Inability to work following COVID-19 vaccination-a relevant aspect for future booster vaccinations.

OBJECTIVES: COVID-19 vaccination is a key prevention strategy to reduce the spread and severity of SARS-CoV-2 infections. However, vaccine-related inability to work among healthcare workers (HCWs) could overstrain healthcare systems. STUDY DESIGN: The study presented was conducted as part of the prospective CoVacSer cohort study. METHODS: This study examined sick leave and intake of pro re nata medication after the first, second, and third COVID-19 vaccination in HCWs. Data were collected by using an electronic questionnaire. RESULTS: Among 1704 HCWs enrolled, 595 (34.9%) HCWs were on sick leave following at least one COVID-19 vaccination, leading to a total number of 1550 sick days. Both the absolute sick days and the rate of HCWs on sick leave significantly increased with each subsequent vaccination. Comparing BNT162b2mRNA and mRNA-1273, the difference in sick leave was not significant after the second dose, but mRNA-1273 induced a significantly longer and more frequent sick leave after the third. CONCLUSION: In the light of further COVID-19 infection waves and booster vaccinations, there is a risk of additional staff shortages due to postvaccination inability to work, which could negatively impact the already strained healthcare system and jeopardise patient care. These findings will aid further vaccination campaigns to minimise the impact of staff absences on the healthcare system.

Thermoneutrality induces vascular dysfunction and impaired metabolic function in male Wistar rats: a new model of vascular disease.

OBJECTIVE: Cardiovascular disease is of paramount importance, yet there are few relevant rat models to investigate its pathology and explore potential therapeutics. Housing at thermoneutral temperature (30 °C) is being employed to humanize metabolic derangements in rodents. We hypothesized that housing rats in thermoneutral conditions would potentiate a high-fat diet, resulting in diabetes and dysmetabolism, and deleteriously impact vascular function, in comparison to traditional room temperature housing (22 °C). METHODS: Male Wistar rats were housed at either room temperature or thermoneutral temperatures for 16 weeks on either a low or high-fat diet. Glucose and insulin tolerance tests were conducted at the beginning and end of the study. At the study's conclusion, vasoreactivity and mitochondrial respiration of aorta and carotid were conducted. RESULTS: We observed diminished vasodilation in vessels from thermoneutral rats ( P  < 0.05), whereas high-fat diet had no effect. This effect was also observed in endothelium-denuded aorta in thermoneutral rats ( P  < 0.05). Vasoconstriction was significantly elevated in aorta of thermoneutral rats ( P  < 0.05). Diminished nitric oxide synthase activity and nitrotyrosine, and elevated glutathione activity were observed in aorta from rats housed under thermoneutral conditions, indicating a climate of lower nitric oxide and excess reactive oxygen species in aorta. Thermoneutral rat aorta also demonstrated less mitochondrial respiration with lipid substrates compared with the controls ( P  < 0.05). CONCLUSION: Our data support that thermoneutrality causes dysfunctional vasoreactivity, decreased lipid mitochondrial metabolism, and modified cellular signaling. These are critical observations as thermoneutrality is becoming prevalent for translational research models. This new model of vascular dysfunction may be useful for dissection of targetable aspects of cardiovascular disease and is a novel and necessary model of disease.

Magnetic Turbulence and Current Drive during Local Helicity Injection.

Magnetic measurements during dc helicity injection tokamak startup indicate Alfvénic turbulence in the injected current streams mediates magnetic relaxation and results in macroscopic plasma current drive. Localization of such activity to the injected current streams, a bias voltage dependence to its onset, and higher-order spectral analysis indicate super-Alfvénic electrons excite instabilities that drive the observed turbulence. Measured fluctuation helicity is consistent with an α-dynamo electromotive force driving net current comparable to the macroscopic equilibrium current density. These results imply new constraints for scaling local helicity injection to larger devices.

Altered plasma serine and 1-deoxydihydroceramide profiles are associated with diabetic neuropathy in type 2 diabetes and obesity.

