Growth and metabolic performance of house fly and black soldier fly larvae differ across densities and waste-based growth substrates.

Large scale production of insect larvae is considered a sustainable way to upcycle various organic waste- and by-products into more valuable food and feed products. The sustainability of insect larvae production depends on the substrates and species being used, but comparative studies that include both growth and efficiency are lacking. Here we compare larval fitness, including survival, development time, weight, substrate conversion efficiency, substrate reduction, and metabolic parameters across different combinations of densities and waste- and by-product-based substrates on the two fly species, the house fly (Musca domestica) and the black soldier fly (Hermetia illucens).

Cholinergic dysfunction in the dorsal striatum promotes habit formation and maladaptive eating.

Dysregulation of habit formation has been recently proposed as pivotal to eating disorders. Here, we report that a subset of patients suffering from restrictive anorexia nervosa have enhanced habit formation compared with healthy controls. Habit formation is modulated by striatal cholinergic interneurons.

Effects of Serotonin and Slow-Release 5-Hydroxytryptophan on Gastrointestinal Motility in a Mouse Model of Depression.

Background & Aims: Mood disorders and constipation are often comorbid, yet their shared etiologies have rarely been explored. The neurotransmitter serotonin (5-HT) regulates central nervous system and enteric nervous system (ENS) development and long-term functions, including gastrointestinal (GI) motility and mood. Therefore, defects in neuron production of 5-HT might result in brain and intestinal dysfunction.

Slow-release delivery enhances the pharmacological properties of oral 5-hydroxytryptophan: mouse proof-of-concept.

5-hydroxytryptophan (5-HTP) has shown therapeutic promise in a range of human CNS disorders. But native 5-HTP immediate release (IR) is poorly druggable, as rapid absorption causes rapid onset of adverse events, and rapid elimination causes fluctuating exposure. Recently, we reported that 5-HTP delivered as slow-release (SR) in mice augmented the brain pro-serotonergic effect of selective serotonin reuptake inhibitors (SSRIs), without the usual adverse events associated with 5-HTP IR.

Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea: The PIONEER 3 Randomized Clinical Trial.

Importance: Phase 3 trials have not compared oral semaglutide, a glucagon-like peptide 1 receptor agonist, with other classes of glucose-lowering therapy.

Objective: To compare efficacy and assess long-term adverse event profiles of once-daily oral semaglutide vs sitagliptin, 100 mg added on to metformin with or without sulfonylurea, in patients with type 2 diabetes.

Design, Setting, And Participants: Randomized, double-blind, double-dummy, parallel-group, phase 3a trial conducted at 206 sites in 14 countries over 78 weeks from February 2016 to March 2018.

No QTc Prolongation with Semaglutide: A Thorough QT Study in Healthy Subjects.

Introduction: Semaglutide is a glucagon-like peptide-1 (GLP-1) analog approved for the once-weekly treatment of type 2 diabetes. The objective of this 16-week, double-blind, single-center thorough QT study was to confirm that semaglutide treatment does not prolong cardiac repolarization versus placebo. Prolongation of the QT interval is a biomarker for ventricular tachyarrhythmia.

Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: a randomised, double-blind, placebo-controlled trial.

Aims/hypothesis: Semaglutide is a glucagon-like peptide-1 analogue in development for the treatment of type 2 diabetes. Its effects on first- and second-phase insulin secretion and other measures of beta cell function and glycaemic control were assessed.

Methods: In this single-centre, double-blind, placebo-controlled, parallel-group trial, conducted at the Profil Institut für Stoffwechselforschung, Germany, 75 adult (aged 18-64 years) participants with type 2 diabetes (eligibility: HbA of 6.

Soluble Ectodomain of Neuroligin 1 Decreases Synaptic Activity by Activating Metabotropic Glutamate Receptor 2.

