Cost-Effectiveness of FreeStyle Libre for Glucose Self-Management Among People with Diabetes Mellitus: A Canadian Private Payer Perspective.

Introduction: For people living with diabetes, effective glucose monitoring is a key component in diabetes care, helping to reduce disease burden, complications, and healthcare utilization. Sensor-based glucose monitoring systems, which can provide more comprehensive information about glucose levels than capillary-based self-monitoring of blood glucose (SMBG), are becoming established among people living with diabetes. The objective of this study was to assess the cost-effectiveness of glucose monitoring with FreeStyle Libre systems, compared with SMBG, from the perspective of a Canadian private payer.

Continuous glucose monitoring for self-management of diabetes in people living with type 2 diabetes mellitus on basal insulin therapy: A microsimulation model and cost-effectiveness analysis from a US perspective with relevance to Medicaid.

Background: Reducing the risks of complications is a primary goal of diabetes management, with effective glycemic control a key factor. Glucose monitoring using continuous glucose monitoring (CGM) technology is an important part of diabetes self-management, helping patients reach and maintain targeted glucose and glycated hemoglobin (HbA1c) levels. Although clinical guidelines recommended CGM use, coverage by Medicaid is limited, likely because of cost concerns.

Cost-utility analysis of a flash continuous glucose monitoring system in the management of people with type 2 diabetes mellitus on basal insulin therapy-An Italian healthcare system perspective.

Aims: To assess the cost-utility of the FreeStyle Libre flash continuous glucose monitoring (CGM) system from an Italian healthcare system perspective, when compared with self-monitoring of blood glucose (SMBG) in people living with type 2 diabetes mellitus (T2DM) receiving basal insulin.

Materials And Methods: A patient-level microsimulation model was run using Microsoft Excel for 10 000 patients over a lifetime horizon, with 3.0% discounting for costs and utilities.

Synthetic silica fibers of different length, diameter and shape: synthesis and interaction with rat (NR8383) and human (THP-1) macrophages in vitro, including chemotaxis and gene expression profile.

Background: Inhalation of biopersistent fibers like asbestos can cause strong chronic inflammatory effects, often resulting in fibrosis or even cancer. The interplay between fiber shape, fiber size and the resulting biological effects is still poorly understood due to the lack of reference materials.

Results: We investigated how length, diameter, aspect ratio, and shape of synthetic silica fibers influence inflammatory effects at doses up to 250 µg cm.

The Determination of Diabetes Utilities, Costs, and Effects Model: A Cost-Utility Tool Using Patient-Level Microsimulation to Evaluate Sensor-Based Glucose Monitoring Systems in Type 1 and Type 2 Diabetes: Comparative Validation.

Objectives: To assess the accuracy and validity of the Determination of Diabetes Utilities, Costs, and Effects (DEDUCE) model, a Microsoft-Excel-based tool for evaluating diabetes interventions for type 1 and type 2 diabetes.

Methods: The DEDUCE model is a patient-level microsimulation, with complications predicted based on the Sheffield and Risk Equations for Complications Of type 2 diabetes models for type 1 and type 2 diabetes, respectively. For this tool to be useful, it must be validated to ensure that its complication predictions are accurate.

Indirect treatment comparisons of the gene therapy etranacogene dezaparvovec versus extended half-life factor IX therapies for severe or moderately severe haemophilia B.

Introduction: Etranacogene dezaparvovec gene therapy for haemophilia B demonstrated superior efficacy at 24 months in reducing bleeds versus a ≥6-month lead-in period of prophylaxis with FIX products in the phase 3 trial, HOPE-B. In the absence of head-to-head comparisons of etranacogene dezaparvovec versus FIX products, indirect treatment comparisons (ITC) can be used.

Aim: To compare the efficacy of etranacogene dezaparvovec versus rIX-FP, rFIXFc and N9-GP using ITC, and support HOPE-B results.

Assessment of MYC and TERT copy number variations in lung cancer using digital PCR.

Objective: Lung cancer is the second most frequent cancer type and the most common cause of cancer-related deaths worldwide. Alteration of gene copy numbers are associated with lung cancer and the determination of copy number variations (CNV) is appropriate for the discrimination between tumor and non-tumor tissue in lung cancer. As telomerase reverse transcriptase (TERT) and v-myc avian myelocytomatosis viral oncogene homolog (MYC) play a role in lung cancer the aims of this study were the verification of our recent results analyzing MYC CNV in tumor and non-tumor tissue of lung cancer patients using an independent study group and the assessment of TERT CNV as an additional marker.

New 2-[(4-Amino-6--substituted-1,3,5-triazin-2-yl)methylthio]--(imidazolidin-2-ylidene)-4-chloro-5-methylbenzenesulfonamide Derivatives, Design, Synthesis and Anticancer Evaluation.

