Search

The “double barrel” technique has been a popular option in reconstituting the iliac-caval confluence in bilateral stenting. It has been mostly used with the Wallstent (Boston Scientific, Marlborough, Mass). The technique, although generally trouble-free, has a unique long-term complication. One stent barrel was found to compress the other from a late developing compliance mismatch. The complication is easily missed unless an intravascular ultrasound examination is performed. A cross-fenestration between the two barrels supported by a Z stent might provide clinical relief if the double barrel extension into the vena cava is relatively short in length.

Summary: Increasing left atrial (LA) size predicts outcomes in patients with isolated mitral regurgitation (MR). Chymase is plentiful in the human heart and affects extracellular matrix remodeling. Chymase activation correlates to LA fibrosis, LA enlargement, and a decreased total LA emptying fraction in addition to having a potential intracellular role in mediating myofibrillar breakdown in LA myocytes. Because of the unreliability of the left ventricular ejection fraction in predicting outcomes in MR, LA size and the total LA emptying fraction may be more suitable indicators for timing of surgical intervention. Key Words: chymase, fibrosis, left atrium, left ventricle, mitral regurgitation, mitral valve

Objective: To better understand the role of the presence or absence of motor-evoked potentials (MEPs) in predicting functional outcomes following a severe-moderate stroke. Design: Retrospective exploratory analysis. We compared the effects of the stimulation condition (active or sham), MEP status (+ or −), and a combination of stimulation condition and MEP status on outcome. Within-group and between-group changes were assessed with longitudinal repeated measures analysis of variance and longitudinal repeated measures analysis of covariance, respectively. The proportions of participants who achieved minimal clinically important differences (MCIDs) for the main outcome measures were calculated. Setting: University research laboratory within a rehabilitation hospital. Participants: A total of 129 subjects with severe-moderate stroke-related motor impairments who participated in previous studies combining neuromodulation and motor training Interventions: Neuromodulation (active or sham) and motor training. Main Outcome Measures: Fugl-Meyer Assessment (FMA) and Action Research Arm Test (ARAT). Results: When participants were grouped by stimulation condition or MEP status, all groups improved from baseline to immediate postintervention and follow-up evaluations (all P.05). Regarding MCIDs, in the MEP−/active group, 14.5% of individuals reached MCID on FMA and 8.3% on ARAT post intervention. In the MEP+/active group, 33.3% of individuals reached MCID on FMA and 27.3% on ARAT post intervention. Conclusion: As expected, the MEP+ group had the greatest improvement in motor function. However, it was shown that individuals without MEPs can also achieve meaningful changes, as reflected by MCID, when neuromodulation is paired with motor training. To our knowledge, this is the first study to differentiate the effects of neuromodulation by MEP status. Keywords: Rehabilitation, Transcranial direct current stimulation, Transcranial magnetic stimulation

Objective: To determine whether chronicity influences outcomes of somatosensory stimulation paired with task-oriented motor training for participants with severe-to-moderate upper extremity hemiparesis. Design: Spearman correlations were used to retrospectively analyze outcomes of a randomized trial. Setting: University research laboratory at a rehabilitation hospital. Participants: Adults, ranging between 3 and 12 months poststroke (N=55). Interventions: About 18 sessions pairing either 2 hours of active (n=33) or sham (n=22) somatosensory stimulation with 4 hours of intensive task-oriented motor training. Main Outcome Measures: The Wolf Motor Function Test (primary), Action Research Arm Test, Stroke Impact Scale, and Fugl-Meyer Assessment were collected as outcome measures. Analyses evaluated whether within-group chronicity correlated with pre-post changes on primary and secondary outcome measures of motor performance. Results: Both groups exhibited improvements on all outcome measures. No significant correlations between chronicity poststroke and the amount of motor recovery were found. Conclusion: Somatosensory stimulation improved motor recovery compared with sham treatment in cases of severe-to-moderate hemiparesis between 3 and 12 months poststroke; and the extent of recovery did not correlate with baseline levels of stroke chronicity. Future studies should investigate a wider period of inclusion, patterns of corticospinal reorganization, differences between cortical and subcortical strokes, and include long-term follow-up periods. Keywords: Humans, Occupational therapy, Rehabilitation, Transcutaneous electric nerve stimulation, Upper extremity

OBJECTIVE: The major human Fc receptor, FcgammaRIIa, is the most widespread activating FcR. Our aim was to determine the role of FcgammaRIIa in a transgenic mouse model of immune complex-mediated autoimmunity and to characterize the development of spontaneous autoimmune disease. METHODS: Arthritis was induced in normal and FcgammaRIIa-transgenic mice by immunization with type II collagen (CII) or by transfer of arthritogenic anti-CII antibodies. Also, mice that spontaneously developed autoimmune disease were assessed by clinical scoring of affected limbs, histology and serology, and measurement of autoantibody titers and cytokine production. RESULTS: FcgammaRIIa-transgenic mice developed collagen-induced arthritis (CIA) more rapidly than did archetypal CIA-sensitive DBA/1 (H-2q) mice, while nontransgenic C57BL/6 (H-2b) mice did not develop CIA when similarly immunized. Passive transfer of a single dose of anti-CII antibody induced a more rapid, severe arthritis in FcgammaRIIa-transgenic mice than in nontransgenic animals. In addition, most immune complex-induced production of tumor necrosis factor alpha by activated macrophages occurred via FcgammaRIIa, not the endogenous mouse FcR. A spontaneous, multisystem autoimmune disease developed in aging (>20 weeks) transgenic mice (n = 25), with a 32% incidence of arthritis, and by 45 weeks, all mice had developed glomerulonephritis and pneumonitis, and most had antihistone antibodies. Elevated IgG2a levels were seen in mice with CIA and in those with spontaneous disease. CONCLUSION: The presence of enhanced passive and induced autoimmunity, as well as the emergence of spontaneous autoimmune disease at 20-45 weeks of age, suggest that FcgammaRIIa is a very important factor in the pathogenesis of autoimmune inflammation and a possible target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

