FAMIN Is a Multifunctional Purine Enzyme Enabling the Purine Nucleotide Cycle.

Mutations in FAMIN cause arthritis and inflammatory bowel disease in early childhood, and a common genetic variant increases the risk for Crohn's disease and leprosy. We developed an unbiased liquid chromatography-mass spectrometry screen for enzymatic activity of this orphan protein. We report that FAMIN phosphorolytically cleaves adenosine into adenine and ribose-1-phosphate. Such activity was considered absent from eukaryotic metabolism. FAMIN and its prokaryotic orthologs additionally have adenosine deaminase, purine nucleoside phosphorylase, and S-methyl-5'-thioadenosine phosphorylase activity, hence, combine activities of the namesake enzymes of central purine metabolism. FAMIN enables in macrophages a purine nucleotide cycle (PNC) between adenosine and inosine monophosphate and adenylosuccinate, which consumes aspartate and releases fumarate in a manner involving fatty acid oxidation and ATP-citrate lyase activity. This macrophage PNC synchronizes mitochondrial activity with glycolysis by balancing electron transfer to mitochondria, thereby supporting glycolytic activity and promoting oxidative phosphorylation and mitochondrial H+ and phosphate recycling.

Endoplasmic reticulum stress in the intestinal epithelium initiates purine metabolite synthesis and promotes Th17 cell differentiation in the gut.

Intestinal IL-17-producing T helper (Th17) cells are dependent on adherent microbes in the gut for their development. However, how microbial adherence to intestinal epithelial cells (IECs) promotes Th17 cell differentiation remains enigmatic. Here, we found that Th17 cell-inducing gut bacteria generated an unfolded protein response (UPR) in IECs. Furthermore, subtilase cytotoxin expression or genetic removal of X-box binding protein 1 (Xbp1) in IECs caused a UPR and increased Th17 cells, even in antibiotic-treated or germ-free conditions. Mechanistically, UPR activation in IECs enhanced their production of both reactive oxygen species (ROS) and purine metabolites. Treating mice with N-acetyl-cysteine or allopurinol to reduce ROS production and xanthine, respectively, decreased Th17 cells that were associated with an elevated UPR. Th17-related genes also correlated with ER stress and the UPR in humans with inflammatory bowel disease. Overall, we identify a mechanism of intestinal Th17 cell differentiation that emerges from an IEC-associated UPR.

Adaptive Pore Opening to Form Tailored Adsorption Sites in a Cooperatively Flexible Framework Enables Record Inverse Propane/Propylene Separation.

A proposed low-energy alternative to the separation of alkanes from alkenes by energy-intensive cryogenic distillation is separation by porous adsorbents. Unfortunately, most adsorbents preferentially take up the desired, high-value major component alkene, requiring frequent regeneration. Adsorbents with inverse selectivity for the minor component alkane would enable the direct production of purified, reagent-grade alkene, greatly reducing global energy consumption. However, such materials are exceedingly rare, especially for propane/propylene separation. Here, we report that through adaptive and spontaneous pore size and shape adaptation to optimize an ensemble of weak noncovalent interactions, the structurally responsive metal-organic framework CdIF-13 (sod-Cd(benzimidazolate)2) exhibits inverse selectivity for propane over propylene with record-setting separation performance under industrially relevant temperature, pressure, and mixture conditions. Powder synchrotron X-ray diffraction measurements combined with first-principles calculations yield atomic-scale insight and reveal the induced fit mechanism of adsorbate-specific pore adaptation and ensemble interactions between ligands and adsorbates. Dynamic column breakthrough measurements confirm that CdIF-13 displays selectivity under mixed-component conditions of varying ratios, with a record measured selectivity factor of α ≈ 3 at 95:5 propylene:propane at 298 K and 1 bar. When sequenced with a low-cost rigid adsorbent, we demonstrated the direct purification of propylene under ambient conditions. This combined atomic-level structural characterization and performance testing firmly establishes how cooperatively flexible materials can be capable of unprecedented separation factors.

