Poor Muscle Status, Dietary Protein Intake, Exercise Levels, Quality of Life and Physical Function in Women with Metastatic Breast Cancer at Chemotherapy Commencement and during Follow-Up.

This study aimed to investigate nutritional status, body composition, dietary protein intake, handgrip strength, 6 min or 4 m walk tests, self-reported physical activity, physical function, and quality of life (QoL-EORTC-QLQc30) at commencement of chemotherapy; to detect changes over time (from commencement of chemotherapy, and after 3, 6, 12, 26 and 52 weeks) in women with metastatic breast cancer (MBC); and to investigate the relationship between nutritional variables. 'Sarcopenia' was defined as low muscle mass and strength, 'myosteatosis' as muscle fat-infiltration (CT scan). Continuous variables were analysed using paired t-tests between baseline and follow-ups. Fifteen women (54y, 95% CI [46.3;61.2]) were recruited. At baseline, malnutrition was present in 3 (20%) participants, sarcopenia in 3 (20%) and myosteatosis in 7 (54%). Thirteen (87%) participants had low protein intake; low handgrip strength was observed in 0, and low walk test distance and physical activity in four (27%) participants. Physical function and QoL were low in 10 (67%) and 9 (60%), respectively. QoL between baseline and 52 weeks decreased by 11.7 (95% CI [2.4;20.9], p = 0.025). Other variables did not significantly change over time. In this small study sample, myosteatosis, low dietary protein intake, low exercise levels and impaired quality of life and physical function are common.

Importance of Chemical Activation and the Effect of Low Operation Voltage on the Performance of Pt-Alloy Fuel Cell Electrocatalysts.

Pt-alloy (Pt-M) nanoparticles (NPs) with less-expensive 3d transition metals (M = Ni, Cu, Co) supported on high-surface-area carbon supports are currently the state-of-the-art (SoA) solution to reach the production phase in proton exchange membrane fuel cells (PEMFCs). However, while Pt-M electrocatalysts show promise in terms of increased activity for oxygen reduction reaction (ORR) and, thus, cost reductions from the significantly lower use of expensive and rare Pt, key challenges in terms of synthesis, activation, and stability remain to unlock their true potential. This work systematically tackles them with a combination of electrocatalyst synthesis and characterization methodologies including thin-film rotating disc electrodes (TF-RDEs), an electrochemical flow cell linked to an inductively coupled plasma mass spectrometer (EFC-ICP-MS), and testing in 50 cm2 membrane electrode assemblies (MEAs). In the first part of the present work, we highlight the crucial importance of the chemical activation (dealloying) step on the performance of Pt-M electrocatalysts in the MEA at high current densities (HCDs). In addition, we provide the scientific community with a preliminary and facile method of distinguishing between a "poorly" and "adequately" dealloyed (activated) Pt-alloy electrocatalyst using a much simpler and affordable TF-RDE methodology using the well-known CO-stripping process. Since the transition-metal cations can also be introduced in a PEMFC due to the degradation of the Pt-M NPs, the second part of the work focuses on presenting clear evidence on the direct impact of the lower voltage limit (LVL) on the stability of Pt-M electrocatalysts. The data suggests that in addition to intrinsic improvements in stability, significant improvements in the PEMFC lifetime can also be obtained via the correct MEA design and applied limits of operation, namely, restricting not just the upper but equally important also the lower operation voltage.

Enzyme replacement therapy and hematopoietic stem cell transplant: a new paradigm of treatment in Wolman disease.

BACKGROUND: Wolman disease is a rare, lysosomal storage disorder in which biallelic variants in the LIPA gene result in reduced or complete lack of lysosomal acid lipase. The accumulation of the substrates; cholesterol esters and triglycerides, significantly impacts cellular function. Untreated patients die within the first 12 months of life. Clinically, patients present severely malnourished, with diarrhoea and hepatosplenomegaly, many have an inflammatory phenotype, including with hemophagocytic lymphohistiocytosis (HLH). Hematopoietic stem cell transplant (HCT) had been historically the only treatment available but has a high procedure-related mortality because of disease progression and disease-associated morbidities. More recently, enzyme replacement therapy (ERT) with dietary substrate reduction (DSR) has significantly improved patient survival. However, ERT is life long, expensive and its utility is limited by anti-drug antibodies (ADA) and the need for central venous access. RESULTS: We describe five Wolman disease patients diagnosed in infancy that were treated at Royal Manchester Children's Hospital receiving ERT with DSR then HCT-multimodal therapy. In 3/5 an initial response to ERT was attenuated by ADA with associated clinical and laboratory features of deterioration. 1/5 developed anaphylaxis to ERT and the other patient died post HCT with ongoing HLH. All patients received allogeneic HCT. 4/5 patients are alive, and both disease phenotype and laboratory parameters are improved compared to when they were on ERT alone. The gastrointestinal symptoms are particularly improved after HCT, with reduced diarrhoea and vomiting. This allows gradual structured normalisation of diet with improved tolerance of dietary fat. Histologically there are reduced cholesterol clefts, fewer foamy macrophages and an improved villous structure. Disease biomarkers also show improvement with ERT, immunotherapy and HCT. Three patients have mixed chimerism after HCT, indicating a likely engraftment-defect in this condition. CONCLUSION: We describe combined ERT, DSR and HCT, multimodal treatment for Wolman disease. ERT and DSR stabilises the sick infant and reduces the formerly described prohibitively high, transplant-associated mortality in this condition. HCT abrogates the problems of ERT, namely attenuating ADA, the need for continuing venous access, and continuing high cost drug treatment. HCT also brings improved efficacy, particularly evident in improved gastrointestinal function and histology. Multimodal therapy should be considered a new paradigm of treatment for Wolman disease patients where there is an attenuated response to ERT, and for all patients where there is a well-matched transplant donor, in order to improve long term gut function, tolerance of a normal diet and quality of life.