NaHCO3 loading causes increased arterial pressure and kidney damage in rats with chronic kidney disease.

Sodium bicarbonate (NaHCO3) is commonly utilized as a therapeutic to treat metabolic acidosis in people with chronic kidney disease (CKD). While increased dietary sodium chloride (NaCl) is known to promote volume retention and increase blood pressure, the effects of NaHCO3 loading on blood pressure and volume retention in CKD remain unclear. In the present study, we compared the effects of NaCl and NaHCO3 loading on volume retention, blood pressure, and kidney injury in both 2/3 and 5/6 nephrectomy remnant kidney rats, a well-established rodent model of CKD. We tested the hypothesis that NaCl loading promotes greater volume retention and increases in blood pressure than equimolar NaHCO3. Blood pressure was measured 24 h daily using radio telemetry. NaCl and NaHCO3 were administered in drinking water ad libitum or infused via indwelling catheters. Rats were housed in metabolic cages to determine volume retention. Our data indicate that both NaHCO3 and NaCl promote hypertension and volume retention in remnant kidney rats, with salt-sensitivity increasing with greater renal mass reduction. Importantly, while NaHCO3 intake was less pro-hypertensive than equimolar NaCl intake, NaHCO3 was not benign. NaHCO3 loading significantly elevated blood pressure and promoted volume retention in rats with CKD when compared with control rats receiving tap water. Our findings provide important insight into the effects of sodium loading with NaHCO3 in CKD and indicate that NaHCO3 loading in patients with CKD is unlikely to be benign.

Determination of the Thermomigration Force on Adatoms.

Thermal gradients in nanomaterials can cause surface mass transport phenomena. However, the atomic fluxes are challenging to quantify and the underlying atomic mechanisms are complex. Using low energy electron microscopy we have examined in operando, under a thermal gradient of 10^{4} K/m, the thermomigration of supercooled Si(111)-1×1 advacancy islands. The islands move in the direction of the thermal gradient at 0.26±0.06 nm/s. This reveals that the adatoms move toward the cold region and the effective force exerted on Si adatoms is 1.4±0.4×10^{-8} eV/nm. We quantify the heat of transport of Si atoms Q^{*}=1.2±0.4 eV and show that it corresponds to the combined effects of adatom creation at step edges and adatom diffusion on atomically flat terraces.

Collinear Laser Spectroscopy of 2

Transition frequencies and fine-structure splittings of the 2 ^{3}S_{1}→2 ^{3}P_{J} transitions in helium-like ^{12}C^{4+} were measured by collinear laser spectroscopy on a 1-ppb level. Accuracy is increased by more than 3 orders of magnitude with respect to previous measurements, enabling tests of recent nonrelativistic (NR) QED calculations including terms up to mα^{7}. Deviations between the theoretical and experimental values are within theoretical uncertainties and are ascribed to mα^{8} and higher-order contributions in the series expansion of the NR QED calculations. Finally, prospects for an all-optical charge radius determination of light isotopes are evaluated.

First Observation of Cyclotron Radiation from MeV-Scale e

We present an apparatus for detection of cyclotron radiation yielding a frequency-based ß^{±} kinetic energy determination in the 5 keV to 2.1 MeV range, characteristic of nuclear ß decays. The cyclotron frequency of the radiating ß particles in a magnetic field is used to determine the ß energy precisely. Our work establishes the foundation to apply the cyclotron radiation emission spectroscopy (CRES) technique, developed by the Project 8 Collaboration, far beyond the 18-keV tritium endpoint region. We report initial measurements of ß^{-}'s from ^{6}He and ß^{+}'s from ^{19}Ne decays to demonstrate the broadband response of our detection system and assess potential systematic uncertainties for ß spectroscopy over the full (MeV) energy range. To our knowledge, this is the first direct observation of cyclotron radiation from individual highly relativistic ß's in a waveguide. This work establishes the application of CRES to a variety of nuclei, opening its reach to searches for new physics beyond the TeV scale via precision ß-decay measurements.

