Intranasal insulin's effects on the sense of smell.

Intranasal insulin (IN) administration is a promising way to deliver the peptide to the central nervous system (CNS), bypassing the blood-brain-barrier and gastrointestinal absorption inhibition. IN receptors are localized in the olfactory mucosa and the brain, mainly in the olfactory bulb, hypothalamus, hippocampus, amygdala, cerebral cortex, and cerebellum. The pleiotropic mechanism of insulin action is characterized by its anti-inflammatory properties, antithrombotic, vasodilatory, and antiapoptotic effects. It prevents energy failure and has regenerative properties, affects neuro-regeneration and counteracts insulin resistance. Hence, insulin has been suggested for various pathological states including neurocognitive disorders, obesity, and as a therapeutic option for smell loss. A sharply increased prevalence of olfactory dysfunction was observed due to the COVID-19 pandemic. The pandemic also emphasized the lack of therapeutic options for smell loss. Intranasal insulin administration has therefore been suggested to serve as potential treatment, influencing the regenerative capacities of the olfactory mucosa. This narrative review summarizes current knowledge on possible effects of intranasal insulin on the sense of smell.

Measurement performance assessment for the ITER CXRS Edge diagnostic system.

Measurement performance assessment has been carried out for the latest design of the ITER Charge Exchange Recombination Spectroscopy (CXRS) Edge diagnostic system. Several plasma scenarios, covering all expected baseline operation regimes for ITER, were used. Various impurity (He, Be, C, and Ne) concentrations for the system whole spatial range (0.5 < r/a < 1.0) were considered. Statistical errors for the measurements of low-Z impurity temperature, density, and rotation velocity were calculated. Other non-statistical error sources were reviewed, including the presence of wall reflections, effects on the active charge-exchange line shape, calibration, and positioning uncertainties. Minimal impurity concentrations, allowing measurements with required accuracy, were obtained. It was shown that the CXRS Edge system will be able to measure primary plasma parameters with required accuracy, space, and time resolution.

Efficacy, safety, and user experience of DIY or open-source artificial pancreas systems: a systematic review.

The do-it-yourself artificial pancreas system (DIYAPS) is a patient-driven initiative with the potential to revolutionise diabetes management, automating insulin delivery with existing pumps and CGM combined with open-source algorithms. Given the considerable interest in this topic within the diabetes community, we have conducted a systematic review of DIYAPS efficacy, safety, and user experience. Following recognised procedures and reporting standards, we identified 10 eligible publications of 730 participants within the peer-reviewed literature. Overall, studies reported improvements in time in range, HbA1c (glycated haemoglobin), reduced hypoglycaemia, and improved quality of life with DIYAPS use. While results were positive, the identified studies were small, and the majority were observational and at high risk of bias. Further research including well-designed randomised trials comparing DIYAPS with appropriate comparators is recommended.

"U-Sniff" - the international odor identification test for children: an extension of its normative database and study of global reliability.

BACKGROUND: To extend the previous study by Schriever and colleagues from 2018 providing normative data and re-investigating the reliability for U-Sniff test in children in additional countries. METHODOLOGY: A total of 388 children (196 boys, 192 girls) from eight countries (China, Germany, Iran, Netherlands, Norway, Oman, Paraguay, and Russia) participated in this study. The children were recruited from public local schools in those particular countries. The odor identification ability was evaluated using the U-Sniff test, a 12-item odor identification test developed for children. In addition, reliability was examined using test-retest design in the children for each country. RESULTS: The mean U-Sniff test score across all children was 10.3 +- 1.7 points. Normative data were established. A high test-retest reliability of the U-Sniff test was demonstrated across the eight participating countries. CONCLUSIONS: The U-Sniff test for children exhibits a high test-retest reliability on a global scale.

Old carbon reservoirs were not important in the deglacial methane budget.

Permafrost and methane hydrates are large, climate-sensitive old carbon reservoirs that have the potential to emit large quantities of methane, a potent greenhouse gas, as the Earth continues to warm. We present ice core isotopic measurements of methane (Δ14C, δ13C, and δD) from the last deglaciation, which is a partial analog for modern warming. Our results show that methane emissions from old carbon reservoirs in response to deglacial warming were small (<19 teragrams of methane per year, 95% confidence interval) and argue against similar methane emissions in response to future warming. Our results also indicate that methane emissions from biomass burning in the pre-Industrial Holocene were 22 to 56 teragrams of methane per year (95% confidence interval), which is comparable to today.

Exploring parental perspectives after commencement of flash glucose monitoring for type 1 diabetes in adolescents and young adults not meeting glycaemic targets: a qualitative study.

