Complete genome sequence of Parvimonas micra strain JM503A, a genetically tractable dental abscess clinical isolate.

Parvimonas micra is a pathobiont of humans that is often found in abundance at sites of mucosal inflammation as well as within malignant tumors. Here, we report the complete genome sequence of P. micra strain JM503A, which is a genetically tractable clinical isolate derived from a human odontogenic abscess specimen.

Two germ granule eIF4E isoforms reside in different mRNPs to hand off C elegans mRNAs from translational repression to activation.

We studied the function of translation factor eIF4E isoforms in regulating mRNAs in germ cell granules/condensates. Translational control of mRNAs plays an essential role in germ cell gene regulation. Messenger ribonucleoprotein (mRNP) complexes assemble on mRNAs as they move from the nucleus into perinuclear germ granules to exert both positive and negative post-transcriptional regulation in the cytoplasm. In C. elegans , germ granules are surprisingly dynamic mRNP condensates that remodel during development. Two eIF4E isoforms (called IFE-1 and IFE-3), eIF4E-Interacting Proteins (4EIPs), RBPs, DEAD-box helicases, polyadenylated mRNAs, Argonautes and miRNAs all occupy positions in germ granules. Affinity purification of IFE-1 and IFE-3 allowed mass spectrometry and mRNA-Seq to identify the proteins and mRNAs that populate stable eIF4E mRNPs. We find translationally controlled mRNAs (e.g. pos-1, mex-3, spn-4, etc.) enriched in IFE-3 mRNPs, but excluded from IFE-1 mRNPs. These mRNAs also require IFE-1 for efficient translation. The findings support a model in which oocytes and embryos utilize the two eIF4Es for opposite purposes on critically regulated germline mRNAs. Careful colocalization of the eIF4Es with other germ granule components suggests an architecture in which GLH-1, PGL-1 and the IFEs are stratified to facilitate sequential interactions for mRNAs. Biochemical characterization demonstrates opposing yet cooperative roles for IFE-3 and IFE-1 to hand-off of translationally controlled mRNAs from the repressed to the activated state, respectively. The model involves eIF4E mRNPs shuttling mRNAs through nuclear pore-associated granules/condensates to cytoplasmic ribosomes.

Effect of cyclic loading on the ultimate tensile strength of small metallic suture anchors used for attaching artificial tendons in rabbits.

Background ­: Suture anchor failures can lead to revision surgeries which are costly and burdensome for patients. The durability of musculoskeletal reconstructions is therefore partly affected by the design of the suture anchors. Purpose ­: The purpose of the study was to quantify the strength of different suture anchors whose sizes are suitable for attaching artificial Achilles and tibialis cranialis tendons in a rabbit model, as well as determine the effect of cyclic loading on the anchoring strength. Method ­: Four anchors (two with embedded eyelet and two with raised eyelet, n=5 per group) were tested with cyclical loading (1000 cycles and 4.5 mm/sec) and without cycling, to inform the failure loads and mode of failure of the suture anchors. An eyebolt screw with smooth eyelet was used as a control for the test groups. Results ­: All samples in all groups completed 1000 cycles and failed via suture breakage in both test conditions. All anchors had failure loads exceeding the peak Achilles tendon force in rabbits during hopping gait. The data analysis showed an effect of anchor type on the maximum tensile force at failure (F max ) in all suture categories but not an effect of loading condition. Also, the Anika anchor had a significantly less adverse effect on suture strength compared to Arthrex anchor (p=0.015), IMEX anchor (p=0.004) and Jorvet anchor (p<0.001). We observed a greater percentage of failure at the mid-section for the anchors with the raised eyelets compared to the anchors with embedded eyelets, which all failed at the knot. Conclusion ­: Anchors with embedded eyelets had clinically preferred mode of failure with less adverse effects on suture and, may be more reliable than anchors with raised eyelets for attaching artificial Achilles and tibialis cranialis tendons in rabbits.

An inflammatory paradox: strategies inflammophilic oral pathobionts employ to exploit innate immunity via neutrophil manipulation.