Nuclear Charge Radius of

Collinear laser spectroscopy was performed on the isomer of the aluminium isotope ^{26m}Al. The measured isotope shift to ^{27}Al in the 3s^{2}3p ^{2}P_{3/2}^{○}→3s^{2}4s ^{2}S_{1/2} atomic transition enabled the first experimental determination of the nuclear charge radius of ^{26m}Al, resulting in R_{c}=3.130(15) fm. This differs by 4.5 standard deviations from the extrapolated value used to calculate the isospin-symmetry breaking corrections in the superallowed ß decay of ^{26m}Al. Its corrected Ft value, important for the estimation of V_{ud} in the Cabibbo-Kobayashi-Maskawa matrix, is thus shifted by 1 standard deviation to 3071.4(1.0) s.

Bayesian approaches to include real-world data in clinical studies.

Randomized clinical trials have been the mainstay of clinical research, but are prohibitively expensive and subject to increasingly difficult patient recruitment. Recently, there is a movement to use real-world data (RWD) from electronic health records, patient registries, claims data and other sources in lieu of or supplementing controlled clinical trials. This process of combining information from diverse sources calls for inference under a Bayesian paradigm. We review some of the currently used methods and a novel non-parametric Bayesian (BNP) method. Carrying out the desired adjustment for differences in patient populations is naturally done with BNP priors that facilitate understanding of and adjustment for population heterogeneities across different data sources. We discuss the particular problem of using RWD to create a synthetic control arm to supplement single-arm treatment only studies. At the core of the proposed approach is the model-based adjustment to achieve equivalent patient populations in the current study and the (adjusted) RWD. This is implemented using common atoms mixture models. The structure of such models greatly simplifies inference. The adjustment for differences in the populations can be reduced to ratios of weights in such mixtures. This article is part of the theme issue 'Bayesian inference: challenges, perspectives, and prospects'.

Total atrial conduction time provides novel information in prediction for stroke in patients with sinus rhythm.

The total atrial conduction time (TACT) measured by echocardiography predicts the risk of atrial fibrillation (AF). This study aimed to investigate whether adding the TACT to the revised Framingham stroke risk profile (rFSRP) improves the efficacy of predicting stroke incidence in patients without prior stroke or known AF. The TACT was measured in 376 consecutive patients > 18 years (58.5 ± 16.3 years; 46% male) receiving echocardiography without any prior history of stroke or AF. The primary endpoint was the occurrence of ischemic stroke, and the secondary endpoint was any documentation of AF during the 2 years of follow-up. During the follow-up period, ischemic strokes occurred in 10 patients (2.65%), and AF in 22 patients (5.85%). The TACT was significantly longer in those who later had a stroke compared with those who did not (169.4 vs. 142.7 ms, p < 0.001). Both rFSRP and TACT predicted the risk for stroke incidence. The univariate model showed that the TACT was a predictor of ischemic stroke incidence (p < 0.001; hazard ratio of 1.94 for every 10 ms; 95% confidence interval, 1.49-2.54). The addition of TACT to rFSRP significantly improved the area under the receiver operating characteristic curve (0.79 vs. 0.85, p = 0.001). Stroke risk prediction was significantly improved by the addition of TACT to rFSRP. The utility of the TACT should be further investigated in large-scale randomized clinical trials.

Surgical therapy of celiac axis and superior mesenteric artery syndrome.

INTRODUCTION: Compression syndromes of the celiac artery (CAS) or superior mesenteric artery (SMAS) are rare conditions that are difficult to diagnose; optimal treatment remains complex, and symptoms often persist after surgery. We aim to review the literature on surgical treatment and postoperative outcome in CAS and SMAS syndrome. METHODS: A systematic literature review of medical literature databases on the surgical treatment of CAS and SMAS syndrome was performed from 2000 to 2022. Articles were included according to PROSPERO guidelines. The primary endpoint was the failure-to-treat rate, defined as persistence of symptoms at first follow-up. RESULTS: Twenty-three studies on CAS (n = 548) and 11 on SMAS (n = 168) undergoing surgery were included. Failure-to-treat rate was 28% for CAS and 21% for SMAS. Intraoperative blood loss was 95 ml (0-217) and 31 ml (21-50), respectively, and conversion rate was 4% in CAS patients and 0% for SMAS. Major postoperative morbidity was 2% for each group, and mortality was described in 0% of CAS and 0.4% of SMAS patients. Median length of stay was 3 days (1-12) for CAS and 5 days (1-10) for SMAS patients. Consequently, 47% of CAS and 5% of SMAS patients underwent subsequent interventions for persisting symptoms. CONCLUSION: Failure of surgical treatment was observed in up to every forth patient with a high rate of subsequent interventions. A thorough preoperative work-up with a careful patient selection is of paramount importance. Nevertheless, the surgical procedure was associated with a beneficial risk profile and can be performed minimally invasive.

