Chronic inflammation has been associated with increased risk for developing gastrointestinal cancer. Interleukin-23 (IL-23) receptor signaling has been correlated with inflammatory bowel disease ...pathogenesis, as well as promotion of tumor growth. However, little is known about the relative potential for IL-23-directed causality in gut tumorigenesis. We report that IL-23 transgene expression was sufficient to induce rapid (3-4 weeks) de novo development of intestinal adenomas with 100% incidence. Initiation of tumorigenesis was independent of exogenous carcinogens, Helicobacter colonization, or pre-existing tumor-suppressor gene mutations. Tumorigenesis was mediated by Thy1(+)IL-23R(+) innate lymphoid cells (ILC3), in part, through IL-17 responses as tumor development was inhibited in RAG(-/-) × IL-17(-/-) double knockout mice. Remarkably, IL-23 initiation of tumorigenesis by resident ILCs consistently occurred before recruitment of conspicuous inflammatory infiltrates. Our results reveal an explicit role for IL-23-mediated initiation of gut tumorigenesis and implicate a key role for IL-23R(+) ILC3 in the absence of overt cellular infiltrate recruitment.
Abstract Hip fracture is associated with considerable morbidity and mortality and occurs in an elderly and infirm group of patients. Periprosthetic fracture after hip hemiarthroplasty is a serious ...complication. In this study, we have reviewed our experience of this injury. The outcome measures used were fracture union, mortality, infection and requirement for further surgery. Method We identified a cohort of 79 patients who sustained periprosthetic fractures after hip hemiarthroplasty from a prospective hip fracture database of 8354 patients (3611 were treated with hemiarthroplasty). Seventy-two percent were female and the mean age was 86 years at time of periprosthetic fracture. Results Sixty-two fractures occurred around uncemented prostheses (Austin Moore n = 61); the remainder occurred around cemented prostheses. The mean time from hip fracture surgery to periprosthetic fracture was 35 months (median time 5 months). Fractures were classified according to the Vancouver system. Fifteen percent ( n = 12) were type A fractures, 26% ( n = 21) were type B1 fractures, 41% ( n = 32) were type B2 fractures, 9% ( n = 7) were type B3 fractures and 9% ( n = 7) were type C fractures. Twenty-eight patients underwent open reduction internal fixation (ORIF), 36 required revision surgery, one required fixation and simultaneous revision and 14 were treated non-operatively. Eleven percent ( n = 9) died within 1 month of periprosthetic fracture, 23% had died by 3 months, 34% by 1 year and 49% by 2 years. Nineteen patients (24%) died before fracture union had occurred. Fracture union occurred in 97% of the remaining cases (58/60). Two patients developed nonunion requiring revision surgery (3%), and three patients developed deep infection requiring debridement (4%), one patient had an infection at the time of the periprosthetic fracture requiring a planned two-stage revision, one patient sustained a second periprosthetic fracture and two patients underwent superficial wound debridement (3%). The incidence of periprosthetic fracture at our institution since 1999 is 1.7% (62 of 3611 patients). The incidence rate after uncemented Austin Moore stem was 2.3% (54/2378) and cemented Exeter stem was 0.5% (4/812); Fisher's exact test p = 0.004. Conclusions This article reports satisfactory outcomes in this complex group of patients. We have established the incidence of 1.7%, with relatively low rates of nonunion, infection and other complications. The mortality rate has been established, and survivorship analysis has identified an increased rate of fracture around the Austin Moore prosthesis.
Niche divergence is expected for species that compete for shared resources, including migrants that occupy similar regions during the non-breeding season. Studies of temperate seabirds indicate that ...both spatial and behavioural segregation can be important mechanisms for reducing competition, but there have been few investigations of resource partitioning by closely related taxa in low productivity, tropical environments. We investigated niche partitioning in 3 gadfly petrel taxa, Pterodroma leucoptera leucoptera (n = 22), P. leucoptera caledonica (n = 7) and P. pycrofti (n = 12), during their non-breeding season in the eastern tropical Pacific Ocean by combining tracking data from geolocator-immersion loggers with remotely sensed environmental data in species distribution models (SDMs), and by comparing feather stable isotope ratios. The 3 taxa showed spatial partitioning: two foraged in the North Equatorial Counter Current and one in the South Equatorial Current. This reflected differences in their realised habitat niches, with significant taxon-specific responses to thermocline depth, sea surface temperature and bathymetry. There were also differences among taxa in activity patterns, and all birds spent a much larger proportion of time in flight at night than during the day, suggesting predominance of nocturnal foraging behaviour. Comparison of stable isotope ratios in feathers suggests that P. l. leucoptera and P. pycrofti mainly consume vertically migrating mesopelagic fishes, whereas the diet of P. l. caledonica also includes some lower trophic levels including crustaceans and squid. Unique insights can be gained from studies of the foraging ecology of tropical pelagic seabirds, in comparison with temperate and polar waters, and are urgently required for understanding and protecting tropical avifauna in key marine habitats.
