Proteomic Profiling of Stem Cell Tissues during Regeneration of Deer Antler: A Model of Mammalian Organ Regeneration.

As the only known mammalian organ that can fully and annually regenerate, deer antler has significant advantages over lower-order animal models when investigating the control of stem-cell-based organ regeneration. Antler regeneration is known to be initiated and maintained by neural-crest-derived stem cells in different states of activation. Antler stem cells can therefore be used as a model to study proteins and pathways involved in the maintenance of a stem cell niche and their activation and differentiation during organ formation. In this study, the MSC markers CD73, CD90, and CD105 were examined within the antler tip. Label-free quantification was performed to investigate the protein profiles of antler stem cells under different stages of activation and included dormant pedicle periosteum (DPP), antler growth center (GC), post-active stem cells from mid-beam antler periosteum (MAP), and deer facial periosteum (FP) as a control (n = 3 per group). PEAKS and IPA software were used to analyze the proteomic data. Our research confirmed the central role of stem cell activation in the development of this mammalian organ by localizing the MSC markers within the antler growth center. Label-free quantification revealed that the greatest number of unique proteins (87) was found in the growth center. There were only 12 proteins found with expression levels that significantly differed between DPP and FP. Protein profiles of these two groups indicated that antler stem cells may use similar mechanisms to maintain dormancy within a stem cell niche. The number of significantly regulated proteins among DPP, MAP, and GC was 153. Among them, the majority were upregulated in the growth center. Activation of antler stem cells was associated with many biological processes and signaling pathways, such as Hippo and canonical Wnt signaling. This work identifies the key pathways, molecular/cellular functions, and upstream regulators involved in mammal organ regeneration. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository with the dataset identifier PXD016824.

Lack of involvement of chitinase in direct toxicity of Beauveria bassiana cultures to the aphid Myzus persicae.

The fungal insect pathogen Beauveria bassiana produces a range of insecticidal metabolites and enzymes, including chitinases and proteases, which may assist the disease progression. The enzymes often play a predominant role in the pathogenicity pathway and both chitinases and proteases have previously been shown to be important in host infection. Spray application of supernatants of B. bassiana broth cultures of an isolate from New Zealand caused significant mortality in the green peach aphid, Myzus persicae, within 24 h, demonstrating an apparent contact toxicity. Three-day-old broth cultures were the most effective, with less insect mortality seen using six-day-old broth. However, aphicidal activity increased again when treating aphids with seven-day-old broth. Cultures grew substantially better and produced more potent aphicidal cultures when cultured in media with an initial pH above 5.5. Chitinase was produced a day earlier than the serine protease Pr1, but the peak production periods of these enzymes did not correlate with the aphicidal activities of three- or six-day-old cultures. Cultures treated with EDTA or heated to inactivate the enzymes still showed strong insecticidal activity. Neither beauvericin nor bassianolide, two known insecticidal metabolites, were detected in the supernatants. Therefore the key aphicidal components of B. bassiana cultures were not associated with chitinase nor Pr1 and are yet to be identified.

ACE inhibitory peptides in standard and fermented deer velvet: an in silico and in vitro investigation.

