Decreased mebrofenin uptake in patients with non-colorectal liver tumors requiring liver volume augmentation-a single-center analysis.

BACKGROUND: Posthepatectomy liver failure (PHLF) remains a life-threatening complication after hepatectomy. To reduce PHLF, a preoperative assessment of liver function is indispensable. For this purpose, 99mTc-mebrofenin hepatobiliary scintigraphy with SPECT (MSPECT) can be used. The aim of the current study was to evaluate the predictive value of MSPECT for PHLF in patients with non-colorectal liver tumors (NCRLT) compared to patients with colorectal liver metastasis (CRLM) undergoing extended liver resection. METHODS: We included all patients undergoing extended liver resections via two-stage procedures between January 2019 and December 2021 at the University Medical Center Hamburg-Eppendorf, Germany. All patients received a preoperative MSPECT. RESULTS: Twenty patients were included. In every fourth patient, PHLF was observed. Four patients had PHLF grade C. There were no differences between patients with CRLM and NCRLT regarding PHLF rate and future liver remnant (FLR) volume. Patients with CRLM had higher mebrofenin uptake in the FLR compared to those with NCRLT (2.49%/min/m2 vs. 1.51%/min/m2; p = 0.004). CONCLUSION: Mebrofenin uptake in patients with NCRLT was lower compared to those patients with CRLM. However, there was no difference in the PHLF rate and FLR volume. Cut-off values for the mebrofenin uptake might need adjustments for different surgical indications, surgical procedures, and underlying diseases.

Implementing a fracture liaison service open model of care utilizing a cloud-based tool.

PURPOSE: Although half of women and one-quarter of men aged 50 and older will sustain an acute low-trauma fracture, less than a quarter receive appropriate secondary fracture prevention. The goal of this quality improvement demonstration project was to implement a Fracture Liaison Service (FLS) focused on secondary prevention of an osteoporotic fracture in three open health care systems aided by a cloud-based tool. METHODS: The pre-post study design examined the proportion of men and women over age 50 who received appropriate assessment (bone mineral density, vitamin D levels) and treatment (calcium/vitamin D, pharmacologic therapy) in the six months following a recently diagnosed fracture. The pre-study (Pre FLS) included a retrospective chart review for baseline data (N = 344 patients) within each health care system. In the post-evaluation (Post FLS, N = 148 patients), the FLS coordinator from each health care system examined these parameters following enrollment and for 6 months following the recently diagnosed fracture. Data were managed in the cloud-based FLS application tool. RESULTS: Ninety-three participants completed the program. The FLS program increased the percentage of patients receiving bone mineral density testing from 21% at baseline to 93% (p < 0.001) Post FLS implementation. Assessments of vitamin D levels increased from 25 to 84% (p < 0.001). Patients prescribed calcium/vitamin D increased from 36% at baseline to 93% (p < 0.001) and those prescribed pharmacologic treatment for osteoporosis increased on average from 20 to 54% (p < 0.001) Post FLS. CONCLUSIONS: We conclude that the FLS model of care in an open health care system, assisted by a cloud-based tool, significantly improved assessment and/or treatment of patients with a recently diagnosed osteoporotic fracture. Future studies are necessary to determine if this model of care is scalable and if such programs result in prevention of fractures. Mini-Abstract: The goal was to implement a Fracture Liaison Service (FLS) focused on secondary prevention of an osteoporotic fracture in open health care systems aided by a cloud-based tool. This model significantly improved assessment and/or treatment of patients with a recently diagnosed fracture.

Selective method for identification and quantification of Bifidobacterium animalis subspecies lactis BB-12 (BB-12) from the gastrointestinal tract of healthy volunteers ingesting a combination probiotic of BB-12 and Lactobacillus rhamnosus GG.

