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.

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.

"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.

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.

[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.

[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.

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.

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.

Inhibiting connexin channels protects against cryopreservation-induced cell death in human blood vessels.

OBJECTIVES: Cryopreserved blood vessels are being increasingly employed in vascular reconstruction procedures but freezing/thawing is associated with significant cell death that may lead to graft failure. Vascular cells express connexin proteins that form gap junction channels and hemichannels. Gap junction channels directly connect the cytoplasm of adjacent cells and may facilitate the passage of cell death messengers leading to bystander cell death. Two hemichannels form a gap junction channel but these channels are also present as free non-connected hemichannels. Hemichannels are normally closed but may open under stressful conditions and thereby promote cell death. We here investigated whether blocking gap junctions and hemichannels could prevent cell death after cryopreservation. MATERIALS AND METHODS: Inclusion of Gap27, a connexin channel inhibitory peptide, during cryopreservation and thawing of human saphenous veins and femoral arteries was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assays and histological examination. RESULTS: We report that Gap27 significantly reduces cell death in human femoral arteries and saphenous veins when present during cryopreservation/thawing. In particular, smooth muscle cell death was reduced by 73% in arteries and 71% in veins, while endothelial cell death was reduced by 32% in arteries and 51% in veins. CONCLUSIONS: We conclude that inhibiting connexin channels during cryopreservation strongly promotes vascular cell viability.

Effectiveness of non-cardiac preoperative testing in non-cardiac elective surgery: a systematic review.

Elective surgery is usually preceded by preoperative diagnostics to minimize risk. The results are assumed to elicit preventive measures or even cancellation of surgery. Moreover, physicians perform preoperative tests as a baseline to detect subsequent changes. This systematic review aims to explore whether preoperative testing leads to changes in management or reduces perioperative mortality or morbidity in unselected patients undergoing elective, non-cardiac surgery. We systematically searched all relevant databases from January 2001 to February 2011 for studies investigating the relationship between preoperative diagnostics and perioperative outcome. Our methodology was based on the manual of the Ludwig Boltzmann Institute for Health Technology Assessment, the Scottish Intercollegiate Guidelines Network (SIGN) handbook, and the PRISMA statement for reporting systematic reviews. One hundred and one of the 25 281 publications retrieved met our inclusion criteria. Three test grid studies used a randomized controlled design and 98 studies used an observational design. The test grid studies show that in cataract surgery and ambulatory surgery, there are no significant differences between patients with indicated preoperative testing and no testing regarding perioperative outcome. The observational studies do not provide valid evidence that preoperative testing is beneficial in healthy adults undergoing non-cardiac surgery. There is no evidence derived from high-quality studies that supports routine preoperative testing in healthy adults undergoing non-cardiac surgery. Testing according to pathological findings in a patient's medical history or physical examination seems justified, although the evidence is scarce. High-quality studies, especially large randomized controlled trials, are needed to explore the effectiveness of indicated preoperative testing.

[Problems and chances of high field magnetic resonance imaging]. / Probleme und Chancen der Hochfeldmagnetresonanztomographie.

CLINICAL/METHODICAL ISSUE: The spatial, temporal and spectral resolution in magnetic resonance imaging (MRI) is in many cases currently not sufficient to detect submillimeter lesions or to image the dynamics of the beating heart. STANDARD RADIOLOGICAL METHODS: At present MRI systems at 1.5 T and 3 T are the standard units for clinical imaging. METHODICAL INNOVATIONS: The use of ultrahigh magnetic fields of 7 T and higher increases the signal-to-noise ratio, which holds promise for a significant improvement of the spatial and/or temporal resolution as well as for new contrast mechanisms. PERFORMANCE: With 7 T MRI, images of the brain have been acquired routinely with a spatial resolution of 0.3 mm. The theoretical improvement of the signal-to-noise ratio is often not fully realized due to B1 inhomogeneities and contrast variations. ACHIEVEMENTS: With MRI at 7 T a notable increase in spatial resolution can be achieved. Methods such as time-of-flight MR angiography and susceptibility-weighted imaging (e.g. neurofunctional MRI, fMRI) profit especially from the higher field strengths. Transmission field inhomogeneities are still a major challenge for ultrahigh field (UHF) MRI and are also a partially unsolved safety problem. PRACTICAL RECOMMENDATIONS: The use of UHF MRI is currently limited to special applications and the expected gain of the high field must be weighed against technical limitations in both image acquisition and interpretation.

[Diagnosis and monitoring of multiple sclerosis: the value of optical coherence tomography]. / Diagnostik und Verlaufsbeurteilung der Multiplen Sklerose: Stellenwert der optischen Kohärenztomographie.

Besides the relapse rate and neurological examination, magnetic resonance imaging (MRI) plays a key role in multiple sclerosis (MS) monitoring. However, MRI is costly and even in Germany not always readily available. Additionally, routine MRI scans are not sensitive enough regarding differentiation between demyelination and neurodegeneration and show a discrepancy between lesion load and the degree of disability. In contrast, optical coherence tomography (OCT) is a validated non-invasive method for the quantification of neurodegenerative processes in the retina, as they appear in MS and other neurological diseases. The OCT is inexpensive, easy to handle and highly reproducible. Additionally, it is well tolerated and thus represents a promising tool for monitoring of neurodegenerative disorders. This article describes in detail the OCT technique and its usefulness for both diagnosis and monitoring of MS.