BACKGROUND: The use of deer velvet antler (DVA) as a potent traditional medicine ingredient goes back for over 2000 years in Asia. Increasingly, though, DVA is being included as a high protein functional food ingredient in convenient, ready to consume products in Korea and China. As such, it is a potential source of endogenous bioactive peptides and of 'cryptides', i.e. bioactive peptides enzymatically released by endogenous proteases, by processing and/or by gastrointestinal digestion. Fermentation is an example of a processing step known to release bioactive peptides from food proteins. In this study, we aimed to identify in silico bioactive peptides and cryptides in DVA, before and after fermentation, and subsequently to validate the major predicted bioactivity by in vitro analysis. METHODS: Peptides that were either free or located within proteins were identified in the DVA samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by database searching. Bioactive peptides and cryptides were identified in silico by sequence matching against a database of known bioactive peptides. Angiotensin-converting enzyme (ACE) inhibitory activity was measured by a colorimetric method. RESULTS: Three free bioactive peptides (LVVYPW, LVVYPWTQ and VVYPWTQ) were solely found in fermented DVA, the latter two of which are known ACE inhibitors. However matches to multiple ACE inhibitor cryptides were obtained within protein and peptide sequences of both unfermented and fermented DVA. In vitro analysis showed that the ACE inhibitory activity of DVA was more pronounced in the fermented sample, but both unfermented and fermented DVA had similar activity following release of cryptides by simulated gastrointestinal digestion. CONCLUSIONS: DVA contains multiple ACE inhibitory peptide sequences that may be released by fermentation or following oral consumption, and which may provide a health benefit through positive effects on the cardiovascular system. The study illustrates the power of in silico combined with in vitro methods for analysis of the effects of processing on bioactive peptides in complex functional ingredients like DVA.

Proteomic tracking of hydrothermal Maillard and redox modification in lactoferrin and ß-lactoglobulin: Location of lactosylation, carboxymethylation, and oxidation sites.

Lactoferrin and ß-lactoglobulin are important protein components of mammalian milk. Maillard reactions, as well as redox chemistry, are of particular interest for dairy products because they are known to occur during common processing steps, notably heating procedures such as pasteurization. Using a redox proteomics approach, we characterized AA residue side-chain modification across a range of heating times and with or without the specific addition of lactose, to both map the key modification sites within these proteins and evaluate their sensitivity to process-induced modification. Heating in the presence of lactose resulted in significant Maillard modification (both lactosylation and carboxymethylation) to both bovine lactoferrin and ß-lactoglobulin. Notably, Lys47, a key residue in the bioactive peptide lactoferricin, was particularly susceptible to modification. Lactoferrin appeared to be fairly robust to hydrothermal treatment, with relatively low levels of oxidative modification observed. In contrast, ß-lactoglobulin was susceptible to significant oxidative modification under hydrothermal treatment, with the range and type of modifications observed suggesting compromised nutritional value. These results have important implications for processing applications in dairy foods where retention of biological function and optimal protein quality is desired.

Accuracy of the ABC/2 Score for Intracerebral Hemorrhage: Systematic Review and Analysis of MISTIE, CLEAR-IVH, and CLEAR III.

BACKGROUND AND PURPOSE: The ABC/2 score estimates intracerebral hemorrhage (ICH) volume, yet validations have been limited by small samples and inappropriate outcome measures. We determined accuracy of the ABC/2 score calculated at a specialized reading center (RC-ABC) or local site (site-ABC) versus the reference-standard computed tomography-based planimetry (CTP). METHODS: In Minimally Invasive Surgery Plus Recombinant Tissue-Type Plasminogen Activator for Intracerebral Hemorrhage Evacuation-II (MISTIE-II), Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR-IVH) and CLEAR-III trials. ICH volume was prospectively calculated by CTP, RC-ABC, and site-ABC. Agreement between CTP and ABC/2 was defined as an absolute difference up to 5 mL and relative difference within 20%. Determinants of ABC/2 accuracy were assessed by logistic regression. RESULTS: In 4369 scans from 507 patients, CTP was more strongly correlated with RC-ABC (r(2)=0.93) than with site-ABC (r(2)=0.87). Although RC-ABC overestimated CTP-based volume on average (RC-ABC, 15.2 cm(3); CTP, 12.7 cm3), agreement was reasonable when categorized into mild, moderate, and severe ICH (κ=0.75; P<0.001). This was consistent with overestimation of ICH volume in 6 of 8 previous studies. Agreement with CTP was greater for RC-ABC (84% within 5 mL; 48% of scans within 20%) than for site-ABC (81% within 5 mL; 41% within 20%). RC-ABC had moderate accuracy for detecting ≥5 mL change in CTP volume between consecutive scans (sensitivity, 0.76; specificity, 0.86) and was more accurate with smaller ICH, thalamic hemorrhage, and homogeneous clots. CONCLUSIONS: ABC/2 scores at local or central sites are sufficiently accurate to categorize ICH volume and assess eligibility for the CLEAR-III and MISTIE III studies and moderately accurate for change in ICH volume. However, accuracy decreases with large, irregular, or lobar clots. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: MISTIE-II NCT00224770; CLEAR-III NCT00784134.