AIM: To develop a novel validated method for the isolation of Bifidobacterium animalis ssp. lactis BB-12 (BB-12) from faecal specimens and apply it to studies of BB-12 and Lactobacillus rhamnosus GG (LGG) recovered from the healthy human gastrointestinal (GI) tract. METHODS AND RESULTS: A novel method for isolating and enumerating BB-12 was developed based on its morphologic features of growth on tetracycline-containing agar. The method identified BB-12 correctly from spiked stool close to 100% of the time as validated by PCR confirmation of identity, and resulted in 97-104% recovery of BB-12. The method was then applied in a study of the recovery of BB-12 and LGG from the GI tract of healthy humans consuming ProNutrients® Probiotic powder sachet containing BB-12 and LGG. Viable BB-12 and LGG were recovered from stool after 21 days of probiotic ingestion compared to baseline. In contrast, no organisms were recovered 21 days after baseline in the nonsupplemented control group. CONCLUSIONS: We demonstrated recovery of viable BB-12, using a validated novel method specific for the isolation of BB-12, and LGG from the GI tract of healthy humans who consumed the probiotic supplement. SIGNIFICANCE AND IMPACT OF THE STUDY: This method will enable more detailed and specific studies of BB-12 in probiotic supplements, including when in combination with LGG.

Clinical outcomes of triclosan-coated barbed suture in open hernia repair: a retrospective cohort study.

PURPOSE: We assessed clinical outcomes of patients undergoing open hernia repair using STRATAFIX™ Symmetric, a barbed triclosan-coated suture (TCS; Ethicon), versus conventional polydioxanone suture (PDS) for abdominal wall closure. METHODS: This single-center retrospective cohort study identified patients undergoing hernia repair. The site used PDS from 2013 to 2016 and switched exclusively to barbed TCS in 2017. Outcomes were assessed at 30, 60, and 90 days. Multivariate regression analyses and Cox proportional hazards models were used. RESULTS: Of 821 hernia repairs, 446 used barbed TCS and 375 used conventional PDS. Surgical site infections (SSIs) were significantly less frequent with barbed TCS (60 days, 5.9% vs. 11.4%; P = 0.0083; 90 days, 5.9% vs. 11.7%; P = 0.006) and this remained consistent after multivariate adjustment (60 days, OR [95% CI]: 0.5 [0.3-0.9]; 90 days, 0.5 [0.3-0.9]). Among patients with SSI, deep SSIs were less frequent with barbed TCS (60 days, 9.1% vs. 35.7%; P = 0.022; 90 days, 9.1% vs. 34.9%; P = 0.0252). Barbed TCS significantly reduced the risk of perioperative complications (HR [95% CI]: 0.5[0.3-0.8]; P = 0.0058). Hospital length of stay was 2.5 days shorter with barbed TCS (mean [95% CI]: 5.7[4.9-6.6] vs. 8.2[7.3-9.1] days; P < 0.0001). No differences in reoperation rate over time were observed by type of suture (HR[95% CI]:1.3 [0.5-3.4]; P = 0.4793). CONCLUSIONS: This study showed that patients who underwent open hernia repair appeared to recover equally well regardless of the suture type. In addition, the use of barbed TCS was associated with significantly reduced risk of perioperative complications and hospital length of stay.

Synthesis of nanowires via helium and neon focused ion beam induced deposition with the gas field ion microscope.

The ion beam induced nanoscale synthesis of platinum nanowires using the trimethyl (methylcyclopentadienyl)platinum(IV) (MeCpPt(IV)Me3) precursor is investigated using helium and neon ion beams in the gas field ion microscope. The He(+) beam induced deposition resembles material deposited by electron beam induced deposition with very small platinum nanocrystallites suspended in a carbonaceous matrix. The He(+) deposited material composition was estimated to be 16% Pt in a matrix of amorphous carbon with a large room-temperature resistivity (∼3.5 × 10(4)-2.2 × 10(5) µΩ cm) and temperature-dependent transport behavior consistent with a granular material in the weak intergrain tunnel coupling regime. The Ne(+) deposited material has comparable composition (17%), however a much lower room-temperature resistivity (∼600-3.0 × 10(3) µΩ cm) and temperature-dependent electrical behavior representative of strong intergrain coupling. The Ne(+) deposited nanostructure has larger platinum nanoparticles and is rationalized via Monte Carlo ion-solid simulations which show that the neon energy density deposited during growth is much larger due to the smaller ion range and is dominated by nuclear stopping relative to helium which has a larger range and is dominated by electronic stopping.

Prognostic factors of poor postoperative outcomes in gastrectomies.

