixth Generation (6G) Internet of Things (IoT) communication systems will place different requirements on the system design. The current 5G waveform, Orthogonal Frequency Division Multiplexing (OFDM), suffers from a list of drawbacks that questions its suitability and ability to fulfill these prerequisites. Filtered multi-carrier waveforms provide viable alternatives for future mobile networks. Based on the best recent advances including contributions by the authors, this work provides a comprehensive assessment of the current status and future challenges related to the design of a next-generation Filter Bank Multi-Carrier/Offset Quadrature Amplitude Modulation (FBMC/OQAM) transceiver. We start by showing how the next-generation FBMC/OQAM waveform can overcome the drawbacks of OFDM. Furthermore, we highlight the advantages and possibilities of extending the next-generation FBMC/OQAM waveform for massive Multiple-Input-Multiple-Output (mMIMO) in well-identified 6G-IoT scenarios. Results show that the next-generation FBMC/OQAM receivers associated with short prototype filters can unleash appealing properties for 6G-IoT applications. Considered a cornerstone for grant-free spectrum and massive access, asynchronous communications are shown to be achievable. Furthermore, a largely improved robustness is observed compared to OFDM under different channel impairments such as carrier frequency offsets, timing offsets, and multipath channels. Compared to the original FBMC/OQAM associated with long filters, this next-generation transceiver achieves a reduction in complexity down to a comparable level to OFDM. Finally, open research opportunities and challenges for the next-generation FBMC/OQAM waveform are discussed.

Abstract Background COVID-19 infections could be complicated by acute respiratory distress syndrome (ARDS), increasing mortality risk. We sought to assess the methylome of peripheral blood mononuclear cells in COVID-19 with ARDS. Methods We recruited 100 COVID-19 patients with ARDS under mechanical ventilation and 33 non-COVID-19 controls between April and July 2020. COVID-19 patients were followed at four time points for 60 days. DNA methylation and immune cell populations were measured at each time point. A multivariate cox proportional risk regression analysis was conducted to identify predictive signatures according to survival. Results The comparison of COVID-19 to controls at inclusion revealed the presence of a 14.4% difference in promoter-associated CpGs in genes that control immune-related pathways such as interferon-gamma and interferon-alpha responses. On day 60, 24% of patients died. The inter-comparison of baseline DNA methylation to the last recorded time point in both COVID-19 groups or the intra-comparison between inclusion and the end of follow-up in every group showed that most changes occurred as the disease progressed, mainly in the AIM gene, which is associated with an intensified immune response in those who recovered. The multivariate Cox proportional risk regression analysis showed that higher methylation of the “Apoptotic execution Pathway” genes (ROC1, ZNF789, and H1F0) at inclusion increases mortality risk by over twofold. Conclusion We observed an epigenetic signature of immune-related genes in COVID-19 patients with ARDS. Further, Hypermethylation of the apoptotic execution pathway genes predicts the outcome. Trial registration: IMRPOVIE study, NCT04473131.