Inflammatory dysbiotic diseases present an intriguing biological paradox. Like most other infectious disease processes, the alarm bells of the host are potently activated by tissue-destructive pathobionts, triggering a cascade of physiological responses that ultimately mobilize immune cells like neutrophils to sites of active infection. Typically, these inflammatory host responses are critical to inhibit and/or eradicate infecting microbes. However, for many inflammatory dysbiotic diseases, inflammophilic pathobiont-enriched communities not only survive the inflammatory response, but they actually obtain a growth advantage when challenged with an inflammatory environment. This is especially true for those organisms that have evolved various strategies to resist and/or manipulate components of innate immunity. In contrast, members of the commensal microbiome typically experience a competitive growth disadvantage under inflammatory selective pressure, hindering their critical ability to restrict pathobiont proliferation. Here, we examine examples of bacteria-neutrophil interactions from both conventional pathogens and inflammophiles. We discuss some of the strategies utilized by them to illustrate how inflammophilic microbes can play a central role in the positive feedback cycle that exemplifies dysbiotic chronic inflammatory diseases.

Attaching artificial Achilles and tibialis cranialis tendons to bone using suture anchors in a rabbit model: assessment of outcomes.

Objective: The purpose of this study was to investigate the factors associated with outcomes of attaching artificial tendons to bone using suture anchors for replacement of biological tendons in rabbits. Study Design: Metal suture anchors with braided composite sutures of varying sizes (USP #1, #2, or #5) were used to secure artificial tendons replacing both the Achilles and tibialis cranialis tendons in 12 New Zealand White rabbits. Artificial tendons were implanted either at the time of (immediate replacement, n=8), or four weeks after (delayed replacement, n=4) resection of the biological tendon. Hindlimb radiographs of the rabbits were obtained immediately after surgery and approximately every other week until the study endpoint (16 weeks post-surgery). Results: All suture anchors used for the tibialis cranialis artificial tendons remained secure and did not fail during the study. The suture linkage between the Achilles artificial tendon and anchor failed in 9 of 12 rabbits. In all cases, the mode of failure was suture breakage distant from the knot. Based on radiographic analysis, the mean estimated failure timepoint was 5.3±2.3 weeks post-surgery, with a range of 2-10 weeks. Analysis of variance (ANOVA) tests revealed no significant effect of tendon implantation timing or suture size on either the timing or frequency of suture anchor failure. Conclusion: Based on the mode of failure, suture mechanical properties, and suture anchor design, we suspect that the cause of failure was wear of the suture against the edges of the eyelet in the suture anchor post, which reduced the suture strength below in vivo loads. Suture anchor designs differed for the tibialis cranialis and did not fail during the period of study. Future studies are needed to optimize suture anchor mechanical performance under different loading conditions and suture anchor design features.

Determining the Economically Optimum Metaphylactic Strategy for Cattle Cohorts of Varied Demographic Characteristics.

Metaphylactic antibiotic use in feeder cattle is a common practice to control respiratory disease. Antimicrobial stewardship is important to ensure continued efficacy and to protect animal welfare. The objective of this study is to identify characteristics of cohorts of cattle that had not received metaphylaxis that would have benefited economically from the use of metaphylaxis. Cohorts (n = 12,785; 2,206,338 head) from 13 feedlots that did not receive metaphylaxis were modeled using an economic model to estimate net returns for three metaphylactic options. Logistic regression models with covariates for entry weight, sex, average daily weight gain, number of animals per cohort, and days on feed, with feedlot as a random effect, were used to determine the model-adjusted probability of cohorts benefiting economically from metaphylaxis. Most (72%) cohorts in this data set that had not received metaphylaxis at arrival would not economically benefit from metaphylaxis. Sex, entry weight category, number of cattle in the cohort, and average daily weight gain were associated with the likelihood of benefitting economically from metaphylaxis. The results illustrated that cattle cohort demographics influenced the probability that cohorts would benefit economically from metaphylaxis and the type of metaphylaxis utilized, and integrating this information has the potential to influence the metaphylaxis decision.

Neoadjuvant chemotherapy is associated with improved disease-free survival in pancreatic cancer patients undergoing pancreaticoduodenectomy with vascular resection.

BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy (NAC) is becoming favored for all pancreatic adenocarcinoma (PDAC). Patients with seemingly resectable disease infrequently still display vascular involvement intraoperatively. Outcomes following NAC versus upfront surgery in patients undergoing pancreaticoduodenectomy (PD) with vascular resection are unknown. METHODS: We performed a retrospective cohort study of PDAC patients who underwent PD with vascular resection between January 1, 2013, to December 31, 2020, within a single academic center. Clinicopathologic characteristics and disease-free survival (DFS) were compared between NAC versus upfront surgery cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model. RESULTS: Eighty-one patients who underwent PD with vascular resection for PDAC were included. Forty-six patients (56%) received NAC. The NAC cohort more often had pathologic N0 status (47.8% vs. 8.6%, p < 0.001), had decreased vascular invasion (11% vs. 40%, p = 0.002), and completed chemotherapy (80% vs. 40%, p < 0.01). The NAC cohort demonstrated improved DFS (40.5 vs. 14.3 months, p = 0.007). In multivariable analysis, NAC remained independently associated with increased DFS (HR = 0.48, p = 0.02). CONCLUSIONS: NAC was associated with improved clinicopathologic outcomes and DFS in PD with vascular resection. These findings demonstrate the advantage of NAC in PDAC patients undergoing PD with vascular resection.

National Beef Quality Audit-2022 Phase 1: face-to-face and digital interviews.

The National Beef Quality Audit (NBQA) has been conducted regularly since 1991 to assess and benchmark quality in the U.S. beef industry, with the most recent iteration conducted in 2022. The goal of NBQA Phase I is to evaluate what needs to be managed to improve beef quality and demand. Interviews (n = 130) of industry personnel were conducted with the aid of routing software. In total, packers (n = 24), retailers (n = 20), further processors (n = 26), foodservice (n = 18), and allied government agencies and trade organizations (n = 42) were interviewed. Interviews were routed in software based on interviewee involvement in either the fed steer and heifer market cow and bull sectors, or both. Interviews were structured to elicit random responses in the order of determining "must-have" criteria (quality factors that are required to make a purchase), best/worst ranking (of quality factors based on importance), how interviewees defined quality terms, a strength, weakness, opportunities, threats (SWOT) analysis, general beef industry questions, and sustainability goals (the latter four being open-ended). Quality factors were 1) visual characteristics, 2) cattle genetics, 3) food safety, 4) eating satisfaction, 5) animal well-being, 6) weight and size, and 7) lean, fat, and bone. Best/worst analysis revealed that "food safety" was the most (P < 0.05) important factor in beef purchasing decisions for all market sectors and frequently was described as "everything" and "a way of business." Culture surrounding food safety changed compared to previous NBQAs with interviewees no longer considering food safety as a purchasing criterion, but rather as a market expectation. The SWOT analysis indicated that "eating quality of U.S. beef" was the greatest strength, and cited that educating both consumers and producers on beef production would benefit the industry. Irrespective of whether companies' products were fed or market cow/bull beef, respondents said that they believed "environmental concerns" were among the major threats to the industry. Perceived image of the beef industry in the market sectors has improved since NBQA-2016 for both fed cattle and market cow/bull beef.

Determining Which Combinatorial Combat-Relevant Factors Contribute to Heterotopic Ossification Formation in an Ovine Model.

Traumatic heterotopic ossification (HO) is frequently observed in Service Members following combat-related trauma. Estimates suggest that ~65% of wounded warriors who suffer limb loss or major extremity trauma will experience some type of HO formation. The development of HO delays rehabilitation and can prevent the use of a prosthetic. To date there are limited data to suggest a standard mechanism for preventing HO. This may be due to inadequate animal models not producing a similar bone structure as human HO. We recently showed that traumatic HO growth is possible in an ovine model. Within that study, we demonstrated that 65% of sheep developed a human-relevant hybrid traumatic HO bone structure after being exposed to a combination of seven combat-relevant factors. Although HO formed, we did not determine which traumatic factor contributed most. Therefore, in this study, we performed individual and various combinations of surgical/traumatic factors to determine their individual contribution to HO growth. Outcomes showed that the presence of mature biofilm stimulated a large region of bone growth, while bone trauma resulted in a localized bone response as indicated by jagged bone at the linea aspera. However, it was not until the combinatory factors were included that an HO structure similar to that of humans formed more readily in 60% of the sheep. In conclusion, data suggested that traumatic HO growth can develop following various traumatic factors, but a combination of known instigators yields higher frequency size and consistency of ectopic bone.