Evaluation of Intestinal Fibrosis with 68Ga-FAPI PET/MR Enterography in Crohn Disease.

Background In Crohn disease, differentiation between active intestinal inflammation and fibrosis has implications for treatment, but current imaging modalities are not reliably accurate. Purpose To evaluate the predictive value of gallium 68 (68Ga)-labeled fibroblast activation protein inhibitor (FAPI) PET/MR enterography for the assessment of bowel wall fibrosis in Crohn disease. Materials and Methods In this prospective single-center study, consecutive participants with Crohn disease and obstructive symptoms underwent preoperative 68Ga-FAPI PET/MR enterography from May 2021 to January 2022. Histopathologic analysis of resected bowel segments was performed to grade active inflammation (A0-A2) and fibrosis (F0-F2), which served as the reference standard. The fibroblast activation protein (FAP) expression in bowel wall layers was analyzed immunohistochemically for each layer. 68Ga-FAPI-derived maximum standardized uptake value (SUVmax) was compared with histopathologic results by using mixed-model analysis of variance and Bonferroni-corrected post hoc tests. Results In 14 participants (mean age, 45 years ± 9 [SD]; 10 men), fibrosis was diagnosed histopathologically in 28 of 51 bowel segments (grade F1, n = 14; grade F2, n = 14). Mean SUVmax was higher in segments with fibrosis than without (7.6 vs 2.0; P < .001). In severe fibrosis, mean SUVmax was higher than in mild to moderate fibrosis (8.9 ± 0.9 vs 6.2 ± 0.9; P = .045). Bowel segments with isolated active inflammation had lower mean 68Ga-FAPI uptake than segments with combined active inflammation and fibrosis (SUVmax, 3.2 ± 0.4 vs 8.1 ± 0.1; P = .005). With an SUVmax cutoff value of 3.5, the area under the receiver operating characteristic curve for the prediction of fibrosis was 0.94 (95% CI: 0.9, 1.0), with sensitivity of 26 of 28 segments (93%) and specificity of five of six segments (83%). 68Ga-FAPI-derived SUVmax correlated with FAP expression across all bowel layers (R2 = 0.50, P < .001). Conclusion Higher gallium 68 fibroblast activation protein inhibitor uptake at PET/MR enterography was associated with histopathologically assessed bowel wall fibrosis in participants with Crohn disease, suggesting diagnostic potential for treatment decisions. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by O'Shea in this issue.

Surprising Use of the Business Innovation Bass Diffusion Model To Accurately Describe Adsorption Isotherm Types I, III, and V.

Using adsorption isotherm data to determine heats of adsorption or predict mixture adsorption using the ideal adsorbed solution theory (IAST) relies on accurate fits of the data with continuous, mathematical models. Here, we derive an empirical two-parameter model to fit isotherm data of IUPAC types I, III, and V in a descriptive way based on the Bass model for innovation diffusion. We report 31 isotherm fits to existing literature data covering all six types of isotherms, various adsorbents, such as carbons, zeolites, and metal-organic frameworks (MOFs), as well as different adsorbing gases (water, carbon dioxide, methane, and nitrogen). We find several cases, especially for flexible MOFs, where previously reported isotherm models reached their limits and either failed to fit the data or could not sufficiently be fitted due to stepped type V isotherms. Moreover, in two instances, models specifically developed for distinct systems are fitted with a higher R2 value compared to the models in the original reports. Using these fits, it is demonstrated how the new Bingel-Walton isotherm can be used to qualitatively assess the hydrophilic or hydrophobic behavior of porous materials from the relative magnitude of the two fitting parameters. The model can also be employed to find matching heats of adsorption values for systems with isotherm steps using one, continuous fit instead of partial, stepwise fits or interpolation. Additionally, using our single, continuous fit to model stepped isotherms in IAST mixture adsorption predictions leads to good agreement with the results from the osmotic framework adsorbed solution theory that was specifically developed for these systems using a stepwise, approximate fitting, which is yet far more complex. Our new isotherm equation accomplishes all of these tasks with only two fitted parameters, providing a simple, accurate method for modeling a variety of adsorption behavior.