Abstract Background The genetic architecture underlying Familial Hypercholesterolemia (FH) in Middle Eastern Arabs is yet to be fully described, and approaches to assess this from population-wide biobanks are important for public health planning and personalized medicine. Methods We evaluate the pilot phase cohort (n = 6,140 adults) of the Qatar Biobank (QBB) for FH using the Dutch Lipid Clinic Network (DLCN) criteria, followed by an in-depth characterization of all genetic alleles in known dominant (LDLR, APOB, and PCSK9) and recessive (LDLRAP1, ABCG5, ABCG8, and LIPA) FH-causing genes derived from whole-genome sequencing (WGS). We also investigate the utility of a globally established 12-SNP polygenic risk score to predict FH individuals in this cohort with Arab ancestry. Results Using DLCN criteria, we identify eight (0.1%) ‘definite’, 41 (0.7%) ‘probable’ and 334 (5.4%) ‘possible’ FH individuals, estimating a prevalence of ‘definite or probable’ FH in the Qatari cohort of ~ 1:125. We identify ten previously known pathogenic single-nucleotide variants (SNVs) and 14 putatively novel SNVs, as well as one novel copy number variant in PCSK9. Further, despite the modest sample size, we identify one homozygote for a known pathogenic variant (ABCG8, p. Gly574Arg, global MAF = 4.49E-05) associated with Sitosterolemia 2. Finally, calculation of polygenic risk scores found that individuals with ‘definite or probable’ FH have a significantly higher LDL-C SNP score than ‘unlikely’ individuals (p = 0.0003), demonstrating its utility in Arab populations. Conclusion We design and implement a standardized approach to phenotyping a population biobank for FH risk followed by systematically identifying known variants and assessing putative novel variants contributing to FH burden in Qatar. Our results motivate similar studies in population-level biobanks – especially those with globally under-represented ancestries – and highlight the importance of genetic screening programs for early detection and management of individuals with high FH risk in health systems.

Drug discovery was initially attributed to coincidence or experimental research. Historically, the traditional approaches were complex, lengthy, and expensive, entailing costly random screening of synthesized compounds or natural products coupled with in vivo validation largely depending on the availability of appropriate animal models. Currently, in silico modeling has become a vital tool for drug discovery and repurposing. Molecular docking and dynamic simulations are being used to find the best match between a ligand and a molecule, an approach that could help predict the biomolecular interactions between the drug and the target host. Beauvericin (BEA) is an emerging mycotoxin produced by the entomopathogenic fungus Beauveria bassiana, being originally studied for its potential use as a pesticide. BEA is now considered a molecule of interest for its possible use in diverse biotechnological applications in the pharmaceutical industry and medicine. In this manuscript, we provide an overview of the repurposing of BEA as a potential therapeutic agent for multiple diseases. Furthermore, considerable emphasis is given to the fundamental role of in silico techniques to (i) further investigate the activity spectrum of BEA, a secondary metabolite, and (ii) elucidate its mode of action.

Epstein–Barr virus (EBV), a Herpesviridae family member, is associated with an increased risk of autoimmune disease development in the host. We previously demonstrated that EBV DNA elevates levels of the pro-inflammatory cytokine IL-17A and that inhibiting Toll-like receptor (TLR) 3, 7, or 9 reduces its levels. Moreover, this DNA exacerbated colitis in a mouse model of inflammatory bowel disease (IBD). In the study at hand, we examined whether inhibition of TLR3, 7, or 9 alleviates this exacerbation. Mice were fed 1.5% dextran sulfate sodium (DSS) water and administered EBV DNA. Then, they were treated with a TLR3, 7, or 9 inhibitor or left untreated. We also assessed the additive impact of combined inhibition of all three receptors. Mice that received DSS, EBV DNA, and each inhibitor alone, or a combination of inhibitors, showed significant improvement. They also had a decrease in the numbers of the pathogenic colonic IL-17A+IFN-γ+ foci. Inhibition of all three endosomal TLR receptors offered no additive benefit over administering a single inhibitor. Therefore, inhibition of endosomal TLRs reduces EBV DNA exacerbation of mouse colitis, offering a potential approach for managing IBD patients infected with EBV.

