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IntroductionHip fractures are common injuries in the elderly, with an incidence that continues to rise. The femoral neck system (FNS) recently emerged as a novel treatment option for femoral neck fractures, but long-term survivability of the implant remains uncertain. The purpose of this study is to evaluate survivability of the FNS and assess risk factors for implant failure.MethodsOne hundred five adult patients who received the FNS (DePuy Synthes, Raynham, MA) for femoral neck fractures (AO/OTA 31B) were included. Surgeries were performed within a regional hospital system comprising 18 facilities. All patients had a minimum follow-up of 1 year. The primary outcome measures were cumulative incidence of implant failure and 1-year mortality, including risk factor analysis.ResultsTwelve implants failed at a follow-up ranging from 17 days to 8 months, and 7 failed within 90 days. Cumulative incidence of implant failure was 2% at 30 days, 7% at 90 days, 12% at 6 months, and 13% at 1 year. Causes of implant failure included cut-out (n = 5), non-union (n = 4), peri-implant fracture (n = 2), and avascular necrosis (n = 1). Univariate Cox regression identified Pauwels type III fractures and an increasing AP Parker ratio as significant risk factors for failure. Pauwels type III fractures showed a 5.48 times higher risk compared to Pauwels types I & II. Every 10% increase in AP Parker ratio increased risk of failure by 2.39 times. The 1-year mortality rate was 21%, and univariate logistic regression identified age as the only risk factor (odds ratio = 3.71).ConclusionsThe incidence of implant failure and 1-year mortality rate in this study suggests that the FNS can provide reliable fixation compared to rates in the literature, but complications are not uncommon. Avoiding Pauwels type III fractures and optimizing implant placement appear crucial to preventing implant failure.Level of EvidenceTherapeutic Level IV.

Displaced intra-articular calcaneus fractures (DIACFs) are difficult injuries to treat and are often encountered by orthopedic surgeons. For DIACFs treated nonoperatively or with open reduction internal fixation (ORIF), a common complication is painful subtalar arthritis and the need for a secondary subtalar fusion, which prolongs the overall recovery time. One treatment option to address this sequela involves ORIF with subtalar fusion as the primary treatment. We describe a reproducible, minimally invasive surgical technique for primary ORIF with subtalar fusion when the calcaneal tuberosity is amendable to cannulated screw fixation to treat these complex calcaneal fractures. Our technique offers advantages compared to other techniques in that it avoids screw traffic, allows easy bony compression of the subtalar joint, and minimizes soft tissue damage via percutaneous screw fixation. Fourteen fractured calcanei in 12 patients underwent our technique and all achieved bony union with a median time to fusion of 107.5 days (range, 54–530 days). Eight patients returned to work with the remaining 4 patients having an unknown work status at last follow-up, although 2 of these 4 patients resumed normal activities. Only 1 patient experienced a complication, which was an infection after achieving bony union, and was treated with successful hardware removal and our infection protocol. Overall, we conclude our surgical technique offers a successful option in the treatment of DIACFs when the calcaneal tuberosity is amendable to cannulated screw fixation.

While amputation techniques have improved over time, questions remain around how to best treat neuromas and severed nerves in the amputee population, specifically for trauma-related amputees. This systematic review investigates and summarizes outcomes following targeted muscle reinnervation (TMR) for the trauma-related amputee population. Studies were classified based on primary or secondary TMR and relevant outcomes, including the ability to use a prosthesis, post-TMR opioid use, Patient-Reported Outcomes Measurement Information System (PROMIS) scores for phantom limb pain and residual limb pain, and overall pain resolution/reduction. Following TMR for trauma-related amputation, most patients experienced neuroma pain resolution (86.2%, 95% confidence interval [CI]: 67.2-95.0%) and overall pain reduction/resolution (90.7%, 95% CI: 82.2-95.4%). No differences were seen between primary and secondary TMR. Preliminary evidence indicates that TMR is effective for preventing or treating pain in patients with trauma-related amputation, whether used in the acute or delayed setting.

Surgical weight loss procedures like vertical sleeve gastrectomy (SG) are sufficient in resolving obesity comorbidities and are touted to reduce the burden of pro-inflammatory cytokines and augment the release of anti-inflammatory cytokines. Recent reports suggest a reduced improvement in weight resolution after SG in Black Americans (BA) versus White Americans (WA). The goal of this study was to determine if differences in immunoglobulin levels and general markers of inflammation after SG in Black Americans (BA) and White Americans (WA) may contribute to this differential resolution. Personal information, anthropometric data, and plasma samples were collected from 58 participants (24 BA and 34 WA) before and 6 weeks after SG for the measurement of immunoglobulin A (IgA), IgG, IgM, C-reactive protein (CRP), and transforming growth factor (TGFβ). Logistic regression analysis was used to determine the relationship of measures of body size and weight and inflammatory markers. Both IgG and CRP were significantly elevated in BA in comparison to WA prior to weight loss. Collectively, IgG, TGFβ, and CRP were all significantly reduced at six weeks following SG. CRP levels in BA were reduced to a similar extent as WA, but IgG levels were more dramatically reduced in BA than WA despite the overall higher starting concentration. No change was observed in IgA and IgM. These data suggest that SG improves markers of immune function in both BA and WA. More diverse markers of immune health should be studied in future work.

