Stakeholders' perspectives on the regulation and integration of complementary and alternative medicine products in Lebanon: a qualitative study

<p>Abstract</p> <p>Background</p> <p>The regulation of the markets for Complementary and Alternative Medicine (CAM) products presents a global challenge. There is a dearth of studies that have examined or evaluated the regulatory policies of CAM products in the Eastern Mediterranean Region (EMR). We investigate the regulatory frameworks and the barriers for the proper regulation and integration of CAM products in Lebanon, as an example of an EMR country with a weak public infrastructure.</p> <p>Methods</p> <p>We utilized a qualitative study design involving a series of semi-structured interviews with stakeholders of the CAM market in Lebanon. Snowball sampling was used to identify interviewees; interviews continued until the "saturation" point was reached. A total of 16 interviews were carried out with decision makers, representatives of professional associations, academic researchers, CAM product importers, policy makers and a media representative. Interviews were transcribed and thematic analysis of scripts was carried out.</p> <p>Results</p> <p>There was a consensus among all stakeholders that the regulation of the market for CAM products in Lebanon needs to be strengthened. Thematic analysis identified a number of impediments jeopardizing the safety of public consumption and hindering the integration of CAM therapies into mainstream medicine; including: weak infrastructure, poor regulation, ineffective policies and politics, weak CAM awareness and sub-optimal coordination and cooperation among stakeholders. With respect to policy instruments, voluntary instruments (self regulation) were deemed ineffective by stakeholders due to poor awareness of both users and providers on safe use of CAM products. Stakeholders' rather recommended the adoption of a combination of mixed (enhancing public awareness and integration of CAM into medical and nursing curricula) and compulsory (stricter governmental regulation) policy instruments for the regulation of the market for CAM products.</p> <p>Conclusions</p> <p>The current status quo with respect to the regulation of CAM products in Lebanon is not conducive to public safety, nor does it support the integration of CAM products into the healthcare system. The Ministry of Health indeed plays a dominant role in the regulation of these products through a combination of mixed and compulsory policy instruments. Yet, the proper implementation of these regulations requires political resolve coupled with the cooperation of all CAM stakeholders.</p

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19.

Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection

The mechanism of DNA unwinding by the eukaryotic replicative helicase

Accurate DNA replication is tightly regulated in eukaryotes to ensure genome stability during cell division and is performed by the multi-protein replisome. At the core an AAA+ hetero-hexameric complex, Mcm2-7, together with GINS and Cdc45 form the active replicative helicase Cdc45/Mcm2-7/GINS (CMG). It is not clear how this replicative ring helicase translocates on, and unwinds, DNA. We measure real-time dynamics of purified recombinant Drosophila melanogaster CMG unwinding DNA with single-molecule magnetic tweezers. Our data demonstrates that CMG exhibits a biased random walk, not the expected unidirectional motion. Through building a kinetic model we find CMG may enter up to three paused states rather than unwinding, and should these be prevented, in vivo fork rates would be recovered in vitro. We propose a mechanism in which CMG couples ATP hydrolysis to unwinding by acting as a lazy Brownian ratchet, thus providing quantitative understanding of the central process in eukaryotic DNA replication

Galectin-3 as a prognostic biomarker for diabetic nephropathy

Hossam Hodeib,1 Maha M Hagras,1 Dina Abdelhai,1 Mona M Watany,1 Amal Selim,2 Mohamed A Tawfik,2 Mohamed A Elsebaey,2 Samah A Elshweikh2 1Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt; 2Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta, Egypt Introduction: Diabetic nephropathy (DN) represents one of the main causes of end-stage renal disease in type 2 diabetes mellitus (DM) patients. Galectin-3 has been implicated in pathogenesis of many pathological conditions. To date, there are limited data regarding the relationship between galectin-3 and DN.&nbsp; Aim of the study: Evaluation of serum galectin-3 as a novel prognostic biomarker in patients with DN.&nbsp; Patients and methods: This prospective study was carried out in the Internal Medicine and Clinical Pathology Departments, Tanta University Hospital, Egypt, from March 2015 to March 2018 on 300 patients with type 2 DM. Patients were divided into three groups: group I included 100 patients with albumin/creatinine ratio (ACR) 300 mg/g (macroalbuminuria). All patients were subjected to the following: full history taking, clinical examination, and laboratory evaluation (HbA1c, creatinine, estimated glomerular filtration rate, ACR, and serum galectin-3). Results: The mean levels of galectin-3 were significantly higher in patients with macroalbuminuria than in those with microalbuminuria and normoalbuminuria. Galectin-3 was a significant predictor for progression to microalbuminuria, macroalbuminuria, dialysis, and death among patients with type 2 DM. Conclusion: Based on this single center prospective study, serum galectin-3 is considered a significant predictor for DN progression among patients with type 2 DM. Keywords: diabetic nephropathy, galectin-3, albumin/creatinine ratio, microalbuminuria, macroalbuminuria, dialysis, diabetes mellitu

CCL2 rs1024611Gene Polymorphism in Philadelphia-Negative Myeloproliferative Neoplasms

Introduction: The onset of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) is caused by acquired somatic mutations in target myeloid genes “driver mutations”. The CCL2 gene is overexpressed by non-Hodgkin lymphomas and multiple solid tumors. Aim of the study: to evaluate the possible association of CCL2 rs1024611 SNP and its expression level and the risk of developing Philadelphia-negative MPNs. Patients and methods: A total of 128 newly diagnosed Philadelphia-negative MPN patient and 141 healthy subjects were evaluated for the genotype distribution of CCL2 rs1024611 and CCL2 expression levels. Results: The CCL2 rs1024611 G/G genotype was more frequent and significantly frequent among PMF and Post-PV/ET-MF patients and the mean CCL2 expression levels were significantly higher in PMF and Post-PV/ET-MF compared to the healthy subjects. The CCL2 rs1024611 SNP was significantly correlated to the CCL2 gene expression level and fibrosis grade. ROC analysis for the CCL2 gene expression level that discriminates MF patients from PV + ET patients revealed a sensitivity of 80.43% and a specificity of 73.17% with an AUC of 0.919 (p < 0.001). Conclusion: The CCL2 rs1024611 polymorphism could be an independent risk factor for developing MF (PMF and Post-PV/ET-MF). Moreover, CCL2 gene expression could be potential genetic biomarker of fibrotic progression