Ethical challenges for nurses delivering coercive interventions in community mental health settings: A scoping review.

The number of Australians subject to coercive interventions in community mental health services continues to increase. This is in the context of a growing awareness of the harms from coercion, increasing concerns about potential breaches of human rights and an ongoing uncertainty regarding the clinical benefits of community treatment orders, the primary instrument of legislated coercion in community mental health services. Nurses in community mental health services are on the frontline with regard to coercion. They police the requirements of the community treatment order, administer medication to people in community settings without their consent and facilitate re-hospitalisation if indicated. Coercive practice contradicts the person-centred, recovery-oriented and trauma-informed care principles that inform contemporary mental health nursing. This contradiction may generate ethical challenges for nurses and result in ethical distress. The aim of this scoping review was to map the research literature on how nurses in community mental health settings recognise and manage the harm associated with the administration of coercive interventions and consider the ethical challenges that may arise within this practice. The search strategy yielded 562 studies with author consensus determining a total of three articles as meeting the inclusion criteria. The resulting literature identified three themes: (1) maintaining the therapeutic relationship, (2) promoting autonomy and (3) using subtle forms of control. This review demonstrated that there is minimal research that has considered the ethical challenges related to the use of coercion by nurses in community mental health settings.

Unlocking the bioactivity of meat proteins: Comparison of meat and meat hydrolysate via simulated gastrointestinal digestion.

Understanding the functional attributes of meat proteins is crucial for determining their nutritional benefits. Depending on the form in which meat proteins are available, the digestive process can release peptides which are valuable for nutrition and may also possess bioactive properties, affecting physiology. Liquid chromatography - mass spectrometry (LC-MS) was used to quantitatively compare the molecular peptide features (representing non-redundant peptides), during the different stages of a simulated gastrointestinal digestion process of a minimally processed powdered meat and its enzymatically produced hydrolysate. Results from a principal component analysis (PCA) indicated that the hydrolysate did not undergo extensive additional digestion whereas the powdered meat was digested both at the gastric and in the intestinal phases. Bioactive peptide sequence prediction identified the meat hydrolysate but not the meat powder as the only source of exact and partial bioactive matches in the angiotensin-I converting enzyme and dipeptidyl peptidase IV inhibition categories. Also, a higher source of cryptides (encrypted bioactive peptides), indicated that meat hydrolysates are potentially a better substrate for the release of these enzyme inhibitory peptides. These observations thus suggest that pre-digestion of a complex food matrix such as meat, may enhance its bioavailability following oral consumption early in the digestion process. SIGNIFICANCE: This work highlights enzymatic hydrolysis of meat proteins prior to ingestion allows for potentially higher bioavailability of bioactive peptides that inhibit angiotensin-I converting enzyme and dipeptidyl peptidase IV, thus possibly aiding high blood pressure and type 2 diabetes management.

Effect of lesion temperature on the durability of percutaneous radiofrequency rhizotomies to treat trigeminal neuralgia.