AIMS: To explore parental perspectives after flash glucose monitoring commencement in adolescents and young adults with type 1 diabetes who were not meeting glycaemic targets. METHODS: Twelve semi-structured interviews were conducted among parents of adolescents and young adults between the ages of 14 and 20 years (inclusive) with type 1 diabetes and not meeting glycaemic targets [HbA1c 81-130 mmol/mol (9.6-14.0%)] participating in a randomized controlled trial. Interviews were transcribed, then thematic analysis was performed to identify themes regarding parental experiences. RESULTS: Four key themes were found: flash glucose monitoring improved parental emotional well-being; flash glucose monitoring reduced diabetes-specific conflict within families; flash glucose monitoring facilitated the parental role in diabetes management; and sensor-related challenges, particularly sensors falling off, interfered with using flash glucose monitoring for diabetes management. The cost of self-funded sensors was the only barrier to continuing flash glucose monitoring that parents reported. CONCLUSIONS: This study provides new insights into the potential benefits and challenges of flash glucose monitoring use, drawn from the perspective of parents of adolescents and young adults not meeting glycaemic targets. As parents are often key partners in obtaining or purchasing this technology, these findings can be used to further inform parental expectations of this technology.

[Magnetic resonance angiography without contrast agents]. / Kontrastmittelfreie Magnetresonanzangiographie.

BACKGROUND: The use of magnetic resonance imaging (MRI) contrast agents should be minimized in MR angiography. OBJECTIVE: Overview of existing native MRI techniques for MR angiography MATERIAL AND METHODS: Native MRI angiography uses the fact that unsaturated flowing blood is hyperintense to static tissue (time-of-flight MRA), that blood flow induces a detectable phase shift (phase contrast MRA), that labeling by selective inversion can dynamically image a bolus passage (arterial spin labeling) and that special MRI sequences exist which utilize the contrast properties of blood. CONCLUSION: Native MRI angiography, if properly selected, can reliably delineate vessels such as cerebral arteries and coronary arteries and can provide additional information about the flow dynamics.

A rate-doubled 10-GHz fiducial comb generator for precision optical timing calibration.

Solid-state optical fiducial timing pulse generators provide a convenient and accurate method to include timing fiducials in a streak-camera image for time-base correction. Current commercially available vertical-cavity surface-emitting lasers (VCSELs) emitting in the visible range can be amplitude modulated up to 5 GHz. An optically passive method is utilized to interleave a time-delayed path of the 5-GHz pulsed light with itself, producing a 10-GHz pulsed fiducial, or comb. Comb pulse rates at 0.5, 1.0, and 2.5 GHz can also be selected. The instrument presented is a self-contained and portable generator with primary use for streak-camera temporal calibration. Applications can also be extended to many other optical timing needs. The VCSEL output is fiber optic coupled at a wavelength of 680 nm (visible red) with a nearly Gaussian pulse shape. The peak power of each ∼50-ps full width at half maximum (FWHM) comb pulse at 5-GHz operation, or picket, is approximately 5 mW. The low phase noise of the internal microwave modulation drive source provides low pulse to pulse jitter. An external reference frequency standard can be utilized to synchronize the output to external timing equipment. A selectable internal reference frequency crystal oscillator is incorporated for stand-alone operation.

The ups and downs of low-carbohydrate diets in the management of Type 1 diabetes: a review of clinical outcomes.

Dietary management has been a mainstay of care in Type 1 diabetes since before the discovery of insulin when severe carbohydrate restriction was advocated. The use of insulin facilitated re-introduction of carbohydrate into the diet. Current management guidelines focus on a healthy and varied diet with consideration of glycaemic load, protein and fat. As a result of frustration with glycaemic outcomes, low-carbohydrate diets have seen a resurgence in popularity. To date, low-carbohydrate diets have not been well studied in the management of Type 1 diabetes. Studies looking at glycaemic outcomes from low-carbohydrate diets have largely been cross-sectional, without validated dietary data and with a lack of control groups. The participants have been highly motivated self-selected individuals who follow intensive insulin management practices, including frequent blood glucose monitoring and additional insulin corrections with tight glycaemic targets. These confounders limit the ability to determine the extent of the impact of dietary carbohydrate restriction on glycaemic outcomes. Carbohydrate-containing foods including grains, fruit and milk are important sources of nutrients. Hence, low-carbohydrate diets require attention to vitamin and energy intake to avoid micronutrient deficiencies and growth issues. Adherence to restricted diets is challenging and can have an impact on social normalcy. In individuals with Type 1 diabetes, adverse health risks such as diabetic ketoacidosis, hypoglycaemia, dyslipidaemia and glycogen depletion remain clinical concerns. In the present paper, we review studies published to date and provide clinical recommendations for ongoing monitoring and support for individuals who choose to adopt a low-carbohydrate diet. Strategies to optimize postprandial glycaemia without carbohydrate restriction are presented.

