[Insulin therapy-new insulin analogues]. / Insulintherapie ­ neue Insulinanaloga.

A multitude of short-acting and long-acting insulin analogues are currently available for the treatment of diabetes mellitus, which mimic physiological insulin secretion better than normal insulins. By the use of ultrarapid insulin analogues postprandial glucose increases can be significantly reduced. Newer long-acting insulin analogues have a very stable action profile and reduce the rate of hypoglycemia, especially nocturnal hypoglycemia, even more than first generation long-acting insulin analogues. Future developments focus on a further acceleration of prandial insulin effects with a simultaneous shorter effect time and an even more prolonged action of long-acting insulin analogues.

Dynamic Optical Tuning of Interlayer Interactions in the Transition Metal Dichalcogenides.

Modulation of weak interlayer interactions between quasi-two-dimensional atomic planes in the transition metal dichalcogenides (TMDCs) provides avenues for tuning their functional properties. Here we show that above-gap optical excitation in the TMDCs leads to an unexpected large-amplitude, ultrafast compressive force between the two-dimensional layers, as probed by in situ measurements of the atomic layer spacing at femtosecond time resolution. We show that this compressive response arises from a dynamic modulation of the interlayer van der Waals interaction and that this represents the dominant light-induced stress at low excitation densities. A simple analytic model predicts the magnitude and carrier density dependence of the measured strains. This work establishes a new method for dynamic, nonequilibrium tuning of correlation-driven dispersive interactions and of the optomechanical functionality of TMDC quasi-two-dimensional materials.

Dynamic Structural Response and Deformations of Monolayer MoS2 Visualized by Femtosecond Electron Diffraction.

Two-dimensional materials are subject to intrinsic and dynamic rippling that modulates their optoelectronic and electromechanical properties. Here, we directly visualize the dynamics of these processes within monolayer transition metal dichalcogenide MoS2 using femtosecond electron scattering techniques as a real-time probe with atomic-scale resolution. We show that optical excitation induces large-amplitude in-plane displacements and ultrafast wrinkling of the monolayer on nanometer length-scales, developing on picosecond time-scales. These deformations are associated with several percent peak strains that are fully reversible over tens of millions of cycles. Direct measurements of electron-phonon coupling times and the subsequent interfacial thermal heat flow between the monolayer and substrate are also obtained. These measurements, coupled with first-principles modeling, provide a new understanding of the dynamic structural processes that underlie the functionality of two-dimensional materials and open up new opportunities for ultrafast strain engineering using all-optical methods.

Recombinant human growth hormone improves cognitive capacity in a pain patient exposed to chronic opioids.

During recent decades, the increasing use of opioids for chronic non-cancer pain has raised concerns regarding tolerance, addiction, and importantly cognitive dysfunction. Current research suggests that the somatotrophic axis could play an important role in cognitive function. Administration of growth hormone (GH) to GH-deficient humans and experimental animals has been shown to result in significant improvements in cognitive capacity. In this report, a patient with cognitive disabilities resulting from chronic treatment with opioids for neuropathic pain received recombinant human growth hormone (rhGH) replacement therapy. A 61-year-old man presented with severe cognitive dysfunction after long-term methadone treatment for intercostal neuralgia and was diagnosed with GH insufficiency by GH releasing hormone-arginine testing. The effect of rhGH replacement therapy on his cognitive capacity and quality of life was investigated. The hippocampal volume was measured using magnetic resonance imaging, and the ratios of the major metabolites were calculated using proton magnetic resonance spectroscopy. Cognitive testing revealed significant improvements in visuospatial cognitive function after rhGH. The hippocampal volume remained unchanged. In the right hippocampus, the N-acetylaspartate/creatine ratio (reflecting nerve cell function) was initially low but increased significantly during rhGH treatment, as did subjective cognitive, physical and emotional functioning. This case report indicates that rhGH replacement therapy could improve cognitive behaviour and well-being, as well as hippocampal metabolism and functioning in opioid-treated patients with chronic pain. The idea that GH could affect brain function and repair disabilities induced by long-term exposure to opioid analgesia is supported.

Positive-pressure breath-hold positron emission tomography/computed tomography is feasible for respiratory-induced artifact reduction in healthy dogs.