Stable isotope mixing models are often used to quantify source contributions to a mixture. Examples include pollution source identification; trophic web studies; analysis of water sources for soils, plants; or water bodies, and many others. A common problem is having too many sources to allow a unique solution. We discuss two alternative procedures for addressing this problem. One option is a priori to combine sources with similar signatures so the number of sources is small enough to provide a unique solution. Aggregation should be considered only when isotopic signatures of clustered sources are not significantly different, and sources are related so the combined source group has some functional significance. For example, in a food web analysis, lumping several species within a trophic guild allows more interpretable results than lumping disparate food sources, even if they have similar isotopic signatures. One result of combining mixing model sources is increased uncertainty of the combined end-member isotopic signatures and consequently the source contribution estimates; this effect can be quantified using the IsoError model (http://www.epa.gov/wed/pages/models/isotopes/isoerror1_04.htm). As an alternative to lumping sources before a mixing analysis, the IsoSource mixing model (http://www.epa.gov/wed/pages/models/isosource/isosource.htm) can be used to find all feasible solutions of source contributions consistent with isotopic mass balance. While ranges of feasible contributions for each individual source can often be quite broad, contributions from functionally related groups of sources can be summed a posteriori, producing a range of solutions for the aggregate source that may be considerably narrower. A paleohuman dietary analysis example illustrates this method, which involves a terrestrial meat food source, a combination of three terrestrial plant foods, and a combination of three marine foods. In this case, a posteriori aggregation of sources allowed strong conclusions about temporal shifts in marine versus terrestrial diets that would not have otherwise been discerned.

Fine roots acquire essential soil resources and mediate biogeochemical cycling in terrestrial ecosystems. Estimates of carbon and nutrient allocation to build and maintain these structures remain uncertain because of the challenges of consistently measuring and interpreting fine-root systems. Traditionally, fine roots have been defined as all roots ≤ 2 mm in diameter, yet it is now recognized that this approach fails to capture the diversity of form and function observed among fine-root orders. Here, we demonstrate how order-based and functional classification frameworks improve our understanding of dynamic root processes in ecosystems dominated by perennial plants. In these frameworks, fine roots are either separated into individual root orders or functionally defined into a shorter-lived absorptive pool and a longer-lived transport fine-root pool. Using these frameworks, we estimate that fine-root production and turnover represent 22% of terrestrial net primary production globally – a c. 30% reduction from previous estimates assuming a single fine-root pool. Future work developing tools to rapidly differentiate functional fine-root classes, explicit incorporation of mycorrhizal fungi into fine-root studies, and wider adoption of a two-pool approach to model fine roots provide opportunities to better understand below-ground processes in the terrestrial biosphere.

While multiple experiments have demonstrated that trees exposed to elevated CO₂can stimulate microbes to release nutrients from soil organic matter, the importance of root‐ versus mycorrhizal‐induced changes in soil processes are presently unknown. We analyzed the contribution of roots and mycorrhizal activities to carbon (C) and nitrogen (N) turnover in a loblolly pine (Pinus taeda) forest exposed to elevated CO₂by measuring extracellular enzyme activities at soil microsites accessed via root windows. Specifically, we quantified enzyme activity from soil adjacent to root tips (rhizosphere), soil adjacent to hyphal tips (hyphosphere), and bulk soil. During the peak growing season, CO₂enrichment induced a greater increase of N‐releasing enzymes in the rhizosphere (215% increase) than in the hyphosphere (36% increase), but a greater increase of recalcitrant C‐degrading enzymes in the hyphosphere (118%) than in the rhizosphere (19%). Nitrogen fertilization influenced the magnitude of CO₂effects on enzyme activities in the rhizosphere only. At the ecosystem scale, the rhizosphere accounted for c. 50% and 40% of the total activity of N‐ and C‐releasing enzymes, respectively. Collectively, our results suggest that root exudates may contribute more to accelerated N cycling under elevated CO₂at this site, while mycorrhizal fungi may contribute more to soil C degradation.

Protein ubiquitination plays an important role in the regulation of almost every aspect of eukaryotic cellular function; therefore, its destabilization is often observed in most human diseases and cancers. Consequently, developing inhibitors of the ubiquitination system for the treatment of cancer has been a recent area of interest. Currently, only a few classes of compounds have been discovered to inhibit the ubiquitin-activating enzyme (E1) and only one class is relatively selective in E1 inhibition in cells. We now report that Largazole and its ester and ketone analogs selectively inhibit ubiquitin conjugation to p27(Kip1) and TRF1 in vitro. The inhibitory activity of these small molecules on ubiquitin conjugation has been traced to their inhibition of the ubiquitin E1 enzyme. To further dissect the mechanism of E1 inhibition, we analyzed the effects of these inhibitors on each of the two steps of E1 activation. We show that Largazole and its derivatives specifically inhibit the adenylation step of the E1 reaction while having no effect on thioester bond formation between ubiquitin and E1. E1 inhibition appears to be specific to human E1 as Largazole ketone fails to inhibit the activation of Uba1p, a homolog of E1 in Schizosaccharomyces pombe. Moreover, Largazole analogs do not significantly inhibit SUMO E1. Thus, Largazole and select analogs are a novel class of ubiquitin E1 inhibitors and valuable tools for studying ubiquitination in vitro. This class of compounds could be further developed and potentially be a useful tool in cells.

Fifty years ago, GE Hutchinson defined the ecological niche as a hypervolume in n‐dimensional space with environmental variables as axes. Ecologists have recently developed renewed interest in the concept, and technological advances now allow us to use stable isotope analyses to quantify these niche dimensions. Analogously, we define the isotopic niche as an area (in δ‐space) with isotopic values (δ‐values) as coordinates. To make isotopic measurements comparable to other niche formulations, we propose transforming δ‐space to p‐space, where axes represent relative proportions of isotopically distinct resources incorporated into an animal's tissues. We illustrate the isotopic niche with two examples: the application of historic ecology to conservation biology and ontogenetic niche shifts. Sustaining renewed interest in the niche requires novel methods to measure the variables that define it. Stable isotope analyses are a natural, perhaps crucial, tool in contemporary studies of the ecological niche.