Distinct roles for major and minor antigen barriers in chimerism-based tolerance under irradiation-free conditions.

Eliminating cytoreductive conditioning from chimerism-based tolerance protocols would facilitate clinical translation. Here we investigated the impact of major histocompatibility complex (MHC) and minor histocompatibility antigen (MiHA) barriers on mechanisms of tolerance and rejection in this setting. Transient depletion of natural killer (NK) cells at the time of bone marrow (BM) transplantation (BMT) (20 × 106 BALB/c BM cells → C57BL/6 recipients under costimulation blockade [CB] and rapamycin) prevented BM rejection. Despite persistent levels of mixed chimerism, BMT recipients gradually rejected skin grafts from the same donor strain. Extending NK cell depletion did not improve skin graft survival. However, F1 (C57BL/6×BALB/c) donors, which do not elicit NK cell-mediated rejection, induced durable chimerism and tolerance. In contrast, if F1 donors with BALB/c background only were used (BALB/c×BALB.B), no tolerance was observed. In the absence of MiHA disparities (B10.D2 donors, MHC-mismatch only), temporal NK cell depletion established stable chimerism and tolerance. Conversely, MHC identical BM (BALB.B donors, MiHA mismatch only) readily engrafted without NK cell depletion but no skin graft tolerance ensued. Therefore, we conclude that under CB and rapamycin, MHC disparities provoke NK cell-mediated BM rejection in nonirradiated recipients whereas MiHA disparities do not prevent BM engraftment but impede skin graft tolerance in established mixed chimeras.

Simple approach for extending the ambiguity-free range of dual-comb ranging.

Dual-comb (DC) ranging is an established method for high-precision and high-accuracy distance measurements. It is, however, restricted by an inherent length ambiguity and the requirement for complex control loops for comb stabilization. Here, we present a simple approach for expanding the ambiguity-free measurement length of DC ranging by exploiting the intrinsic intensity modulation of a single-cavity dual-color DC for simultaneous time-of-flight and DC distance measurements. This measurement approach enables the measurement of distances up to several hundred kilometers with the precision and accuracy of a DC interferometric setup while providing a high data acquisition rate (≈2kHz) and requiring only the repetition rate of one of the combs to be stabilized.

Flexible all-PM NALM Yb:fiber laser design for frequency comb applications: operation regimes and their noise properties.

We present a flexible all-polarization-maintaining (PM) mode-locked ytterbium (Yb):fiber laser based on a nonlinear amplifying loop mirror (NALM). In addition to providing detailed design considerations, we discuss the different operation regimes accessible by this versatile laser architecture and experimentally analyze five representative mode-locking states. These five states were obtained in a 78-MHz configuration at different intracavity group delay dispersion (GDD) values ranging from anomalous (-0.035 ps2) to normal (+0.015 ps2). We put a particular focus on the characterization of the intensity noise as well as the free-running linewidth of the carrier-envelope-offset (CEO) frequency as a function of the different operation regimes. We observe that operation points far from the spontaneous emission peak of Yb (∼1030 nm) and close to zero intracavity dispersion can be found, where the influence of pump noise is strongly suppressed. For such an operation point, we show that a CEO linewidth of less than 10-kHz at 1 s integration can be obtained without any active stabilization.

Hepatic Steatosis in Lean Patients: Risk Factors and Impact on Mortality.