Abstract Background Nuclear factor 90 (NF90) is a double-stranded RNA-binding protein involved in a multitude of different cellular mechanisms such as transcription, translation, viral infection, and mRNA stability. Recent data suggest that NF90 might influence the abundance of target mRNAs in the cytoplasm through miRNA- and Argonaute 2 (Ago2)-dependent activity. Results Here, we identified the interactome of NF90 in the cytoplasm, which revealed several components of the RNA-induced silencing complex (RISC) and associated factors. Co-immunoprecipitation analysis confirmed the interaction of NF90 with the RISC-associated RNA helicase, Moloney leukemia virus 10 (MOV10), and other proteins involved in RISC-mediated silencing, including Ago2. Furthermore, NF90 association with MOV10 and Ago2 was found to be RNA-dependent. Glycerol gradient sedimentation of NF90 immune complexes indicates that these proteins occur in the same protein complex. At target RNAs predicted to bind both NF90 and MOV10 in their 3′ UTRs, NF90 association was increased upon loss of MOV10 and vice versa. Interestingly, loss of NF90 led to an increase in association of Ago2 as well as a decrease in the abundance of the target mRNA. Similarly, during hypoxia, the binding of Ago2 to vascular endothelial growth factor (VEGF) mRNA increased after loss of NF90, while the level of VEGF mRNA decreased. Conclusions These findings reveal that, in the cytoplasm, NF90 can associate with components of RISC such as Ago2 and MOV10. In addition, the data indicate that NF90 and MOV10 may compete for the binding of common target mRNAs, suggesting a role for NF90 in the regulation of RISC-mediated silencing by stabilizing target mRNAs, such as VEGF, during cancer-induced hypoxia.

Background and Purpose: In online adaptive stereotactic body radiotherapy treatments, linear accelerator delivery accuracy is essential. Recently introduced double stack multileaf collimators (MLCs) have new facets in their calibration. We established a radiation-based leaf-individual calibration (LIMCA) method for double stack MLCs. Materials and Methods: MLC leaf positions were evaluated from four cardinal angles with test patterns at measurement positions throughout the radiation field on EBT3 radiochromic film for each single stack. The accuracy of the method and repeatability of the results were assessed. The effect of MLC positioning errors was characterized for a measured output factor curve and a clinical patient plan. Results: All positions in the motor step – position calibration file were optimized in the established LIMCA method. The resulting double stack mean accuracy for all angles was 0.2 ± 0.1 mm for X1 (left bank) and 0.2 ± 0.2 mm for X2 (right bank). The accuracy of the leaf position evaluation was 0.2 mm (95% confidence level). The MLC calibration remained stable over four months. Small MLC leaf position errors (e.g. 1.2 mm field size reduction) resulted in important dose errors (−5.8 %) for small quadratic fields of 0.83 × 0.83 cm2. Single stack position accuracy was essential for highly modulated treatment plans. Conclusions: LIMCA is a new double stack MLC calibration method that increases treatment accuracy from four angles and for all moving leaves.

AimsWe aimed to assess the impact of diabetes on sudden cardiac arrest (SCA) in US patients hospitalized for ST-elevation myocardial infarction (STEMI).MethodsWe used the National Inpatient Sample (2005–2017) data to identify adult patients with STEMI. The primary outcome was in-hospital SCA. Secondary outcomes included in-hospital mortality, ventricular tachycardia (VT), ventricular fibrillation (VF), cardiogenic shock (CS), acute renal failure (ARF), and the revascularization strategy in SCA patients.ResultsSCA significantly increased from 4% in 2005 to 7.6% in 2018 in diabetes patients and from 3% in 2005 to 4.6% in 2018 in non-diabetes ones (p

AimsPrimary hyperaldosteronism (PA) is a common cause of hypertension. It is more prevalent in patients with diabetes. We assessed the cardiovascular impact of PA in patients with established hypertension and diabetes.MethodsData from the National Inpatient Sample (2008-2016) was used to identify adults with PA with hypertension and diabetes comorbidities and then compared to non-PA patients. The primary outcome was in-hospital death. Secondary outcomes included ischemic stroke, hemorrhagic stroke, acute renal failure, atrial fibrillation, and acute heart failure.ResultsA total of 48,434,503 patients with hypertension and diabetes were included in the analysis, of whom 12,850 (0.03%) were diagnosed with primary hyperaldosteronism (PA). Compared to patients with hypertension and diabetes but no PA, those with PA were more likely to be younger [63(13) vs. 67 (14), male (57.1% vs. 48.3%), and African-Americans (32% vs. 18.5%) (p