In the search for new compounds with antitumor activity, new potential anticancer agents were designed as molecular hybrids containing the structures of a triazine ring and a sulfonamide fragment. Applying the synthesis in solution, a base of new sulfonamide derivatives - was obtained by the reaction of the corresponding esters - with appropriate biguanide hydrochlorides. The structures of the compounds were confirmed by spectroscopy (IR, NMR), mass spectrometry (HRMS or MALDI-TOF/TOF), elemental analysis (C,H,N) and X-ray crystallography.

Age-dependent effects of Igf2bp2 on gene regulation, function, and aging of hematopoietic stem cells in mice.

Increasing evidence links metabolism, protein synthesis, and growth signaling to impairments in the function of hematopoietic stem and progenitor cells (HSPCs) during aging. The Lin28b/Hmga2 pathway controls tissue development, and the postnatal downregulation of this pathway limits the self-renewal of adult vs fetal hematopoietic stem cells (HSCs). Igf2bp2 is an RNA binding protein downstream of Lin28b/Hmga2, which regulates messenger RNA stability and translation.

Abundance and size of hyaluronan in naked mole-rat tissues and plasma.

Large amounts of ultra-high molecular weight hyaluronan (HA) have been described as the main cause of cancer resistance in naked mole-rats (Heterocephalus glaber, NMR). Our work examined HA metabolism in these rodents more closely. HA was localized and quantified using HA binding proteins.

Life expectancy, family constellation and stress in giant mole-rats ().

Giant mole-rats () are remarkably long-lived subterranean rodents (maximum recorded lifespan as reported here greater than 26 years) that live in families with one reproductive pair (breeders) and their non-reproductive offspring (non-breeders). Previous studies have shown that breeders live on average approximately twice as long as non-breeders, a finding contradicting the classic trade-off between reproduction and lifespan. Because recent evidence points to the hypothalamic-pituitary-adrenal axis as playing an important role in shaping the pace of ageing in mole-rats, we analysed the influence of the social environment of giant mole-rats on intrafamilial aggression levels, indicators of long-term stress, and, ultimately, mortality.

Benefits of fracture liaison services (FLS) in four Latin American countries: Brazil, Mexico, Colombia, and Argentina.

Aims: Fracture liaison services (FLS) use a multidisciplinary approach to treat patients who have experienced an osteoporotic fracture to reduce the risk of subsequent fractures. To date, there has been minimal FLS implementation in Latin America where fractures continue to be undertreated. This study aims to estimate the number of fractures averted, bed days avoided, and costs saved resulting from universal FLS implementation in Brazil, Mexico, Colombia, and Argentina.

Tnfaip2/exoc3-driven lipid metabolism is essential for stem cell differentiation and organ homeostasis.

Lipid metabolism influences stem cell maintenance and differentiation but genetic factors that control these processes remain to be delineated. Here, we identify Tnfaip2 as an inhibitor of reprogramming of mouse fibroblasts into induced pluripotent stem cells. Tnfaip2 knockout impairs differentiation of embryonic stem cells (ESCs), and knockdown of the planarian para-ortholog, Smed-exoc3, abrogates in vivo tissue homeostasis and regeneration-processes that are driven by somatic stem cells.

Synthesis, Antitumor Evaluation, Molecular Modeling and Quantitative Structure-Activity Relationship (QSAR) of Novel 2-[(4-Amino-6--substituted-1,3,5-triazin-2-yl)methylthio]-4-chloro-5-methyl--(1-benzo[]imidazol-2(3)-ylidene)Benzenesulfonamides.

A series of novel 2-[(4-amino-6-R-1,3,5-triazin-2-yl)methylthio]-4-chloro-5-methyl--(5-R--benzo[]imidazol-2()-ylidene)benzenesulfonamides - was synthesized by the reaction of 5-substituted ethyl 2-{5-R-2-[-(5-chloro--benzo[]imidazol-2()-ylidene)sulfamoyl]-4-methylphenylthio}acetate with appropriate biguanide hydrochlorides. The most active compounds, and , showed significant cytotoxic activity and selectivity against colon (HCT-116), breast (MCF-7) and cervical cancer (HeLa) cell lines (IC: 7-11 µM; 15-24 µM and 11-18 µM), respectively. Further QSAR (Quantitative Structure-Activity Relationships) studies on the cytotoxic activity of investigated compounds toward HCT-116, MCF-7 and HeLa were performed by using different topological (2D) and conformational (3D) molecular descriptors based on the stepwise multiple linear regression technique (MLR).

Synthesis, Anticancer Evaluation and Structure-Activity Analysis of Novel ()- 5-(2-Arylvinyl)-1,3,4-oxadiazol-2-yl)benzenesulfonamides.