An in vivo trial was conducted to determine the apparent digestibility coefficients (ADCs) of insect meals for rainbow trout, Oncorhynchus mykiss. Rainbow trout (approximately 370 g ± 23 g, mean ± SD initial weight) were stocked 25 per tank into 400-liter tanks. Fish were fed a reference diet, or 1 of 5 test diets created by blending the reference diet in a 70:30 ratio (dry-weight basis) with menhaden fish meal (MFM), 2 house cricket (Acheta domesticus) meals (cricket A and cricket B), Galleria mellonella meal, and yellow mealworm (Tenebrio molitor) meal. Diets were assigned to 3 replicate tanks of fish and fed twice daily for 14 days prior to fecal collection. Ingredients, diets, and fecal matter were analyzed in duplicate for proximate, mineral, and amino acid composition. House cricket meals were 67.3% and 69.0% protein (CP) and 16.6% and 17.1% lipid (CL), for house cricket A and B, respectively. Yellow mealworm meal contained 56.5% CP and 27.7% CL, and G. mellonella larvae meal contained 32.5% CP and 54.2% CL. Protein ADCs were 78.9 for G. mellonella larvae meal, 78.0 for yellow mealworm meal, and 76.5 for house cricket A and not different from the MFM protein ADC of 76.6, while house cricket B protein ADC was 65.8 and was significantly lower than the MFM protein ADC (F = 7.39; df = 4,14; P = 0.0049). Together, these nutritional values suggest house crickets, and yellow mealworms show promise as alternative protein sources in salmonid feeds, with the potential of G. mellonella as an alternative lipid source., (Published by Oxford University Press on behalf of Entomological Society of America 2024.)

Three novel nickel-phosphate structures are reported, Ni 2 (PO 4 )(OH) ( I ), Ni 7 (PO 4 ) 3 (HPO 4 )(OH) 3 ( II ), and NaNiPO 4 ( III ). Each new system was prepared via a high-temperature hydrothermal synthesis at 600-650 °C. All three compounds are built of quasi-one-dimensional (quasi-1-D) Ni 2+ containing chains with varying phosphate bridging modes and were characterized by single crystal X-ray diffraction and magnetic susceptibility. All three compounds display very different magnetic behavior. Anisotropic magnetic data is reported for Ni 2 (PO 4 )(OH) ( I ) exhibiting slow antiferromagnetic ordering in the high-temperature regime with substructures that begin to form below 32 K at different field strengths. These characteristics affirm I as being one of the few Haldane-like material candidates. The Ni 7 (PO 4 ) 3 (HPO 4 )(OH) 3 ( II ) material is a member of the unusual ellenbergerite structural family and displays complex inter- and intrachain magnetic interactions while NaNiPO 4 ( III ) shows antiferromagnetic ordering near 18 K. This magnetic behavior is correlated with their structures.

The steep learning curve associated with learning laparoscopic techniques and limited training opportunities represents a challenge to general surgery resident training. The objective of this study was to use a live porcine model to improve surgical training in laparoscopic technique and management of bleeding. Nineteen general surgery residents (ranging from PGY 3 to 5) completed the porcine simulation and completed pre-lab and post-lab questionnaires. The institution's industry partner served as sponsors and educators on hemostatic agents and energy devices. Residents had a significant increase in confidence with laparoscopic techniques and the management of hemostasis ( P = .01 and P = .008, respectively). Residents agreed and then strongly agreed that a porcine model was suitable to simulate laparoscopic and hemostatic techniques, but there was no significant change between pre- and post-lab opinions. This study demonstrates that a porcine lab is an effective model for surgical resident education and increases resident confidence.

Abstract: Pediatric scalp avulsions represent a reconstructive challenge because of the unique features of scalp tissue. When microsurgical reimplantation is not feasible, alternative approaches such as skin grafting, free flap transfer with latissimus flap, or tissue expansion are considered. Generally, there is no consensus regarding management of this trauma, and, oftentimes, multiple reconstructive techniques may be needed for definitive coverage. This case study describes the reconstruction of a pediatric subtotal scalp avulsion using a dermal regeneration template and novel autologous homologous skin construct. This case was complicated by the absence of original tissue for reimplantation, excessive size of the defect relative to body habitus, and family concerns for future hair-bearing function. The reconstruction successfully provided definitive coverage and significantly reduced the size of the donor site and associated compilations. However, the hair-bearing potential of the tissue has yet to be determined., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Analyze efficacy of self-directed resident microvascular training versus a mentor-led course., Study Design: Randomized, single-blinded cohort study., Setting: Academic tertiary care center., Methods: Sixteen resident and fellow participants were randomized into two groups stratified by training year. Group A completed a self-directed microvascular course with instructional videos and self-directed lab sessions. Group B completed a traditional mentor-led microvascular course. Both groups spent equal time in the lab. Video recorded pre and post-course microsurgical skill assessments were performed to assess the efficacy of the training. Two microsurgeons, blinded to participant identity, evaluated the recordings and inspected each microvascular anastomosis (MVA). Videos were scored using an objective-structured assessment of technical skills (OSATS), a global rating scale (GRS), and quality of anastomosis scoring (QoA)., Results: The pre-course assessment identified that the groups were well matched with only "Economy of Motion" on the GRS favoring the mentor led group ( p  = .02). This difference remained significant on the post assessment ( p  = .02) Both groups significantly improved in OSATS and GRS scoring ( p  < .05). There was no significant difference in OSATS improvement between the two groups ( p  = .36) or improvement in MVA quality between groups ( p  > .99). Time to completion of MVA significantly improved overall by a mean of 8 min and 9 s ( p  = .005) with no significant difference between post training times to complete ( p  = .63)., Conclusion: Different microsurgical training models have previously been validated as effective methods for improved MVA performance. Our findings indicate that a self-directed microsurgical training model is an effective alternative to a traditional mentor driven models., Level of Evidence: Level 2., Competing Interests: None., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Background The 2022-2023 residency match cycle will be the first cycle that program directors will have to consider some applicants with a numerical United States Medical Licensing Examination (USMLE) Step 1 score while other applicants will only report pass/fail for USMLE Step 1. Previous studies have explored how USMLE Step 1 becoming pass/fail will alter the residency selection process, but it is not yet known when program directors from each specialty expect those changes to be implemented. Methods Residency program director's contact information was extracted from the American Medical Association (AMA) residency program site, Fellowship and Residency Electronic Interactive Database (FREIDA). Of the 5190 programs, 4877 were determined eligible for this study of which 1274 (26.8%) responded. Results Of the 1274 US residency program directors included in this survey, 77.0% do not intend to adjust their usage of USMLE Step 1 as a metric in candidate evaluation until the score is no longer reported. Conclusion Residency candidates applying during the upcoming cycle can expect the majority of residency programs will not significantly alter their previous utilization of an applicant's USMLE Step 1 score during the current 2022-2023 residency match cycle., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Powell et al.)