Benchmarking outcomes for distal pancreatectomy: critical evaluation of four multicenter studies.

BACKGROUND: Benchmarking is a validated tool for outcome assessment and international comparison of best achievable surgical outcomes. The methodology is increasingly applied in pancreatic surgery and the aim of the review was to critically compare available benchmark studies evaluating distal pancreatectomy (DP). METHODS: A literature search of English articles reporting on benchmarking DP was conducted of the electronic databases MEDLINE and Web of Science (until April 2023). Studies on open (ODP), laparoscopic (LDP), and robotic DP (RDP) were included. RESULTS: Four retrospective multicenter studies were included. Studies reported on outcomes of minimally invasive DP only (n = 2), ODP and LDP (n = 1), and RDP only (n = 1). Either the Achievable Benchmark of Care™ method or the 75th percentile from the median was selected to define benchmark cutoffs. Robust and reproducible benchmark values were provided by the four studies for intra- and postoperative short-term outcomes. CONCLUSION: Benchmarking DP is a valuable tool for obtaining internationally accepted reference outcomes for open and minimally invasive DP approaches with only minor variances in four international cohorts. Benchmark cutoffs allow for outcome comparisons between institutions, surgeons, and to monitor the introduction of novel minimally invasive DP techniques.

Influence of kinematic alignment on femorotibial kinematics in medial stabilized TKA design compared to mechanical alignment.

INTRODUCTION: Worldwide more and more primary knee replacements are being performed. Kinematic alignment (KA) as one of many methods of surgical alignment has been shown to have a significant impact on kinematics and function. The aim of the present study was to compare KA and mechanical alignment (MA) with regard to femorotibial kinematics. MATERIALS AND METHODS: Eight fresh frozen human specimens were tested on a knee rig during active knee flexion from 30 to 130°. Within the same specimen a medial stabilized (MS) implant design was used first with KA and then with MA. RESULTS: The femorotibial kinematics showed more internal rotation of the tibia in KA compared to MA. At the same time, there was a larger medial rotation point in KA. Both alignment methods showed femoral rollback over the knee bend. CONCLUSION: Relating to an increased internal rotation and a more precise medial pivot point, it can be concluded that KA combined with a MS implant design may partially support the reproduction of physiological knee joint mechanics.

ß-Nuclear-Recoil Correlation from

We report the first precise measurement of a ß-recoil correlation from a radioactive noble gas (^{6}He) confined via a magneto-optical trap. The measurement is motivated by the search for exotic tensor-type contributions to the charged weak current. Interpreted as tensor currents with right-handed neutrinos, the measurements yield |C_{T}/C_{A}|^{2}≤0.022 (90% confidence limit, C.L.). On the other hand, for left-handed neutrinos the limits are 0.007

Impact of a mid-urethral synthetic mesh sling on long-term risk of systemic conditions in women with stress urinary incontinence: a national cohort study.