ContextSince 2013, the World Health Organization has recommended integrated control strategies for neglected tropical diseases (NTDs) with skin manifestations. We evaluated the implementation of an integrated approach to the early detection and rapid treatment of skin NTDs based on mobile clinics in the Ouémé and Plateau areas of Benin.MethodsThis descriptive cross-sectional study was performed in Ouémé and Plateau in Benin from 2018 to 2020. Consultations using mobile teams were performed at various sites selected by reasoned choice based on the epidemiological data of the National Program for the Control of Leprosy and Buruli Ulcer. All individuals presenting with a dermatological lesion who voluntarily approached the multidisciplinary management team on the day of consultation were included. The information collected was kept strictly anonymous and was entered into an Excel 2013 spreadsheet and analyzed with Stata 11 software.ResultsIn total, 5,267 patients with various skin conditions consulted the medical team. The median age of these patients was 14 years (IQR: 7-34 years). We saw 646 (12.3%) patients presenting NTDs with skin manifestations, principally scabies, in 88.4% (571/646), followed by 37 cases of Buruli ulcer (5.8%), 22 cases of leprosy (3.4%), 15 cases of lymphatic filariasis (2.3%) and one case of mycetoma (0.2%). We detected no cases of yaws.ConclusionThis sustainable approach could help to decrease the burden of skin NTDs in resource-limited countries.

Abstract Background Elevated endothelial microparticles (EMPs) levels are surrogate markers of vascular dysfunction. We analyzed EMPs with apoptotic characteristics and assessed the angiogenic contents of microparticles in the blood of patients with type 2 diabetes (T2D) according to the presence of coronary artery disease (CAD). Methods A total of 80 participants were recruited and equally classified as (1) healthy without T2D, (2) T2D without cardiovascular complications, (3) T2D and chronic coronary artery disease (CAD), and (4) T2D and acute coronary syndrome (ACS). MPs were isolated from the peripheral circulation, and EMPs were characterized using flow cytometry of CD42 and CD31. CD62E was used to determine EMPs’ apoptotic/activation state. MPs content was extracted and profiled using an angiogenesis array. Results Levels of CD42- CD31 + EMPs were significantly increased in T2D with ACS (257.5 ± 35.58) when compared to healthy subjects (105.7 ± 12.96, p

Polar codes are one of the most recent additions to the family of forward error correction (FEC) codes, having recently been adopted in the 5G New Radio (NR) standard for the control channel. However, the stringent requirements introduced by the 5G standard in terms of block length and code rate flexibility, along with low end-to-end latency and high error correction performance represent a major challenge for their hardware implementation. In this context, we study the impact of main code and decoder design parameters on the latency, throughput, and the hardware complexity of semi-parallel decoding architectures. The impact of these parameters on the hardware efficiency of semi-parallel architectures is significant. Therefore, we propose two multi-frame decoding approaches that increase the throughput and improve the utilisation rate of the processing units of these architectures. Detailed analytical and logic synthesis results are provided and compared for a large range of values in order to constitute a reference for the implementation of flexible, yet efficient FEC decoders for polar codes.