Background:  Traditionally, the United States Medical Licensing Examination (USMLE) Step 1 3-digit score has been used as a metric to stratify plastic surgery residency candidates. The transition to a pass/fail exam may impact the manner in which integrated plastic surgery residency program directors (PS-RPD) evaluate candidates. It may also limit opportunities for applicants to differentiate themselves from their counterparts., Methods: A 14-question survey was distributed via email to 76 PS-RPDs collected from the American Medical Association (AMA) residency program site, FRIEDA. It was sent three times from March 3 - March 14, 2020. McNemar tests were performed on the current metrics of evaluation in comparison to metrics expected to be used in the absence of a 3-digit Step 1 score, assuming a P < 0.05 level for statistical significance.  Results: Of the 76 integrated plastics programs surveyed, 24 PS-RPDs responded (31.6% response rate); 91.3% of PS-RPDs strongly disagree or disagree that Step 1 should be pass/fail; 78.3% of PS-RPDs strongly disagree or disagree that diversity will increase. The top five evaluation metrics PS-RPDs expect to utilize following the transition to pass/fail are: letters of recommendation (87.0%; CI 72% - 100%; p=0.500), Step 2 score (78.3%; CI 60% - 96%; p=0.001), research (56.5%; CI 35% - 78%; p=0.125), elective rotation (56.5%; CI 35% - 78%; p=1.000), and personal knowledge of the applicant (52.2%; CI 30% - 74%; p=0.500).  Conclusions: In the absence of a Step 1 score, PS-RPDs may require more holistic metric(s) to evaluate the best fit for their program. This study found that PS-RPDs expect their candidate evaluation process to remain highly similar with the only statistically significant change being an increased emphasis on the candidate's Step 2 score., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Powell et al.)

Objective: We hypothesized that a Chief Resident Service educational model provides safe care for patients compared to that received on standard academic services where rotating residents adopt the practices and preferences of their attending., Design: We retrospectively identified patients undergoing inguinal hernia repairs from July 2016 through June 2019 and matched Chief's service patients to standard academic service patients 1:1 on CPT, sex and age. We compared patient characteristics, recurrence rates, outcomes and complications., Setting: Tertiary care center, single institution., Participants: Overall, 77 patients undergoing inguinal hernia repairs (66% open and 34% laparoscopic) on the Chief's service matched successfully to 77 standard academic service patients during the study period., Results: Age, BMI and ASA were similar between the services, but Chief's service patients were less likely to be current smokers (1.3% vs. 24.7%) and more likely to be former smokers (59.7% vs. 26.0%) than standard academic service patients (p < 0.01). Patients presenting with incarcerated hernias (5.2% vs. 9.1%), recurrent (10.4% vs. 5.2%) and bilateral hernias (19.5% vs. 10.4%) were similar between the Chief's service and standard academic services, respectively (all p > 0.05). Operative times were longer for the Chief's service for open (123 min vs. 67, p < 0.01) and laparoscopic (112 min vs. 79, p = 0.02) repairs. Recurrence rates (6.5% vs. 3.9%, p = 0.47) and complications including infection, seroma or hematoma requiring evacuation and need for reoperation were similarly low (p > 0.05) between the Chief's and standard academic services, respectively. Despite low complication rates, Chief's service patients were more likely to present to the ED post-op (14.3% vs. 1.3%; p = 0.001), but readmission rates were similarly low (2.6% vs. 0%, p = 0.09)., Conclusions: Providing general surgery chief residents with a supervised opportunity to direct, plan and provide surgical care in clinic and the operating room, as a transition to independent practice following graduation, is safe for patients presenting with inguinal hernias. Concerns about patient safety should not be a barrier to maximizing entrustment for the evaluation and operative management of select core general surgery diagnoses and operations., (Copyright © 2022 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Biliary dyskinesia (BD) is a poorly understood functional gallbladder disorder. Diagnosis is made with abdominal pain and an intact gallbladder without signs of anatomical obstruction on imaging or pathology. Our aim was to assess whether laparoscopic cholecystectomy (LC) resolves hyperkinetic BD symptoms., Methods: Records of patients ≥18 years of age, who underwent LC by four surgeons at a tertiary care center between 2012 and 2020, were retrospectively reviewed. Patients were excluded if they had a documented gallbladder ejection fraction (GBEF) <80% or had biliary stones or sludge on pathology or imaging. Demographic information, HIDA results, preoperative testing, operative details, gallbladder pathology, and symptom status at follow-up were collected from electronic medical records. Improvement in BD symptoms was assessed using McNemar's test. Risk differences with standard errors were employed to estimate percent reduction in symptoms., Results: Ninety-eight patients met inclusion criteria. Of those who presented for follow-up (n = 91), 92.3% (n = 84) reported partial or complete resolution of symptoms. Preoperative symptoms, including back pain (16.7%, 95% CI: [7.9%, 25.5%]; P < .0001), epigastric pain (31.1% [21.3%, 41.3%]; P < .0001), nausea (56.7% [45.0%, 65.8%]; P < .0001), RUQ pain (57.8% [46.1%, 66.9%]; P < .0001), and vomiting (27.8% [18.4%, 37.7%]; P < .0001) showed significant improvement after LC. Chronic cholecystitis and/or cholesterolosis were present on pathology in 79.8% of gallbladders., Discussion: Our study currently represents the largest cohort of patients with hyperkinetic BD. Laparoscopic cholecystectomy appears to result in resolution of symptoms for this clinical entity.

Competing Interests: The authors report no conflicts of interest.