OBJECTIVE: To compare the incidence of systemic conditions between women who had surgical treatment for stress incontinence with mesh and without mesh. DESIGN: National cohort study. SETTING: English National Health Service. POPULATION: Women with no previous record of systemic disease who had first-time urinary incontinence surgery between 1 January 2006 and 31 December 2013, followed up to the earliest of 10 years or 31 March 2019. METHODS: Competing-risks regression was used to estimate hazard ratios (HR), adjusted for patient characteristics, with HR > 1 indicating increased incidence following mesh surgery. MAIN OUTCOME MEASURES: First postoperative admission with a record of autoimmune disease, fibromyalgia or myalgic encephalomyelitis up to 10 years following the first incontinence procedure. RESULTS: The cohort included 88 947 women who had mesh surgery and 3389 women who had non-mesh surgery. Both treatment groups were similar with respect to age, socio-economic deprivation, comorbidity and ethnicity. The 10-year cumulative incidence of autoimmune disease, fibromyalgia or myalgic encephalomyelitis was 8.1% (95% CI 7.9-8.3%) in the mesh group and 9.0% (95% CI 8.0-10.1%) in the non-mesh group (adjusted HR 0.89, 95% CI 0.79-1.01; P = 0.07). A sensitivity analysis including only autoimmune diseases as an outcome returned a similar result. CONCLUSIONS: These findings do not support claims that synthetic mesh slings cause systemic disease. TWEETABLE ABSTRACT: No evidence of increased risk of systemic conditions after stress incontinence treatment with a mesh sling.

iRFP (near-infrared fluorescent protein) imaging of subcutaneous and deep tissue tumours in mice highlights differences between imaging platforms.

BACKGROUND: In vivo imaging using fluorescence is used in cancer biology for the detection, measurement and monitoring of tumours. This can be achieved with the expression of fluorescent proteins such as iRFP, which emits light at a wavelength less attenuated in biological tissues compared to light emitted by other fluorescent proteins such as GFP or RFP. Imaging platforms capable of detecting fluorescent tumours in small animals have been developed but studies comparing the performance of these platforms are scarce. RESULTS: Through access to three platforms from Xenogen, Bruker and Li-Cor, we compared their ability to detect iRFP-expressing subcutaneous tumours as well as tumours localised deeper within the body of female NSG mice. Each platform was paired with proprietary software for image analyse, but the output depends on subjective decisions from the user. To more objectively compare platforms, we developed an 'in house' software-based approach which results in lower measured variability between mice. CONCLUSIONS: Our comparisons showed that all three platforms allowed for reliable detection and monitoring of subcutaneous iRFP tumour growth. The biggest differences between platforms became apparent when imaging deeper tumours with the Li-Cor platform detecting most tumours and showing the highest dynamic range.

Fit-for-Discharge Criteria after Esophagectomy: An International Expert Delphi Consensus.

There are no internationally recognized criteria available to determine preparedness for hospital discharge after esophagectomy. This study aims to achieve international consensus using Delphi methodology. The expert panel consisted of 40 esophageal surgeons spanning 16 countries and 4 continents. During a 3-round, web-based Delphi process, experts voted for discharge criteria using 5-point Likert scales. Data were analyzed using descriptive statistics. Consensus was reached if agreement was ≥75% in round 3. Consensus was achieved for the following basic criteria: nutritional requirements are met by oral intake of at least liquids with optional supplementary nutrition via jejunal feeding tube. The patient should have passed flatus and does not require oxygen during mobilization or at rest. Central venous catheters should be removed. Adequate analgesia at rest and during mobilization is achieved using both oral opioid and non-opioid analgesics. All vital signs should be normal unless abnormal preoperatively. Inflammatory parameters should be trending down and close to normal (leucocyte count ≤12G/l and C-reactive protein ≤80 mg/dl). This multinational Delphi survey represents the first expert-led process for consensus criteria to determine 'fit-for-discharge' status after esophagectomy. Results of this Delphi survey may be applied to clinical outcomes research as an objective measure of short-term recovery. Furthermore, standardized endpoints identified through this process may be used in clinical practice to guide decisions regarding patient discharge and may help to reduce the risk of premature discharge or prolonged admission.

Atomic Transport in Au-Ge Droplets: Brownian and Electromigration Dynamics.