Background: Gastric cancer is one of the most common cancers worldwide and is the third most common cause of cancer related death. Improving postoperative results by understanding risk factors which impact outcomes is important. The current study aimed to compare immediate perioperative outcomes following gastrectomy. Methods: 302 patients following gastric resections over a 10-year period (January 2009-January 2020) were identified in a database and retrospectively analysed. Epidemiological as well as perioperative data was analysed, and a univariate and multivariate analysis performed to identify risk factors for in-hospital mortality. Results: In general, gastrectomies were mainly performed electively (total vs. subtotal 95% vs. 85%, p = 0.004). Patients having subtotal gastrectomy needed significantly more PRBC transfusions compared to total gastrectomy (p = 0.039). Most emergency surgeries were performed for benign diseases, such as ulcer perforations or bleeding and gastric ischaemia. Only emergency surgery was significantly associated with poorer overall survival (HR 2.68, 95% CI 1.32-5.05, p = 0.003). Conclusion: In-hospital mortality was comparable between total and subtotal gastrectomies. Only emergency interventions increased postoperative fatality risk.

Low-threshold Buprenorphine Treatment in a Syringe Services Program: Program Description and Outcomes.

OBJECTIVES: Low-threshold buprenorphine treatment aims to reduce barriers to evidence-based opioid use disorder treatment. We aimed to describe the treatment philosophy, practices, and outcomes of a low-threshold syringe services program (SSP)-based buprenorphine program developed through an SSP-academic medical center partnership. METHODS: We included all SSP participants who received 1 or more buprenorphine prescription from Feb 5, 2019 to October 9, 2020. We collected data on patient characteristics, substance use, buprenorphine prescriptions, and urine drug tests (UDTs). We evaluated buprenorphine treatment retention using prescription data and buprenorphine adherence using UDTs. We used 2 retention definitions: (1) percentage of patients with buprenorphine prescriptions at 30, 90, and 180 days; and (2) total percentage of days "covered" with buprenorphine prescriptions through 180 days. RESULTS: One-hundred and eighteen patients received 1 or more buprenorphine prescriptions. Patients were largely middle-aged (mean age 44, standard deviation 11), male (68%), Hispanic (31%) or Non-Hispanic Black (32%), with heroin (90%) and crack/cocaine (62%) use, and injection drug use (59%). Retention was 62%, 43%, and 31% at 30, 90, and 180 days, respectively. The median percentage of days covered with buprenorphine prescriptions through 180 days was 43% (interquartile range 8%-92%). Of the 82 patients who completed 2 or more UDTs, the median percentage of buprenorphine-positive UDTs was 71% (interquartile range 40%-100%). CONCLUSIONS: In an SSP-based low-threshold buprenorphine treatment program, approximately one-third of patients continued buprenorphine treatment for 180 days or more, and buprenorphine adherence was high. SSPs can be a pathway to buprenorphine treatment for patients at high risk for opioid-related harms.

Real-world practices to prevent venous thromboembolism with pharmacological prophylaxis in US orthopedic surgery patients: an analysis of an integrated healthcare database.

Major orthopedic surgery patients are at high risk of venous thromboembolism (VTE) in-hospital and post-discharge. This study assessed real-world inpatient and outpatient thromboprophylaxis practices following knee or hip arthroplasty. Patients from the Henry Ford Health System aged ≥18 years undergoing knee and hip arthroplasty (January 1997-June 2007) were identified using Current Procedural Terminology codes from administrative databases. Patients with <18 months of continuous enrollment in the system's health maintenance organization or with a current diagnosis of atrial fibrillation were excluded. Both inpatient and outpatient pharmacological prophylaxis was assessed. The analysis included 1393 (58.5%) patients following knee arthroplasty and 989 (41.5%) following hip arthroplasty. Average length of hospitalization was 4.9 days over the study period, although the median stay decreased from 5 days in 1997 to 3 days in 2007. Of patients included, 72.7% received pharmacological prophylaxis only in the inpatient setting following knee arthroplasty and 73.9% following hip arthroplasty. Both inpatient and outpatient pharmacological prophylaxis was received by 12.5% of knee and 12.3% of hip arthroplasty patients. Total length of pharmacological prophylaxis fluctuated between 2 to 4 days between 1997 and 2005, but increased to 11.5 ± 9.0 days in 2007. Although the duration of prophylaxis has recently increased, considerable numbers of hip and knee arthroplasty patients only receive prophylaxis for part of the time period recommended by guidelines. Further efforts are required to ensure the recommended duration of thromboprophylaxis is prescribed to all patients and continued outpatient VTE prophylaxis is provided.