To learn more about the structure-activity relationships of ()-3-(5-styryl-1,3,4-oxadiazol-2-yl)benzenesulfonamide derivatives, which in our previous research displayed promising in vitro anticancer activity, we have synthesized a group of novel ()-5-[(5-(2-arylvinyl)-1,3,4-oxadiazol-2-yl)]-4-chloro-2-R-benzenesulfonamides - as well as ()-4-[5-styryl1,3,4-oxadiazol-2-yl]benzenesulfonamides - and ()-2-(2,4-dichlorophenyl)-5-(2-arylvinyl)-1,3,4-oxadiazols - All target derivatives were evaluated for their anticancer activity on HeLa, HCT-116, and MCF-7 human tumor cell lines. The obtained results were analyzed in order to explain the influence of a structure of the 2-aryl-vinyl substituent and benzenesulfonamide scaffold on the anti-tumor activity. Compound , bearing 5-nitrothiophene moiety, exhibited the most potent anticancer activity against the HCT-116, MCF-7, and HeLa cell lines, with IC50 values of 0.

Comment on 'Naked mole-rat mortality rates defy Gompertzian laws by not increasing with age'.

Ruby et al. recently analyzed historical lifespan data on more than 3200 naked mole-rats, collected over a total observation period of about 38 years (Ruby et al., 2018).

The burden of osteoporosis in four Latin American countries: Brazil, Mexico, Colombia, and Argentina.

Osteoporosis is under-diagnosed and under-treated worldwide. Information on the burden of osteoporosis in Latin American countries is limited. This study aimed to estimate the economic burden of osteoporosis in adults aged 50-89 years in Brazil, Mexico, Colombia, and Argentina.

Higher gene expression stability during aging in long-lived giant mole-rats than in short-lived rats.

Many aging-associated physiological changes are known to occur in short- and long-lived species with different trajectories. Emerging evidence suggests that numerous life history trait differences between species are based on interspecies variations in gene expression. Little information is available, however, about differences in transcriptome changes during aging between mammals with diverging lifespans.

Conserved Pbp1/Ataxin-2 regulates retrotransposon activity and connects polyglutamine expansion-driven protein aggregation to lifespan-controlling rDNA repeats.

Ribosomal DNA (rDNA) repeat instability and protein aggregation are thought to be two major and independent drivers of cellular aging. Pbp1, the yeast ortholog of human ATXN2, maintains rDNA repeat stability and lifespan via suppression of RNA-DNA hybrids. ATXN2 polyglutamine expansion drives neurodegeneration causing spinocerebellar ataxia type 2 and promoting amyotrophic lateral sclerosis.

Resting cells rely on the DNA helicase component MCM2 to build cilia.

Minichromosome maintenance (MCM) proteins facilitate replication by licensing origins and unwinding the DNA double strand. Interestingly, the number of MCM hexamers greatly exceeds the number of firing origins suggesting additional roles of MCMs. Here we show a hitherto unanticipated function of MCM2 in cilia formation in human cells and zebrafish that is uncoupled from replication.

Synthesis of 2-alkylthio--(quinazolin-2-yl)benzenesulfonamide derivatives: anticancer activity, QSAR studies, and metabolic stability.

Abstract: A new series of 2-alkylthio--(quinazolin-2-yl)benzenesulfonamide derivatives have been synthesized and evaluated in vitro for their antiproliferative activity by MTT assay against cancer cell lines HCT-116, MCF-7, and HeLa as well as the NCI-60 human tumor cell lines screen. In NCI screen, three compounds inhibited approximately 50% growth of RPMI-8226 and A549/ATCC cell lines. The mean of IC calculated in MTT assays for three tested cell lines was about 45 μM for four compounds.

Target-based drug discovery through inversion of quantitative structure-drug-property relationships and molecular simulation: CA IX-sulphonamide complexes.

In this work, a target-based drug screening method is proposed exploiting the synergy effect of ligand-based and structure-based computer-assisted drug design. The new method provides great flexibility in drug design and drug candidates with considerably lower risk in an efficient manner. As a model system, 45 sulphonamides (33 training, 12 testing ligands) in complex with carbonic anhydrase IX were used for development of quantitative structure-activity-lipophilicity (property)-relationships (QSPRs).

Naked mole-rat transcriptome signatures of socially suppressed sexual maturation and links of reproduction to aging.

Background: Naked mole-rats (NMRs) are eusocially organized in colonies. Although breeders carry the additional metabolic load of reproduction, they are extremely long-lived and remain fertile throughout their lifespan. This phenomenon contrasts the disposable soma theory of aging stating that organisms can invest their resources either in somatic maintenance, enabling a longer lifespan, or in reproduction, at the cost of longevity.

Species comparison of liver proteomes reveals links to naked mole-rat longevity and human aging.

Background: Mammals display a wide range of variation in their lifespan. Investigating the molecular networks that distinguish long- from short-lived species has proven useful to identify determinants of longevity. Here, we compared the livers of young and old long-lived naked mole-rats (NMRs) and the phylogenetically closely related, shorter-lived, guinea pigs using an integrated omics approach.