Recent studies suggest that the accumulation of atypical, 1-deoxysphingolipids that lack the C1 hydroxyl group may be associated with diabetic neuropathy (DN). We hypothesized that specific plasma 1-deoxysphingolipids associate with DN severity, and that alterations in plasma serine and alanine associate with 1-deoxysphingolipid elevation in patients with type 2 diabetes (T2D). We examined individual 1-deoxysphingolipid species using LC/MS/MS in plasma samples from 75 individuals including lean controls (LC, n = 19), those with obesity (n = 19), obesity with T2D without DN (ob/T2D, n = 18), and obesity with T2D with DN (Ob/T2D/DN, n = 19). We observed a step wise increase in 1-deoxydihydroceramides across these four groups (spearman correlation coefficient r = 0.41, p = 0.0002). Mean total concentrations of 1-deoxydihydroceramides, and most individual 1-deoxydihydroceramide species, were higher in ob/T2D/DN versus LC group (8.939 vs. 5.195 pmol/100 µL for total 1-deoxydihydroceramides p = 0.005). No significant differences in 1-deoxydihydroceramides were observed between the ob/T2D and ob/T2D/DN groups. l-alanine was higher and l-serine lower in ob/T2D/DN versus LC groups (326.2 vs. 248.0 µM, p = 0.0086 and 70.2 vs. 89.8 µM, p = 0.0110), consistent with a potential contribution of these changes to the observed 1-deoxysphingolipids profiles. 1-deoxydihydroceramides correlated inversely with leg intraepidermal nerve fiber density (CC -0.40, p = 0.003). These findings indicate that 1-deoxydihydroceramides may be important biomarkers and/or mediators of DN.

Radially scanning magnetic probes to study local helicity injection dynamics.

Two new magnetic probes have been deployed on the Pegasus spherical tokamak to study the dynamics of local helicity injection non-solenoidal plasma start-up and current drive. The magnetic radial array probe consists of 15 pickup coils (∼5 × 8 mm each) that measure B ̇ z ( R ) over a 15 cm linear extent. The coils consist of traces embedded in a printed circuit board. Three coil designs are utilized to balance frequency response and coil sensitivity. Helmholtz coil measurements are used to measure coil and full assembly bandwidths (∼2 MHz and ∼200 kHz, respectively) and sensitivities (0.18/0.35/0.96 mV T-1 s). The magnetic radial scanning probe is an array of Hall effect sensors that measure field strength ( | B | ≤ 177 mT) and direction at 8 spatial points (ΔR = 1.5 cm), supporting the studies of equilibrium field structure and low-frequency (≤5 kHz) current dynamics. It uses commercial surface-mount Hall effect sensors with chip-integrated amplifiers and compensators that are mounted in a 3-D printed frame. Helmholtz coil measurements indicate negligible cross-field gain nonlinearity and provide absolute calibration of the diagnostic. Both probes are constructed as an electrostatically shielded insertable air-side assembly that mounts within a radially translatable ultrahigh vacuum assembly from an existing probe.

Sepiapterin Improves Vascular Reactivity and Insulin-Stimulated Glucose in Wistar Rats.

In the vasculature, sedentary behavior leads to endothelial abnormalities, resulting in elevated cardiovascular disease risk. Endothelial nitric oxide synthase (eNOS) aberrations characterize endothelial dysfunction; eNOS also regulates mitochondrial function. We hypothesized that sepiapterin (a precursor to eNOS cofactor tetrahydrobiopterin (BH4)) supplementation would improve endothelium-dependent vascular relaxation in sedentary animals via modulation of NOS function and mitochondrial activity. Sedentary male Wistar rats were fed ad libitum for a total of 10 weeks. Sepiapterin was administered in diet during the final 5 weeks. Intraperitoneal insulin and glucose tolerance tests (IP-ITT/IP-GTT) were conducted at baseline and endpoint. Aorta was assessed for vasoreactivity and mitochondrial respiration. Insulin tolerance, determined by IP-ITT, significantly improved in rats treated with sepiapterin (p < 0.05, interaction of time and treatment). Acetylcholine- (ACh-) driven vasodilation was significantly greater in aorta from sepiapterin-treated rats as compared with control (76.4% versus 54.9% of phenylephrine contraction at 20 µM ACh, p < 0.05). Sepiapterin treatment resulted in significantly elevated state 3 (9.00 oxygen pmol/sec∗mg versus 8.17 oxygen pmol/sec∗mg, p < 0.05) and 4 (7.28 oxygen pmol/sec∗mg versus 5.86 oxygen pmol/sec∗mg, p < 0.05) aortic mitochondrial respiration with significantly lower respiratory control ratio (p < 0.05) during octanoylcarnitine-driven respiration. Vasodilation and insulin sensitivity were improved through targeting NOS via sepiapterin supplementation.