Interest in long-acting injectable buprenorphine among syringe services program participants.

OBJECTIVE: To examine syringe services program (SSP) participants' interest in long-acting injectable buprenorphine. DESIGN: SSP participants completed a 136-item questionnaire by phone. Items assessed quantitative ratings of interest in sublingual and injectable buprenorphine, preference for sublingual versus injectable buprenorphine, and reasons for preferences. SETTING: Two large urban SSPs. PARTICIPANTS: SSP participants ≥18 years of age with current or lifetime opioid use disorder (OUD). MAIN OUTCOME MEASURE(S): (1) Interest in sublingual and injectable buprenorphine, respectively, on a scale from 0 to 10 (0 = no interest and 10 = high interest); and (2) preference for sublingual buprenorphine versus injectable buprenorphine. Participants were also asked whether they agreed with statements that presented potential reasons for preferring each formulation. RESULTS: A total of 104 unique participants were interviewed, of which 72 (69 percent) were currently receiving or considering buprenorphine treatment. Among these 72 participants, the median level of interest in starting or continuing sublingual buprenorphine was 8 out of 10 (interquartile range [IQR]: 6-10) and in starting injectable buprenorphine was 5 out of 10 (IQR: 1-9). Thirty-six (50 percent) preferred sublingual, 27 (38 percent) preferred injectable, and 9 (13 percent) preferred neither or declined to answer. Participants who preferred injectable buprenorphine most commonly agreed that the convenience of the monthly injection was the reason for their preference. CONCLUSIONS: Among SSP participants with OUD, we found moderate interest in injectable buprenorphine. Introducing this new form of buprenorphine treatment at SSPs could help meet the needs of individuals who are not well-served by standard OUD treatment models.

Membrane interactions influence the peptide binding behavior of DR1.

We analyzed the binding of an influenza matrix protein-derived peptide, MAT(17-31), to cell surface and purified DR1. The pH dependence of peptide binding was dramatically influenced by the membrane environment. Cell surface binding was enhanced at low pH, with little or no binding detected at neutral pH and optimal binding at pH 4. By contrast, hydrogen ion concentration had minimal effect on peptide binding to purified DR1. Exposure to low pH in the absence of peptide did not affect the peptide binding capacity of cell-associated DR1. Purified DR1 was stable at low pH, excluding the possibility that enhanced binding was offset by a competing denaturation event at low pH. The striking effect of pH on peptide binding characteristic of cell surface DR1 was recovered after reconstitution of purified DR1 in B cell membranes by detergent dialysis. This behavior was partially recovered by reconstitution of full-length, but not truncated DR1 in vesicles containing purified lipid. Our results demonstrate that interactions involving membrane components influence the peptide-binding behavior of DR1.

Mantle phase changes and deep-earthquake faulting in subducting lithosphere.

Inclined zones of earthquakes are the primary expression of lithosphere subduction. A distinct deep population of subduction-zone earthquakes occurs at depths of 350 to 690 kilometers. At those depths ordinary brittle fracture and frictional sliding, the faulting processes of shallow earthquakes, are not expected. A fresh understanding of these deep earthquakes comes from developments in several areas of experimental and theoretical geophysics, including the discovery and characterization of transformational faulting, a shear instability connected with localized phase transformations under nonhydrostatic stress. These developments support the hypothesis that deep earthquakes represent transformational faulting in a wedge of olivine-rich peridotite that is likely to persist metastably in coldest plate interiors to depths as great as 690 km. Predictions based on this deep structure of mantle phase changes are consistent with the global depth distribution of deep earthquakes, the maximum depths of earthquakes in individual subductions zones, and key source characteristics of deep events.

Self-release of CLIP in peptide loading of HLA-DR molecules.