Aims: We aimed to assess diabetes outcomes in heart failure (HF) patients with hypertrophic cardiomyopathy (HCM).Methods: The National Inpatient Sample database was analyzed to identify records from 2005 to 2015 of patients hospitalized for HF with concomitant HCM. We examined the prevalence of diabetes in those patients, assessed the temporal trend of in-hospital mortality, ventricular fibrillation, atrial fibrillation, and cardiogenic shock and compared diabetes patients to their non-diabetes counterparts.Results: Among patients with HF, 0.26% had HCM, of whom 29.3% had diabetes. Diabetes prevalence increased from 24.8% in 2005 to 32.7% in 2015. The mean age of patients with diabetes decreased from 71 ± 13 to 67.6 ± 14.2 (p < 0.01), but the prevalence of cardiovascular risk factors significantly increased. In-hospital mortality decreased from 4.3% to 3.2% between 2005 and 2015. Interestingly, cardiogenic shock, VF, and AF followed an upward trend. Age (OR = 1.04 [1.03–1.05]), female gender (OR = 1.50 [0.72–0.88]), and cardiovascular risk factors were associated with a higher in-hospital mortality risk in diabetes. Compared to non-diabetes patients, the ones with diabetes were younger and had more comorbidities. Unexpectedly, the adjusted risks of in-hospital mortality (aOR = 0.88 [0.76–0.91]), ventricular fibrillation (aOR = 0.79 [0.71–0.88]) and atrial fibrillation (aOR 0.80 [0.76–0.85]) were lower in patients with diabetes, but not cardiogenic shock (aOR 1.01 [0.80–1.27]). However, the length of stay was higher in patients with diabetes, and so were the total charges per stay.Conclusion: In total, we observed a temporal increase in diabetes prevalence among patients with HF and HCM. However, diabetes was paradoxically associated with lower in-hospital mortality and arrhythmias.

AimsWe aimed to assess the impact of hypoglycemia in ST-elevation myocardial infarction (STEMI).BackgroundHypoglycemia increases the risk of mortality in patients with diabetes and high cardiovascular risk.MethodsWe used the National Inpatient Sample (2005–2017) database to identify adult patients with STEMI as the primary diagnosis. The secondary diagnosis was hypoglycemia. We compared cardiovascular and socio-economic outcomes between STEMI patients with and without hypoglycemia and assessed temporal trends.ResultsHypoglycemia tends to complicate 0.17% of all cases hospitalized for STEMI. The mean age (±SD) of STEMI patients hospitalized with hypoglycemia decreased from 67 ± 15 in 2005 to 63 ± 12 in 2017 (p = 0.046). Mortality was stable with time, but the prevalence of ventricular tachycardia, ventricular fibrillation, acute renal failure, cardiogenic shock, total charges, and length of stay (LOS) increased with time (p < 0.05 for all). Compared to non-hypoglycemic patients, those who developed hypoglycemia were older and more likely to be black; only 6.7% had diabetes compared to 28.5% of STEMI patients (p = 0.001). Cardiovascular events were more likely to occur in hypoglycemia: mortality risk increased by almost 2.5-fold (adjusted OR = 2.625 [2.095–3.289]). There was a higher incidence of cardiogenic shock (adjusted OR = 1.718 [1.387–2.127]), atrial fibrillation (adjusted OR = 1.284 [1.025–1.607]), ventricular fibrillation (adjusted OR = 1.799 [1.406–2.301]), and acute renal failure (adjusted OR = 2.355 [1.902–2.917]). Patients who developed hypoglycemia were less likely to have PCI (OR = 0.596 [0.491–0.722]) but more likely to have CABG (OR = 1.792 [1.391–2.308]). They also had a longer in-hospital stay and higher charges/stay.ConclusionHypoglycemia is a rare event in patients hospitalized with STEMI. However, it was found to have higher odds of mortality, arrhythmias, and other comorbidities, irrespective of diabetes.

Abstract Transcatheter aortic valve replacement (TAVR) has shown to reduce mortality compared to surgical aortic valve replacement (sAVR). However, it is unknown which procedure is associated with better post-procedural valvular function. We conducted a meta-analysis of randomized clinical trials that compared TAVR to sAVR for at least 2 years. The primary outcome was post-procedural patient-prosthesis-mismatch (PPM). Secondary outcomes were post-procedural and 2-year: effective orifice area (EOA), paravalvular gradient (PVG) and moderate/severe paravalvular leak (PVL). We identified 6 trials with a total of 7022 participants with severe aortic stenosis. TAVR was associated with 37% (95% CI [0.51–0.78) mean RR reduction of post-procedural PPM, a decrease that was not affected by the surgical risk at inclusion, neither by the transcatheter heart valve system. Postprocedural changes in gradient and EOA were also in favor of TAVR as there was a pooled mean difference decrease of 0.56 (95% CI [0.73–0.38]) in gradient and an increase of 0.47 (95% CI [0.38–0.56]) in EOA. Additionally, self-expandable valves were associated with a higher decrease in gradient than balloon ones (beta = 0.38; 95% CI [0.12–0.64]). However, TAVR was associated with a higher risk of moderate/severe PVL (pooled RR: 9.54, 95% CI [5.53–16.46]). All results were sustainable at 2 years.