Synaptic cell adhesion molecules represent important targets for neuronal activity-dependent proteolysis. Postsynaptic neuroligins (NLs) form trans-synaptic complexes with presynaptic neurexins (NXs). Both NXs and NLs are cleaved from the cell surface by metalloproteases in an activity-dependent manner, releasing a soluble extracellular fragment and membrane-tethered C-terminal fragment.

Effect of Semaglutide on the Pharmacokinetics of Metformin, Warfarin, Atorvastatin and Digoxin in Healthy Subjects.

Background And Objective: Semaglutide is a glucagon-like peptide-1 analogue in development for the once-weekly treatment of type 2 diabetes mellitus. Its effect on the rate and extent of absorption of concomitant oral medications (metformin, warfarin, atorvastatin and digoxin) was evaluated in healthy subjects.

Methods: Subjects received metformin (500 mg twice daily for 3.

Pharmacokinetics and Tolerability of a Single Dose of Semaglutide, a Human Glucagon-Like Peptide-1 Analog, in Subjects With and Without Renal Impairment.

Background: The pharmacokinetics and tolerability of semaglutide, a once-weekly human glucagon-like peptide-1 analog in development for the treatment of type 2 diabetes mellitus, were investigated in subjects with/without renal impairment (RI).

Methods: Fifty-six subjects, categorized into renal function groups [normal, mild, moderate, severe, and end-stage renal disease (ESRD)], received a single subcutaneous dose of semaglutide 0.5 mg.

Pharmacokinetic and Pharmacodynamic Properties of Faster-Acting Insulin Aspart versus Insulin Aspart Across a Clinically Relevant Dose Range in Subjects with Type 1 Diabetes Mellitus.

Background: Absorption of current rapid-acting insulins is too slow for patients with diabetes mellitus to achieve optimal postprandial glucose control. Faster-acting insulin aspart (faster aspart) is insulin aspart in a new formulation with faster early absorption. We compared the pharmacokinetic/pharmacodynamic properties of faster aspart and insulin aspart across a clinically relevant dose range.

A Comparison of Pharmacokinetic and Pharmacodynamic Properties Between Faster-Acting Insulin Aspart and Insulin Aspart in Elderly Subjects with Type 1 Diabetes Mellitus.

Background: Due to population aging, an increasing number of elderly patients with diabetes use insulin. It is therefore important to investigate the characteristics of new insulins in this population. Faster-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with faster absorption.

Adjunctive 5-Hydroxytryptophan Slow-Release for Treatment-Resistant Depression: Clinical and Preclinical Rationale.

Serotonin transporter (SERT) inhibitors treat depression by elevating brain extracellular 5-hydroxytryptamine (5-HT). However, only one-third of patients respond adequately. Treatment-resistant depression (TRD) is a major unmet need.

SSRI Augmentation by 5-Hydroxytryptophan Slow Release: Mouse Pharmacodynamic Proof of Concept.

Drugs, notably SSRIs, that elevate brain extracellular 5-HT (5-HTExt) are antidepressants. Unfortunately, most patients fail to remit. Multipronged clinical evidence suggests that elevating 5-HTExt beyond the SSRI effect enhances antidepressant efficacy, but previous such drug strategies had prohibitive limitations.

Survival in patients with breast cancer with bone metastasis: a Danish population-based cohort study on the prognostic impact of initial stage of disease at breast cancer diagnosis and length of the bone metastasis-free interval.

Objectives: Since population-based data on prognostic factors affecting survival in patients with breast cancer with bone metastasis (BM) are currently limited, we conducted this nationwide retrospective cohort study to examine the prognostic role of disease stage at breast cancer diagnosis and length of BM-free interval (BMFI).

Setting: Denmark.

Participants: 2427 women with a breast cancer diagnosis between 1997 and 2011 in the Danish Cancer Registry and a concurrent or subsequent BM diagnosis in the Danish National Registry of Patients.

Patient comorbidity is associated with conservative treatment of localized prostate cancer.

Objective: The aim of this study was to investigate how prostate cancer treatment varies by level of comorbidity among men with localized prostate cancer.