OBJECTIVE: Percutaneous radiofrequency rhizotomy is a common procedure for trigeminal neuralgia (TN) that creates thermocoagulative lesions in the trigeminal ganglion. Lesioning parameters for the procedure are left to the individual surgeon's discretion, and published guidance is primarily anecdotal. The purpose of this work was to assess the role of lesioning temperature on long-term surgical outcomes. METHODS: This was a retrospective analysis of patients who underwent percutaneous radiofrequency rhizotomy from 2009 to 2020. Patient data, including demographics, disease presentation, surgical treatment, and outcomes, were collected from medical records. The primary endpoint was the recurrence of TN pain. Univariate and multivariate Cox proportional hazards regressions were used to assess the impact of chosen covariates on pain-free survival. RESULTS: A total of 280 patients who had undergone 464 procedures were included in the analysis. Overall, roughly 80% of patients who underwent rhizotomy would have a recurrence within 10 years. Lower lesion temperature was predictive of longer periods without pain recurrence (HR 1.05, p < 0.001). The inclusion of lesion time, postoperative numbness, prior history of radiofrequency rhizotomy, surgeon, and multiple sclerosis as confounding variables did not affect the hazard ratio or the statistical significance of this finding. Postoperative numbness and the absence of multiple sclerosis were significant protective factors in the model. CONCLUSIONS: The study findings suggest that lower lesion temperatures and, separately, postoperative numbness result in improved long-term outcomes for patients with TN who undergo percutaneous radiofrequency rhizotomies. Given the limitations of retrospective analysis, the authors suggest that a prospective multisite clinical trial testing lesion temperatures would provide definitive guidance on this issue with specific recommendations about the number needed to treat and trial design.

Low patient enrollment sites in multicenter randomized clinical trials of cerebrovascular diseases: associated factors and impact on trial outcomes.

Wide variability in patient enrollment among participating sites is a common phenomenon in multicenter trials. We examined stroke trial-related factors associated with the proportion of sites with low patient enrollment and the effect of these low-enrollment sites on trial outcome. We identified efficacy clinical trials enrolling patients with cerebrovascular diseases between 1980 and 2008 using an electronic database. The trials included in our analyses were multicenter randomized controlled trials (RCTs) comparing efficacy endpoints between two or more treatment groups and having >5 sites. Sites enrolling <10 patients or <2% of total trial patients were defined as low- enrollment sites. Trials were classified into tertiles based on the proportion of low-enrollment sites. Factors associated with trials that could be ascertained through a systematic review of published data were identified and examined. The association between low enrollment and a conclusive trial designation (defined by the ability to reject the primary null hypothesis either at or before target enrollment or demonstrate equivalence/noninferiority with adequate statistical power, depending on the initial design) was assessed using a multivariate logistic regression model. We identified 51 trials that met the inclusion criteria and provided information regarding patients enrolled per center. A total of 3059 participating centers enrolled a total of 53,742 trial participants; 78% of the participating sites enrolled <2% of trial participants. Trials enrolling acute stroke patients (within 24 hours of symptom onset) or those evaluating endovascular/surgical intervention had a higher proportion of low-enrollment sites (<10 patients per site). Studies with a higher proportion of low-enrollment sites were more likely to target acute stroke patients and less likely to randomize ≥1000 patients, use general efficacy endpoints, and stratify by site. There was no association between the studies with a higher proportion of low-enrollment sites and designation as a conclusive trial. A better understanding of factors associated with low-enrollment sites in clinical trials and the impact on a trial's ability to demonstrate conclusive outcomes may lead to strategies to make trial enrollments more efficient and cost-effective.

The practical limits of high-quality magnetic resonance imaging for the diagnosis and classification of trigeminal neuralgia.

BACKGROUND: Neurovascular compression (NVC) has been the primary hypothesis for the underlying mechanism of classical trigeminal neuralgia (TN). However, a substantial body of literature has emerged highlighting notable exceptions to this hypothesis. The purpose of this study is to assess the reliability and diagnostic accuracy of high resolution, high contrast MRI-determined neurovascular contact for TN. METHODS: We performed a retrospective, randomized, and blinded parallel characterization of neurovascular interaction and diagnosis in a population of TN patients and controls using four expert reviewers. Performance statistics were calculated, as well as assessments for generalizability using shuffled bootstraps. RESULTS: Fair to moderate agreement (ICC: 0.32-0.68) about diagnosis between reviewers was observed using MRIs from 47 TN patients and 47 controls. On average reviewers performed no better than chance when diagnosing participants, with an accuracy of 0.57 (95% CI 0.40, 0.59) per patient. CONCLUSION: While MRI is useful in determining structural causes in secondary TN, expert reviewers do no better to only slightly better than chance with distinguishing TN with MRI, despite moderate agreement. Further, the causal role of NVC for TN is not clear, limiting the applicability of MRI to diagnose or prognosticate treatment of TN.