Abstract Multi-drug resistance is posing major challenges in suppressing the population of pests. Many herbivores develop resistance, causing a prolonged survival after exposure to a previously effective pesticide. Consequently, resistant pests reduce the yield of agricultural production, causing significant economic losses and reducing food security. Therefore, overpowering resistance acquisition of crop pests is a must. The ATP binding cassette transporters (ABC transporters) are considered as the main participants to the pesticide efflux and their neutralization will greatly contribute to potentiate failed treatments. Real-Time PCR analysis of 19 ABC transporter genes belonging to the ABCB, ABCC, ABCG, and ABCH revealed that a broad range of efflux pumps is activated in response to the exposure to pesticides. In this study, we used beauvericin (BEA), a known ABC transporters modulator, to resensitize different strains of Tetranychus urticae after artificial selection for resistance to cyflumetofen, bifenazate, and abamectin. Our results showed that the combinatorial treatment of pesticide (manufacturer’s recommended doses) + BEA (sublethal doses: 0.15 mg/L) significantly suppressed the resistant populations of T. urticae when compared to single-drug treatments. Moreover, after selective pressure for 40 generations, the LC50 values were significantly reduced from 36.5, 44.7, and 94.5 (pesticide) to 8.3, 12.5, and 23.4 (pesticide + BEA) for cyflumetofen, bifenazate, and abamectin, respectively. While the downstream targets for BEA are still elusive, we demonstrated hereby that it synergizes with sub-lethal doses of different pesticides and increases their effect by inhibiting ABC transporters. This is the first report to document such combinatorial activity of BEA against higher invertebrates paving the way for its usage in treating refractory cases of resistance to pesticides. Moreover, we demonstrated, for the first time, using in silico techniques, the higher affinity of BEA to ABC transformers subfamilies when compared to xenobiotics; thus, elucidating the pathway of the mycotoxin.

Abstract The prevalence and incidence of diabetes mellitus (DM) are increasing worldwide. We aim to assess mortality and socio-economic outcomes among patients hospitalized for stroke and diabetes in the US and evaluate their recent trends. We examined: in-hospital mortality, length of stay (LoS), and overall hospital charges in diabetic patients over 18 years old who were hospitalized with a stroke from 2005 to 2014, included in the National Inpatient Sample. In those patients, the mean (SD) age slightly decreased from 70 (13) years to 69 (13) years (p-trend

Abstract Background Vitamin D deficiency is diagnosed by total serum 25-hydroxyvitamin D (25(OH)D) concentration and is associated with poor health and increased mortality; however, some populations have low 25(OH) D concentrations without manifestations of vitamin D deficiency. The Vitamin D Metabolite Ratio (VMR) has been suggested as a superior indicator of vitamin D status. Therefore, VMR was determined in a population with type 2 diabetes at high risk for vitamin D deficiency and correlated with diabetic complications. Research design and methods Four hundred sisty patients with type 2 diabetes (T2D) were recruited, all were vitamin D3 supplement naive. Plasma concentration of 25-hydroxyvitamin D3 (25(OH)D3) and its metabolites 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) and its epimer, 3-epi-25-hydroxyvitamin D3 (3-epi-25(OH)D3), were measured by LC-MS/MS analysis. VMR-1 was calculated as a ratio of 24,25(OH)2D3:25(OH)D3; VMR-2 as a ratio of 1,25(OH)2D3:25(OH)D3; VMR-3 was calculated as a ratio of 3-epi-25(OH)D3: 25(OH)D3. Results An association means that there were significant differences between the ratios found for those with versus those without the various diabetic complications studied. VMR-1 was associated with diabetic retinopathy (p = 0.001) and peripheral artery disease (p = 0.012); VMR-2 associated with hypertension (p