Impacts of economic factors influencing net returns of beef feedlot heifers administered two implant programs and fed for differing days-on-feed from pooled randomized controlled trials.

The objective of this research was to evaluate the effects of two implant programs and differing days-on-feed (DOF) on net returns of beef feedlot heifers using sensitivity analyses of key economic factors. Crossbred beef heifers [n = 10,583; initial weight 315 kg (± 20.1 SD)] were enrolled across three trials (one Kansas, two Texas feedlot trials). Heifers were blocked by arrival and randomly allocated to one of six pens, resulting in a total of 144 pens and 24 blocks. Pen was randomly assigned to treatment as a 2 × 3 factorial. Implant programs were: IH + 200-Revalor-IH at initial processing, and a terminal implant after approximately 90 DOF (Revalor-200), or, XH-a single implant at initial processing (Revalor-XH). The DOF treatments were: heifers fed to a standard baseline endpoint (BASE) or heifers fed for an additional + 21 or + 42 d beyond BASE. Pen-level partial budgets were used for economic sensitivity analyses, which varied price points of single pricing components with all other components fixed. Variable components were live-fed cattle prices, base carcass prices (i.e., dressed), Choice-Select spread (CS-spread), and feed and yardage prices (FYP). For each, a Low, Mid-Low, Middle, Mid-High, and High price was chosen. Linear mixed models were fit for statistical analyses (α = 0.05). There were no significant two-way interactions (P-values ≥ 0.14). Regardless of the variable component evaluated, XH heifers had poorer net returns than IH + 200 at all prices (P ≤ 0.04). Selling live, the + 21 and (or) + 42 heifers had lower net returns than BASE at every fed cattle price point (P < 0.01). Selling dressed, the + 21 and (or) + 42 heifers had lower returns than BASE at Low, Mid-Low, and Middle fed cattle base prices (P < 0.01); there were no significant DOF differences at Mid-High, or High prices (P ≥ 0.24). Net returns were lower for + 42 than BASE at all CS-spreads (P ≤ 0.03), while BASE and + 21 did not differ significantly. Longer DOF had lower net returns than BASE when selling live at every FYP (P < 0.01) except at the Low price (P = 0.14). Selling dressed, there was no significant effect of DOF at Low or Mid-Low FYP (P ≥ 0.11); conversely, extended DOF had lower net returns than BASE at Middle, Mid-High, and High FYP (P < 0.01). Overall, there was minimal economic evidence to support extending feedlot heifer DOF beyond the BASE endpoint, and when feeding longer, larger reductions in return were observed when marketing live as opposed to dressed.

Editorial Commentary: Biologic Augmentation of Rotator Cuff Repair: Platelet-Rich Plasma May Be of Significant Benefit, Whereas Atelocollagen Cannot Be Recommended.

The field of orthobiologics continues to advance at a rapid pace and theoretically holds some promise to augment the biologic healing response in rotator cuff repair (RCR). However, the clinical evidence for use of substances such as platelet-rich plasma (PRP) for RCR remains inconclusive. Atelocollagen, as a synthetic collagen substitute, has been proposed as another alternative to provide more collagen substrate for healing, but outcomes data with this technique is lacking. In contrast, (biologic) PRP has been well studied, does not show adverse outcomes, and has been shown to improve healing of large to massive tears, as well as RCR outcomes. As biologic augmentation options continue to push the envelope on indications, due diligence is required to carefully examine options for safety and efficacy. Evolutions in RCR should also continue to motivate sports medicine surgeons and researchers to seek out further innovations to improve patient outcomes. That said, PRP outcome improvement for RCR is not definitive and requires further study. RCR can humble even the best of surgeons and demands that we continue to look for ways to improve outcomes.