Background: To describe a case of pediatric sarcoidosis which initially presented as papillary conjunctivitis before manifesting as bilateral lacrimal gland swelling without other known systemic involvement., Case Presentation: A 10-year-old female presented to the pediatric ophthalmology clinic with complaints of bilateral eyelid swelling, tearing and itching for approximately 1 month. Her history and exam were most consistent with allergic conjunctivitis, for which she was started on a standard topical regimen. Despite initial improvement, she re-presented with significantly worsened eyelid swelling and minimal allergic symptoms. Enlargement of the lacrimal glands were palpable at this time. Lacrimal gland biopsy was obtained which demonstrated noncaseating granulomas. Systemic workup did not reveal evidence of disease involvement elsewhere., Conclusions: Sarcoidosis in the pediatric population may present in a myriad of ways and is well-known to mimic other disease entities. We present a case of pediatric sarcoidosis which presented initially as papillary conjunctivitis before manifesting as bilateral lacrimal gland swelling without systemic involvement., (© 2021. The Author(s).)

Background: The chief resident service provides surgical trainees in their final year of training the opportunity to maximize responsibility, continuity, and decision-making. Although supervised, chief residents operate according to personal preferences instead of adapting to their attendings' preferences. We hypothesized that outcomes following cholecystectomy are equivalent between the chief resident service and standard academic services., Methods: We matched adults undergoing cholecystectomy from 07/2016-06/2019 on the chief resident service to two standard academic service patients based on operative indication and age. We compared demographics, operative details, and 30-d complications., Results: This study included 186 patients undergoing cholecystectomy. Body mass index (32.4 versus 32.0, P = 0.49) and Charlson comorbidity index (0.9 versus 1.4, P = 0.16) were similar between chief resident and standard academic services, respectively. Operative approach was similar (95.2% laparoscopic on chief resident service versus 94.4% on standard service), but residents on the chief resident service performed cholangiograms more often (48.4% versus 22.6%, P < 0.01) and averaged longer operative times during laparoscopic cholecystectomy with cholangiogram (146±28 versus 85±22 min, P < 0.01) and without (94±31 versus 76±35 min, P < 0.01) compared with standard academic services, respectively. 30-d complication rates were similar (5.2% chief resident versus 5.0% standard, P = 0.95). No patients suffered bile leak, bile duct injury, or reoperation. Emergency Department visits were similar (12.1% chief resident versus 7.4% standard, P = 0.32); readmissions were less frequent on the chief resident service (0.0% versus 5.0% standard, P = 0.03)., Conclusions: With appropriate supervision, chief residents provide safe care for patients undergoing cholecystectomy while directing medical decisions and practicing according to their preferences., (Copyright © 2021. Published by Elsevier Inc.)

Thin films of trinitrotoluene (TNT) were shock compressed using the ultrafast laser shock apparatus at Los Alamos National Laboratory. Visible (VIS) and mid-infrared (MIR) transient absorption spectroscopies were simultaneously performed to probe for electronic and vibrational changes during shock compression of TNT. Three shock pressures (16 GPa, 33 GPa, and 45 GPa) were selected to observe no reaction, incipient reaction, and strongly developed reactions for TNT within the experimental time scale of <250 ps. Negligible absorption changes in MIR or VIS absorptions were observed at 16 GPa. At 33 GPa, MIR absorptions in the 3000 cm -1 -4000 cm -1 range were observed to increase during the shock and continue to increase during the rarefaction, in contrast to the VIS absorption measurements, which increased during the shock and almost fully recovered during rarefaction. At 45 GPa, both VIS and MIR absorptions were strong and irreversible. The intense and spectrally broad MIR absorptions were attributed to short lived intermediates with strong, spectrally broad absorptions that dominate the spectral response. The MIR and VIS absorption changes observed at 33 GPa and 45 GPa were credited to shock induced chemistry, most likely including the formation of a very broad hydrogenic stretch feature. The results from these experiments are consistent with the chemical mechanisms that include O-H or N-H formation such as CH 3 oxidation or C-N homolysis.

Thin films of pentaerythritol tetranitrate (PETN) were shock compressed using the laser driven shock apparatus at Los Alamos National Laboratory (LANL). Two spectroscopic probes were available to this apparatus: visible white light transient absorption spectroscopy (VIS) from 400 to 700 nm and mid-infrared transient absorption spectroscopy (MIR) from 1150 to 3800 cm -1 . Important PETN vibrational modes are the symmetric and antisymmetric NO 2 stretches at 1280 and 1650 cm -1 , respectively, as well as CH stretches at ∼2900 cm -1 . Shock strength was varied from approximately 3 to 55 GPa to span from the chemically unreactive regime to the regime in which fast chemical reaction took place on the 250 ps time scale of the measurements. VIS and MIR results suggest irreversible chemistry was induced in PETN at pressures above 30 GPa. At lower shock pressures, the spectroscopy showed minimal changes attributable to pressure induced effects. Under the higher-pressure reactive conditions, the frequency region at the antisymmetric NO 2 stretch mode had a significantly increased absorption while the region around the symmetric NO 2 stretch did not. No observable increased absorption occurred in the higher frequency regions where CH-, NH-, and OH- bond absorptions would be observed. A broad absorption appeared on the shoulder at the red-edge of the CO 2 vibrational band around 2200 cm -1 . In addition to the experiments, reactive molecular dynamics were carried out under equivalent shock conditions to correlate the evolution of the infrared spectrum to molecular processes. The simulations show results consistent to experiments up to 30 GPa but suggest that NO and NO 2 related features provided the strongest contributions to the shocked infrared changes. Proposed mechanisms for shocked PETN chemistry are analyzed as consistent or inconsistent with the data presented here. Our experimental data suggests C≡O or N 2 O bond formation, nitrite formation, and absence of significant hydroxyl or amine concentrations in the initial chemistry steps in PETN shocked above 30 GPa.

Background: The technique for attaining photographic evidence of the critical view of safety (CVS) in laparoscopic cholecystectomy (LC) has previously been defined; however, the consistency, accuracy, and feasibility of CVS in practice is unknown. The aim of this study was to use an already established image sharing and grading system to determine the feasibility of timely feedback after sharing intraoperative images of the CVS and to evaluate if and how cholecystitis affects the ability to attain a CVS., Study Design: We studied 193 laparoscopic cholecystectomies performed by 14 surgeons between August 2017 and January 2019. Anterior and posterior intraoperative CVS images were shared using a standard multimedia messaging system (MMS). Images were graded remotely by members of the group using an established scoring system, and their times to response and scores were recorded. Response data were analyzed for the ability to attain timely and consistent CVS scores., Results: There were 74 urgent laparoscopic cholecystectomies for acute cholecystitis and 119 nonurgent cholecystectomies performed during the study period. Scoring of shared images occurred in less than 5 minutes, and peer review (mean 3 responses) showed agreement that was not significantly different. In patients with acute cholecystitis, a small but significant difference was observed between anterior and posterior image scoring agreement., Conclusions: An established image sharing and grading system for CVS can be used for real-time intraoperative feedback without increasing operative time or compromising private health information. The CVS is almost always attainable; however, decreases in CVS quality and grading agreement are observed in patients with acute cholecystitis., (Published by Elsevier Inc.)