The deposition of Au on Ge(111)-sqrt[3]×sqrt[3]-Au above the eutectic temperature results in the formation of AuGe liquid droplets that reach the liquidus composition by digging a hole in the Ge substrate. The combination of low-energy electron microscopy and atomic force microscopy measurements shows that AuGe droplets randomly migrate or electromigrate under an applied electric current dragging their underneath hole. The droplet motion is due to a mass transport phenomenon based on Ge dissolution at the droplet front and Ge crystallization at its rear. At high temperature the mass transport is limited by attachment or detachment at the solid-liquid interface and the activation energy is 1.05±0.3 eV. At low temperature the effective activation energy increases as a function of the droplet radius. This behavior is attributed to the nucleation of 2D layers at the faceted liquid-solid interface.

STRIDER NZAus: a multicentre randomised controlled trial of sildenafil therapy in early-onset fetal growth restriction.

OBJECTIVE: To assess the effect of maternal sildenafil therapy on fetal growth in pregnancies with early-onset fetal growth restriction. DESIGN: A randomised placebo-controlled trial. SETTING: Thirteen maternal-fetal medicine units across New Zealand and Australia. POPULATION: Women with singleton pregnancies affected by fetal growth restriction at 22+0 to 29+6 weeks. METHODS: Women were randomised to oral administration of 25 mg sildenafil citrate or visually matching placebo three times daily until 32+0 weeks, birth or fetal death (whichever occurred first). MAIN OUTCOME MEASURES: The primary outcome was the proportion of pregnancies with an increase in fetal growth velocity. Secondary outcomes included live birth, survival to hospital discharge free of major neonatal morbidity and pre-eclampsia. RESULTS: Sildenafil did not affect the proportion of pregnancies with an increase in fetal growth velocity; 32/61 (52.5%) sildenafil-treated, 39/57 (68.4%) placebo-treated [adjusted odds ratio (OR) 0.49, 95% CI 0.23-1.05] and had no effect on abdominal circumference Z-scores (P = 0.61). Sildenafil use was associated with a lower mean uterine artery pulsatility index after 48 hours of treatment (1.56 versus 1.81; P = 0.02). The live birth rate was 56/63 (88.9%) for sildenafil-treated and 47/59 (79.7%) for placebo-treated (adjusted OR 2.50, 95% CI 0.80-7.79); survival to hospital discharge free of major neonatal morbidity was 42/63 (66.7%) for sildenafil-treated and 33/59 (55.9%) for placebo-treated (adjusted OR 1.93, 95% CI 0.84-4.45); and new-onset pre-eclampsia was 9/51 (17.7%) for sildenafil-treated and 14/55 (25.5%) for placebo-treated (OR 0.67, 95% CI 0.26-1.75). CONCLUSIONS: Maternal sildenafil use had no effect on fetal growth velocity. Prospectively planned meta-analyses will determine whether sildenafil exerts other effects on maternal and fetal/neonatal wellbeing. TWEETABLE ABSTRACT: Maternal sildenafil use has no beneficial effect on growth in early-onset FGR, but also no evidence of harm.

Preemptive endoluminal vacuum therapy to reduce anastomotic leakage after esophagectomy: a game-changing approach?

Endoluminal vacuum therapy (EVT) is an accepted treatment for anastomotic leakage (AL) after esophagectomy. A novel concept is to use this technology in a preemptive setting, with the aim to reduce the AL rate and postoperative morbidity. Preemptive EVT (pEVT) was performed intraoperatively in 19 consecutive patients undergoing minimally invasive esophagectomy, immediately after completion of esophagogastrostomy. Twelve patients (63%) were high-risk cases with severe comorbidity. The EVT device was removed routinely three to six (median 5) days after esophagectomy. The endpoints of this study were AL rate and postoperative morbidity. There were 20 anastomoses at risk in 19 patients. One patient (5.3%) experienced major morbidity (Clavien-Dindo grade IIIb) unrelated to anastomotic healing. He underwent open reanastomosis at postoperative day 12 with pEVT for redundancy of the gastric tube and failure of transition to oral diet. Mortality after 30 days was 0% and anastomotic healing was uneventful in 19/20 anastomoses (95%). One minor contained AL healed after a second course of EVT. Except early proximal dislodgement in one patient, there were no adverse events attributable to pEVT. The median comprehensive complication index 30 days after surgery was 20.9 (IQR 0-26.2). PEVT appears to be a safe procedure that may have the potential to improve surgical outcome in patients undergoing esophagectomy.