The assembly and transport of major histocompatibility complex (MHC) class II molecules require interaction with the invariant chain. A fragment of the invariant chain, CLIP, occupies the peptide-binding groove of the class II molecule. At endosomal pH, the binding of CLIP to human MHC class II HLA-DR molecules was counteracted by its amino-terminal segment (residues 81 to 89), which facilitated rapid release. The CLIP (81-89) fragment also catalyzed the release of CLIP(90-105) and a subset of other self-peptides, probably by transient interaction with an effector site outside the groove. Thus, CLIP may facilitate peptide loading through an allosteric release mechanism.

Precision cutting and patterning of graphene with helium ions.

We report nanoscale patterning of graphene using a helium ion microscope configured for lithography. Helium ion lithography is a direct-write lithography process, comparable to conventional focused ion beam patterning, with no resist or other material contacting the sample surface. In the present application, graphene samples on Si/SiO2 substrates are cut using helium ions, with computer controlled alignment, patterning, and exposure. Once suitable beam doses are determined, sharp edge profiles and clean etching are obtained, with little evident damage or doping to the sample. This technique provides fast lithography compatible with graphene, with approximately 15 nm feature sizes.

Receptor clustering and transmembrane signaling in T cells.

T cells are activated via engagement of their cell-surface receptors with molecules of the major histocompatibility complex (MHC) displayed on another cell surface. This process, which is a key step in the recognition of foreign antigens by the immune system, involves oligomerization of receptor components. Recent characterization of the T-cell response to soluble arrays of MHC-peptide complexes has provided insights into the triggering mechanism for T-cell activation.

Antigenic peptide binding by class I and class II histocompatibility proteins.

The recent determination of the structure of a class II MHC molecule complexed to a specific peptide reveals both similarities and differences with peptide binding by class I MHC.

The class II MHC protein HLA-DR1 in complex with an endogenous peptide: implications for the structural basis of the specificity of peptide binding.

BACKGROUND: Class II major histocompatibility complex (MHC) proteins are cell surface glycoproteins that bind peptides and present them to T cells as part of the mechanism for detecting and responding to foreign material in the body. The peptide-binding activity exhibits allele-specific preferences for particular sidechains at some positions, although the structural basis of these preferences is not understood in detail. We have determined the 2.45 A crystal structure of the human class II MHC protein HLA-DR1 in complex with the tight binding endogenous peptide A2 (103-117) in order to discover peptide-MHC interactions that are important in determining the binding motif and to investigate conformational constraints on the bound peptide. RESULTS: The bound peptide adopts a polyproline II-like conformation and places several sidechains within pockets in the binding site. Bound water molecules mediate MHC-peptide contacts at several sites. A tryptophan residue from the beta 2 'lower' domain of HLA-DR1 was found to project into a pocket underneath the peptide-binding domain and may be important in modulating interdomain interactions in MHC proteins. CONCLUSIONS: The peptide-binding motif of HLA-DR1 includes an aromatic residue at position +1, an arginine residue at position +2, and a small residue at position +6 (where the numbering refers to the normal MHC class II convention); these preferences can be understood in light of interactions observed in the peptide-MHC complex. Comparison of the structure with that of another MHC-peptide complex shows that completely different peptide sequences bind in essentially the same conformation and are accommodated with only minimal rearrangement of HLA-DR1 residues. Small conformational differences that are observed appear to be important in interactions with other proteins.

Serial left ventricular wall measurements in Duchenne's muscular dystrophy.

In 19 patients with Duchenne's muscular dystrophy, left ventricular wall thickness in end-systole and end-diastole was determined serially every 12 months by echocardiography and compared with ventricular wall growth in normal subjects. In the normal subjects, left ventricular wall thickness increased linearly with increasing body surface area. A control group of wheelchair-bound patients with a variety of neurologic disorders, although not followed serially, had a distribution of end-diastolic wall thickness values similar to that of the normal subjects. In patients with muscular dystrophy, wall thickness increased linearly with respect to body surface area for some time and then began to thin. The time at which thinning began was not directly related to age, although it was more common in older than in younger patients. Those patients who died demonstrated marked deviation from normal wall growth. Free wall thinning is probably a result of fibrosis and loss of myofibrils.

