Does Type 2 Diabetes Genetic Testing and Counseling Reduce Modifiable Risk Factors? A Randomized Controlled Trial of Veterans

Objective

We examined the clinical utility of supplementing type 2 diabetes mellitus (DM) risk counseling with DM genetic test results and counseling.

Research Design and Methods

In this randomized controlled trial, non-diabetic overweight/obese veteran outpatients aged 21 to 65 years received DM risk estimates for lifetime risk, family history, and fasting plasma glucose, followed by either genetic test results (CR+G; N = 303) or control eye disease counseling (CR+EYE; N = 298). All participants received brief lifestyle counseling encouraging weight loss to reduce the risk of DM.

Results

The mean age was 54 years, 53% of participants were black, and 80% were men. There was no difference between arms in weight (estimated mean difference between CR+G vs. CR+EYE at 3 months = 0.2 kg, 95% CI: −0.3 to 0.7; at 6 months = 0.4 kg, 95 % CI: −0.3 to 1.1), insulin resistance, perceived risk, or physical activity at 3 or 6 months. Calorie and fat intake were lower in the CR+G arm at 3 months (p’s ≤ 0.05) but not at 6 months (p’s > 0.20).

Conclusions

Providing patients with genetic test results was not more effective in changing patient behavior to reduce the risk of DM compared to conventional risk counseling.Trial registration: ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01060540","term_id":"NCT01060540"}}NCT01060540 http://clinicaltrials.gov/show/{"type":"clinical-trial","attrs":{"text":"NCT01060540","term_id":"NCT01060540"}}NCT01060540

Electronic supplementary material

The online version of this article (doi:10.1007/s11606-015-3315-5) contains supplementary material, which is available to authorized users.KEY WORDS: Diabetes mellitus, Genetic counseling, Risk factors     

Mutagenesis analysis of a conserved region involved in acetyl coenzyme A binding in the aminoglycoside 6'-N-acetyltransferase type Ib encoded by plasmid pJHCMW1

Alanine scanning of motif A in the pJHCMW1-encoded aminoglycoside 6'-N-acetyltransferase type Ib identified amino acids important for the ability of the enzyme to confer wild-type levels of resistance to kanamycin and amikacin. The replacement of two amino acids, D117 or L120, with alanine residues resulted in complete loss of the resistance phenotype.     

Crimean‐Congo hemorrhagic fever in the COVID‐19 pandemic: A case study

In the COVID‐19 pandemic, the overlap of clinical features between other viral infections makes a reliable diagnosis difficult in the initial stage of illness. We describe a confirmed case of CCHF in Tehran Province during this year, who was first misdiagnosed as COVID‐19 infection.     

A review on lawsone-based benzo[a]phenazin-5-ol: synthetic approaches and reactions

Phenazine systems are an important class of aza-polycyclic compounds that are easily found in nature and isolated as secondary metabolites primarily from Pseudomonas, Streptomyces, and a few other genera from soil or marine habitats. Moreover, various synthetic phenazine analogs are known for their pharmaceutical activities. Among various phenazines, benzo[a]phenazines are structural subunits in a variety of important natural products and have been given special attention due to their unique biological properties in various fields. In this review article, we highlight the synthesis of benzo[a]phenazin-5-ol derivatives from lawsone and benzene-1,2-diamines and their applications for the construction of a variety of five and six membered fused heterocycles such as pyranophenazines, spiropyranophenazines, pyridophenazines, furophenazines, benzochromenophenazines and oxazinophenazines during the period of 1995 to 2021.

Phenazine systems are an important class of aza-polycyclic compounds that are easily found in nature and isolated as secondary metabolites primarily from Pseudomonas, Streptomyces, and a few other genera from soil or marine habitats.     

High-level co-expression of complement regulators on vascular endothelium in transgenic mice: CD55 and CD59 provide greater protection from human complement-mediated injury than CD59 alone

Abstract: High-level endothelial expression of the human complement regulatory factor CD59 has been shown to protect transgenic mouse hearts from human complement-mediated injury in an ex vivo perfusion model. In this study we examine whether co-expression of CD55 provides additional protection. CD55/CD59 double-transgenic mice were generated by co-injection of CD55 and CD59 expression constructs driven by the human intercellular adhesion molecule 2 (ICAM-2) promoter. A line was established from one mouse that exhibited strong expression of CD55 and CD59 on vascular endothelium in the heart and other transplantable organs. An ex vivo perfusion model was used to compare hearts from these CD55/CD59 mice with hearts from a previously established line, which expressed CD59 at a similar level to the double transgenic line. CD59 hearts displayed prolonged survival compared to wild-type hearts during perfusion with 40% human plasma and maintained approximately 20% maximum work after 60 min. CD55/CD59 hearts were further protected, with work maintained at 35% of the maximum level after 60 min. The data demonstrate that high-level endothelial co-expression of CD55 and CD59 provides greater protection from human complement-mediated injury in this model than expression of CD59 alone.     