Socioeconomic status as a predictor of adherence to treatment guidelines for early-stage ovarian cancer

Objective Investigate the impact of socioeconomic status and other demographic variables on adherence to the National Comprehensive Cancer Network ovarian cancer treatment guidelines among patients with stage I/II disease. Methods Patients diagnosed with stage I/II epithelial ovarian cancer between 1/1/96-12/31/06 were identified from the California Cancer Registry. Univariate analysis and multivariate logistic regression models were used to evaluate differences in surgical procedures, chemotherapy regimens, and overall adherence to the NCCN guidelines according to increasing SES quintiles (SES-1 to SES-5). Results A total of 5445 stage I and II patients were identified. The median age at diagnosis was 54.0 years (range = 18-99 years); 72.5% of patients had stage I disease, while 27.5% had stage II disease. With a median follow-up time of 5 years, the 5-year ovarian cancer-specific survival for all patients was 82.7% (SE = 0.6%). Overall, 23.7% of patients received care that was adherent to the NCCN guidelines. Compared to patients in the highest SES quintile (SES-5), patients in the lowest SES quintile (SES-1) were significantly less likely to receive proper surgery (27.3% vs 47.9%, p &lt; 0.001) or chemotherapy (42.4% vs 53.6%, p &lt; 0.001). There were statistically significant trends between increasing SES and the likelihood of overall treatment plan adherence to the NCCN guidelines: SES-1 = 16.4%, SES-2 = 19.0%, SES-3 = 22.4%, SES-4 = 24.2% and SES-5 = 31.6% (p &lt; 0.001). Multivariate logistic regression analysis revealed that compared to SES-5, decreasing SES was independently predictive of a higher risk of non-standard overall care. Conclusions For patients with early-stage ovarian cancer, low SES is a significant and independent predictor of deviation from the NCCN guidelines for surgery, chemotherapy, and overall treatment

Genetic Risk Profiling Associated with Recurrent Unprovoked Venous Thromboembolism

Introduction: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and/or pulmonary embolism (PE), is a common, acute, multifactorial disease with a five-years cumulative incidence of recurrence of approximately 25%. Actually, no single genetic defect can predict the risk of recurrence of VTE. Therefore, individual genetic risk profiling could be useful for the prediction of VTE recurrence. Aim of the study: To assess the combined effect of the common prothrombotic genotypes on the risk of recurrence of VTE in recently diagnosed unprovoked VTE patients. Patients and methods: This population based, prospective follow-up study was carried out from January 2015 to December 2020 in (internal medicine, cardiovascular medicine and anesthesia and ICU departments, Tanta University Hospital, Egypt) on 224 recently diagnosed unprovoked VTE patients. Whole blood was collected by standard venipuncture at the time of admission prior to the beginning of anticoagulant therapy. Genomic DNA was extracted and was genotyped for the 5-SNPs Genetic risk score (GRS), previously validated for first venous thrombosis (FVL rs6025, PTM rs1799963, ABO rs8176719, FGG rs2066865 and FXI rs2036914). Results: The main important finding in the present study was that patients having ≥3 risk alleles were associated with higher risk of VTE recurrence compared to those having ≤2 risk alleles (the reference group) (HR 2.5, 95% CI 1.48–4.21) (p = 0.001). Patients with GRS ≥ 3 had a significantly shorter time recurrence free survival (43.07 months) compared to the low risk group of patients with GRS (0–2) (p &lt; 0.001). Conclusion: GRS model could be an effective and useful model in risk stratification of VTE patients, and genetic risk profiling of VTE patients could be used for the prediction of recurrence of VTE

The Impact of SKP2 Gene Expression in Chronic Myeloid Leukemia

Introduction: The prognosis of chronic myeloid leukemia (CML) patients has been dramatically improved with the introduction of imatinib (IM), the first tyrosine kinase inhibitor (TKI). TKI resistance is a serious problem in IM-based therapy. The human S-phase kinase-associated protein 2 (SKP2) gene may play an essential role in the genesis and progression of CML. Aim of the study: We try to explore the diagnostic/prognostic impact of SKP2 gene expression to predict treatment response in first-line IM-treated CML patients at an early response stage. Patients and methods: The gene expression and protein levels of SKP2 were determined using quantitative RT-PCR and ELISA in 100 newly diagnosed CML patients and 100 healthy subjects. Results: SKP2 gene expression and SKP2 protein levels were significantly upregulated in CML patients compared to the control group. The receiver operating characteristic (ROC) analysis for the SKP2 gene expression level, which that differentiated the CML patients from the healthy subjects, yielded a sensitivity of 86.0% and a specificity of 82.0%, with an area under the curve (AUC) of 0.958 (p &lt; 0.001). The ROC analysis for the SKP2 gene expression level, which differentiated optimally from the warning/failure responses, yielded a sensitivity of 70.59% and a specificity of 71.21%, with an AUC of 0.815 (p &lt; 0.001). Conclusion: The SKP2 gene could be an additional diagnostic and an independent prognostic marker for predicting treatment responses in first-line IM-treated CML patients at an early time point (3 months)