Enhanced crystallization of the Cys18 to Ser mutant of bovine gammaB crystallin.

The cysteine residues of the gamma crystallins, a family of ocular lens proteins, are involved in the aggregation and phase separation of these proteins. Both these phenomena are implicated in cataract formation. We have used bovine gammaB crystallin as a model system to study the role of the individual cysteine residues in the aggregation and phase separation of the gamma crystallins. Here, we compare the thermodynamic and kinetic behavior of the recombinant wild-type protein (WT) and the Cys18 to Ser (C18S) mutant. We find that the solubilities of the two proteins are similar. The kinetics of crystallization, however, are different. The WT crystallizes slowly enough for the metastable liquid-liquid coexistence to be easily observed. C18S, on the other hand, crystallizes rapidly; the metastable coexisting liquid phases of the pure mutant do not form. Nevertheless, the coexistence curve of C18S can be determined provided that crystallization is kinetically suppressed. In this way we found that the coexistence curve coincides with that of the WT. Despite the difference in the kinetics of crystallization, the two proteins were found to have the same crystal forms and almost identical X-ray structures. Our results demonstrate that even conservative point mutations can bring about dramatic changes in the kinetics of crystallization. The implications of our findings for cataract formation and protein crystallization are discussed.

A diverse set of oligomeric class II MHC-peptide complexes for probing T-cell receptor interactions.

BACKGROUND: T-cells are activated by engagement of their clonotypic cell surface receptors with peptide complexes of major histocompatibility complex (MHC) proteins, in a poorly understood process that involves receptor clustering on the membrane surface. Few tools are available to study the molecular mechanisms responsible for initiation of activation processes in T-cells. RESULTS: A topologically diverse set of oligomers of the human MHC protein HLA-DR1, varying in size from dimers to tetramers, was produced by varying the location of an introduced cysteine residue and the number and spacing of sulfhydryl-reactive groups carried on novel and commercially available cross-linking reagents. Fluorescent probes incorporated into the cross-linking reagents facilitated measurement of oligomer binding to the T-cell surface. Oligomeric MHC-peptide complexes, including a variety of MHC dimers, trimers and tetramers, bound to T-cells and initiated T-cell activation processes in an antigen-specific manner. CONCLUSION: T-cell receptor dimerization on the cell surface is sufficient to initiate intracellular signaling processes, as a variety of MHC-peptide dimers differing in intramolecular spacing and orientation were each able to trigger early T-cell activation events. The relative binding affinities within a homologous series of MHC-peptide oligomers suggest that T-cell receptors may rearrange in the plane of the membrane concurrent with oligomer binding.

Serum resistin is not associated with obesity or insulin resistance in humans.

BACKGROUND: Resistin has proposed link with obesity related insulin resistance and type 2 diabetes. The physiologic role of resistin in humans remains unknown. It is suggested that circulating resistin levels are not associated with obesity or insulin resistance in humans. However, the effects of weight loss on serum resistin concentration has not been studied. In order to better understand the physiologic role of resistin in human obesity, we measured the serum resistin concentration in subjects with severe obesity (before and after 6-months of dietary intervention) to test the hypothesis that serum resistin concentrations are elevated amongst individuals with severe obesity and weight loss would reduce these levels. METHODS: Seventy-one obese subjects (defined as BMI > 35 kg/m2) who were randomized to low fat (LF) vs low carbohydrates (LC) diets and who completed the 6-month follow-up were studied. Their baseline demographic information was collected and serum resistin, insulin, glucose were measured at baseline and at 6-months. RESULTS: Subjects in LC diet lost more weight than LF (-19.54 +/- 7.87 lbs vs -7.83 +/- 11.23 lbs., p = 0.001). Insulin sensitivity (HOMA) improved in LC group compared with LF group [-3.72 +/- 9.84 (LC) vs +1.31 +/- 7.31 (LF), p = 0.006]. Serum resistin levels did not decrease in either diet. CONCLUSIONS: Our study found that despite a significant weight loss and improvement in insulin sensitivity there was no reduction in serum resistin concentration in morbidly obese men with metabolic syndrome suggesting that resistin does not play a central role in obesity related insulin resistance.