Common Ti:sapphire chirped pulse amplified laser systems can be readily adapted to be both a generator of adjustable pressure shock waves and a source for multiple probes of the ensuing ultrafast shock dynamics. In this paper, we detail experimental considerations for optimizing the shock generation, interferometric characterization, and spectroscopic probing of shock dynamics with visible and mid-infrared transient absorption. While we have reported results using these techniques elsewhere, here we detail how the spectroscopies are integrated with the shock and interferometry experiment. The interferometric characterization uses information from beams at multiple polarizations and angles of incidence combined with thin film equations and shock dynamics to determine the shock velocity, particle velocity, and shocked refractive index. Visible transient absorption spectroscopy uses a white light supercontinuum in a reflection geometry, synchronized to the shock wave, to time resolve shock-induced changes in visible absorption such as changes to electronic structure or strongly absorbing products and intermediates due to reaction. Mid-infrared transient absorption spectroscopy uses two color filamentation supercontinuum generation combined with a simple thermal imaging microbolometer spectrometer to enable broadband single shot detection of changes in the vibrational spectra. These methods are demonstrated here in the study of shock dynamics at stresses from 5 to 30 GPa in organic materials and from a few GPa to >70 GPa in metals with spatial resolution of a few micrometers and temporal resolution of a few picoseconds. This experiment would be possible to replicate in any ultrafast laser laboratory containing a single bench top commercial chirped pulse amplification laser system.

The current study examines expression of S100 genes, a group of calcium-sensing proteins poorly characterized in fishes. In mammals, these proteins are known to play roles beyond calcium-signaling, including mediation of inflammatory processes. Some S100 proteins also serve as biomarkers for a variety of autoinflammatory conditions. It is well known that salmonids exhibit varying degrees of intestinal enteritis when exposed to alternative feed ingredients containing antinutritional factors, with soybean meal (SBM) being one of the best characterized. The etiology of soy-caused distal enteritis isn't entirely understood but displays similar histopathological alterations to the gut observed in human mucosal inflammatory bowel diseases. We sought to determine if teleost S100 genes show a concomitant response like that observed in mammals, utilizing rainbow trout fed high-soy diets as a model for intestinal inflammation. We examined expression of fourteen known salmonid S100 genes in the liver, first segment of the mid-intestine (proximal intestine), and second segment of the mid-intestine (distal intestine). After 12 weeks on a high-soy diet containing 40% SBM, we observed upregulation of several S100 genes in the distal intestine (S100I2, A10a, V1, V2, and W), no changes in the proximal intestine, and downregulation of S100V2 in the liver. Overall, our results provide further knowledge of the expression of S100 genes and provide targets for future research regarding inflammatory processes in the rainbow trout gut., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Laparoscopic-assisted transgastric endoscopic retrograde cholangiopancreatography (LAERCP) is used for treatment in patients after Roux-en-Y gastric bypass (RYGB), where transoral access to the biliary tree is not possible. We describe our technique and experience with this procedure., Methods: Electronic medical record search was performed from September 2012 to January 2016, identifying patients who underwent LAERCP per operative records. Charts were reviewed for demographic, clinical, and outcomes data., Results: Sixteen patients were identified. Average time since bypass was 6.9 years, and length of stay was 3.7 days. Five patients underwent simultaneous cholecystectomy. Eleven patients, or 43%, had cholecystectomy more than 2 years previously. ERCP with sphincterotomy was completed in 15 of 16 patients (94%). Our technique involves access to the bypassed stomach via a laparoscopically placed 15 mm port. We observed one major complication of post-ERCP necrotizing pancreatitis. No minor complications nor mortalities were seen in our series., Conclusion: Biliary obstruction can occur many years after RYGB and cholecystectomy. Our findings suggest that RYGB patients may be at a higher risk of primary CBD stone formation. LAERCP is a reliable option for common bile duct (CBD) clearance; our technique of LAERCP is technically simple and associated with low complication rate, making it appealing to surgeons not trained in advanced laparoscopy.

We have employed, to the best of our knowledge, a novel excitation scheme to perform the first high-repetition-rate planar laser-induced fluorescence (PLIF) measurements of a CN radical in combustion. The third harmonic of a Nd:YVO 4 laser at 355 nm due to its relatively large linewidth overlaps with several R branch transitions in a CN ground electronic state. Therefore, the 355 nm beam was employed to directly excite the CN transitions with good efficiency. The CN measurements were performed in premixed CH 4 -N 2 O flames with varying equivalence ratios. A detailed characterization of the high-speed CN PLIF imaging system is presented via its ability to capture statistical and dynamical information in these premixed flames. Single-shot CN PLIF images obtained over a HMX pellet undergoing self-supported deflagration are presented as an example of the imaging system being applied towards characterizing the flame structure of energetic materials.

The interleukin-23 (IL-23) pathway, T helper 17 (Th17) cells and γδ T cells, which respond to IL-23, have major pro-inflammatory roles. We have used unique IL-23 receptor (IL-23R) subunit-specific monoclonal antibodies, X67 and X68, and IL-12 receptor beta-1 subunit (IL-12Rβ1) expression levels to evaluate the IL-23R complex on CD4 αβ TCR Th17 cells and on γδ T cells. Both IL-23R and IL-12Rβ1 subunits constitute the functional IL-23R. Expression of the IL-23R subunit by cultured Th17 cells was heterogeneous. Th17 cells expressed consistent high levels of the IL-12Rβ1 subunit, which appeared a better predictor of responsiveness to IL-23 than the expression of the IL-23R subunit. Moreover, sorting memory CD4 T cells by high IL-12Rβ1 expression selectively enriched cells committed to IL-17 production from the blood. IL-23R expression was also observed on freshly isolated and cultured γδ T cells and the cultured γδ T cells were not responsive to IL-23.