BACKGROUND: The prognostic impact of liver steatosis in obese patients is well established. Limited data on the risk factors for and impact of hepatic steatosis in lean patients are available. AIMS: Assess risk factors for liver steatosis in lean patients and investigate its impact on survival. METHODS: Patients without viral hepatitis and with a BMI ≤ 25 kg/m2 undergoing liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) by transient elastography were retrospectively identified. Clinical characteristics and laboratory test results were obtained at the time of LSM/CAP measurement. National death registry data were obtained in order to assess survival. RESULTS: Among n = 218 lean patients, n = 97 (34.5%) showed significant liver steatosis (CAP ≥ 268 dB/m), while n = 184 (65.5%) had no or just mild steatosis (CAP < 268 dB/m). Patients with steatosis had higher GGT (238.0(± 450.3) vs. 112.1(± 180.0) IU/mL; p = 0.013), AST (63(± 67.4) vs. 38.5(± 32.9) IU/mL; p = 0.001), ALT (59.1(± 58.8) vs. 44.3(± 52.7) IU/mL; p = 0.048) and triglyceride levels (120.1(± 80.3) vs. 96.1(± 58.2) mg/dL; p = 0.014), and showed a trend toward more severe fibrosis (LSM 15.6(± 19.5) vs. 12.0(± 15.7) kPa; p = 0.115). In multivariate binary logistic regression analysis, only serum uric acid levels were independently associated with liver steatosis (odds ratio 1.43 per unit mg/dL; 95% CI 1.001-2.054; p = 0.049). During a mean follow-up of 38.9(± 10.6) months, n = 14 patients (5.0%) died. In the absence of advanced fibrosis, survival after 1 year was similar in patients without (98.7%) and with (98.6%) significant steatosis. Patients with advanced fibrosis had worse 1-year survival without concomitant significant steatosis (84.8%) than patients with steatosis (95.8%; log-rank p < 0.001). CONCLUSIONS: High serum uric acid levels increase the risk of liver steatosis in lean patients. Liver fibrosis but not hepatic steatosis is a risk factor for impaired survival in lean patients.

The relationship between learner engagement and teaching effectiveness: a novel assessment of student engagement in continuing medical education.

BACKGROUND: Continuing medical education (CME) often uses passive educational models including lectures. However, numerous studies have questioned the effectiveness of these less engaging educational strategies. Studies outside of CME suggest that engaged learning is associated with improved educational outcomes. However, measuring participants' engagement can be challenging. We developed and determined the validity evidence for a novel instrument to assess learner engagement in CME. METHODS: We conducted a cross-sectional validation study at a large, didactic-style CME conference. Content validity evidence was established through review of literature and previously published engagement scales and conceptual frameworks on engagement, along with an iterative process involving experts in the field, to develop an eight-item Learner Engagement Instrument (LEI). Response process validity was established by vetting LEI items on item clarity and perceived meaning prior to implementation, as well as using a well-developed online platform with clear instructions. Internal structure validity evidence was based on factor analysis and calculating internal consistency reliability. Relations to other variables validity evidence was determined by examining associations between LEI and previously validated CME Teaching Effectiveness (CMETE) instrument scores. Following each presentation, all participants were invited to complete the LEI and the CMETE. RESULTS: 51 out of 206 participants completed the LEI and CMETE (response rate 25%) Correlations between the LEI and the CMETE overall scores were strong (r = 0.80). Internal consistency reliability for the LEI was excellent (Cronbach's alpha = 0.96). To support validity to internal structure, a factor analysis was performed and revealed a two dimensional instrument consisting of internal and external engagement domains. The internal consistency reliabilities were 0.96 for the internal engagement domain and 0.95 for the external engagement domain. CONCLUSION: Engagement, as measured by the LEI, is strongly related to teaching effectiveness. The LEI is supported by robust validity evidence including content, response process, internal structure, and relations to other variables. Given the relationship between learner engagement and teaching effectiveness, identifying more engaging and interactive methods for teaching in CME is recommended.

Controlled attenuation parameter does not predict hepatic decompensation in patients with advanced chronic liver disease.