OBJECTIVE: To perform qualitative and quantitative analysis of positron emission tomography (PET)/CT images using spontaneous ventilation (SV) and positive-pressure breath-hold (PPBH) techniques in order to demonstrate the feasibility of PPBH PET/CT to decrease respiration-induced artifacts. ANIMALS: 5 healthy female mixed-breed dogs. PROCEDURES: 2-([18F]fluoro)-2-deoxy-D-glucose (was administered to each anesthetized dog. An SV PET/CT scan was performed from the head to the femur using 8 bed positions (3 min/bed) followed by a PPBH scan centered over the diaphragm with a single bed position (1.5 min/bed). PET image quality, the misalignment of organs between PET and CT images, and standardized uptake values (SUVs) of liver adjacent to diaphragm were compared between SV and PPBH. RESULTS: Overall image quality and conspicuity of anatomic structures were superior in PPBH than in SV PET images. PPBH induced significantly less misalignment of the liver and diaphragm in all planes compared to SV. For the gall bladder, PPBH showed significantly less misalignment than SV only in the transverse plane. The maximum SUV in all of the liver areas was significantly higher with PPBH compared to SV. PPBH exhibited significantly higher mean SUV in the liver adjacent to the left diaphragmatic dome and left lateral border and higher minimum SUV only in the liver adjacent to the left diaphragmatic dome. CLINICAL RELEVANCE: PPBH was demonstrated to be a feasible PET/CT protocol with higher PET image quality, less organ misalignment on fused PET/CT, and more accurate SUVs of the liver compared to SV PET/CT in healthy dogs.

Aberrant migration and surgical removal of a heartworm (Dirofilaria immitis) from the femoral artery of a cat.

A cat was evaluated for an acute-onset of right pelvic limb paresis. Thoracic radiographs revealed normal cardiac size and tortuous pulmonary arteries. Abdominal ultrasound identified a heartworm (HW) extending from the caudal abdominal aorta into the right external iliac artery and right femoral artery. The cat was HW-antigen positive. Echocardiography revealed a HW within the right branch of the main pulmonary artery and evidence of pulmonary hypertension. An agitated-saline contrast echocardiogram revealed a small right to left intracardiac shunt at the level of the atria. Surgical removal of the HW was performed with no substantial postoperative complications. There was return of blood flow and improved motor function to the limb. The cat remains mildly paretic on the affected limb with no other clinical signs.

Oncofertility and the Rights to Future Fertility.

The field of oncofertility, or fertility preservation for patients facing a cancer diagnosis, has seen significant scientific breakthroughs that allow adults and children undergoing fertility-threatening cancer treatment to preserve their fertility for a life after cancer. These breakthroughs also raise complex legal issues for patients and clinicians. While the current scholarship tangentially discusses the disposition of genetic material in regards to pediatric patients, this Special Communication examines the current legal framework as applied to disputes regarding the disposition of genetic material between the oncofertility patient and donor, and provides a potential new solution for courts to use in determining the rights of parties in disputes involving donated genetic material.

Early detection of microcirculatory impairment in diabetic patients with foot at risk.

OBJECTIVE: To assess microcirculatory impairment and alterations of the skin oxygen supply in diabetic patients with foot at risk. RESEARCH DESIGN AND METHODS: This study evaluated skin blood flow in 21 type 2 diabetic patients with a foot at risk (defined as a foot with neuropathy but without ulceration or previous ulcerations), 20 type 2 diabetic patients without foot lesions or neuropathy, and 21 normal subjects as a control group. The skin blood flow was determined by measuring the transcutaneous oxygen pressure (TcPO(2)) at the dorsum of the foot in supine and sitting position. The clinical assessment included standard measures of peripheral and autonomic neuropathy, but peripheral vascular disease was excluded by Doppler ultrasound. RESULTS: In supine position, TcPO(2) was significantly reduced (means +/- SE) in diabetic patients with foot at risk (6.04 +/- 0.52 kPa) compared with diabetic (7.14 +/- 0.43 kPa, P = 0.035) and nondiabetic (8.10 +/- 0.44 kPa, P = 0.01) control subjects. The sitting/supine TcPO(2) difference was higher in diabetic subjects with foot at risk (3.13 +/- 0.27 kPa) compared with both diabetic (2.00 +/- 0.18, P = 0.004) and nondiabetic (1.77 +/- 0.15 kPa, P = 0.0003) control subjects. The mean sitting/supine ratio was 1.70 +/- 0.12 in diabetic patients with foot at risk, 1.32 +/- 0.04 in diabetic control subjects, and 1.25 +/- 0.03 in nondiabetic control subjects (P = 0.007). The sitting/supine TcPO(2) ratio was negatively correlated with the heart rate variation coefficient at rest (r = -0.32, P = 0.044) and at deep respiration (r = -0.31, P = 0.046). CONCLUSIONS: Our data indicate that skin oxygen supply is reduced in type 2 diabetic patients with foot at risk. This is probably due to an impaired neurogenic blood flow regulation and may contribute to capillary hypertension, followed by disturbed endothelial function leading to edema and skin damage of the foot. The determination of TcPO(2) appears to be a useful tool in screening type 2 diabetic patients for foot at risk.