Noninductively Driven Tokamak Plasmas at Near-Unity Toroidal Beta.

Access to and characterization of sustained, toroidally confined plasmas with a very high plasma-to-magnetic pressure ratio (ß_{t}), low internal inductance, high elongation, and nonsolenoidal current drive is a central goal of present tokamak plasma research. Stable access to this desirable parameter space is demonstrated in plasmas with ultralow aspect ratio and high elongation. Local helicity injection provides nonsolenoidal sustainment, low internal inductance, and ion heating. Equilibrium analyses indicate ß_{t} up to ∼100% with a minimum |B| well spanning up to ∼50% of the plasma volume.

Control and automation of the Pegasus multi-point Thomson scattering system.

A new control system for the Pegasus Thomson scattering diagnostic has recently been deployed to automate the laser operation, data collection process, and interface with the system-wide Pegasus control code. Automation has been extended to areas outside of data collection, such as manipulation of beamline cameras and remotely controlled turning mirror actuators to enable intra-shot beam alignment. Additionally, the system has been upgraded with a set of fast (∼1 ms) mechanical shutters to mitigate contamination from background light. Modification and automation of the Thomson system have improved both data quality and diagnostic reliability.

A novel, cost-effective, multi-point Thomson scattering system on the Pegasus Toroidal Experiment (invited).

A novel, cost-effective, multi-point Thomson scattering system has been designed, implemented, and operated on the Pegasus Toroidal Experiment. Leveraging advances in Nd:YAG lasers, high-efficiency volume phase holographic transmission gratings, and increased quantum-efficiency Generation 3 image-intensified charge coupled device (ICCD) cameras, the system provides Thomson spectra at eight spatial locations for a single grating/camera pair. The on-board digitization of the ICCD camera enables easy modular expansion, evidenced by recent extension from 4 to 12 plasma/background spatial location pairs. Stray light is rejected using time-of-flight methods suited to gated ICCDs, and background light is blocked during detector readout by a fast shutter. This ∼103 reduction in background light enables further expansion to up to 24 spatial locations. The implementation now provides single-shot Te(R) for ne > 5 × 1018 m-3.

Type 2 diabetes exaggerates exercise effort and impairs exercise performance in older women.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is associated with high levels of disability and mortality. Regular exercise prevents premature disability and mortality, but people with T2DM are generally sedentary for reasons that are not fully established. We previously observed that premenopausal women with T2DM report greater effort during exercise than their counterparts without diabetes, as measured by the Rating of Perceived Exertion (RPE) scale. We hypothesized that RPE is greater in older women with T2DM versus no T2DM. RESEARCH DESIGN AND METHODS: We enrolled overweight, sedentary women aged 50-75 years with (n=26) or without T2DM (n=28). Participants performed submaximal cycle ergometer exercise at 30 W and 35% of individually-measured peak oxygen consumption (35% VO2peak). We assessed exercise effort by RPE (self-report) and plasma lactate concentration. RESULTS: VO2peak was lower in T2DM versus controls (p=0.003). RPE was not significantly greater in T2DM versus controls (30 W: Control, 10.4±3.2, T2DM, 11.7±2.3, p=0.08; 35% VO2peak: Control, 11.1±0.5, T2DM, 12.1±0.5, p=0.21). However, lactate was greater in T2DM versus controls (p=0.004 at 30 W; p<0.05 at 35% VO2peak). Greater RPE was associated with higher lactate, higher heart rate, and a hypertension diagnosis (p<0.05 at 30 W and 35% VO2peak). CONCLUSIONS: Taken together, physiological measures of exercise effort were greater in older women with T2DM than controls. Exercise effort is a modifiable and thereby targetable end point. In order to facilitate regular exercise, methods to reduce exercise effort in T2DM should be sought. TRIAL NUMBER: NCT00785005.

Design of a retarding potential grid system for a neutral particle analyzer.