[Spin echo and gradient echo : Methodological duo of MRI]. / Spinecho und Gradientenecho : Methodisches Duo der MR-Bildgebung.

Clinical magnetic resonance imaging (MRI) offers a multitude of different techniques with which anatomical, functional and metabolic information can be gained. The technical basis of an MRI method is the so-called pulse sequence, which determines the manner in which data is acquired. Pulse sequences are differentiated between gradient and spin echo sequences. The aim of this article is to present the principal physical properties of both techniques. From these properties, specific applications arise that are routinely used in clinical practice.

Pre-operative evaluation of adults undergoing elective noncardiac surgery: Updated guideline from the European Society of Anaesthesiology

The purpose of this update of the European Society of Anaesthesiology (ESA) guidelines on the pre-operative evaluation of the adult undergoing noncardiac surgery is to present recommendations based on the available relevant clinical evidence. Well performed randomised studies on the topic are limited and therefore many recommendations rely to a large extent on expert opinion and may need to be adapted specifically to the healthcare systems of individual countries. This article aims to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthesiologists all over Europe to integrate - wherever possible - this knowledge into daily patient care. The Guidelines Committee of the ESA formed a task force comprising members of the previous task force, members of ESA scientific subcommittees and an open call for volunteers was made to all individual active members of the ESA and national societies. Electronic databases were searched from July 2010 (end of the literature search of the previous ESA guidelines on pre-operative evaluation) to May 2016 without language restrictions. A total of 34 066 abtracts were screened from which 2536 were included for further analysis. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the level of evidence and to grade recommendations. The final draft guideline was posted on the ESA website for 4 weeks and the link was sent to all ESA members, individual or national (thus including most European national anaesthesia societies). Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines.(AU)

Spectral anomalies and Gouy rotation around the singularity of ultrashort vortex pulses.

Spectral anomalies of femtosecond pulses with orbital angular momentum were studied in the vicinity of singularities. Bessel-Gauss (BG) beams were generated with mode-locked Ti:sapphire oscillators and dispersion-compensated diffractive axicons acting as spiral phase plates (SPPs). High-resolution two-dimensional spectral mapping was performed with a scanning fiber probe. Progressive rotation of the most pronounced features, known as "spectral eyes", in the maps of spectral moments was found at increasing propagation distance. The phenomenon is explained by a wavelength-dependent Gouy phase shift of interfering spectral components in the twisted wavefront. Spatial "spectral switching" was detected for few-cycle pulses. Possible improvements of selectivity are proposed.

Ho:YLF chirped pulse amplification at kilohertz repetition rates - 4.3 ps pulses at 2 µm with GW peak power.

A 2 µm chirped pulse amplification source generates 55 mJ picosecond pulses at a 1 kHz repetition rate. The system consists of a high-gain Ho:YLF regenerative amplifier (RA) operating in the single-energy regime and a dual-rod Ho:YLF power amplifier. Pulses of ∼10 mJ energy from the RA are linearly scaled up to 55 mJ in the power amplifier, corresponding to a high overall extraction efficiency of >20%. The system displays an exceptional high stability with a pulse-to-pulse rms as low as 0.3%. Pulse compression is performed up to the 25 mJ energy level, resulting in pulses close to the Fourier-transform limit with a duration of 4.3 ps and a peak power of 4.4 GW.

A photoelastic-modulator-based motional Stark effect polarimeter for ITER that is insensitive to polarized broadband background reflections.

A motional Stark effect polarimeter insensitive to polarized broadband light is proposed. Partially polarized background light is anticipated to be a significant source of systematic error for the ITER polarimeter. The proposed polarimeter is based on the standard dual photoelastic modulator approach, but with the introduction of a birefringent delay plate, it generates a sinusoidal spectral filter instead of the usual narrowband filter. The period of the filter is chosen to match the spacing of the orthogonally polarized Stark effect components, thereby increasing the effective signal level, but resulting in the destructive interference of the broadband polarized light. The theoretical response of the system to an ITER like spectrum is calculated and the broadband polarization tolerance is verified experimentally.

Intra-patient comparison of parietal pleural biopsies by rigid forceps, flexible forceps and cryoprobe obtained during medical thoracoscopy: a prospective series of 80 cases with pleural effusion.

