Sex differences in lifespan extension with acarbose and 17‐α estradiol: gonadal hormones underlie male‐specific improvements in glucose tolerance and mTORC2 signaling

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140036/1/acel12656.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140036/2/acel12656_am.pd

The effects of caloric restriction on adipose tissue and metabolic health are sex- and age-dependent

Caloric restriction (CR) is a nutritional intervention that reduces the risk of age-related diseases in numerous species, including humans. CR's metabolic effects, including decreased fat mass and improved insulin sensitivity, play an important role in its broader health benefits. However, the extent and basis of sex differences in CR's health benefits are unknown. We found that 30% CR in young (3-month-old) male mice decreased fat mass and improved glucose tolerance and insulin sensitivity, whereas these effects were blunted or absent in young female mice. Females' resistance to fat and weight loss was associated with decreased lipolysis, lower systemic energy expenditure and fatty acid oxidation, and increased postprandial lipogenesis compared to males. Positron emission tomography-computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) showed that peripheral glucose uptake was comparable between sexes. Instead, the sex differences in glucose homeostasis were associated with altered hepatic ceramide content and substrate metabolism: compared to CR males, CR females had lower TCA cycle activity but higher blood ketone concentrations, a marker of hepatic acetyl-CoA content. This suggests that males use hepatic acetyl-CoA for the TCA cycle whereas in females it accumulates, thereby stimulating gluconeogenesis and limiting hypoglycaemia during CR. In aged mice (18-months old), when females are anoestrus, CR decreased fat mass and improved glucose homeostasis to a similar extent in both sexes. Finally, in a cohort of overweight and obese humans CR-induced fat loss was also sex- and age-dependent: younger females (<45 years) resisted fat loss compared to younger males while in older subjects (>45 years) this sex difference was absent. Collectively, these studies identify age-dependent sex differences in the metabolic effects of CR and highlight adipose tissue, the liver and oestrogen as key determinants of CR's metabolic benefits. These findings have important implications for understanding the interplay between diet and health and for maximising the benefits of CR in humans

Abiotic ammonium formation in the presence of Ni-Fe metals and alloys and its implications for the Hadean nitrogen cycle

Experiments with dinitrogen-, nitrite-, nitrate-containing solutions were conducted without headspace in Ti reactors (200°C), borosilicate septum bottles (70°C) and HDPE tubes (22°C) in the presence of Fe and Ni metal, awaruite (Ni80Fe20) and tetrataenite (Ni50Fe50). In general, metals used in this investigation were more reactive than alloys toward all investigated nitrogen species. Nitrite and nitrate were converted to ammonium more rapidly than dinitrogen, and the reduction process had a strong temperature dependence. We concluded from our experimental observations that Hadean submarine hydrothermal systems could have supplied significant quantities of ammonium for reactions that are generally associated with prebiotic synthesis, especially in localized environments. Several natural meteorites (octahedrites) were found to contain up to 22 ppm Ntot. While the oxidation state of N in the octahedrites was not determined, XPS analysis of metals and alloys used in the study shows that N is likely present as nitride (N3-). This observation may have implications toward the Hadean environment, since, terrestrial (e.g., oceanic) ammonium production may have been supplemented by reduced nitrogen delivered by metal-rich meteorites. This notion is based on the fact that nitrogen dissolves into metallic melts

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Journal of Shellfish Research 15 2 488

Although 1993 landings of lobsters were valued at $300 million in Canada and$210 million in the United States, postharvest losses are 10-15% annually. "Bumper car" disease of lobsters caused by the scuticociliate Anophryoides haemophila, can be significant in coldwater impoundments. Although outbreaks occur more frequently and with greater severity, the epidemiology and economic impact of "bumper car" disease are not well documented. The ciliates are maintained in cell-free, defined medium at 5 degree C. Cultured ciliates require longer and more parasites to kill lobsters than those transmitted by intrahaemocoelic injection from lobster to lobster. Horizontal transmission likely occurs across gills of lobsters. Several licensed disinfectants and chemotherapeutants are efficacious against A. haemophila in vitro. Additional to indirect fluorescent antibody testing utilizing monoclonal antibodies prepared to sonicated ciliates, parasites are detected with oligonucleotide probes based on ssu-rDNA of A. haemophila. The prevalence of A. haemophila in wild-caught lobsters should be reevaluated with more sensitive and specific diagnostic tools. A definition of healthy versus ciliate-infected lobsters is being prepared, based on haematology and clinical chemistry of haemolymph. Our novel bar-coded labelling system for aquatic organisms facilitates experimental design and randomization protocols of lobsters. The model of "bumper car" disease will aid study of health and infectious disease processes of lobsters

Journal of Shellfish Research 13 1 296

The status of Perkinsus parasites continues to challenge scientists. Are they fungi or protistans? Are they apicomplexans? How many species of Perkinsus exist? Molecular biology is a powerful tool which has been used to address these questions of taxonomy and phylogeny. In particular, nucleotide sequence data from the internal transcribed spacers in the ribosomal RNA gene cluster differ between some described Perkinsus species and data from the small subunit of this gene cluster have indicated the phylogenetic affinities of the Perkinsea. We will discuss our current project which uses data from the ribosomal RNA gene cluster to investigate the taxonomy of Perkinsus parasites found in Canadian and American shellfish and determine their affinities to protistan parasites of uncertain phylogeny, including Dermocystidium spp. from fish and Labyrinthuloides haliotidis from abalone

91 120 Boca Raton, Florida, USA: CRC Press, Inc.

This review critically examines information on structure and developmental cycles, systematics and diagnosis, techniques, pathogenesis of infection, immunological responses, epidemiology, control and directions for future research on species of Sarcocystis in man, livestock, wildlife and other hosts.