The ion energy distribution in a magnetically confined plasma can be inferred from charge exchange neutral particles. On the Madison Symmetric Torus (MST), deuterium neutrals are measured by the Florida A&M University compact neutral particle analyzer (CNPA) and the advanced neutral particle analyzer (ANPA). The CNPA energy range covers the bulk deuterium ions to the beginning of the fast ion tail (0.34-5.2 keV) with high-energy resolution (25 channels) while the ANPA covers the vast majority of the fast ion tail distribution (∼10-45 keV) with low energy resolution (10 channels). Though the ANPA has provided insight into fast ion energization in MST plasma, more can be gained by increasing the energy resolution in that energy range. To utilize the energy resolution of the CNPA, fast ions can be retarded by an electric potential well, enabling their detection by the diagnostic. The ion energy distribution can be measured with arbitrary resolution by combining data from many similar MST discharges with different energy ranges on the CNPA, providing further insight into ion energization and fast ion dynamics on MST.

Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonist albiglutide (HARMONY 1 trial): 52-week primary endpoint results from a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes mellitus not controlled on pioglitazone, with or without metformin.

AIMS: To show that albiglutide, a glucagon-like peptide-1 receptor agonist, is an effective and generally safe treatment to improve glycaemic control in patients with type 2 diabetes mellitus whose hyperglycaemia is inadequately controlled with pioglitazone (with or without metformin). METHODS: In this 3-year, randomized, double-blind, placebo-controlled study, 310 adult patients on a regimen of pioglitazone (with or without metformin) were randomly assigned to receive additional treatment with albiglutide [30 mg subcutaneous (s.c.) once weekly, n = 155] or matching placebo (n = 155). The primary efficacy endpoint was change from baseline to week 52 (intention-to-treat) in glycated haemoglobin (HbA1c). RESULTS: The model-adjusted change from baseline in HbA1c at week 52 was significantly better with albiglutide than with placebo (-0.8%, 95% confidence interval -1.0, -0.6; p < 0.0001). Change from baseline fasting plasma glucose was -1.3 mmol/l in the albiglutide group and +0.4 mmol/l in the placebo group (p < 0.0001); a significantly higher percentage of patients reached the HbA1c goals with albiglutide (p < 0.0001), and the rate of hyperglycaemia rescue up to week 52 for albiglutide was 24.4 versus 47.7% for placebo (p < 0.0001). Albiglutide plus pioglitazone had no impact on weight, and severe hypoglycaemia was observed rarely (n = 2). With few exceptions, the results of safety assessments were similar between the groups, and most adverse events (AEs) were mild or moderate. The 52-week incidence rates for gastrointestinal AEs for albiglutide and placebo were: 31.3 and 29.8%, respectively (diarrhoea: 11.3 and 8.6%; nausea: 10.7 and 11.3%; vomiting: 4.0 and 4.0%). CONCLUSIONS: Albiglutide 30 mg administered once weekly as an add-on to pioglitazone (with or without metformin) provided effective and durable glucose lowering and was generally well tolerated.

Gestational diabetes outcome in a single center study: higher BMI in children after six months.

The aim of the study was to examine obstetric outcomes and metabolic disorders in patients with gestational diabetes mellitus (GDM) and their offspring compared to mothers without GDM and their offspring. We performed a retrospective single center cohort study of mothers with GDM using a questionnaire with items concerning the maternal medical history, neonatal complications, and child development. Mothers with gestational diabetes (GDM; n=130) and those with normal glucose tolerance (NGT; n=77) were recruited. GDM mothers were older (37.58 years vs. 34.32 years, p<0.0001) and had a greater body mass index (25.18 kg/m² vs. 23.37 kg/m², p<0.01). There were no significant differences regarding the mean birth weight, the frequency of Cesarean sections, and the prevalence of macrosomia (> 4 000 g). At follow-up (pediatric U5 screening visit after 6 months of birth) children of mothers with GDM had significantly higher BMI than the children of the NGT group (17.07 kg/m² vs. 16.59 kg/m², p=0.042). GDM women in need of insulin therapy during pregnancy had higher BMI than dieting GDM mothers and experienced more frequently an operative vaginal delivery (17.95% vs. 6.17%, OR 3.23, p=0.04). We found less significant differences between GDM mothers with treatment of impaired glucose tolerance and NGT mothers concerning the neonatal outcome than expected. Despite higher BMI of the GDM group's offspring at follow-up U5 visit, the children did not show any other development disorder. In conclusion treatment of GDM could minimize the frequency of obstetric and neonatal complications in this risk group.