BACKGROUND & AIMS: Assessment of hepatic steatosis by transient elastography (TE)-based controlled attenuation parameter (CAP) might predict hepatic decompensation. Therefore, we aimed to evaluate the prognostic value of CAP in patients with compensated advanced chronic liver disease (cACLD) and decompensated cirrhosis (DC). METHODS: A total of 430 patients who underwent TE (liver stiffness ≥10 kPa) and CAP measurements were included in this retrospective analysis. Half of patients (n = 189) underwent simultaneous HVPG measurement. In cACLD patients, first hepatic decompensation was defined by new onset of ascites, hepatic encephalopathy or variceal bleeding. In patients with DC, the following events were considered as further hepatic decompensation: requirement of paracentesis, admission for/development of grade 3/4 hepatic encephalopathy, variceal (re-)bleeding or liver-related death. RESULTS: First hepatic decompensation occurred in 25 of 292 (9%) cACLD patients, while 46 of 138 (33%) DC patients developed further hepatic decompensation during a median follow-up of 22 and 12 months respectively. CAP was not predictive of first (cACLD; per 10 dB/m; hazard ratio [HR]: 0.97, 95% confidence interval [95% CI]: 0.91-1.03, P = 0.321) or further hepatic decompensation (DC; HR: 0.99, 95% CI: 0.94-1.03, P = 0.554) in adjusted analysis. Using the well-established CAP cut-off of ≥248 dB/m for hepatic steatosis, the incidence of first (cACLD; P = 0.065) and further hepatic decompensation (DC; P = 0.578) was similar in patients with hepatic steatosis or without. Serum albumin levels (per mg/dL; HR: 0.83, 95% CI: 0.77-0.89, P < 0.001) and MELD-Na (per point; HR: 1.15, 95% CI: 1.04-1.28, P = 0.006) in cACLD and MELD-Na (per point; HR: 1.12, 95% CI: 1.05-1.19, P < 0.0001) in DC patients were the only parameters independently associated with first and further hepatic decompensation, respectively. CONCLUSION: Controlled attenuation parameter does not predict the development of first (cACLD)/further (DC) hepatic decompensation, while serum albumin levels and MELD-Na are of prognostic value.

Management of portal hypertension before and after liver transplantation.

Orthotopic liver transplantation (OLT) represents a curative treatment option for end-stage liver disease (ESLD). Although epidemiology of ESLD has recently changed due to the rising prevalence of nonalcoholic fatty liver disease and the decreased burden of hepatitis C virus infections due to highly effective antiviral regimens, the management of portal hypertension (PHT) remains a clinical challenge in the pre- and post-OLT setting. The measurement of the hepatic venous pressure gradient represents the most reliable but invasive tool for assessment of the severity of PHT. Although novel liver ultrasound and magnetic resonance-based elastography methods have been developed, their value to screen for liver fibrosis and PHT in transplanted patients remains to be established. Nonselective beta-blockers represent the cornerstone of medical treatment of PHT, but more studies on their effects on clinical endpoints after OLT are needed. Statins are widely used to treat hyperlipidemia, which is a common condition after OLT. Although a growing body of evidence suggests that statins decrease portal pressure and PHT-related complications in ESLD, studies on potential benefits of statins after OLT are lacking. Finally, transjugular intrahepatic portosystemic shunts (TIPS) are effective in decreasing PHT and seem to decrease mortality on the OLT waiting list. Moreover, TIPS does not have an impact on liver function nor complicate the transplant surgical procedures. TIPS may also be used after OLT, but the evidence is limited. In conclusion, whereas the management of PHT in patients with ESLD is based on strong evidence, further data on the value of noninvasive monitoring tools as well as on medical and invasive treatment options in the post-OLT setting are needed to improve management strategies in patients with recurrent PHT after liver transplantation. Liver Transplantation 24 112-121 2018 AASLD.

More Than Talking About the Weekend: Content of Case-Irrelevant Communication Within the OR Team.

