Effect of Three Legumes Containing Different Condensed Tannin Concentrations on the in Vitro Formation of the Pastoral Flavour Compound; Skatole

Feeding legumes, such as white clover (Trifolium repens), results in higher intakes and increased animal production compared to grasses (Ulyatt, 1981). Skatole is produced in the rumen from plant protein fermentation and is associated with undesirable pastoral flavours in meat (Young et al. 2002). Feeding white clover causes a greater skatole concentration in the rumen compared to perennial ryegrass (Lolium perenne) or Lotus corniculatus, as the protein in white clover is highly soluble and rapidly degraded (Schreurs et al., 2004). The condensed tannins (CT) in Lotus species slow protein degradation in the rumen (Aerts et al., 1999). The aim of this study was to determine the effect of legumes with different concentrations of CT on skatole formation

Metastasectomy for colorectal pulmonary metastases: a survey among members of the European Society of Thoracic Surgeons.

Surgical management of pulmonary metastases in colorectal cancer patients is a debated topic. There is currently no consensus on this matter, which sparks considerable risk for international practice variation. The European Society of Thoracic Surgeons (ESTS) ran a survey to assess current clinical practices and to determine criteria for resection among ESTS members. All ESTS members were invited to complete an online questionnaire of 38 questions on current practice and management of pulmonary metastases in colorectal cancer patients. In total, 308 complete responses were received (response rate: 22%) from 62 countries. Most respondents consider that pulmonary metastasectomy for colorectal pulmonary metastases improves disease control (97%) and improves patients' survival (92%). Invasive mediastinal staging in case of suspicious hilar or mediastinal lymph nodes is indicated (82%). Wedge resection is the preferred type of resection for a peripheral metastasis (87%). Minimally invasive approach is the preferred approach (72%). For a centrally located colorectal pulmonary metastasis, the preferred form of treatment is a minimally invasive anatomical resection (56%). During metastasectomy, 67% of respondents perform mediastinal lymph node sampling or dissection. Routine chemotherapy is rarely or never given following metastasectomy (57% of respondents). This survey among the ESTS members underlines the change in practice of pulmonary metastasectomy with an increasing tendency in favour of minimally invasive metastasectomy and surgical resection is preferred over other types of local treatment. Criteria for resectability vary and controversy remains regarding lymph node assessment and the role of adjuvant treatment

No clinically relevant difference in patient-reported outcomes between the direct superior approach and the posterolateral or anterior approach for primary total hip arthroplasty:analysis of 37,976 primary hip arthroplas-ties in the Dutch Arthroplasty Registry

Background and purpose — The direct superior approach (DSA) is a modification of the posterolateral approach (PLA) for total hip arthroplasty (THA). Patient-reported outcome measures (PROMs) of the DSA have not been investigated previously using nationwide data. Our aim was to assess PROMs after THA using the DSA compared with the PLA and, secondarily, with the anterior approach (DAA). Patients and methods — In this population-based cohort study we included 37,976 primary THAs performed between 2014 and 2020 (PLA: n = 22,616; DAA: n = 15,017; DSA: n = 343) using Dutch Arthroplasty Registry data. PROMs (NRS pain, EQ-5D, HOOS-PS, and OHS) were mea-sured preoperatively, and at 3 and 12 months postoperatively. Repeated measurements were analyzed using mixed-effects models, adjusted for confounders, to investigate the associa-tion between surgical approach and PROMs over time. Results — From baseline to 3 and 12 months, improve-ments for NRS pain scores, EQ-5D, and OHS were com-parable for the DSA compared with the PLA or DAA. No difference was found in HOOS-PS improvement 3 months postoperatively between DSA and PLA (–0.2, 95% confidence interval [CI] –2.4 to 1.9) and between DSA and DAA (–1.7, CI –3.9 to 0.5). At 12 months postoperatively, patients in the DSA group had improved –2.8 points (CI –4.9 to –0.6) more in HOOS-PS compared with the DAA, but not with the PLA group (–1.0, CI –3.2 to 1.1). Conclusion — Our study showed no clinically meaning-ful differences between the DSA and either PLA or DAA.</p

No clinically relevant difference in patient-reported outcomes between the direct superior approach and the posterolateral or anterior approach for primary total hip arthroplasty:analysis of 37,976 primary hip arthroplas-ties in the Dutch Arthroplasty Registry