Effect of a randomised controlled vitamin D trial on insulin resistance and glucose metabolism in patients with type 2 diabetes mellitus.

The aim of our study was to investigate the influence of a 6-month vitamin D supplementation in patients with noninsulin-requiring type 2 diabetes mellitus. We included 86 patients in a placebo-controlled, randomised, double-blind study. During 6 months patients received Vigantol oil once a week corresponding to a daily dose of 1904 IU or placebo oil, followed by 6 months of follow-up. At start and at 3-month intervals 25OHD, PTH, body mass index, HbA1c, insulin, C-peptide, and homeostasis model assessment-index were measured. The primary outcome was a change in fasting blood glucose and insulin levels. After 6 months of therapy, the verum group's 25OHD had increased to a median of 35 ng/ml in comparison to the placebo group (median 20 ng/ml, p<10-6). PTH tended to decrease in the verum group (25.5 pg/ml vs. 35.0 pg/ml, p=0.08). After 6 months of therapy, 31 patients (78%) achieved a 25OHD concentration of >20 ng/ml. Their HbA1c was significantly lower at baseline (p=0.008) and after therapy (p=0.009) than in patients with 25OHD below 20 ng/ml. C-Peptide, insulin, and HOMA-index did not change significantly in the verum group but fasting insulin was positively correlated with 25OHD concentrations after 6 months of therapy in both groups. There were no significant effects of vitamin D with a daily dose of 1904 IU on metabolic parameters in type 2 diabetes. However, the correlative findings of this study suggest a link of the 25OHD status and metabolic function in type 2 diabetes. Whether vitamin D therapy with higher doses can improve glucose metabolism needs to be investigated in follow-up trials.

Adipose tissue insulin resistance in adolescents with and without type 2 diabetes.

BACKGROUND: The incidence of type 2 diabetes mellitus (T2D) is increasing in youth, yet little is known about the underlying pathophysiology. Decreased insulin suppression of lipolysis and elevated non-esterified free fatty acid (NEFA) concentrations are known to be associated with insulin resistance and T2D in adults, but less is known about the relationship in adolescents. OBJECTIVES: This study aimed to assess adipose tissue insulin resistance (IR; insulin suppression of lipolysis) and its metabolic correlates in lean, obese and T2D adolescents. METHODS: Forty-seven lean, obese and T2D youth underwent hyperinsulinaemic (80 mU*m(-2) *min(-1)) euglycaemic clamps. NEFAs were measured at baseline and during steady state. Insulin-mediated suppression of lipolysis (%NEFA suppression from baseline) was calculated, and metabolic risk factors were assessed by %NEFA suppression tertile. RESULTS: There was expected variability in %NEFA suppression within obese and T2D youth, but a subset had significantly reduced suppression of lipolysis. NEFA suppression tertile was significantly inversely associated with fasting triglycerides (P = 0.0001), log alanine aminotransferase (ALT; P = 0.02) and low-density lipoprotein cholesterol (P = 0.0002). CONCLUSIONS: Marked adipose tissue IR occurs in some obese and T2D adolescents, which may result in release of triglycerides into the circulation and liver deposition of fatty acids, as evidenced by higher ALT in poor NEFA suppressors.

Stereotactic ablative radiotherapy for small lung tumors with a moderate dose. Favorable results and low toxicity.