Epidermal growth factor improves lentivirus vector gene transfer into primary mouse hepatocytes.

Partial resistance of primary mouse hepatocytes to lentiviral (LV) vector transduction poses a challenge for ex vivo gene therapy protocols in models of monogenetic liver disease. We thus sought to optimize ex vivo LV gene transfer while preserving the hepatocyte integrity for subsequent transplantation into recipient animals. We found that culture media supplemented with epidermal growth factor (EGF) and, to a lesser extent, hepatocyte growth factor (HGF) markedly improved transduction efficacy at various multiplicities of infection. Up to 87% of primary hepatocytes were transduced in the presence of 10 ng EGF, compared with ~30% in standard culture medium (SCMs). The increased number of transgene-expressing cells correlated with increased nuclear import and more integrated pro-viral copies per cell. Higher LV transduction efficacy was not associated with proliferation, as transduction capacity of gammaretroviral vectors remained low (<1%). Finally, we developed an LV transduction protocol for short-term (maximum 24 h) adherent hepatocyte cultures. LV-transduced hepatocytes showed liver repopulation capacities similar to freshly isolated hepatocytes in alb-uPA mouse recipients. Our findings highlight the importance of EGF for efficient LV transduction of primary hepatocytes in culture and should facilitate studies of LV gene transfer in mouse models of monogenetic liver disease.

Ultrashort highly localized wavepackets.

The recently introduced concept of radially non-oscillating, temporally stable ultrashort-pulsed Bessel-like beams we referred to as needle beams is generalized to a particular class of highly localized wavepackets (HLWs). Spatio-temporally quasi-nondiffracting pulses propagating along extended zones are shaped from Ti:sapphire oscillator radiation with a spatial light modulator and characterized with spatially resolved second order autocorrelation. Few-cycle wavepackets tailored to resemble circular disks, rings and bars of light represent the closest approximation of linear-optical light bullets known so far. By combining multiple HLWs, complex pulsed nondiffracting patterns are obtained.

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.

Acoustic noise-optimized VERSE pulses.

Variable-rate selective excitation RF pulses modulate the slice selection gradients during RF transmission, especially to reduce the total RF power. Amplitude-modulated slice selection gradients can lead to increased gradient noise, in particular in high-field MRI where variable-rate selective excitation techniques are often used. In this work, an algorithm is presented that calculates a variable-rate selective excitation pulse modulation from given RF pulses with constant slice selection gradient. The algorithm avoids the known acoustic resonance frequencies of the gradient system to minimize sound pressure levels. It was tested with four different slice-selective RF pulse shapes (Sinc, Gaussian, and two Shinnar-LeRoux). Sound measurements revealed a reduction of the mean sound pressure level by up to 13 dB, and simultaneously, the specific absorption rate was reduced by 55%.

Sustainability of an interdisciplinary secondary prevention program for hairdressers.

OBJECTIVE: Two hundred and fifteen hairdressers suffering from occupational skin diseases (OSD) have attended a 6-month combined dermatological and educational prevention program with an education and counseling scheme as well as an intervention in the respective hairdressers' shops. The aim of this program, conducted from 1994 to 1997, was to enable the affected hairdressers to remain at work without suffering from major OSD. METHODS: To assess the sustainability of this interdisciplinary medical and educational training program, the intervention group (IG, N = 215) and a control group (CG, hairdressers with OSD who solely received dermatological treatment, N = 85) were followed up 9 month and 5 years after their individual project participation by a standardized questionnaire. A subcohort of the intervention group (IG(1994), participants in 1994, N = 62) was followed up again 10 years after their participation. RESULTS: The follow-up survey 9 months after the beginning of the program (response rate: IG: N = 163, 75.8%; CG: N = 80, 94.1%) showed that 71.8% (N = 117) of the intervention group could remain in work as opposed to 60.0% (N = 48) in the control group. In the intervention group 14.7% gave up work due to OSD versus 22.5% in the control group (no statistically significant effect). In the 5-year follow-up (response rate: IG: N = 172, 80%; CG: N = 55, 64.7%) 58.7% (N = 101) of the IG remained at work versus 29.1% (N = 16) of the CG. In the IG 12.8% had stopped work because of OSD versus 27.3% in the CG (p < 0.001, Cramer's V = 0.26). Ten years after intervention, the follow-up showed a stabilization of the effects shown by the 5-year follow-up results. In addition to the criteria 'remaining' or 'not remaining at work' the results show that our interdisciplinary intervention program led to an increased and sustained knowledge on OSD and more adequate prevention at the work place in the IG. The results confirm that interdisciplinary training can be successful in effecting self-protection against workplace hazards by using positive approaches that include the learning of "safe" behavior and insuring transferability to real workplace settings ("empowerment"). Combined preventive measures as studied in this program have recently become the standard offered by different statutory accident liability insurances for patients in different wet work occupations with OSD in Germany.

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.