Once-Weekly Exenatide Versus Once- or Twice-Daily Insulin Detemir: Randomized, open-label, clinical trial of efficacy and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas

OBJECTIVEdThis multicenter, open-label, parallel-arm study compared the efficacy and safety of exenatide once weekly (EQW) with titrated insulin detemir in patients with type 2 diabetes inadequately controlled with metformin (with or without sulfonylureas). RESEARCH DESIGN AND METHODSdPatients were randomized to EQW (2 mg) or detemir (once or twice daily, titrated to achieve fasting plasma glucose #5.5 mmol/L) for 26 weeks. The primary outcome was proportion of patients achieving A1C #7.0% and weight loss $1.0 kg at end point, analyzed by means of logistic regression. Secondary outcomes included measures of glycemic control, cardiovascular risk factors, and safety and tolerability. RESULTSdOf 216 patients (intent-to-treat population), 111 received EQW and 105 received detemir. Overall, 44.1% (95% CI, 34.7–53.9) of EQW-treated patients compared with 11.4% (6.0–19.1) of detemir-treated patients achieved the primary outcome (P , 0.0001). Treatment with EQW resulted in significantly greater reductions than detemir in A1C (least-square mean 6 SE, 21.30 6 0.08% vs. 20.88 6 0.08%; P , 0.0001) and weight (22.7 6 0.3 kg vs. +0.8 6 0.4 kg; P , 0.0001). Gastrointestinal-related and injection site–related adverse events occurred more frequently with EQW than with detemir. There was no major hypoglycemia in either group. Five (6%) patients in the EQW group and six (7%) patients in the detemir group experienced minor hypoglycemia; only one event occurred without concomitant sulfonylureas (detemir group). CONCLUSIONSdTreatment with EQW resulted in a significantly greater proportion of patients achieving target A1C and weight loss than treatment with detemir, with a low risk of hypoglycemia. These results suggest that EQW is a viable alternative to insulin detemir treatment in patients with type 2 diabetes with inadequate glycemic control using oral antidiabetes drugs

The missing gonadotropin-releasing hormone agonist trigger leading to missing oocytes

Authors present a case of Genuine EFS in a young woman where no oocytes were retrieved in the first stimulation cycle after single ovulation trigger. However, a repeat stimulation performed with double ovulation trigger yielded enough oocytes

Development of a semi-automated method for measuring urinary iodine and its application in epidemiological studies in Brazilian schoolchildren

In this study we developed a semi-automated method for the measurement of urinary iodine using firstly ammonium persulfate for digestion of urine followed by estimation of iodine content in the Sandell-Kolthoff reaction, in which iodine acts as a catalyst for the reduction of cerium. This method was validated in the 3rd Brazilian National Survey of iodine deficiency in 1994. We studied 16,803 casual urine samples from schoolchildren of 401 cities and found 4 moderately-deficient towns (Almas, Arraias, and Parana, in the State of Tocantins, and Cocos, in the State of Bahia), and 116 mildly-deficient. This work suggests that despite the salt iodization program, there was some iodine-deficient areas in Brazil in 1994. Recent surveys, involving less cities, are indicating an excess of iodine ingestion. Therefore, in a country of continental dimensions and very heterogeneous in terms of public health, periodical evaluations are necessary to monitor the real situation of iodine nutrition in Brazil. the method developed in this paper is suitable for these surveys.Univ Estadual Maringa, Dept Med, Ctr Ciencias Saude, Maringa, Parana, BrazilUniversidade Federal de São Paulo, Mol Endocrinol Lab, Disciplina Endocrinol, Dept Med,Escola Paulista Med, BR-04032029 São Paulo, BrazilUniversidade Federal de São Paulo, Mol Endocrinol Lab, Disciplina Endocrinol, Dept Med,Escola Paulista Med, BR-04032029 São Paulo, BrazilWeb of Scienc

Impact of Cardio-Renal-Metabolic Comorbidities on Cardiovascular Outcomes and Mortality in Type 2 Diabetes Mellitus