[Drug treatment of Alzheimer's dementia : Status quo and perspectives]. / Pharmakologische Therapie der Alzheimer-Demenz : Aktueller Stand und Perspektiven.

Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system. AD is characterized by progressive impairments of memory as well as other cognitive functions and an increasing loss of autonomy in everyday life. This review article provides an overview of the current state-of-the-art (symptomatic) pharmacological treatment of Alzheimer's disease, specifics in the context of concomitant neuropsychiatric symptoms in multimorbid patients, and drugs currently under development that have a potentially causal (disease modifying) effect are also mentioned.

Whole genome microarray expression analysis in blood identifies pathways linked to signs and symptoms of a patient with hypercalprotectinaemia and hyperzincaemia.

A child, 2 years with the 'hypercalprotectinaemia with hyperzincaemia' clinical syndrome, presented with atypical symptoms and signs, notably persistent fever of approximately 38°C, thrombocythaemia of > 700 × 109 /l and a predominance of persistent intestinal symptoms. In an effort to find a cure by identifying the dysregulated pathways we analysed whole-genome mRNA expression by the Affymetrix HG U133 Plus 2·0 array in blood on three occasions 3-5 months apart. Major up-regulation was demonstrated for the Janus kinase/signal transducer and activators of transcription (JAK/STAT) pathway including, in particular, CD177, S100A8, S100A9 and S100A12, accounting for the thrombocytosis; a large number of interleukins, their receptors and activators, accounting for the febrile apathic state; and the high mobility group box 1 (HMBG1) gene, possibly accounting for part of the intestinal symptoms. These results show that gene expression array technology may assist the clinician in the diagnostic work-up of individual patients with suspected syndromal states of unknown origin, and the expression data can guide the selection of optimal treatment directed at the identified target pathways.

LapTrain: multi-modality training curriculum for laparoscopic cholecystectomy-results of a randomized controlled trial.

BACKGROUND: Multiple training modalities for laparoscopy have different advantages, but little research has been conducted on the benefit of a training program that includes multiple different training methods compared to one method only. This study aimed to evaluate benefits of a combined multi-modality training program for surgical residents. METHODS: Laparoscopic cholecystectomy (LC) was performed on a porcine liver as the pre-test. Randomization was stratified for experience to the multi-modality Training group (12 h of training on Virtual Reality (VR) and box trainer) or Control group (no training). The post-test consisted of a VR LC and porcine LC. Performance was rated with the Global Operative Assessment of Laparoscopic Skills (GOALS) score by blinded experts. RESULTS: Training (n = 33) and Control (n = 31) were similar in the pre-test (GOALS: 13.7 ± 3.4 vs. 14.7 ± 2.6; p = 0.198; operation time 57.0 ± 18.1 vs. 63.4 ± 17.5 min; p = 0.191). In the post-test porcine LC, Training had improved GOALS scores (+ 2.84 ± 2.85 points, p < 0.001), while Control did not (+ 0.55 ± 2.34 points, p = 0.154). Operation time in the post-test was shorter for Training vs. Control (40.0 ± 17.0 vs. 55.0 ± 22.2 min; p = 0.012). Junior residents improved GOALS scores to the level of senior residents (pre-test: 13.7 ± 2.7 vs. 18.3 ± 2.9; p = 0.010; post-test: 15.5 ± 3.4 vs. 18.8 ± 3.8; p = 0.120) but senior residents remained faster (50.1 ± 20.6 vs. 25.0 ± 1.9 min; p < 0.001). No differences were found between groups on the post-test VR trainer. CONCLUSIONS: Structured multi-modality training is beneficial for novices to improve basics and overcome the initial learning curve in laparoscopy as well as to decrease operation time for LCs in different stages of experience. Future studies should evaluate multi-modality training in comparison with single modalities. TRIAL REGISTRATION: German Clinical Trials Register DRKS00011040.