A versatile bioelectronic interface programmed for hormone sensing.

Precision medicine requires smart, ultrasensitive, real-time profiling of bio-analytes using interconnected miniaturized devices to achieve individually optimized healthcare. Here, we report a versatile bioelectronic interface (VIBE) that senses signaling-cascade-guided receptor-ligand interactions via an electronic interface. We show that VIBE offers a low detection limit down to sub-nanomolar range characterised by an output current that decreases significantly, leading to precise profiling of these peptide hormones throughout the physiologically relevant concentration ranges.

Afamelanotide Is Associated with Dose-Dependent Protective Effect from Liver Damage Related to Erythropoietic Protoporphyria.

Unlabelled: In animal models, melanocyte-stimulating hormones (MSHs) protect the liver from various injuries. Erythropoietic protoporphyria (EPP), a metabolic disorder, leads to the accumulation of protoporphyrin (PPIX). In addition to the most prominent symptom of incapacitating phototoxic skin reactions, 20% of EPP patients exhibit disturbed liver functioning and 4% experience terminal liver failure caused by the hepatobiliary elimination of excess PPIX.

Beyond pigmentation: signs of liver protection during afamelanotide treatment in Swiss patients with erythropoietic protoporphyria, an observational study.

Unlabelled: Erythropoietic protoporphyria (EPP) is an ultra-rare inherited disorder with overproduction of protoporphyrin in maturating erythroblasts. This excess protoporphyrin leads to incapacitating phototoxic burns in sunlight exposed skin. Its biliary elimination causes cholestatic liver injury in 20% and terminal liver failure in 4% of EPP patients.

Ganglion cell layer thickening in well-controlled patients with type 1 diabetes: an early sign for diabetic retinopathy?

Purpose: To evaluate early changes in retinal layers using optical coherence tomography (OCT) in patients with long-standing type 1 diabetes (DM1) receiving intensified insulin therapy.

Methods: In a cross-sectional case-control study 150 patients with DM1 and 150 age- and sex-matched healthy control participants underwent OCT imaging. Scans of both eyes were analysed for different layers (NFL, GCL (+IPL), INL, outer layer complex (OLC, including OPL, ONL and ELM) and photoreceptors (PR)) in all subfields of an ETDRS grid.

Glucose Variations During Driving in People With Type 1 Diabetes Using a Continuous Glucose Monitoring System.

Objective: Hypoglycemic events during driving are life-threatening complications in people with type 1 diabetes (T1D). While preliminary studies showed increased glucose demand in driving simulations, we investigated interstitial fluid (ISF) glucose when driving under real-life circumstances.

Research Design And Methods: We measured ISF glucose in 10 participants with stable T1D during a 2-h driving course using a continuous glucose monitoring system.

The prevalence of retinopathy in patients with type 1 diabetes treated with education-based intensified insulin therapy and its association with parameters of glucose control.

Aim: Prevalence of retinopathy (DR) in patients with type 1 diabetes treated with education-based intensified insulin therapy (EBIIT) and its association with parameters of glucose control.

Methods: 151 patients with mean diabetes duration of 14.3 years [SD ± 5.

[Porphyria - when to think about how to clarify and treat?].

Porphyria - when to think about how to clarify and treat? Abstract. Porphyrias are a group of metabolic disorders that are mostly hereditary. They manifest either as abdominal colic or as skin changes at light-exposed areas.

Generation of glucose-sensitive insulin-secreting beta-like cells from human embryonic stem cells by incorporating a synthetic lineage-control network.

We previously reported novel technology to differentiate induced pluripotent stem cells (IPSCs) into glucose-sensitive insulin-secreting beta-like cells by engineering a synthetic lineage-control network regulated by the licensed food additive vanillic acid. This genetic network was able to program intricate expression dynamics of the key transcription factors Ngn3 (neurogenin 3, OFF-ON-OFF), Pdx1 (pancreatic and duodenal homeobox 1, ON-OFF-ON) and MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homologue A, OFF-ON) to guide the differentiation of IPSC-derived pancreatic progenitor cells to beta-like cells. In the present study, we show for the first time that this network can also program the expression dynamics of Ngn3, Pdx1 and MafA in human embryonic stem cell (hESC)-derived pancreatic progenitor cells and drive differentiation of these cells into glucose-sensitive insulin-secreting beta-like cells.

Self-adjusting synthetic gene circuit for correcting insulin resistance.

By using tools from synthetic biology, sophisticated genetic devices can be assembled to reprogram mammalian cell activities. Here, we demonstrate that a self-adjusting synthetic gene circuit can be designed to sense and reverse the insulin-resistance syndrome in different mouse models. By functionally rewiring the mitogen-activated protein kinase (MAPK) signalling pathway to produce MAPK-mediated activation of the hybrid transcription factor TetR-ELK1, we assembled a synthetic insulin-sensitive transcription-control device that self-sufficiently distinguished between physiological and increased blood insulin levels and correspondingly fine-tuned the reversible expression of therapeutic transgenes from synthetic TetR-ELK1-specific promoters.

A synthetic biology-based device prevents liver injury in mice.