Low-dose recombinant tissue-type plasminogen activator enhances clot resolution in brain hemorrhage: the intraventricular hemorrhage thrombolysis trial.

BACKGROUND AND PURPOSE: Patients with intracerebral hemorrhage and intraventricular hemorrhage have a reported mortality of 50% to 80%. We evaluated a clot lytic treatment strategy for these patients in terms of mortality, ventricular infection, and bleeding safety events, and for its effect on the rate of intraventricular clot lysis. METHODS: Forty-eight patients were enrolled at 14 centers and randomized to treatment with 3 mg recombinant tissue-type plasminogen activator (rtPA) or placebo. Demographic characteristics, severity factors, safety outcomes (mortality, infection, bleeding), and clot resolution rates were compared in the 2 groups. RESULTS: Severity factors, including admission Glasgow Coma Scale, intracerebral hemorrhage volume, intraventricular hemorrhage volume, and blood pressure were evenly distributed, as were adverse events, except for an increased frequency of respiratory system events in the placebo-treated group. Neither intracranial pressure nor cerebral perfusion pressure differed substantially between treatment groups on presentation, with external ventricular device closure, or during the active treatment phase. Frequency of death and ventriculitis was substantially lower than expected and bleeding events remained below the prespecified threshold for mortality (18% rtPA; 23% placebo), ventriculitis (8% rtPA; 9% placebo), symptomatic bleeding (23% rtPA; 5% placebo, which approached statistical significance; P=0.1). The median duration of dosing was 7.5 days for rtPA and 12 days for placebo. There was a significant beneficial effect of rtPA on rate of clot resolution. CONCLUSIONS: Low-dose rtPA for the treatment of intracerebral hemorrhage with intraventricular hemorrhage has an acceptable safety profile compared to placebo and historical controls. Data from a well-designed phase III clinical trial, such as CLEAR III, will be needed to fully evaluate this treatment.

Antler development was inhibited or stimulated by cryosurgery to periosteum or skin in a central antlerogenic region respectively.

Antler development is triggered by interactions between antler stem cells resident in the antlerogenic periosteum (AP) and the niche cells in the upper portion of overlying skin mediated by diffusible molecules. These interactive cell populations are interposed by the lower portion of the skin and the subcutaneous loose connective tissue (SLCT). It is known that mechanical deletion of just the central AP (having an area equivalent to the size of a pedicle base) by cutting through the skin and SLCT effectively stimulates the marginal AP to initiate antler development. This study was designed to investigate whether the SLCT layer plays a role in antler development by acting as a physical barrier. The results showed that the marginal AP failed to give rise to an antler after the central AP was cryosurgically destroyed with the preservation of the collagen structure of the SLCT. Furthermore, antler development was significantly advanced when the collagen structures of the skin and SLCT layers were substantially attenuated by repeated sprays with liquid nitrogen while keeping the central AP intact. Therefore, we conclude that the interposing SLCT layer acts as a physical barrier between antler stem cells and the niche cell types, and that timing of antler development is primarily controlled by the permeability of the SLCT layer to the putative interactive diffusible molecules.

Claims of Safety in Neurosurgical Literature: We Shouldn't Call Something Safe Without Strong Justification.