Background and purpose — The direct superior approach (DSA) is a modification of the posterolateral approach (PLA) for total hip arthroplasty (THA). Patient-reported outcome measures (PROMs) of the DSA have not been investigated previously using nationwide data. Our aim was to assess PROMs after THA using the DSA compared with the PLA and, secondarily, with the anterior approach (DAA). Patients and methods — In this population-based cohort study we included 37,976 primary THAs performed between 2014 and 2020 (PLA: n = 22,616; DAA: n = 15,017; DSA: n = 343) using Dutch Arthroplasty Registry data. PROMs (NRS pain, EQ-5D, HOOS-PS, and OHS) were mea-sured preoperatively, and at 3 and 12 months postoperatively. Repeated measurements were analyzed using mixed-effects models, adjusted for confounders, to investigate the associa-tion between surgical approach and PROMs over time. Results — From baseline to 3 and 12 months, improve-ments for NRS pain scores, EQ-5D, and OHS were com-parable for the DSA compared with the PLA or DAA. No difference was found in HOOS-PS improvement 3 months postoperatively between DSA and PLA (–0.2, 95% confidence interval [CI] –2.4 to 1.9) and between DSA and DAA (–1.7, CI –3.9 to 0.5). At 12 months postoperatively, patients in the DSA group had improved –2.8 points (CI –4.9 to –0.6) more in HOOS-PS compared with the DAA, but not with the PLA group (–1.0, CI –3.2 to 1.1). Conclusion — Our study showed no clinically meaning-ful differences between the DSA and either PLA or DAA.</p

Potential Dietary Countermeasure Against Spaceflight-Induced Bone Loss

As humans venture further into space and beyond low Earth orbit, space radiation is one of the main challenges for astronauts' health. Radiation-induced bone loss is a potential health problem for long duration habitation in space. We showed that a dietary countermeasure prevents bone loss in mice exposed to total body irradiation (TBI). We used a range of ionizing radiation, gamma (137Cs), proton (1H), iron (56Fe), and a combination of sequential proton and iron beam (1H/56Fe/1H) to evaluate skeletal responses. These TBI cover a range of linear energy transfer (LET), from low-LET such as proton, to high-LET such as 56Fe (HZE: high Z- high energy) at doses between 1-2 Gy. The countermeasure diet, composed of 25% Dried Plum (DP) was effective at preventing radiation-induced cancellous bone loss in appendicular bone (tibia). Furthermore, exposing mice to HZE radiation, such as 56Fe (1Gy), impaired ex vivo growth of marrow-derived, bone-forming osteoblasts, which led to reduced mineralization capacity (-77%). In contrast, mice fed the DP diet did not display these deficits, showing the diet's capacity to protect marrow-derived osteoprogenitors. Dietary DP prevented the increase of bone resorbing osteoclast cells, inflammation and oxidative stress, while protecting the osteoprogenitors and mesenchymal stem cells, which few drugs against osteoporosis may achieve. Spaceflight is a combination of multiple factors including microgravity, in addition to space radiation. Therefore, we conducted additional studies to determine if the DP diet could prevent simulated spaceflight (simulated microgravity and radiation combined) bone loss. Mice were exposed to gamma (TBI, 137Cs, 2 Gy), simulated microgravity (using the hindlimb unloading system, HU) or TBI+HU. While we observed bone loss in mice fed the control diet (CD) due to both treatments (TBI=14%, HU=20%), and a worse effect with combined treatments (TBI+HU=25%), mice fed the DP diet did not sustain significant bone loss relative to untreated controls. The DP diet prevented microarchitectural decrements in both appendicular bone (tibia) and axial bone (vertebrae). In addition, the DP diet mitigated HU-induced deficits in osteoblastogenesis. Interestingly, lower doses of DP diet (5%, 10%) did not appear to prevent cancellous bone loss, which shows the importance of identifying the active component(s) of DP. Finally, we have preliminary data showing the potential of DP to prevent radiation-induced damage at a systematic level.. In summary, this novel dietary countermeasure is a promising candidate nutritional countermeasure for spaceflight-induced bone loss and tissue damage

Uterine bathing with sonography gel prior to IVF/ICSI-treatment in patients with endometriosis, a multicentre randomised controlled trial

