Effects of Feeding Time on Markers of Muscle Metabolic Flexibility Following Acute Aerobic Exercise in Trained Mice Undergoing Time Restricted Feeding

Time-restricted feeding (TRF) is becoming a popular way of eating in physically active populations, despite a lack of research on metabolic and performance outcomes as they relate to the timing of food consumption in relation to the time of exercise. The purpose of this study was to determine if the timing of feeding/fasting after exercise training differently affects muscle metabolic flexibility and response to an acute bout of exercise. Male C57BL/6 mice were randomized to one of three groups for 8 weeks. The control had ad libitum access to food before and after exercise training. TRF-immediate had immediate access to food for 6 h following exercise training and the TRF-delayed group had access to food 5-h post exercise for 6 h. The timing of fasting did not impact performance in a run to fatigue despite TRF groups having lower hindlimb muscle mass. TRF-delayed had lower levels of muscle HSL mRNA expression and lower levels of PGC-1α expression but displayed no changes in electron transport chain enzymes. These results suggest that in young populations consuming a healthy diet and exercising, the timing of fasting may not substantially impact metabolic flexibility and running performance.     

CCopeY: A Mixed-Methods Coproduced Study on the Mental Health Status and Coping Strategies of Young People During COVID-19 UK Lockdown

PurposeExploring the impact of the COVID-19 pandemic on young people’s mental health is an increasing priority. Studies to date are largely surveys and lack meaningful involvement from service users in their design, planning, and delivery. The study aimed to examine the mental health status and coping strategies of young people during the first UK COVID-19 lockdown using coproduction methodology.MethodsThe mental health status of young people (aged 16–24) in April 2020 was established utilizing a sequential explanatory coproduced mixed methods design. Factors associated with poor mental health status, including coping strategies, were also examined using an online survey and semi-structured interviews.ResultsSince the lockdown, 30.3% had poor mental health, and 10.8% had self-harmed. Young people identifying as Black/Black-British ethnicity had the highest increased odds of experiencing poor mental health (odds ratio [OR] 3.688, 95% CI .54–25.40). Behavioral disengagement (OR 1.462, 95% CI 1.22–1.76), self-blame (OR 1.307 95% CI 1.10–1.55), and substance use (OR 1.211 95% CI 1.02–1.44) coping strategies, negative affect (OR 1.109, 95% CI 1.07–1.15), sleep problems (OR .915 95% CI .88–.95) and conscientiousness personality trait (OR .819 95% CI .69–.98) were significantly associated with poor mental health. Three qualitative themes were identified: (1) pre-existing/developed helpful coping strategies employed, (2) mental health difficulties worsened, and (3) mental health and nonmental health support needed during and after lockdown.ConclusionPoor mental health is associated with dysfunctional coping strategies. Innovative coping strategies can help other young people cope during and after lockdowns, with digital and school promotion and application.     

Timing of cranial reconstruction after cranioplasty infections: are we ready for a re-thinking? A comparative analysis of delayed versus immediate cranioplasty after debridement in a series of 48 patients

Neurosurgical Review - The optimal management of cranioplasty infections remains a matter of debate. Most authors have suggested that the infected bone/implant removal is mandatory, combined with...     

Significance and clinical impact of routinely tested urinary ethyl glucuronide after liver transplantation – development of a risk score

Alcohol abuse after liver transplantation can seriously impact graft and patient survival. However, to date, there is no defined standard procedure to identify patients consuming alcohol after liver transplantation. The aim of this study was to analyze the diagnostic value and clinical impact of routinely measured urinary ethyl glucuronide (uEtG) – a metabolite of ethanol – in patients after liver transplantation. Data of 362 consecutive patients after liver transplantation who visited the University Hospital of Tuebingen for outpatient follow-up were analyzed. Forty-eight patients (13%) displayed positive uEtG results. The uEtG positive group contained significantly more patients with pretransplant alcoholic liver disease. However, two thirds of the uEtG positive patients had no history of pretransplant alcoholic liver disease. Several clinical parameters were significantly associated with positive uEtG. In order to enable a more cost-effective application of uEtG in the future, a clinical risk score was developed (specificity 0.95). In conclusion, routine testing for uEtG reveals a considerable percentage of patients practicing alcohol intake after liver transplantation. Application of our proposed risk score could help focusing uEtG testing on patients at risk.     

Chemotherapy-Associated Liver Injuries: Unmet Needs and New Insights for Surgical Oncologists

Annals of Surgical Oncology -     

Multiviszerale Resektion des fortgeschrittenen kolorektalen Karzinoms Multivisceral resection in advanced colorectal carcinoma

Zusammenfassung Berichtet wird über die operative Behandlung von 1232 Patienten mit einem kolorektalen Karzinom aus dem Zeitraum 1.09.1984 bis 1.01.1990. Entsprechend einer Resektionsquote von 90,3 % wurden 1112 Patienten (kurativ: n = 917, palliativ: n = 195) reseziert. Bei 82 Patienten war wegen Organüberschreitung des Tumors eine multiviszerale Resektion von einem oder mehreren benachbarten Organen (69mal kurativ, 13mal palliativ) notwendig. Komplikationsraten (26,7% zu 27,5 %) und die 30-Tageletalität (3,4% zu 2,9 %) waren in beiden Gruppen der kurativ and kurativ erweitert resezierten Patienten gleich. Die Berechnung der Fünfjahresüberlebensrate ergab für die kurativ resezierten Patienten ohne Erweiterung einen Wert von 58% gegenüber 55 mit Erweiterung. Auch die Subgruppenanalyse ergab keinen Unterschied in den einzelnen Stadien. Die Ergebnisse lassen den Schlul zu, da bei gleicher Komplikations-und Letalitätsrate die kurativ erweiterte Resektion von pT3- and pT4-Tumoren gleiche Spdtergebnisse wie die entsprechende Behandlung von nicht erweitert resezierten pT3-Tumoren erwarten lät. Die Daten zeigen, da eine Infiltration von Nachbarorganen durch ein kolorektales Karzinom nicht als Inoperabilitätskriterium gelten darf.