A study was conducted to test whether an anthocyanidin mixture (peonidin, cyanidin and pelargonidin chloride) modulates myogenesis in both induced and non-induced myogenic cells from juvenile rainbow trout (Oncorhynchus mykiss). We evaluated three different anthocyanidin concentrations (1×, 2.5× and 10×) at two sampling times (24 and 36h). To test for treatment effects, we analyzed the expression of myoD and pax7 as well as two target genes of the Notch signaling pathway, hey2 and her6. In induced myogenic cells, the lowest and middle anthocyanidin doses caused significantly greater expression of myoD after 24h of treatment compared to control. A significantly higher expression of pax7 in cells exposed to either anthocyanidin treatment during 36h compared was observed. Similarly, the pax7/myoD ratio was significantly lower in cells exposed to the lowest anthocyanidin doses during 24h compared to control. No significant effect of anthocyanidin treatments on the expression of hey2 and her6 at either sampling point was detected. In non-induced cells, we observed no effect of anthocyanidins on myoD expression and significant down-regulation on pax7 expression in cells exposed to either anthocyanidin mixture concentrations after 24 and 36h of treatment compared to control. Further, the pax7/myoD ratio was significantly lower in cells exposed to either anthocyanidin doses at both sampling time. In non-induced cells, the highest anthocyanidin dose provoked significantly greater expression of hey2 after 24h of treatment compared to control. We detected no such effect in non-induced cells exposed to the lowest and middle anthocyanidin doses during 24h of treatment. The expression of her6 was unaffected by anthocyanidin treatments at either sampling time or doses compared to control. Collectively, these findings provide evidence that anthocyanidins modulate specific components of the myogenic programming in fish, thereby potentially affecting somatic growth in fish fed plant-derived extracts rich in this type of polyphenols. Moreover, in early differentiating myogenic cells, the anthocyanidin effect on myogenic programming appears to differ based upon the exposure time and the differentiation stage of the myogenic cells by boosting myogenic differentiation signaling after 24h treatment while pausing differentiation, potentially favoring cell survival after 36h treatment. Further research to determine whether plant-derived secondary metabolites including alkaloids, terpenoids, tannins, saponins, glycosides, flavonoids, phenolics, steroids and essential oils can modulate myogenic programming in myogenic cells isolated from finfish species is warranted., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Complications after gastric bypass (RYGB) are well documented. Reversal of RYGB is indicated in select cases but can lead to weight gain. Conversion from RYGB to sleeve gastrectomy (SG) has been proposed for correction of complications of RYGB without associated weight gain. However, little is known about outcomes after this procedure., Objectives: To examine outcomes after conversion from RYGB to SG., Setting: University hospital., Methods: A retrospective study of patients who underwent RYGB to SG conversion was undertaken., Results: Twelve patients underwent RYGB to SG conversion for refractory marginal ulceration, stricture, dumping, gastrogastric fistula, hypoglycemia, and failed weight loss. No deaths occurred. Four patients experienced 7 major complications, including portal vein thrombosis, bleeding, pancreatic leak, pulmonary embolus, seroma, anastomotic leak, and stricture. Two required reoperation, and 6 were readmitted within 30 days. Four required nasoenteric feeding postoperatively because of prolonged nausea. The complication of RYGB resolved in 11 of 12 patients. At 14.7 months, change in body mass index for all patients was a decrease of 2.2 kg/m(2). In 5 patients with morbid obesity at conversion, the change in body mass index was a decrease of 6.4 kg/m(2) at 19 months., Conclusions: Laparoscopic conversion from RYGB to SG is successful in resolving certain complications of RYGB and does not result in short-term weight gain. However, conversion has a high rate of major complications as well as a high rate of readmission and need for supplemental nutrition. Although conversion to SG may be appropriate in carefully-selected patients, other options for patients with severe chronic complications after RYGB should be considered., (Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

The effector memory CD4+ Th17 cells play critical roles in bacterial immunity and pathological inflammation in autoimmune conditions. ZSWIM1 is a gene encoding a protein of unknown function in leukocytes-but containing a zinc finger SWIM motif. In peripheral blood mononuclear cells, the expression of ZSWIM1 is highest in lymphocytes, and in particular shows greatest abundance in naive CD4+ T cells. Upon polarisation of naïve CD4+ T cells, ZSWIM1 expression is retained in Th17 cells but is selectively down regulated in Th1 cells. Similarly in in vitro expanded effector memory CD4+ T cells, ZSWIM1 was more abundant in Th17 cells compared to Th1 or Th17 polyfunctional (Th17pf) cells, which produce IL-17A and IFNγ. Although stimulation of cytokine production by PMA and ionomycin reduced ZSWIM1 expression, the relative differences in abundance between the cell types were maintained. The activation sensitive nature of ZSWIM1 expression suggests that it may play a novel role in the development or function of T helper cells., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Glycation occurs when glucose reacts non-enzymatically with proteins. This reaction depends upon time, ambient glucose concentration, and the molecular conformation of reactive amino acids. Little is known about protein glycation in fishes and the main objective of this study was to measure glycated hemoglobin (GHb) in rainbow trout, a glucose-intolerant species, under normoglycemic and hyperglycemic conditions. We also identified GHb isoforms in vivo and analyzed the structural environment surrounding potential glycation sites. Despite similar glycemia to healthy humans, GHb was an order of magnitude lower in rainbow trout (0.6%) compared with humans (6%) and was not affected by long-term hyperglycemia. Species differences in GHb appear to be related to differences in erythrocyte glucose, and differential expression and glycation of hemoglobin (Hb) isoforms may explain intraspecific differences in rainbow trout GHb. Computer analysis of glucose isomers (ringed-open and α- and β-pyranoses) interacting with the β-chain of rainbow trout HbI and HbIV, and human HbA did not reveal structural or energetic constraints for glucose binding (the initial step of glycation) for rainbow trout Hbs. Overall, there are significant differences between Hb glycation in humans and rainbow trout, and GHb does not appear to be an accurate indicator of glycemia over time in rainbow trout., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Interleukin 17 producing T helper cells (Th17) and IFNγ producing Th1 cells are distinct subsets of effector memory CD4(+) T cells that are crucial to host immunity and have been linked to the pathology of certain inflammatory autoimmune diseases. We have developed a method for the isolation and long term culture of human Th17 and Th1 cells. Using allogeneic stimulation we have cultured homogeneous populations of Th17 and Th1 cells to large cell numbers. These alloreactive cell lines were established from CD4(+)CD45RO(+) memory T cells expressing, or lacking, CCR6 and CCR4. The Th17 cells were derived only from cells expressing both CCR6 and CCR4 whereas the Th1 cells, secreting IFNγ, were derived from cells lacking CCR6 and CCR4. The CCR6(+) and CCR4(+) memory T cells also gave rise to a third population of polyfunctional cells expressing both IL-17 and IFNγ. All cell populations expressed the TCR αβ and the Th17 cells characteristically expressed CCR6, CCR4 and CD161. The use of this protocol will ultimately allow for the comparative analysis of the Th17 and Th1 cells., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Over the past 20 years bariatric surgery proved to be a valid treatment for reduction and elimination of obesity-related diseases and long-term sustainable weight loss. Minimally invasive or laparoscopic techniques such as laparoscopic Roux-en-Y (LRNY) have replaced open procedures. Many factors play important roles in the small intricacies and variations of the procedure, chief of which is the creation and size of the gastrojejunostomy. Regardless of the variations in technique, the LRNY remains the gold standard for the surgical treatment of clinically severe or morbid obesity, with relatively low morbidity and mortality., (Copyright © 2011. Published by Elsevier Inc.)