BACKGROUND: Stereotactic ablative body radiotherapy (SBRT, SABR) is being increasingly applied because of its high local efficacy, e.g., for small lung tumors. However, the optimum dosage is still under discussion. Here, we report data on 45 lung lesions [non-small cell lung cancer (NSCLC) or metastases] in 39 patients treated between 2009 and 2010 by SABR. PATIENTS AND METHODS: SABR was performed with total doses of 35 Gy (5 fractions) or 37.5 Gy (3 fractions) prescribed to the 60% isodose line encompassing the planning target volume. Three-monthly follow-up CT scans were supplemented by FDG-PET/CT if clinically indicated. RESULTS: The median follow-up was 17 months. Local progression-free survival rates were 90.5% (all patients), 95.0% (NSCLC), and 81.8% (metastases) at 1 year. At 2 years, the respective local progression-free survival rates were 80.5%, 95.0%, and 59.7%. Overall survival rates were 71.1% (all patients), 65.4% (NSCLC), and 83.3% (metastases) at 1 year. Overall survival rates at 2 years were 52.7%, 45.9%, and 66.7%, respectively. Acute side effects were mild. CONCLUSION: With the moderate dose schedule used, well-tolerated SABR led to favorable local tumor control as in other published series. Standardization in reporting the dose prescription for SABR is needed to allow comparison of different series in order to determine optimum dosage.

Time-resolved ion energy distribution measurements using an advanced neutral particle analyzer on the MST reversed-field pinch.

An advanced neutral particle analyzer (ANPA) capable of simultaneously measuring hydrogen and deuterium ions of energies up to 45 keV has recently been developed for use on the Madison Symmetric Torus. The charge-to-mass separation allows for separate analysis of bulk deuterium ions and hydrogen ions injected with a 1 MW, 25 keV neutral beam. Orientation of the ANPA allows sampling of different regions of ion velocity space; a radial viewport favors collection of ions with high v(perpendicular)∕|v| while a recently installed tangential viewport favors ions with high v(||)∕|v|, such as those from the core-localized fast ion population created by the neutral beam. Signals are observed in the ANPA's highest energy channels during periodic magnetic reconnection events, which are drivers of anisotropic, non-Maxwellian ion energization in the reversed-field pinch. ANPA signal strength is dependent on the background neutral density, which also increases during magnetic reconnection events, so careful analysis must be performed to identify the true change in the ion distribution. A Monte Carlo neutral particle tracing code (NENE) is used to reconstruct neutral density profiles based on D(α) line emission, which is measured using a 16-chord filtered photodiode array.

Calibration of an advanced neutral particle analyzer for the Madison Symmetric Torus reversed-field pinch.

A new E∥B neutral particle analyzer, which has recently been installed on Madison Symmetric Torus (MST) reversed-field pinch (RFP), has now been calibrated, allowing the measurement of the fast ion density and energy distribution. This diagnostic, dubbed the advanced neutral particle analyzer (ANPA), can simultaneously produce time resolved measurements of the efflux of both hydrogen and deuterium ions from the plasma over a 35 keV energy range with an energy resolution of 2-4 keV and a time resolution of 10 µs. These capabilities are needed to measure both majority ion heating that occurs during magnetic reconnection events in MST and the behavior of the fast ions from the 1 MW hydrogen neutral beam injector on MST. Calibration of the ANPA was performed using a custom ion source that resides in the flight tube between the MST and the ANPA. In this work, the ANPA will be described, the calibration procedure and results will be discussed, and initial measurements of the time evolution of 25 keV neutral beam injection-born fast ions will be presented.

Improvements to the calibration of the MST Thomson scattering diagnostic.

Calibration of the Madison Symmetric Torus Thomson scattering system has been refined to improve temperature fluctuation measurements. Multiple avalanche photodiodes have been directly calibrated for use as reference detectors during calibration, improving accuracy and ease of use. From the absolute calibration we calculate corrections to the gain for variation in detector operating temperature. We also measure the spatial uniformity of detector responsivity for several photodiodes, and present a method of accounting for non-uniformity in the calibration process. Finally, the gain and noise enhancement are measured at multiple wavelengths to improve temperature and uncertainty measurements.

Experimental evidence for a reduction in electron thermal diffusion due to trapped particles.

New high time resolution measurements of the electron thermal diffusion χ(e) throughout the sawtooth cycle of the Madison Symmetric Torus reversed-field pinch have been made by utilizing the enhanced capabilities of the upgraded multipoint, multipulse Thomson scattering system. These measurements are compared to the χ(e) due to magnetic diffusion predicted by using information from a new high spectral resolution zero-ß nonlinear resistive magnetohydrodynamic simulation performed, for the first time, at the Lundquist number of high current Madison Symmetric Torus plasmas (S≈4×10(6)). Agreement between the measured and predicted values is found only if the reduction in thermal diffusion due to trapped particles is taken into account.