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From 1 September to 1 January 1990, a total of 1232 patients underwent surgery for colorectal cancer. Resection was performed on 1112 (90.3%) patients. It was curative in 917 cases and palliative in 195. Multivisceral resection was necessary 82 times because of tumour infiltration of adjacent organs (curative: 69 cases; palliative: 13 cases). The complication rate (26.7% vs 27.5%) and mortality rate (3.4% vs 2.9%) were similar to those for curative resections without multivisceral extension. The 5-year survival rate was also similar in the two groups (58% vs 55%). These results show that curative multivisceral resections can lead to the same long-term results as conventional curative resections. These data are encouraging, and tumour infiltration of neighbouring organs should not be taken to demonstrate inoperability.

     

Analysis of receptor-G protein interactions in permeabilized cells

Receptor-induced binding of the stable GTP analogue, guanosine 5-[-thio]triphosphate (GTP [S]), to guanine nucleotide-binding regulatory proteins (G proteins) was measured in various permeabilized cells. In myeloid differentiated human leukemia (HL-60) cells, permeabilized with either digitonin, streptolysin O or Staphylococcus aureus -toxin, binding of GTP [S] induced by three distinct chemoattractant receptors was observed. The extent of receptor-stimulated GTP [S] binding (maximally about 2-fold) was independent of the type of permeabilizing agent used. In human erythroleukemia cells permeabilized with digitonin, agonist activation of thrombin and neuropeptide Y receptors increased GTP [S] binding by 1.8- and 1.5-fold, respectively. Finally, in adherently grown human embryonic kidney cells permeabilized with digitonin, activation of the stably expressed human muscarinic m3 receptor increased GTP[S] binding by about 1.6-fold. In digitonin-permeabilized HL-60 cells, a quantitative analysis of formyl peptide receptors and interacting G proteins was performed. About 50,000 formyl peptide receptors per cell were detected. Agonist binding to these receptors was fully sensitive to regulation by guanine nucleotides and pertussis toxin. The number of high-affinity GTP [S] binding sites, most likely representing heterotrimeric G proteins, was calculated to be about 670,000 per cell. Stimulation of formyl peptide receptors led to the activation of about 130,000 of high-affinity GTP [S] binding sites, indicating a ratio of about three activated G proteins per one agonist-activated receptor.Overall, this study indicates that receptor-stimulated GTP [S] binding to G proteins in permeabilized cells is a sensitive and rapid method for analyzing receptor-G protein interactions, which can be applied to a variety of cultured cells and for various receptor systems.     

Pharmacokinetics of 4′-O-tetrahydropyranyladriamycin given on a weekly schedule in patients with advanced breast cancer

Improved quality of life has gained importance over shortly lasting remissions in yet incurable metastatic breast cancer. Fractionation of drug administration is one of the possible approaches to reduce the concentration-dependent toxicity of anthracyclines. We evaluated the pharmacokinetics of 4-O-tetrahydropyranyladriamycin (THP-ADM) under weekly administration in patients with advanced breast cancer (dose escalation, from 20 to 27 mg/m₂ THP-ADM). The concentration-time curves of THP-ADM in plasma were best described by an open three-compartment model [half-life of the first disposition phase (t_1/2), 3.15 min; terminal elimination half-life (t _1/2), 13.9 h] with a mean area under the curve (AUC) of 12.2 ng h ml^–1mg^–1m^–2, resulting in a mean plasma clearance of 86.91 h^–1m^–2. Metabolism included the formation of Adriamycin (ADM), Adriamycinol (ADM-OH), 13-dihydro-4-O-tetrahydropyranyladriamycin (THP-OH), 7-deoxyadriamycinone (7H-ADn), and 7-deoxy-13-dihydroadrimycinone (7H-ADn-OH), with maximal plasma concentrations ranging from 2.8 to 5.5 ng/ml. The mean total amount of cytotoxic anthracyclines excreted into urine, mainly as the parent drug, was 5% of the delivered dose. ADM and ADM-OH, but not the parent drug, were observed in urine at up to 4 weeks after the last therapeutic cycle. There was a significant correlation between the leukocyte nadir under therapy and the AUC of ADM-OH (r=0.800,P<0.05). Since no shift in the plasma kinetics was observed from the first to the sixth cycle, the favorable ratio of the AUCs of THP-ADM and ADM after fractionation of THP-ADM suggests lower toxic side effects attributable to ADM. This hypothesis was confirmed in a clinical study, where no severe cardiotoxicity and only mild alopecia were observed in 19 patients. Thus, pharmacokinetics studies might be helpful in both individualization of therapy with THP-ADM and optimization of the administration schedule.