Global signal peptide profiling reveals principles of selective Sec61 inhibition.

Cotransins target the Sec61 translocon and inhibit the biogenesis of an undefined subset of secretory and membrane proteins. Remarkably, cotransin inhibition depends on the unique signal peptide (SP) of each Sec61 client, which is required for cotranslational translocation into the endoplasmic reticulum. It remains unknown how an SP's amino acid sequence and biophysical properties confer sensitivity to structurally distinct cotransins. Here we describe a fluorescence-based, pooled-cell screening platform to interrogate nearly all human SPs in parallel. We profiled two cotransins with distinct effects on cancer cells and discovered a small subset of SPs, including the oncoprotein human epidermal growth factor receptor 3 (HER3), with increased sensitivity to the more selective cotransin, KZR-9873. By comparing divergent mouse and human orthologs, we unveiled a position-dependent effect of arginine on SP sensitivity. Our multiplexed profiling platform reveals how cotransins can exploit subtle sequence differences to achieve SP discrimination.

Replacement of tibialis cranialis tendon with polyester, silicone-coated artificial tendon preserves biomechanical function in rabbits compared to tendon excision only.

BACKGROUND: Artificial tendons may be an effective alternative to autologous and allogenic tendon grafts for repairing critically sized tendon defects. The goal of this study was to quantify the in vivo hindlimb biomechanics (ground contact pressure and sagittal-plane motion) during hopping gait of rabbits having a critically sized tendon defect of the tibialis cranialis and either with or without repair using an artificial tendon. METHODS: In five rabbits, the tibialis cranialis tendon of the left hindlimb was surgically replaced with a polyester, silicone-coated artificial tendon (PET-SI); five operated control rabbits underwent complete surgical excision of the biological tibialis cranialis tendon in the left hindlimb with no replacement (TE). RESULTS: At 8 weeks post-surgery, peak vertical ground contact force in the left hindlimb was statistically significantly less compared to baseline for the TE group (p = 0.0215). Statistical parametric mapping (SPM) analysis showed that, compared to baseline, the knee was significantly more extended during stance at 2 weeks post-surgery and during the swing phase of stride at 2 and 8 weeks post-surgery for the TE group (p < 0.05). Also, the ankle was significantly more plantarflexed during swing at 2 and 8 weeks postoperative for the TE group (p < 0.05). In contrast, there were no significant differences in the SPM analysis among timepoints in the PET-SI group for the knee or ankle. CONCLUSIONS: Our findings suggest that the artificial tibialis cranialis tendon effectively replaced the biomechanical function of the native tendon. Future studies should investigate (1) effects of artificial tendons on other (e.g., neuromuscular) tissues and systems and (2) biomechanical outcomes when there is a delay between tendon injury and artificial tendon implantation.

Clinical utility of a genetic diagnosis in individuals with cerebral palsy and related motor disorders.

OBJECTIVE: Evaluation of the clinical utility of a genetic diagnosis in CP remains limited. We aimed to characterize the clinical utility of a genetic diagnosis by exome sequencing (ES) in patients with CP and related motor disorders. METHODS: We enrolled participants with CP and "CP masquerading" conditions in an institutional ES initiative. In those with genetic diagnoses who had clinical visits to discuss results, we retrospectively reviewed medical charts, evaluating recommendations based on the genetic diagnosis pertaining to medication intervention, surveillance initiation, variant-specific testing, and patient education. RESULTS: We included 30 individuals with a molecular diagnosis and clinical follow-up. Nearly all (28 out of 30) had clinical impact resulting from the genetic diagnosis. Medication interventions included recommendation of mitochondrial multivitamin supplementation (6.67%, n = 2), ketogenic diet (3.33%, n = 1), and fasting avoidance (3.33%, n = 1). Surveillance-related actions included recommendations for investigating systemic complications (40%, n = 12); referral to new specialists to screen for systemic manifestations (33%, n = 10); continued follow-up with established specialists to focus on specific manifestations (16.67%, n = 5); referral to clinical genetics (16.67%, n = 5) to oversee surveillance recommendations. Variant-specific actions included carrier testing (10%, n = 3) and testing of potentially affected relatives (3.33%, n = 1). Patient education-specific actions included referral to experts in the genetic disorder (30%, n = 9); and counseling about possible changes in prognosis, including recognition of disease progression and early mortality (36.67%, n = 11). INTERPRETATION: This study highlights the clinical utility of a genetic diagnosis for CP and "CP masquerading" conditions, evident by medication interventions, surveillance impact, family member testing, and patient education, including possible prognostic changes.