Globally, priority areas for biodiversity are relatively well known, yet few detailed plans exist to direct conservation action within them, despite urgent need. Madagascar, like other globally ...recognized biodiversity hot spots, has complex spatial patterns of endemism that differ among taxonomic groups, creating challenges for the selection of within-country priorities. We show, in an analysis of wide taxonomic and geographic breadth and high spatial resolution, that multitaxonomic rather than single-taxon approaches are critical for identifying areas likely to promote the persistence of most species. Our conservation prioritization, facilitated by newly available techniques, identifies optimal expansion sites for the Madagascar government's current goal of tripling the land area under protection. Our findings further suggest that high-resolution multitaxonomic approaches to prioritization may be necessary to ensure protection for biodiversity in other global hot spots.
Acute protein turnover studies suggest lower anabolic response after ingestion of plant vs. animal proteins. However, the effects of an exclusively plant-based protein diet on resistance ...training-induced adaptations are under investigation.
To investigate the effects of dietary protein source exclusively plant-based vs. mixed diet on changes in muscle mass and strength in healthy young men undertaking resistance training.
Nineteen young men who were habitual vegans (VEG 26 ± 5 years; 72.7 ± 7.1 kg, 22.9 ± 2.3 kg/m
) and nineteen young men who were omnivores (OMN 26 ± 4 years; 73.3 ± 7.8 kg, 23.6 ± 2.3 kg/m
) undertook a 12-week, twice weekly, supervised resistance training program. Habitual protein intake was assessed at baseline and adjusted to 1.6 g kg
day
via supplemental protein (soy for VEG or whey for OMN). Dietary intake was monitored every four weeks during the intervention. Leg lean mass, whole muscle, and muscle fiber cross-sectional area (CSA), as well as leg-press 1RM were assessed before (PRE) and after the intervention (POST).
Both groups showed significant (all p < 0.05) PRE-to-POST increases in leg lean mass (VEG: 1.2 ± 1.0 kg; OMN: 1.2 ± 0.8 kg), rectus femoris CSA (VEG: 1.0 ± 0.6 cm
; OMN: 0.9 ± 0.5 cm
), vastus lateralis CSA (VEG: 2.2 ± 1.1 cm
; OMN: 2.8 ± 1.0 cm
), vastus lateralis muscle fiber type I (VEG: 741 ± 323 µm
; OMN: 677 ± 617 µm
) and type II CSA (VEG: 921 ± 458 µm
; OMN: 844 ± 638 µm
), and leg-press 1RM (VEG: 97 ± 38 kg; OMN: 117 ± 35 kg), with no between-group differences for any of the variables (all p > 0.05).
A high-protein (~ 1.6 g kg
day
), exclusively plant-based diet (plant-based whole foods + soy protein isolate supplementation) is not different than a protein-matched mixed diet (mixed whole foods + whey protein supplementation) in supporting muscle strength and mass accrual, suggesting that protein source does not affect resistance training-induced adaptations in untrained young men consuming adequate amounts of protein.
NCT03907059. April 8, 2019. Retrospectively registered.
Tuberculosis remains an important preventable disease in the United States. An effective strategy for reducing the transmission, morbidity, and mortality of active disease is the identification and ...treatment of latent tuberculosis infection (LTBI) to prevent progression to active disease.
To issue a current US Preventive Services Task Force (USPSTF) recommendation on screening for LTBI.
The USPSTF reviewed the evidence on screening for LTBI in asymptomatic adults seen in primary care, including evidence dating from the inception of searched databases.
The USPSTF found adequate evidence that accurate screening tests for LTBI are available, treatment of LTBI provides a moderate health benefit in preventing progression to active disease, and the harms of screening and treatment are small. The USPSTF has moderate certainty that screening for LTBI in persons at increased risk for infection provides a moderate net benefit.
The USPSTF recommends screening for LTBI in populations at increased risk. (B recommendation).