BACKGROUND: Case-irrelevant communication (CIC) is defined as "any conversation" irrelevant to the case. It includes small talk, but also communication related to other work issues besides the actual task. CIC during surgeries is generally seen as distracting, despite a lack of knowledge about the content of CIC and its regulation in terms of adjustments to the situation of CIC. Primary goal of the study was to evaluate CIC content; secondary goal was to evaluate whether surgical teams regulate CIC according to different concentration demands of surgical procedures. METHODS: In 125 surgeries, 1396 CIC events were observed. CIC were content coded into work-related CIC (pertaining to other tasks or work in general) and social CIC (pertaining to acquaintance talk, gossip, or private conversation). The impact of different phases and the difficulty of the surgical procedure on CIC were assessed. RESULTS: Work-related CIC were significantly more frequent (2.49 per hour, SD = 2.17) than social CIC (1.42 per hour, SD = 2.17). Across phases, frequency of work-related CIC was constant, whereas social CIC increased significantly across phases. In surgeries assessed as highly difficult by the surgeons, social CIC were observed at a lower frequency, and less work-related CIC were observed during the main phase compared to surgeries assessed as less difficult. CONCLUSION: The high proportion of work-related CIC indicates that surgical teams deal with other tasks during surgeries. Surgical teams adapt CIC according to the demands of the procedure. Hospital policies should support these adaptations rather than attempt to suppress CIC entirely.

An intra-individual surgical wound comparison shows that octenidine-based hydrogel wound dressing ameliorates scar appearance following abdominoplasty.

Hypertrophic scar formation because of surgical procedures is associated with higher levels of pain, a lower quality of life, and poor cosmetic outcome and requires more resources in follow-up management. An octenidine-based hydrogel has been shown to modulate immunological function in an in vitro wound model, suggesting an improved scar formation. In this prospective, randomised, observer-blinded, and intra-patient-controlled study, 45 patients who underwent abdominoplasty or mastectomy with transverse rectus abdominis muscle (TRAM) flap reconstruction were given both a standard postoperative wound dressing on one wound side and an octenidine-based hydrogel with transparent film dressing, covered with standard postoperative dressing on the other side. Four instances of hypertrophia were reported in the gel side versus 12 in the standard dressing side. Visual Analogue Scale (VAS) pain scores taken during postoperative dressing changes showed reduced scores on the gel side at all time points. Vancouver Scar Scale (VSS) scores showed improvement in the gel side at 3, 6, and 12 months postoperatively. Skin distensibility measured using a cutometer showed significantly improved measures in gel-treated wounds, similar to measures of healthy skin. Trans-epidermal water loss (TEWL), measured using a tewameter, showed improved values on the gel side soon after surgery, with both the control and the gel side normalising after approximately 6 months. The octenidine-based wound dressing demonstrates improved wound healing associated with a lower incidence of hypertrophic scar formation.

Use of the pause procedure in continuing medical education: A randomized controlled intervention study.

During lectures, a pause procedure (the presenter pauses so students can discuss content) can improve educational outcomes. We aimed to determine whether (1) continuing medical education (CME) presentations with a pause procedure were evaluated more favorably and (2) a pause procedure improved recall. In this randomized controlled intervention study of all participants (N = 214) at the Mayo Clinic Internal Medicine Board Review course, 48 lectures were randomly assigned to an intervention (pause procedure) or control (traditional lecture) group. The pause procedure was a 1-min pause at the middle and end of the presentation. Study outcomes were (1) presentation evaluation instrument scores and (2) number of recalled items per lecture. A total of 214 participants returned 145 surveys (response rate, 68%). Mean presentation evaluation scores were significantly higher for pause procedure than for traditional presentations (70.9% vs 65.8%; 95%CI for the difference, 3.5-6.7; p < .0001). Mean number of rapid recall items was higher for pause procedure presentations (0.68 vs 0.59; 95%CI for the difference, 0.02-0.14; p = .01). In a traditional CME course, presentations with a pause procedure had higher evaluation scores and more content was recalled. The pause procedure could arm CME presenters with an easy technique to improve educational content delivery.