BACKGROUND: We evaluated the incremental contribution of chronic kidney disease (CKD) to the risk of major adverse cardiovascular (CV) events (MACE), heart failure (HF), and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) patients and its importance relative to the presence of other cardio-renal-metabolic (CaReMe) comorbidities. METHODS: Patients (≥40 years) were identified at the time of T2DM diagnosis from US (Humedica/Optum) and UK (Clinical Practice Research Datalink) databases. Patients were monitored post-diagnosis for modified MACE (myocardial infarction, stroke, ACM), HF, and ACM. Adjusted hazard ratios were obtained using Cox proportional-hazards regression to evaluate the relative risk of modified MACE, HF, and ACM due to CKD. Patients were stratified by the presence or absence of atherosclerotic CV disease (ASCVD) and age. RESULTS: Between 2011 and 2015, of 227,224 patients identified with incident T2DM, 40,063 (17.64%) had CKD. Regardless of prior ASCVD, CKD was associated with higher risk of modified MACE, HF, and ACM; this excess hazard was more pronounced in older patients with prior ASCVD. In time-to-event analyses in the overall cohort, patients with T2DM + CKD or T2DM + CKD + hypertension + hyperlipidemia had increased risks for modified MACE, HF, and ACM versus patients with T2DM and no CaReMe comorbidities. Patients with CKD had higher risks for and shorter times to modified MACE, HF, and ACM than those without CKD. CONCLUSION: In T2DM patients, CKD presence was associated with higher risk of modified MACE, HF, and ACM. This may have risk-stratification implications for T2DM patients based on background CKD and highlights the potential importance of novel renoprotective strategies

Overall Health and the Influence of Physical Therapy on Physical Function Following Total Ankle Arthroplasty

Background: The overall health and the importance of physical therapy for people following total ankle arthroplasty (TAA) have been understudied. Our purpose was to characterize the overall health of patients following TAA, and explore the frequency, influence, and patient-perceived value of physical therapy. Methods: People who received a TAA participated in this retrospective cohort online survey study. The survey included medical history questions and items from the Patient-Reported Outcomes Measurement Information System (PROMIS) Short Forms. Seven PROMIS domains, reflecting the biopsychosocial model of care (physical, mental, social), were included to examine participant overall health status in comparison to the general population. Items regarding physical therapy participation (yes/no), number of visits, and perceived value (scale 0-10; 10 = extremely helpful) were also included. Descriptive statistics were generated for participant characteristics, PROMIS domain T scores, and physical therapy questions. The influence of participant characteristics or physical therapy visits on PROMIS domain T scores that scored below the population mean were examined with multiple linear regression or ordinal regression. Results: The response rate was 61% (n=95). Average postoperative time was approximately 3 years (mean [SD]: 40.0 [35.3] months). Physical function and ability to participate in social roles and activities domain T scores were at least 1 SD below the population mean. Most patients received physical therapy (86%; 17.1 [11.0] visits) and found it helpful (7.2 [3.0]). Participant characteristics were minimally predictive of physical function and social participation T scores. Number of physical therapy visits predicted physical function T scores (P = .03). Conclusions: Most health domain scores approached the population mean. Physical therapy was perceived to have a high value, and greater visits were related to greater physical function. However, lower physical function and social participation scores suggest that postoperative care directed toward these domains could improve the value of TAA and promote overall health

A high pressure XRD setup at ADXRD beamline (BL-12) on Indus-2

A high pressure XRD measurement setup in the angle dispersive geometry has been setup in the Angle Dispersive X-ray diffraction beamline (BL-12) in Indus-2 synchrotron facility. The X-ray beam is collimated inside the Diamond Anvil Cell (DAC) using a pair of cross-slit collimators and 100 micron orifice in a 400 micron thick Ta sheet. With the use of an adaptive optics to ensure a converging beam at the sample position, the need of an X-ray beam collimator is eliminated making the alignment of the DAC quite easy. The alignment of the DAC with respect to the incident X-ray beam is made by placing it on a computer controlled sample mounting and alignment stage developed specifically for this setup. Interactive software has been developed to make the alignment of the X-ray through the DAC very easy and accurate. NIST standard LaB6 powder was used for test runs, and a few fine pieces of gold served as pressure calibrator. The data was recorded on a MAR345 Image plate detector