The interaction of Abs with their specific FcRs is of primary importance in host immune effector systems involved in infection and inflammation, and are the target for immune evasion by pathogens. FcγRIIa is a unique and the most widespread activating FcR in humans that through avid binding of immune complexes potently triggers inflammation. Polymorphisms of FcγRIIa (high responder/low responder [HR/LR]) are linked to susceptibility to infections, autoimmune diseases, and the efficacy of therapeutic Abs. In this article, we define the three-dimensional structure of the complex between the HR (arginine, R134) allele of FcγRIIa (FcγRIIa-HR) and the Fc region of a humanized IgG1 Ab, hu3S193. The structure suggests how the HR/LR polymorphism may influence FcγRIIa interactions with different IgG subclasses and glycoforms. In addition, mutagenesis defined the basis of the epitopes detected by FcR blocking mAbs specific for FcγRIIa (IV.3), FcγRIIb (X63-21), and a pan FcγRII Ab (8.7). The epitopes detected by these Abs are distinct, but all overlap with residues defined by crystallography to contact IgG. Finally, crystal structures of LR (histidine, H134) allele of FcγRIIa and FcγRIIa-HR reveal two distinct receptor dimers that may represent quaternary states on the cell surface. A model is presented whereby a dimer of FcγRIIa-HR binds Ag-Ab complexes in an arrangement that possibly occurs on the cell membrane as part of a larger signaling assembly.

The majority of human subjects who receive subcutaneous allergen immunotherapy (IT) develop decreased sensitivity to their allergens. Multiple factors may explain the efficacy of IT, some evidence support a role for allergen specific IgG antibodies. There is controversy whether such antibodies act by blocking allergen binding to IgE or initiation of active inhibitory signaling through low affinity IgG receptors (FcgammaRIIB) on mast cells and basophils. In this study, we addressed this question using peripheral blood from cat non-allergic, cat allergic, and immunotherapy-treated cat allergic subjects. Blood from subjects who received IT contain IgG antibodies that mediate inhibition of basophil activation by a mechanism that is blocked by antibodies specific for the inhibitory IgG receptor FcgammaRIIB. Surprisingly, inhibition was also blocked by aglycosylated, putatively non-FcR binding, antibodies that are specific for the FcgammaRIIA, suggesting a contribution of this receptor to the observed effect. Consistent with a cooperative effect, ex vivo basophils were found to express both IgG receptors. In other studies we found that basophils from subjects who were both chronically exposed to allergen and were producing both cat allergen specific IgE and IgG, are hyporesponsive to allergen. These studies confirm that IgG antibodies produced during IT act primarily by stimulation of inhibitory signaling, and suggest that FcgammaRIIA and FcgammaRIIB function cooperatively in activation of inhibitory signaling circuit. We suggest that under normal physiologic conditions in which only a small proportion of FcepsilonRI are occupied by IgE of a single allergen specificity, FcgammaRIIA co-aggregation may, by providing activated Lyn, be required to fuel activation of inhibitory FcgammaRIIB function., (Copyright 2009 Elsevier B.V. All rights reserved.)

The major human Fc receptor, huFcgammaRIIa, is implicated in the development of autoimmune arthritis in humans but until recently has not been studied in mouse models. We evaluated potential roles of FcgammaRIIa by using transgenic mice expressing the receptor. We examined two models of induced autoimmune arthritis pristane-induced arthritis (PIA) and collagen-induced arthritis (CIA) as well as the anti-collagen-II antibody-induced arthritis (CAIA) model. In the induced arthritis models PIA and CIA, the transgenic mice developed a more severe arthritis than the other arthritis-prone SJL or DBA1 mice. Interestingly, anti-collagen-II antibodies were elevated in PIA in the susceptible mice. In the CIA model, the highly susceptible transgenic mouse had IgG subclass levels equivalent to the unaffected and disease resistant C57BL/6 mouse strain implying that the FcgammaRIIa lowers the threshold of IgG dependent leukocyte activation. This is consistent with the greatly enhanced sensitivity of the FcgammaRIIa transgenic mice to CAIA which clearly indicates a role for the receptor at least at the inflammatory effector cell level. Other roles for huFcgammaRIIa or other gene products in the development of autoimmunity cannot be ruled out however, especially as the mice exhibited elevated Th1 or Th17 CD4 T cells in the draining lymph nodes., (Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.)

The objective of this study was to evaluate patterns of intrauterine growth in fetal gastroschisis. This was a retrospective review of prenatally diagnosed cases of fetal gastroschisis delivered at the University of North Carolina Hospital from January 2000 to January 2007. Fetal growth (biparietal diameter, head circumference, abdominal circumference, femur length, and estimated fetal weight) and amniotic fluid volume were evaluated by gestational age. Gastroschisis was diagnosed in 83 pregnancies; outcomes were available in 71 fetuses. The mean gestational age at diagnosis was 17 weeks and 1 day. The mean gestational age at delivery was 35 weeks and 4 days. Mean birth weight was 2306 g. As early as the second trimester, all morphometric measures demonstrated impaired in utero growth, with growth curves shifted to the right of the 50th percentile when compared with a standard population. Estimated fetal weight below the 10th percentile was suspected in 23% of pregnancies, and birth weight at less than the 10th percentile occurred in 47% of neonates. Amniotic fluid volumes remained stable throughout gestation. Fetuses with gastroschisis display impaired intrauterine growth, which is noted in the midsecond trimester of pregnancy and does not appear to progress throughout gestation., (Thieme Medical Publishers.)