A small proportion of patients have persistent pain after total knee replacement (TKR). The primary aim of this study was to record the prevalence of pain after TKR at specific intervals ...post-operatively and to ascertain the impact of neuropathic pain. The secondary aim was to establish any predictive factors that could be used to identify patients who were likely to have high levels of pain or neuropathic pain after TKR. A total of 96 patients were included in the study. Their mean age was 71 years (48 to 89); 54 (56%) were female. The mean follow-up was 46 months (39 to 51). Pre-operative demographic details were recorded including a Visual Analogue Score (VAS) for pain, the Hospital Anxiety and Depression score as well as the painDETECT score for neuropathic pain. Functional outcome was assessed using the Oxford Knee score. The mean pre-operative VAS was 5.8 (1 to 10); and it improved significantly at all time periods post-operatively (p < 0.001): (from 4.5 at day three to five (1 to 10), 3.2 at six weeks (0 to 9), 2.4 at three months (0 to 7), 2.0 at six months (0 to 9), 1.7 at nine months (0 to 9), 1.5 at one year (0 to 8) and 2.0 at mean 46 months (0 to 10)). There was a high correlation (r > 0.7; p < 0.001) between the mean VAS scores for pain and the mean painDETECT scores at three months, one year and three years post-operatively. There was no correlation between the pre-operative scores and any post-operative scores at any time point. We report the prevalence of pain and neuropathic pain at various intervals up to three years after TKR. Neuropathic pain is an underestimated problem in patients with pain after TKR. It peaks at between six weeks and three-months post-operatively. However, from these data we were unable to predict which patients are most likely to be affected.
To cite this article: Brożek JL, Akl EA, Compalati E, Kreis J, Terracciano L, Fiocchi A, Ueffing E, Andrews J, Alonso‐Coello P, Meerpohl JJ, Lang DM, Jaeschke R, Williams JW Jr, Phillips B, Lethaby ...A, Bossuyt P, Glasziou P, Helfand M, Watine J, Afilalo M, Welch V, Montedori A, Abraha I, Horvath AR, Bousquet J, Guyatt GH, Schünemann HJ, for the GRADE Working Group. Grading quality of evidence and strength of recommendations in clinical practice guidelines. Part 3 of 3. The GRADE approach to developing recommendations. Allergy 2011; 66: 588–595.
This is the third and last article in the series about the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the quality of evidence and the strength of recommendations in clinical practice guidelines and its application in the field of allergy. We describe the factors that influence the strength of recommendations about the use of diagnostic, preventive and therapeutic interventions: the balance of desirable and undesirable consequences, the quality of a body of evidence related to a decision, patients’ values and preferences, and considerations of resource use. We provide examples from two recently developed guidelines in the field of allergy that applied the GRADE approach. The main advantages of this approach are the focus on patient important outcomes, explicit consideration of patients’ values and preferences, the systematic approach to collecting the evidence, the clear separation of the concepts of quality of evidence and strength of recommendations, and transparent reporting of the decision process. The focus on transparency facilitates understanding and implementation and should empower patients, clinicians and other health care professionals to make informed choices.
The pelagic food web of the Scotia Sea was studied by analysing natural abundances of nitrogen and carbon stable isotopes of primary producers and pelagic consumers, sampled from the seasonal ice ...edge in the south to the Antarctic Polar Front in the north. The analysis covered, within a single mid-summer period, particulate organic matter (POM) and 38 taxa, ranging from suspension feeding copepods and salps to omnivorous euphausiids, pelagic fish and higher, land-based predators including fur seals, penguins and flying birds. Spatial variation in δ
15N of POM correlated well with nutrient availability and primary productivity. Latitudinal differences in δ
13C of POM were closely linked to variations in temperature, nutrients and productivity depending on the frontal region sampled. This translated to equivalent (although smaller) regional δ
13C differences among higher trophic levels. The trophic positions of species based on isotope values broadly agreed with previously published dietary data with three important exceptions. First, the carnivorous amphipod
Themisto gaudichaudii had anomalously low δ
15N values. Second,
Euphausia superba had δ
15N values that were also surprisingly low, considering the abundant literature suggesting its omnivory. Third, the copepod
Rhincalanus gigas, considered a suspension feeder, had unexpectedly high δ
15N values rather more in keeping with omnivorous feeding. The consumer δ
15N values ranged from 1.2‰ (min.) measured in
Salpa thompsoni (designated here as trophic level (TL) 2 across all regions) to 15.2‰ (max.) measured in white-chinned petrels (
Procellaria aequinoctialis, calculated as TL5 relative to the TL2 of salps). Excluding seabirds, the resulting food chain length of 3.7 TL (above POM at TL1) was lower than in most other Southern Ocean and temperate marine pelagic ecosystems. The majority (60%) of vertebrate predators occupied only 1–1.5 trophic levels above the herbivorous suspension feeders such as krill. This indicates the existence of the classic short food chain of POM–suspension feeder–vertebrate predator. However the presence of trophic levels 4 and above indicates the existence of alternative trophic pathways, for example involving myctophid fish or carrion, and that some wide-ranging predators which breed at South Georgia also feed outside the region. This conclusion is supported first by the continuum of δ
15N values between krill, suspension feeding copepods and myctophid fish, and secondly by higher trophic levels in several of the myctophid species in the low-krill region of the northern Scotia Sea, suggesting latitudinal differences in food web structure and food chain length.
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