Adverse Events After Isolated Posterior Cruciate Ligament Reconstruction: A National Database Study.

Background: Optimal management after posterior cruciate ligament (PCL) injury remains an active area of research, as reconstruction is technically challenging and poses unique risks in the posterior knee. Studies have reported variable rates of complications. Purpose: To describe the rates of readmission, emergency department (ED) visits, and postoperative complications within 90 days of isolated PCL reconstruction (PCLR) in a large, national cohort to better understand the perioperative variables that influence a practitioner's decision of whether to pursue operative versus nonoperative management. Study Design: Descriptive epidemiology study. Methods: PCLRs from January 1, 2010, through August 31, 2020, were identified in PearlDiver, a national administrative database. Patients with concomitant ligament surgery and those with fewer than 90 days of postoperative database activity were excluded. Deep vein thromboses, pulmonary embolisms, surgical site infections, compartment syndrome, and vascular events within 90 days of surgery were identified, as were 90-day readmissions and ED visits. Logistic regression models were built in PearlDiver to calculate odds ratios (ORs) for ED utilization. Results: The final cohort consisted of 1154 patients with isolated PCLR (mean age, 34 ± 16 years; 62% male). Most patients were located in the Southern United States (n = 417; 36.1%), and most had commercial insurance (n = 992; 86%). The 90-day rates of adverse events were as follows: deep vein thrombosis (13; 1.1%), pulmonary embolism (19; 1.6%), surgical site infection (<11; <1%), compartment syndrome (<11; <1%), vascular event (<11; <1%), readmission (13, 1.1%), and ED utilization (99; 8.6%). The majority of emergency department visits (52%) occurred in the first 2 weeks postoperatively. Predictive factors for ED utilization included Elixhauser Comorbidity Index score (OR = 1.31 per 2-point increase) and Medicaid insurance (OR = 2.03 relative to commercial insurance). Conclusion: The current study reported rates of adverse events after isolated PCLR in a large, national cohort. The results provide important context for decisions about optimal management of PCL injury.

Mutational Analysis of the Nitrogenase Carbon Monoxide Protective Protein CowN Reveals That a Conserved C-Terminal Glutamic Acid Residue Is Necessary for Its Activity.

Nitrogenase is the only enzyme that catalyzes the reduction of nitrogen gas into ammonia. Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Many nitrogen fixing bacteria protect nitrogenase from CO inhibition using the protective protein CowN. This work demonstrates that a conserved glutamic acid residue near the C-terminus of Gluconacetobacter diazotrophicus CowN is necessary for its function. Mutation of the glutamic acid residue abolishes both CowN's protection against CO inhibition and the ability of CowN to bind to nitrogenase. In contrast, a conserved C-terminal cysteine residue is not important for CO protection by CowN. Overall, this work uncovers structural features in CowN that are required for its function and provides new insights into its nitrogenase binding and CO protection mechanism.

Employing Cloning-Independent Mutagenesis of Parvimonas micra for the Study of Cell Wall Biogenesis.

The cell wall plays an important structural role for bacteria and is intimately tied to a variety of critical processes ranging from growth and differentiation to pathogenesis. Our understanding of cell wall biogenesis is primarily derived from a relatively small number of heavily studied model organisms. Consequently, these processes can only be inferred for the vast majority of prokaryotes, especially among groups of uncharacterized and/or genetically intractable organisms. Recently, we developed the first tractable genetic system for Parvimonas micra, which is a ubiquitous Gram-positive pathobiont of the human microbiome involved in numerous types of inflammatory infections as well as a variety of malignant tumors. P. micra is also the first, and currently only, member of the entire Tissierellia class of the Bacillota phylum in which targeted genetic manipulation has been demonstrated. Thus, it is now possible to study cell wall biogenesis mechanisms within a member of the Tissierellia, which may also reveal novel aspects of P. micra pathobiology. Herein, we describe a procedure for cloning-independent genetic manipulation of P. micra, including allelic replacement mutagenesis and genetic complementation. The described techniques are also similarly applicable for the study of other aspects of P. micra pathobiology and physiology.