Paraoxonase 1 192 Gln/Arg gene polymorphism and cerebrovascular disease: interaction with type 2 diabetes.

Paraoxonase 1 (PON1) is an HDL-associated enzyme which protects HDL and LDL particles from lipid peroxidation. Its enzymatic serum activity varies 10-40-fold between individuals, and its biallelic gene polymorphism at codon 192 (glutamine-->arginine, Gln/Arg) has been associated with coronary artery disease in diabetic patients. To evaluate the role of this PON1 gene polymorphism in cerebrovascular disease, we determined the PON1 192 genotype in 149 patients with hemodynamically relevant extracranial artery stenosis and in 241 controls. The PON1 192 Gln/Arg genotype was determined using polymerase chain reaction followed by Alw I digestion and polyacrylamide gel electrophoresis. Among all subjects, there was no association between the PON1 192 Gln/Arg genotype and cerebrovascular disease (Odds ratio for Arg/Arg and Gln/Arg vs Gln/Gln 0.99, 95%-CI 0.70-1.39). In contrast, in the subgroup of type 2 diabetic patients the PON1 192 Arg allele conferred about twice the risk of cerebrovascular stenosis compared to those homozygous for the Gln allele (Odds ratio 2.00, 95%-CI 0.92-4.38). Our data indicate that in the general population the PON1 192 Gln/Arg gene polymorphism cannot be regarded as a major risk marker for cerebrovascular disease. The observed interaction with type 2 diabetes, however, is supporting the hypothesis that the effect of the PON1 192 Arg allele on atherosclerosis is modulated by other risk factors like diabetes.

Anti-MPO-ANCA-positive microscopic polyangiitis following subacute bacterial endocarditis.

Although infectious agents such as Staphylococcus aureus have been implicated in the pathogenesis of Wegener's granulomatosis, the role of bacterial infections in the pathogenesis of other types of small-vessel vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA) is less clear. We describe a patient who developed a non-granulomatous necrotising small vessel vasculitis and perinuclear ANCA (p-ANCA) directed against myeloperoxidase (MPO) after recurrent episodes of bacterial endocarditis due to Staph. aureus. Although cytoplasmic ANCA (c-ANCA) directed against proteinase 3 have been reported in single patients with bacterial endocarditis, to our knowledge this patient is the first reported case of an anti-MPO-ANCA positive systemic vasculitis following bacterial endocarditis.

Ultrafast electronic and structural response of monolayer MoS2 under intense photoexcitation conditions.

We report on the dynamical response of single layer transition metal dichalcogenide MoS2 to intense above-bandgap photoexcitation using the nonlinear-optical second order susceptibility as a direct probe of the electronic and structural dynamics. Excitation conditions corresponding to the order of one electron-hole pair per unit cell generate unexpected increases in the second harmonic from monolayer films, occurring on few picosecond time-scales. These large amplitude changes recover on tens of picosecond time-scales and are reversible at megahertz repetition rates with no photoinduced change in lattice symmetry observed despite the extreme excitation conditions.

[Woman with type 1 diabetes mellitus and rapidly progressive edema]. / Patientin mit Diabetes mellitus Typ 1 und akut aufgetretenen Ödemen.

HISTORY AND CLINICAL FINDINGS: A 47-year-old woman with type 1 diabetes mellitus was presented for evaluation of progressive oedema, fatigue and weight gain. Her medical history was significant for arterial hypertension and autoimmune thyroiditis requiring substitution therapy with levothyroxine. Physical examination revealed bilateral malleolar and crural oedema, swelling of the eyelids and two-sided pleural effusions. DIAGNOSTIC, TREATMENT AND COURSE: The blood level of albumin was very low, urine analysis showed proteinuria of > 8 g/day. The kidney biopsy revealed only slight changes. This led in combination with the blood and urine results to the diagnosis of minimal change glomerulopathy. After initiation of high dose prednisolone the patient achieved near total remission within four weeks. Prednisolone therapy was tapered over several months. CONCLUSION: In patients with diabetes mellitus and suddenly occurring nephrotic syndrome other diseases than diabetic nephropathy have to be considered. In most cases a kidney biopsy is mandatory.