Objectives: The increase in resistance to antibiotics has led to the revival of colistin as the last option for treatment, which automatically led to an increase of colistin-resistant, Gram-negative bacteria. In this study, we report the presence of clinical colistin-resistant Enterobacteriaceae isolated from a Lebanese hospital. Methods: From 23 rectal swabs, eight colistin-resistant clinical strains (five Escherichia coli, two Enterobacter cloacae, and one Klebsiella pneumoniae) were isolated. Antibiotic susceptibility testing was performed using the disk diffusion method and Etest. The broth microdilution method was used to determine colistin susceptibility. Reverse transcription polymerase chain reaction (RT-PCR), standard PCR and sequencing were used to investigate genes encoding for extended-spectrum β-lactamases, carbapenemases and colistin resistance. Genotyping of these isolates was conducted by multilocus sequence typing (MLST). Results: Results of antibiotic susceptibility testing revealed that all isolates were resistant to colistin. They had MICs for colistin that ranged from 8 to 32 mg/L. Real-time PCR results showed that five strains harboured blaTEM-1 and one strain harboured blaTEM-163. Moreover, four strains were positive for blaCTX-M-15, blaCTX-M-103 and blaCTX-M-189, and K. pneumoniae harboured blaSHV-1. Observed colistin resistance was linked to amino acid substitutions into protein sequences of pmrA/B, phoP/Q, and mgrB. Interestingly, we report here a mutation in the mgrB regulator and pmrA/B, phoP/Q in colistin-resistant E. cloacae and E. coli clinical isolates for the first time in Lebanon. Conclusion: This study highlights the presence of colistin-resistant Gram-negative bacteria in a Lebanese hospital, which is worrisome. An urgent strategy needs to be adopted to avoid the spread of such bacteria.

Abstract Aims Vitamin D measurement is a composite of vitamin D2 (25(OH)D2) and D3 (25(OH)D3) levels, and its deficiency is associated with the development of type 2 diabetes (T2DM) and diabetic complications; vitamin D deficiency may be treated with vitamin D2 supplements. This study was undertaken to determine if vitamin D2 and D3 levels differed between those with and without T2DM in this Middle Eastern population, and the relationship between diabetic microvascular complications and vitamin D2 and vitamin D3 levels in subjects with T2DM. Methods Four hundred ninety-six Qatari subjects, 274 with and 222 without T2DM participated in the study. Plasma levels of total vitamin D2 and D3 were measured by LC-MS/MS analysis. Results All subjects were taking vitamin D2 and none were taking D3 supplements. Vitamin D2 levels were higher in diabetics, particularly in females, and higher levels were associated with hypertension and dyslipidemia in the diabetic subjects (p

AimsWe aimed to assess the trend and outcome of aortic valve replacement in patients with diabetes.BackgroundDiabetes is associated with higher cardiovascular events.MethodsData from the National Inpatient Sample was analyzed between 2012 and 2017. We compared hospitalizations and in-hospital cardiovascular outcomes in patients with diabetes to those without diabetes, hospitalized for aortic valve replacement.ResultsIn diabetes patients undergoing TAVR, the mean age of participants decreased from 79.6 ± 8 to 67.8 ± 8, hospitalizations increased from 0.97 to 7.68/100,000 US adults (p < 0.002 for both). There was a significant temporal decrease in mortality, acute renal failure (ARF), and stroke. Compared to non-diabetic patients, those with diabetes had a higher risk of stroke, ARF, and pacemaker requirement [adjusted OR = 1.174 (1.03–1.34), 1.294 (1.24–1.35), 1.153 (1.11–1.20), respectively], but a similar adjusted mortality risk. In diabetes patients undergoing sAVR, the mean age of participants decreased from 70.4 ± 10 to 68 ± 9 (p < 0.001), hospitalizations dropped from 7.72 to 6.63/100,000 US adults (p = 0.025), so did mortality, bleeding, and ARF. When compared to non-diabetes patients, those with diabetes were older and had a higher adjusted risk of mortality, stroke, and ARF [adjusted OR= 1.115 (1.06–1.17), 1.140 (1.05–1.23), 1.217 (1.18–1.26); respectively].ConclusionThe recent temporal trend of aortic valve replacement in patients with diabetes shows a significant increase in TAVR coupled with a decrease in sAVR. Mortality and other cardiovascular outcomes decreased in both techniques. sAVR, but not TAVR, was associated with higher in-hospital mortality risk.