STUDY QUESTION What is the effect of uterine bathing with sonography gel prior to IVF/ICSI-treatment on live birth rates after fresh embryo transfer in patients with endometriosis? SUMMARY ANSWER After formal interim analysis and premature ending of the trial, no significant difference between uterine bathing using a pharmacologically neutral sonography gel compared to a sham procedure on live birth rate after fresh embryo transfer in endometriosis patients (26.7% vs. 15.4%, relative risk (RR) 1.73, 95% confidence interval (CI) 0.81–3.72; P-value 0.147) could be found, although the trial was underpowered to draw definite conclusions. WHAT IS KNOWN ALREADY Impaired implantation receptivity contributes to reduced clinical pregnancy rates after IVF/ICSI-treatment in endometriosis patients. Previous studies have suggested a favourable effect of tubal flushing with Lipiodol® on natural conceptions. This benefit might also be explained by enhancing implantation through endometrial immunomodulation. Although recent studies showed no beneficial effect of endometrial scratching, the effect of mechanical stress by intrauterine infusion on the endometrium in endometriosis patients undergoing IVF/ICSI-treatment has not been investigated yet. STUDY DESIGN, SIZE, DURATION We performed a multicentre, patient-blinded, randomised controlled trial in which women were randomly allocated to either a Gel Infusion Sonography (GIS, intervention group) or a sham procedure (control group) prior to IVF/ICSI-treatment. Since recruitment was slow and completion of the study was considered unfeasible, the study was halted after inclusion of 112 of the planned 184 women. PARTICIPANTS/MATERIALS, SETTING, METHODS We included infertile women with surgically confirmed endometriosis ASRM stage I–IV undergoing IVF/ICSI-treatment. After informed consent, women were randomised to GIS with intrauterine instillation of ExEm-gel® or sonography with gel into the vagina (sham). This was performed in the cycle preceding the embryo transfer, on the day GnRH analogue treatment was started. The primary endpoint was live birth rate after fresh embryo transfer. Analysis was performed by both intention-to-treat and per-protocol. MAIN RESULTS AND THE ROLE OF CHANCE Between July 2014 to September 2018, we randomly allocated 112 women to GIS (n = 60) or sham procedure (n = 52). The live birth rate after fresh embryo transfer was 16/60 (26.7%) after GIS versus 8/52 (15.4%) after the sham (RR 1.73, 95% CI 0.81–3.72; P-value 0.147). Ongoing pregnancy rate was 16/60 (26.7%) after GIS versus 9/52 (17.3%) in the controls (RR 1.54, 95% CI 0.74–3.18). Miscarriage occurred in 1/60 (1.7%) after GIS versus 5/52 (9.6%) in the controls (RR 0.17, 95% CI 0.02–1.44) women. Uterine bathing resulted in a higher pain score compared with a sham procedure (visual analogue scale score 2.7 [1.3–3.5] vs. 1.0 [0.0–2.0], P < 0.001). There were two adverse events after GIS compared with none after sham procedures. LIMITATIONS, REASONS FOR CAUTION The study was terminated prematurely due to slow recruitment and trial fatigue. Therefore, the trial is underpowered to draw definite conclusions regarding the effect of uterine bathing with sonography gel on live birth rate after fresh embryo transfer in endometriosis patients undergoing IVF/ICSI-treatment. WIDER IMPLICATIONS OF THE FINDINGS We could not demonstrate a favourable effect of uterine bathing procedures with sonography gel prior to IVF/ICSI-treatment in patients with endometriosis. STUDY FUNDING/COMPETING INTEREST(S) Investigator initiated study. IQ Medical Ventures provided the ExEm FOAM® kits free of charge, they were not involved in the study design, data management, statistical analyses and/or manuscript preparation, etc. C.B.L. reports receiving grants from Ferring, Merck and Guerbet, outside the submitted work. C.B.L. is Editor-in-Chief of Human Reproduction. V.M. reports grants and other from Guerbet, outside the submitted work. B.W.M. reports grants from NHMRC (GNT1176437), personal fees from ObsEva, Merck and Merck KGaA, Guerbet and iGenomix, outside the submitted work. N.P.J. reports research funding from Abb-Vie and Myovant Sciences and consultancy for Vifor Pharma, Guerbet, Myovant Sciences and Roche Diagnostics, outside the submitted work. K.D. reports personal fees from Guerbet, outside the submitted work. The other authors do not report any conflicts of interest. No financial support was provided. TRIAL REGISTRATION NUMBER NL4025 (NTR4198) TRIAL REGISTRATION DATE 7 October 2013 DATE OF FIRST PATIENT’S ENROLMENT 22 July 201

Interaction between Purkinje Cells and Inhibitory Interneurons May Create Adjustable Output Waveforms to Generate Timed Cerebellar Output

We develop a new model that explains how the cerebellum may generate the timing in classical delay eyeblink conditioning. Recent studies show that both Purkinje cells (PCs) and inhibitory interneurons (INs) have parallel signal processing streams with two time scales: an AMPA receptor-mediated fast process and a metabotropic glutamate receptor (mGluR)-mediated slow process. Moreover, one consistent finding is an increased excitability of PC dendrites (in Larsell's lobule HVI) in animals when they acquire the classical delay eyeblink conditioning naturally, in contrast to in vitro studies, where learning involves long-term depression (LTD). Our model proposes that the delayed response comes from the slow dynamics of mGluR-mediated IP3 activation, and the ensuing calcium concentration change, and not from LTP/LTD. The conditioned stimulus (tone), arriving on the parallel fibers, triggers this slow activation in INs and PC spines. These excitatory (from PC spines) and inhibitory (from INs) signals then interact at the PC dendrites to generate variable waveforms of PC activation. When the unconditioned stimulus (puff), arriving on the climbing fibers, is coupled frequently with this slow activation the waveform is amplified (due to an increased excitability) and leads to a timed pause in the PC population. The disinhibition of deep cerebellar nuclei by this timed pause causes the delayed conditioned response. This suggested PC-IN interaction emphasizes a richer role of the INs in learning and also conforms to the recent evidence that mGluR in the cerebellar cortex may participate in slow motor execution. We show that the suggested mechanism can endow the cerebellar cortex with the versatility to learn almost any temporal pattern, in addition to those that arise in classical conditioning