Background & Aims: The liver performs a panoply of complex activities coordinating metabolic, immunologic and detoxification processes. Despite the liver's robustness and unique self-regeneration capacity, viral infection, autoimmune disorders, fatty liver disease, alcohol abuse and drug-induced hepatotoxicity contribute to the increasing prevalence of liver failure. Liver injuries impair the clearance of bile acids from the hepatic portal vein which leads to their spill over into the peripheral circulation where they activate the G-protein-coupled bile acid receptor TGR5 to initiate a variety of hepatoprotective processes.

A programmable synthetic lineage-control network that differentiates human IPSCs into glucose-sensitive insulin-secreting beta-like cells.

Synthetic biology has advanced the design of standardized transcription control devices that programme cellular behaviour. By coupling synthetic signalling cascade- and transcription factor-based gene switches with reverse and differential sensitivity to the licensed food additive vanillic acid, we designed a synthetic lineage-control network combining vanillic acid-triggered mutually exclusive expression switches for the transcription factors Ngn3 (neurogenin 3; OFF-ON-OFF) and Pdx1 (pancreatic and duodenal homeobox 1; ON-OFF-ON) with the concomitant induction of MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homologue A; OFF-ON). This designer network consisting of different network topologies orchestrating the timely control of transgenic and genomic Ngn3, Pdx1 and MafA variants is able to programme human induced pluripotent stem cells (hIPSCs)-derived pancreatic progenitor cells into glucose-sensitive insulin-secreting beta-like cells, whose glucose-stimulated insulin-release dynamics are comparable to human pancreatic islets.

Synthetic gene network restoring endogenous pituitary-thyroid feedback control in experimental Graves' disease.

Graves' disease is an autoimmune disorder that causes hyperthyroidism because of autoantibodies that bind to the thyroid-stimulating hormone receptor (TSHR) on the thyroid gland, triggering thyroid hormone release. The physiological control of thyroid hormone homeostasis by the feedback loops involving the hypothalamus-pituitary-thyroid axis is disrupted by these stimulating autoantibodies. To reset the endogenous thyrotrophic feedback control, we designed a synthetic mammalian gene circuit that maintains thyroid hormone homeostasis by monitoring thyroid hormone levels and coordinating the expression of a thyroid-stimulating hormone receptor antagonist (TSHAntag), which competitively inhibits the binding of thyroid-stimulating hormone or the human autoantibody to TSHR.

[Arterial hypertension secondary to endocrine disorders].

Endocrine hypertension offers a potentially curative therapy if the underlying cause is identified and treated accordingly. In contrast to the high prevalence of arterial hypertension especially in the elderly, the classical endocrine causes remain a rare entity. Among patients with arterial hypertension the prevalence of Cushing's syndrome or pheochromocytoma is less than 1%.

Catecholamine metabolism in paraganglioma and pheochromocytoma: similar tumors in different sites?

Pheochromocytoma (PHEO) and paraganglioma (PGL) are catecholamine-producing neuroendocrine tumors that arise respectively inside or outside the adrenal medulla. Several reports have shown that adrenal glucocorticoids (GC) play an important regulatory role on the genes encoding the main enzymes involved in catecholamine (CAT) synthesis i.e.

Successful Pregnancy in a Woman with Maple Syrup Urine Disease: Case Report.

We present the positive outcome of a pregnancy in a woman with severe classic maple syrup urine disease (MSUD). Maintaining the maternal plasma levels of leucine between 200 and 300 μmol/L allowed normal development of the foetus. Tolerance of protein and leucine increased continuously from the 16th gestational week until delivery.

Prevalence of vascular disease in systemic lupus erythematosus compared with type-1 diabetes mellitus: a cross-sectional study of two cohorts.

Objectives: Systemic lupus erythematosus (SLE) is associated with considerable cardiovascular morbidity that has not yet been directly compared with other diseases with known cardiovascular risk.

Methods: Two hundred and forty-one patients of the multicentre Swiss SLE cohort study (SSCS) were cross-sectionally assessed for coronary heart disease (CHD), cerebrovascular disease (CVD) and peripheral artery disease (PAD). SLE patients were compared with a cohort of 193 patients with type-1 diabetes mellitus being followed at the University Hospital Basel.

Vagal blocking improves glycemic control and elevated blood pressure in obese subjects with type 2 diabetes mellitus.

Background: An active device that downregulates abdominal vagal signalling has resulted in significant weight loss in feasibility studies.

Objective: To prospectively evaluate the effect of intermittent vagal blocking (VBLOC) on weight loss, glycemic control, and blood pressure (BP) in obese subjects with DM2.

Methods: Twenty-eight subjects were implanted with a VBLOC device (Maestro Rechargeable System) at 5 centers in an open-label study.

Acute thyroid swelling and elevated C reactive protein.

A 34-year-old lady presented with a painful swelling of the left thyroid lobe since 1 week and elevated C reactive protein (CRP) above 100 mg/L. An ultrasound examination revealed a thyroid cyst with partly solid component, suitable with a haemorrhage into a cyst. The serum thyroid stimulating hormone (TSH), as well as peripheral thyroid hormones, was in the normal range.