Structure-Function Analysis of the Mcl-1 Protein Identifies a Novel Senescence-regulating Domain.

Unlike other antiapoptotic Bcl-2 family members, Mcl-1 also mediates resistance to cancer therapy by uniquely inhibiting chemotherapy-induced senescence (CIS). In general, Bcl-2 family members regulate apoptosis at the level of the mitochondria through a common prosurvival binding groove. Through mutagenesis, we determined that Mcl-1 can inhibit CIS even in the absence of its apoptotically important mitochondrion-localizing domains. This finding prompted us to generate a series of Mcl-1 deletion mutants from both the N and C termini of the protein, including one that contained a deletion of all of the Bcl-2 homology domains, none of which impacted anti-CIS capabilities. Through subsequent structure-function analyses of Mcl-1, we identified a previously uncharacterized loop domain responsible for the anti-CIS activity of Mcl-1. The importance of the loop domain was confirmed in multiple tumor types, two in vivo models of senescence, and by demonstrating that a peptide mimetic of the loop domain can effectively inhibit the anti-CIS function of Mcl-1. The results from our studies appear to be highly translatable because we discerned an inverse relationship between the expression of Mcl-1 and of various senescence markers in cancerous human tissues. In summary, our findings regarding the unique structural properties of Mcl-1 provide new approaches for targeted cancer therapy.

Prevention of heterotopic ossification: an experimental study using a plasma expander in a murine model.

BACKGROUND: Heterotopic ossification (HO) is a frequent complication following orthopedic and trauma surgery. It often leads to substantial morbidity as many affected patients suffer from pain and joint contractures. Current prophylactic measures include nonsteroidal anti-inflammatory drugs (NSAID) and local radiation. However, several disadvantages such as delayed fracture healing and impaired ossification have been reported. For this reason, a novel approach for prevention of HO was searched for. We hypothesized that systemic administration of hydroxyethyl starch (HES), a substance known to influence microcirculation, would reduce formation of HO in a murine model. METHODS: A pre-established murine model was used where HO has been shown to develop following Achilles tendon tenotomy. Twenty CD1 mice were randomly assigned to a control (n = 10) or treatment group (n = 10). The treatment group received two intravenous HES injections perioperatively, while the control group underwent tenotomy only. After ten weeks, the mice were euthanized and micro CT scans of the hind limbs were performed. HO was manually identified and quantitatively assessed. A Wilcoxon rank sum test was used for comparison of both groups. RESULTS: The mean heterotopic bone volume in the control group was significantly larger compared to the HES group (2.276 mm(3) vs. 0.271 mm(3), p = 0.005). A reduction of mean ectopic bone volume of 88 % was found following administration of HES. CONCLUSION: A substantial reduction of HO formation was found following perioperative short-term administration of HES. This work represents a preliminary study, necessitating further studies before drawing ultimate conclusions. However, this simple addition to current prophylactic measures might lead to a more effective prevention of HO in the future.

Determining Surface Areas and Pore Volumes of Metal-Organic Frameworks.

The surface area and pore volume of a metal-organic framework (MOF) can provide insight into its structure and potential applications. Both parameters are commonly determined using the data from nitrogen sorption experiments; commercial instruments to perform these measurements are also widely available. These instruments will calculate structural parameters, but it is essential to understand how to select input data and when calculation methods apply to the sample MOF. This article outlines the use of the Brunauer-Emmett-Teller (BET) method and Barrett-Joyner-Halenda (BJH) method for the calculation of surface area and pore volume, respectively. Example calculations are performed on the representative MOF UiO-66. Although widely applicable to MOFs, sample materials and adsorption data must meet certain criteria for the calculated results to be considered accurate, in addition to proper sample preparation. The assumptions and limitations of these methods are also discussed, along with alternative and complementary techniques for the MOF pore space characterization.