Enteral N-acetylcysteine to reduce serum cobalt concentrations secondary to prosthetic knee-associated metallosis: A case report.

PURPOSE: Cobalt metallosis is a rare but dangerous complication of total joint arthroplasty resulting from deterioration of the joint leading to metal-on-metal friction and breakdown. Potential manifestations vary in severity and include dilated cardiomyopathy, thyroid dysfunction, cognitive disturbances, neuropathy, fatigue, and weakness. The therapeutic role of N-acetylcysteine in metallosis has been investigated due to its ability to chelate with heavy metal ions, such as cobalt and chromium. SUMMARY: Here we report the case of a 71-year-old female who presented with suspected metallosis diagnosed in the outpatient setting due to symptoms of significant weight loss and failure to thrive. This metallosis was secondary to the hardware breakdown of a left knee revision roughly 6 years previously. The patient was not a surgical candidate due to her poor nutrition status and was started on nasojejunal tube feeds along with N-acetylcysteine 600 mg by mouth twice daily for 45 days. The patient's serum cobalt levels decreased from 61.7 µg/L on admission to 16.2 µg/L prior to her undergoing proper revision of the left knee roughly 2 months after admission to the hospital. The patient tolerated treatment well and was able to be discharged the day after surgery, with no further complaints or complications. CONCLUSION: This case report contributes to the body of literature suggesting that administration of N-acetylcysteine can reduce serum cobalt concentrations, without notable adverse effects, in the context of prosthetic knee-associated metallosis.

Development and validation of a large animal ovine model for implant-associated spine infection using biofilm based inocula.

Postoperative implant-associated spine infection remains poorly understood. Currently there is no large animal model using biofilm as initial inocula to study this challenging clinical entity. The purpose of the present study was to develop a sheep model for implant-associated spine infection using clinically relevant biofilm inocula and to assess the in vivo utility of methylene blue (MB) for visualizing infected tissues and guiding debridement. This 28-day study used five adult female Rambouillet sheep, each with two non-contiguous surgical sites- in the lumbar and thoracic regions- comprising randomized positive and negative infection control sites. A standard mini-open approach to the spine was performed to place sterile pedicle screws and Staphylococcus aureus biofilm-covered (positive control), or sterile (negative control) spinal fusion rods. Surgical site bioburden was quantified at the terminal procedure. Negative and positive control sites were stained with MB and staining intensity quantified from photographs. Specimens were analyzed with x-ray, micro-CT and histologically. Inoculation rods contained ∼10.44 log10 colony forming units per rod (CFU/rod). Biofilm inocula persisted on positive-control rod explants with ∼6.16 log10 CFU/rod. There was ∼6.35 log10 CFU/g of tissue in the positive controls versus no identifiable bioburden in the negative controls. Positive controls displayed hallmarks of deep spine infection and osteomyelitis, with robust local tissue response, bone resorption, and demineralization. MB staining was more intense in infected, positive control sites. This work presents an animal-efficient sheep model displaying clinically relevant implant-associated deep spine infection.

Approximating the global economic (market) value of farmed animals.

Understanding the global economic importance of farmed animals to society is essential as a baseline for decision making about future food systems. We estimated the annual global economic (market) value of live animals and primary production outputs, e.g., meat, eggs, milk, from terrestrial and aquatic farmed animal systems. The results suggest that the total global market value of farmed animals ranges between 1.61 and 3.3 trillion USD (2018) and is expected to be similar in absolute terms to the market value of crop outputs (2.57 trillion USD). The cattle sector dominates the market value of farmed animals. The study highlights the need to consider other values of farmed animals to society, e.g., finance/insurance value and cultural value, in decisions about the sector's future.