AimsWe aimed to assess temporal trends in outcomes of ST-elevation myocardial infarction (STEMI) patients with diabetes and heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) and compared both groups.MethodsData from the National Inpatient Sample was analyzed between 2005 and 2017. We assessed hospitalizations rate and in-hospital mortality, ventricular tachycardia (VT), ventricular fibrillation (VF), atrial fibrillation (AF), cardiogenic shock (CS), ischemic stroke, acute renal failure (ARF), and revascularization strategy. Socio-economic outcomes consisted of the length of stay (LoS) and total charges/stay.ResultsHospitalization rate steadily decreased with time in STEMI patients with diabetes and HFrEF. Mean age (SD) decreased from 71 ± 12 to 67 ± 12 (p < 0.01), while the prevalence of comorbidities increased. Mortality was stable (around 9%). However, VT, VF, AF, CS, ischemic stroke, and ARF significantly increased with time. In STEMI patients with HFpEF and diabetes, the hospitalization rate significantly increased with time while mean age was stable. The prevalence of comorbidities increased, mortality remained stable (around 4%), but VF, ischemic stroke, and ARF increased with time. Compared to patients with HFrEF, HFpEF patients were 2 years older, more likely to be females, suffered from more cardio-metabolic risk factors, and had a higher prevalence of cardiovascular diseases. However, HFpEF patients were less likely to die [adjusted OR = 0.635 (0.601-0.670)] or develop VT [adjusted OR = 0.749 (0.703-0.797)], VF [adjusted OR = 0.866 (0.798-0.940)], ischemic stroke [adjusted OR = 0.871 [0.776-0.977)], and CS [adjusted OR = 0.549 (0.522-0.577)], but more likely to develop AF [adjusted OR = 1.121 (1.078-1.166)]. HFpEF patients were more likely to get PCI but less likely to get thrombolysis or CABG. Total charges per stay increased by at least 2-fold in both groups. There was a slight temporal reduction over the study period in the LoS of the HFpEF.ConclusionWhile hospitalizations for STEMI in patients with diabetes and HFpEF followed an upward trend, we observed a temporal decrease in those with HFrEF. Mortality was unchanged in both HF groups despite the temporal increase in risk factors. Nevertheless, HFpEF patients had lower in-hospital mortality and cardiovascular events, except for AF.

The COVID-19 pandemic involved millions of people and diabetes was identified as an associated comorbidity. Initiation of systemic corticosteroids in patients suffering from severe COVID-19 was associated with lower mortality. A surge of invasive fungal infections of the maxillofacial region, namely mucormycosis, was linked to a deadly infection known as black fungus. Black fungus, diabetes, corticosteroids, and coronavirus disease 2019 (COVID-19) all have a dysregulated immune response in common, which partly could also be attributed to interleukin 37 (IL-37). IL-37, a new cytokine of the IL-1 family, known for broadly reducing innate inflammation as well as acquired immune responses. The use of corticosteroids in diabetic COVID-19 patients, crowded hospitals, and lack of medical oxygen should be carefully considered to reduce COVID-associated secondary infections.