Phosphofructo-1-Kinase Deficiency Leads to a Severe Cardiac and Hematological Disorder in Addition to Skeletal Muscle Glycogenosis

Mutations in the gene for muscle phosphofructo-1-kinase (PFKM), a key regulatory enzyme of glycolysis, cause Type VII glycogen storage disease (GSDVII). Clinical manifestations of the disease span from the severe infantile form, leading to death during childhood, to the classical form, which presents mainly with exercise intolerance. PFKM deficiency is considered as a skeletal muscle glycogenosis, but the relative contribution of altered glucose metabolism in other tissues to the pathogenesis of the disease is not fully understood. To elucidate this issue, we have generated mice deficient for PFKM (Pfkm−/−). Here, we show that Pfkm−/− mice had high lethality around weaning and reduced lifespan, because of the metabolic alterations. In skeletal muscle, including respiratory muscles, the lack of PFK activity blocked glycolysis and resulted in considerable glycogen storage and low ATP content. Although erythrocytes of Pfkm−/− mice preserved 50% of PFK activity, they showed strong reduction of 2,3-biphosphoglycerate concentrations and hemolysis, which was associated with compensatory reticulocytosis and splenomegaly. As a consequence of these haematological alterations, and of reduced PFK activity in the heart, Pfkm−/− mice developed cardiac hypertrophy with age. Taken together, these alterations resulted in muscle hypoxia and hypervascularization, impaired oxidative metabolism, fiber necrosis, and exercise intolerance. These results indicate that, in GSDVII, marked alterations in muscle bioenergetics and erythrocyte metabolism interact to produce a complex systemic disorder. Therefore, GSDVII is not simply a muscle glycogenosis, and Pfkm−/− mice constitute a unique model of GSDVII which may be useful for the design and assessment of new therapies

Metaproteomic evidence of changes in protein expression following a change in electrode potential in a robust biocathode microbiome

Microorganisms that respire electrodes may be exploited for biotechnology applications if key pathways for extracellular electron transfer (EET) can be identified and manipulated through bioengineering. To determine whether expression of proposed Biocathode-MCL EET proteins are changed by modulating electrode potential without disrupting the relative distribution of microbial constituents, metaproteomic and 16S rRNA gene expression analyses were performed after switching from an optimal to suboptimal potential based on an expected decrease in electrode respiration. Five hundred and seventy-nine unique proteins were identified across both potentials, the majority of which were assigned to three previously defined Biocathode-MCL metagenomic clusters: a Marinobacter sp., a member of the family Chromatiaceae, and a Labrenzia sp. Statistical analysis of spectral counts using the Fisher's exact test identified 16 proteins associated with the optimal potential, five of which are predicted electron transfer proteins. The majority of proteins associated with the suboptimal potential were involved in protein turnover/turnover, motility, and membrane transport. Unipept and 16S rRNA gene expression analyses indicated that the taxonomic profile of the microbiome did not change after 52 hours at the suboptimal potential. These findings show that protein expression is sensitive to the electrode potential without inducing shifts in community composition, a feature that may be exploited for engineering Biocathode-MCL

Photoconductivity of biased graphene

Graphene is a promising candidate for optoelectronic applications such as photodetectors, terahertz imagers, and plasmonic devices. The origin of photoresponse in graphene junctions has been studied extensively and is attributed to either thermoelectric or photovoltaic effects. In addition, hot carrier transport and carrier multiplication are thought to play an important role. Here we report the intrinsic photoresponse in biased but otherwise homogeneous graphene. In this classic photoconductivity experiment, the thermoelectric effects are insignificant. Instead, the photovoltaic and a photo-induced bolometric effect dominate the photoresponse due to hot photocarrier generation and subsequent lattice heating through electron-phonon cooling channels respectively. The measured photocurrent displays polarity reversal as it alternates between these two mechanisms in a backgate voltage sweep. Our analysis yields elevated electron and phonon temperatures, with the former an order higher than the latter, confirming that hot electrons drive the photovoltaic response of homogeneous graphene near the Dirac point