Understanding the effects of dietary carbohydrates on transcription factors that regulate myogenesis provides insight into the role of nutrient sensing by satellite cells towards myocyte differentiation. We evaluated the influence of dietary carbohydrate level (0, 15, 25 or 35%) on the temporal mRNA expression patterns (4, 8 or 12 weeks) of transcription factors that regulate satellite cell myocyte addition (MA) in rainbow trout (Oncorhynchus mykiss), a vertebrate with indeterminate growth. Relative to the 0% carbohydrate (NC) diet, 15 (IC-15) and 25% (IC-25) carbohydrate containing diets significantly up-regulate MyoD and Myf5, but not Pax7, after 12 weeks of feeding. Simultaneously, the Pax7/MyoD mRNA expression ratio declined significantly with both the IC diets. Myogenin mRNA expression also increased in rainbow trout (RBT) fed the IC-15 diet. The high carbohydrate (HC) diet (35%) attenuated the increased mRNA expression of these transcription factors. It is of note that the 4 and 8 week samples lacked the promyogenic expression patterns. The myogenic gene expression in fish fed the IC-15 diet for 12 weeks indicate a transcriptional signature that reflects increased satellite cell myogenesis. Our results suggest a potential role for satellite cells in the nutrient sensing ability of a vertebrate with indeterminate skeletal muscle growth.

The interaction of immune complexes with the human Fc receptor, FcgammaRIIa, initiates the release of inflammatory mediators and is implicated in the pathogenesis of human autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus, so this FcR is a potential target for therapy. We have used the three-dimensional structure of an FcgammaRIIa dimer to design small molecule inhibitors, modeled on a distinct groove and pocket created by receptor dimerization, adjacent to the ligand-binding sites. These small chemical entities (SCEs) blocked immune complex-induced platelet activation and aggregation and tumor necrosis factor secretion from macrophages in a human cell line and transgenic mouse macrophages. The SCE appeared specific for FcgammaRIIa, as they inhibited only immune complex-induced responses and had no effect on responses to stimuli unrelated to FcR, for example platelet stimulation with arachidonic acid. In vivo testing of the SCE in FcgammaRIIa transgenic mice showed that they inhibited the development and stopped the progression of collagen-induced arthritis (CIA). The SCEs were more potent than methotrexate and anti-CD3 in sustained suppression of CIA. Thus, in vitro and in vivo activity of these SCE FcgammaRIIa receptor antagonists demonstrated their potential as anti-inflammatory agents for autoimmune diseases involving immune complexes.

We used microarray and quantitative real-time PCR (qRT-PCR) analyses in adult female zebrafish (Danio rerio) to identify metabolic pathways regulated by starvation in the liver and brain. The transcriptome of whole zebrafish brain showed little response to 21 days of starvation. Only agouti-related protein 1 (agrp1) significantly responded, with increased expression in brains of starved fish. In contrast, a 21-day period of starvation significantly downregulated 466 and upregulated 108 transcripts in the liver, indicating an overall decrease in metabolic activity, reduced lipid metabolism, protein biosynthesis, proteolysis, and cellular respiration, and increased gluconeogenesis. Starvation also regulated expression of many components of the unfolded protein response, the first such report in a species other than yeast (Saccharomyces cerevisiae) and mice (Mus musculus). The response of the zebrafish hepatic transcriptome to starvation was strikingly similar to that of rainbow trout (Oncorhynchus mykiss) and less similar to mouse, while the response of common carp (Cyprinus carpio) differed considerably from the other three species.

The aggregation of cell surface Fc receptors by immune complexes induces a number of important antibody-dependent effector functions. It is becoming increasingly evident that the organization of key immune proteins has a significant impact on the function of these proteins. Comparatively little is known, however, about the nature of Fc receptor spatiotemporal organization. This review outlines the current literature concerning human Fc receptor spatial organization and physiological function.

Collagen binding to glycoprotein VI (GPVI) induces signals critical for platelet activation in thrombosis. Both ligand-induced GPVI signaling through its coassociated Fc-receptor gamma-chain (FcRgamma) immunoreceptor tyrosine-activation motif (ITAM) and the calmodulin inhibitor, W7, dissociate calmodulin from GPVI and induce metalloproteinase-mediated GPVI ectodomain shedding. We investigated whether signaling by another ITAM-bearing receptor on platelets, FcgammaRIIa, also down-regulates GPVI expression. Agonists that signal through FcgammaRIIa, the mAbs VM58 or 14A2, potently induced GPVI shedding, inhibitable by the metalloproteinase inhibitor, GM6001. Unexpectedly, FcgammaRIIa also underwent rapid proteolysis in platelets treated with agonists for FcgammaRIIa (VM58/14A2) or GPVI/FcRgamma (the snake toxin, convulxin), generating an approximate 30-kDa fragment. Immunoprecipitation/pull-down experiments showed that FcgammaRIIa also bound calmodulin and W7 induced FcgammaRIIa cleavage. However, unlike GPVI, the approximate 30-kDa FcgammaRIIa fragment remained platelet associated, and proteolysis was unaffected by GM6001 but was inhibited by a membrane-permeable calpain inhibitor, E64d; consistent with this, micro-calpain cleaved an FcgammaRIIa tail-fusion protein at (222)Lys/(223)Ala and (230)Gly/(231)Arg, upstream of the ITAM domain. These findings suggest simultaneous activation of distinct extracellular (metalloproteinase-mediated) and intracellular (calpain-mediated) proteolytic pathways irreversibly inactivating platelet GPVI/FcRgamma and FcgammaRIIa, respectively. Activation of both pathways was observed with immunoglobulin from patients with heparin-induced thrombocytopenia (HIT), suggesting novel mechanisms for platelet dysfunction by FcgammaRIIa after immunologic insult.