BACKGROUND: There is only few data available on the use of cryotechnique during medical thoracoscopy. METHODS: Medical thoracoscopy was performed in consecutive patients with pleural effusion. Prospectively, biopsies were taken by rigid forceps, flexible forceps and cryoprobe. Specimen size, depth and diagnostic yield were compared. RESULTS: 80 Patients were included. 408 biopsies were taken (205 rigid biopsies, 104 flexible biopsies, 99 cryobiopsies). Mean surface area of rigid biopsies was 22.6 ± 20.4 mm(2) (flexible biopsies: 7.1 ± 9.3 mm(2), cryobiopsies: 14.4 ± 12.8 mm(2)). Rigid biopsies were significantly larger than cryobiopsies (p < 0.001) and flexible biopsies (p < 0.001), crybiopsies were significantly larger than flexible biopsies (p < 0.01). A deep biopsy containing fatty tissue was harvested in 63 % of rigid biopsies (cryobiopsy: 49.5 % flexible biopsy: 39.5 %). In 79/80 cases (98.7 % 95 % CI cannot be calculated) a diagnosis was obtained by rigid biopsy (cryobiopsy: 73/80 cases (91.3 % 95 % CI 86.0 - 96.5 %), flexible biopsy: 74/80 cases (92.5 % 95 % CI 88.6 - 97.4 %)). Diagnostic yield achieved with cryobiopsies was inferior to the yield of rigid biopsies (Difference: 12.7 %), but non-inferior to flexible biopsies (Difference: 6.5 %). CONCLUSION: Cryobiopsies in medical thoracoscopy are safe with high diagnostic yield, non-inferior to flexible biopsies with increased tissue quantity and quality. Cryotechnique can develop an important role in medical thoracoscopy in the near future when rigid thoracoscopy is not available.

Fluoxetine suppresses calcium signaling in human T lymphocytes through depletion of intracellular calcium stores.

Selective serotonin reuptake inhibitors, such as fluoxetine, have recently been shown to exert anti-inflammatory and immunosuppressive effects. Although the effects on cytokine secretion, proliferation and viability of T lymphocytes have been extensively characterized, little is known about the mechanism behind these effects. It is well known that Ca(2+) signaling is an important step in the signaling transduction pathway following T cell receptor activation. Therefore, we investigated if fluoxetine interferes with Ca(2+) signaling in Jurkat T lymphocytes. Fluoxetine was found to suppress Ca(2+) signaling in response to T cell receptor activation. Moreover, fluoxetine was found to deplete intracellular Ca(2+) stores, thereby leaving less Ca(2+) available for release upon IP3- and ryanodine-receptor activation. The Ca(2+)-modifying effects of fluoxetine are not related to its capability to block the serotonin transporter, as even a large excess of 5HT did not abolish the effects. In conclusion, these data show that fluoxetine decreases IP3- and ryanodine-receptor mediated Ca(2+) release in Jurkat T lymphocytes, an effect likely to be at the basis of the observed immunosuppression.

Spatio-temporal coherence mapping of few-cycle vortex pulses.

Light carrying an orbital angular momentum (OAM) displays an optical phase front rotating in space and time and a vanishing intensity, a so-called vortex, in the center. Beyond continuous-wave vortex beams, optical pulses with a finite OAM are important for many areas of science and technology, ranging from the selective manipulation and excitation of matter to telecommunications. Generation of vortex pulses with a duration of few optical cycles requires new methods for characterising their coherence properties in space and time. Here we report a novel approach for flexibly shaping and characterising few-cycle vortex pulses of tunable topological charge with two sequentially arranged spatial light modulators. The reconfigurable optical arrangement combines interferometry, wavefront sensing, time-of-flight and nonlinear correlation techniques in a very compact setup, providing complete spatio-temporal coherence maps at minimum pulse distortions. Sub-7 fs pulses carrying different optical angular momenta are generated in single and multichannel geometries and characterised in comparison to zero-order Laguerre-Gaussian beams. To the best of our knowledge, this represents the shortest pulse durations reported for direct vortex shaping and detection with spatial light modulators. This access to space-time coupling effects with sub-femtosecond time resolution opens new prospects for tailored twisted light transients of extremely short duration.

Instrumentation for a multichord motional Stark effect diagnostic in KSTAR.

The motional Stark effect (MSE) diagnostic is used to measure the radial magnetic pitch angle profile in neutral beam heated plasmas. This information is used to calculate the safety factor, q, with magnetic equilibrium reconstruction codes such as EFIT. The MSE diagnostic is important during active shaping of the q profile to optimize confinement and stability, and it has become a key diagnostic in high performance tokamaks. A multichord photo-elastic modulator (PEM) based MSE system is being developed for a real-time plasma current profile control in Korea Superconducting Tokamak Advanced Research (KSTAR). The PEM-based approach is a standard method that measures the polarization direction of a single Stark line with narrow tunable bandpass filters. A tangential view of the heating beam provides good spatial resolution of 1-3 cm, which provides an opportunity to install 25 spatial channels spanning the major radius from 1.74 m to 2.84 m. Application of real-time control is a long-term technical goal after commissioning the diagnostic in KSTAR, which is expected in 2015. In this paper, we describe the design of this newly-constructed multichord MSE diagnostic in KSTAR.