Materials And Methods: A nationwide cohort study was conducted of all patients younger than 75 years of age with incident localized prostate cancer registered in the Danish Cancer Registry from 1 October 2003 to 31 December 2010. Number and percentages were tabulated, and the prevalence ratios were calculated of patients treated with radical prostatectomy or radiotherapy during the first year after prostate cancer diagnosis according to comorbidity level at the time of prostate cancer diagnosis.

Short look-back periods in pharmacoepidemiologic studies of new users of antibiotics and asthma medications introduce severe misclassification.

Purpose: The aim of this study was to quantify the effect of the look back period on the misclassification of new users of antibiotics and asthma medications.

Methods: We included all children born in Denmark from 1995 through 2006 and all prescriptions of antibiotics and asthma medication from 1995 through 2011. The study period was 2007 through 2011.

Long-term mortality and recurrence after colorectal cancer surgery with preoperative stenting: a Danish nationwide cohort study.

Background And Study Aims: Self-expanding metal stents (SEMS) used as a bridge to surgery for obstructive colorectal cancer (CRC) have fallen under suspicion for inducing tumor dissemination, and thereby increasing recurrence risk and long-term mortality. The aim of this study was to compare overall mortality and CRC recurrence in patients receiving preoperative SEMS vs. patients undergoing urgent resection.

Bone metastasis, skeletal-related events, and mortality in lung cancer patients: a Danish population-based cohort study.

Objectives: To estimate the incidence rate of bone metastasis and subsequent skeletal-related events (SREs) (radiation to bone, spinal cord compression, fracture, and surgery to bone) in lung cancer patients and to quantify their impact on mortality.

Materials And Methods: We conducted a nationwide cohort study of patients diagnosed with lung cancer between 1999 and 2010 in Denmark. We computed the cumulative incidence (%) of bone metastasis and subsequent SREs (treating death as a competing risk) and corresponding incidence rates (per 1000 person-years).

The interaction of escitalopram and R-citalopram at the human serotonin transporter investigated in the mouse.

Rationale: Escitalopram appears to be a superior antidepressant to racemic citalopram. It has been hypothesized that binding of R-citalopram to the serotonin transporter (SERT) antagonizes escitalopram binding to and inhibition of the SERT, there by curtailing the elevation of extracellular 5-hydroxytryptamine (5-HTExt), and hence anti-depressant efficacy. Further, it has been suggested that a putative allosteric binding site is important for binding of escitalopram to the primary, orthosteric, site, and for R-citalopram's inhibition here of.

Eighteen-year trends in stroke mortality and the prognostic influence of comorbidity.

Objectives: To examine 18-year trends in short-term and long-term stroke mortality and the prognostic influence of comorbidity.

Methods: We conducted a nationwide population-based cohort study. Using the Danish National Registry of Patients, covering all Danish hospitals, we identified all 219,354 patients with a first-time hospitalization for stroke during 1994-2011.

Perinatal characteristics and bone cancer risk in offspring--a Scandinavian population-based study.

Background: We investigated perinatal factors in relation to bone cancer subtypes, osteosarcoma (OS), Ewing Sarcoma (ES) and chondrosarcoma (CS).

Materials And Methods: All cases in Norway (1970-2009), Sweden (1974-2009) and Denmark (1980-2010)<43 years were included (n=914); 10 controls per case were selected from birth registries (which provided information on pregnancies) matched on birth country, sex and birth year (n=9140). Unconditional logistic regression models including sex and birth year were used to compute relative risk (RR) and 95% confidence intervals (CI).

Engineering of photosynthetic mannitol biosynthesis from CO2 in a cyanobacterium.

D-Mannitol (hereafter denoted mannitol) is used in the medical and food industry and is currently produced commercially by chemical hydrogenation of fructose or by extraction from seaweed. Here, the marine cyanobacterium Synechococcus sp. PCC 7002 was genetically modified to photosynthetically produce mannitol from CO2 as the sole carbon source.