Adverse reaction of methylprednisolone pulse therapy: Acute respiratory distress syndrome

Methylprednisolone pulse therapy has significant anti‐inflammatory effects in multiple sclerosis. Acute respiratory distress syndrome as a probable adverse effect of methylprednisolone pulse therapy in MS patients should be considered.     

Comparing inhaled colistin with inhaled fosfomycin/tobramycin as an adjunctive treatment for ventilator-associated pneumonia: An open-label randomized controlled trial

Purpose

Although investigations are limited, adjunctive aerosolized antibiotics have been advised in the setting of gram-negative ventilator-associated pneumonia (VAP). This study aimed to compare the efficiency of inhaled colistin with inhaled fosfomycin/tobramycin in treating VAP due to extensively drug-resistant (XDR) Acinetobacter baumannii.

Methods

This single center open-label randomized controlled trial included 60 patients who developed XDR A. bumannii VAP. Eligible participants were randomly assigned to two groups (no. 30). Regardless of the assignment, all participants received meropenem (2 g as a 3-h extended infusion every 8 h) plus intravenous colistin (a loading dose of 9 million IU and then 4.5 million IU every 12 h). The control group was given inhaled colistin (1 million IU every 8 h), and the case group received inhaled tobramycin/fosfomycin (300 mg every 12 h/80 mg every 12 h) as adjunctive therapy. The primary outcome was treatment duration, and the secondary outcomes were Clinical Pulmonary Infection Score (CPIS) trend and mortality rate in the groups. The decision to stop treatment was made by the treating physician.

Results

The mean treatment duration was 13.73 ± 3.22 days in the colistin group and 10.85 ± 2.84 days in the tobramycin/fosfomycin group; the mean treatment duration in the latter group was lower significantly (P = 0.001). CPIS was decreased in the groups significantly (P < 0.001), but the mean changes of CPIS were significantly different between the groups, and in the inhaled tobramycin/fosfomycin group, a greater reduction (P = 0.005) was observed. Two (6.67%) patients in the control group and three (10%) patients in the case group died.

Conclusion

The use of inhaled tobramycin/fosfomycin in cases with XDR A. bumannii VAP was associated with a shorter treatment duration in this open-label trial.     

Anti-Vascular Endothelial Growth Factor Effects of Sorafenib and Arsenic Trioxide in Acute Myeloid Leukemia Cell Lines

Acute myeloid leukemia (AML), is a clonal disorder caused by acquired somatic mutations and chromosomal rearrangements. According to some evidence, progression of hematolymphoid malignancies depends on the induction of new blood vessel formation under the influence of acute leukemia. Various factors are produced by cancer cells under hypoxic conditions to increase vascular formation. Among these, vascular endothelial growth factor (VEGF) plays a crucial role. Cytotoxicity and anticancer effects of arsenic trioxide (ATO) have been reported in many cancers. Sorafenib, known as an angiogenic inhibitor, decreases leukemic cell survival. The aim of this study was to indicate combination effects of ATO and sorafenib in two AML cell lines, KG-1 and U937. Effective doses was determined by MTT assay for both single and combination treatments. Percentages of apoptotic cells were evaluated by Annexin V FITC staining and mRNA levels of VEGF isoforms and receptor expression were investigated by Real-Time PCR. Our data show that sorafenib (5μM and 7μM in KG-1 and U937 cell lines respectively), ATO (1.618μM and 1μM in KG-1 and U937 cell lines respectively), and also their combination significantly increased the percentage of apoptotic cells. In addition the mRNA level of VEGF isoforms was downregulated in the U937 cell line while upregulated in KG-1 cells. Taken together, our results suggest that the VEGF autocrine loop may have an influence on AML development and progression and could be consider as a therapeutic target. The combination of sorafenib as a VEGF inhibitor with ATO synergistically inhibits cell proliferation and promotes apoptosis.     

Back door modulation of the farnesoid X receptor: design, synthesis, and biological evaluation of a series of side chain modified chenodeoxycholic acid derivatives

Carbamate derivatives of bile acids were synthesized with the aim of systematically exploring the potential for farnesoid X receptor (FXR) modulation endowed with occupancy of the receptor's back door, localized between loops H1-H2 and H4-H5. Since it was previously shown that bile acids bind to FXR by projecting the carboxylic tail opposite the transactivation function 2 (AF-2, helix 12), functionalization of the side chain is not expected to interfere directly with the orientation of H12 but can result in a more indirect way of receptor modulation. The newly synthesized compounds were extensively characterized for their ability to modulate FXR function in a variety of assays, including the cell-free fluorescence resonance energy transfer (FRET) assay and the cell-based luciferase transactivation assay, and displayed a broad range of activity from full agonism to partial antagonism. Docking studies clearly indicate that the side chain of the new derivatives fits in a so far unexploited receptor cavity localized near the "back door" of FXR. We thus demonstrate the possibility of achieving a broad FXR modulation without directly affecting the H12 orientation.