BACKGROUND: Many articles published in the neurosurgical literature make claims of safety regarding interventions. The strength of evidence supporting these claims has not been systematically evaluated. OBJECTIVE: To evaluate the quality of evidence supporting claims of safety in the neurosurgery literature. METHODS: The 14 neurosurgical journals listed in the Web of Science database with the highest impact factors for 2018 were included in the study. The titles and abstracts of all the articles published in these journals in 2018 were searched for the word "safety" and reviewed by 2 independent observers to identify those making a claim of safety and assess their evidence. RESULTS: The search identified 323 articles, representing 5% of the articles published in the 14 searched journals in 2018. Of these, 114 (1.8% of all articles and 35% of the identified articles) were judged to make a claim of safety of a neurosurgical intervention. A total of 98 (86%) of the 114 articles making a safety claim were retrospective cohort studies. Patient cohort sizes ranged from 1 to 1565 (median of 34), leading to wide variations in the CIs for estimated complication rates. No article made a statement of the assumptions underlying its claim of safety. CONCLUSION: Almost no articles that make claims of safety for neurosurgical interventions explicitly state the (1) patient population, (2) comparison intervention, nor (3) specific outcomes. To assure that claims of safety are supported by high-quality evidence, authors should address these elements early and systematically when designing studies.

Ruminant Milk-Derived Extracellular Vesicles: A Nutritional and Therapeutic Opportunity?

Milk has been shown to contain a specific fraction of extracellular particles that are reported to resist digestion and are purposefully packaged with lipids, proteins, and nucleic acids to exert specific biological effects. These findings suggest that these particles may have a role in the quality of infant nutrition, particularly in the early phase of life when many of the foundations of an infant's potential for health and overall wellness are established. However, much of the current research focuses on human or cow milk only, and there is a knowledge gap in how milk from other species, which may be more commonly consumed in different regions, could also have these reported biological effects. Our review provides a summary of the studies into the extracellular particle fraction of milk from a wider range of ruminants and pseudo-ruminants, focusing on how this fraction is isolated and characterised, the stability and uptake of the fraction, and the reported biological effects of these fractions in a range of model systems. As the individual composition of milk from different species is known to differ, we propose that the extracellular particle fraction of milk from non-traditional and minority species may also have important and distinct biological properties that warrant further study.

Stem cells responsible for deer antler regeneration are unable to recapitulate the process of first antler development-revealed through intradermal and subcutaneous tissue transplantation.

Antlers offer a unique model for the study of whether regeneration recapitulates development in a mammalian organ. Research, to date, supports the full recapitulation in antler, but a recent report that subcutaneously transplanted (ST) pedicle periosteum (PP) failed to induce that ectopic antler formation could argue against recapitulation, as antlerogenic periosteum (AP) can readily do so. However, it was not clear in that study whether the result was caused by inability of the PP to interact with the skin or owing to failure to create the required close contact to it. This study was designed to clarify this uncertainty by adopting intradermal transplantation (IT) to achieve the required close contact without the need for significant mass expansion. The results showed that IT of 1/8 of the original AP mass or more was sufficient for antler induction, whereas ST of 1/4-AP or less could not do so within 2 years. The minimum amount of AP required for antler induction using the IT approach was somewhere between 1/8 and 1/12-AP (<30 mg). The results further demonstrated that IT of 62-84 mg PP failed to induce ectopic antler formation, even if the PP had fused with the surrounding skin. Because this mass of PP was 2-3 times the minimum amount of AP required for antler induction, we conclude that PP does not recapitulate AP in induction of ectopic antler development. It is likely that PP has been restricted for antler regeneration and lost the potential to initiate antler development.

A Proof of Concept for Applying the Radicchi Index (hf) to Compare Academic Productivity and Scientific Impact Among Medical Specialties.

Many indices have been developed to assess the impact of scientific publications by investigators, disciplines, and institutions. The h-index has emerged as a leading tool in the assessment of the productivity of authors. Differences in publication and citation opportunity among specialties create inappropriate conclusions when the h-index is used to compare authors across different disciplines. An alternative, the Radicchi index, hf, has been proposed to assess the impact of publications across disciplines. We curated a database of all articles published from 2002 to 2015 from the 3 highest impact factor medical journals: New England Journal of Medicine (NEJM), the Lancet, and the Journal of American Medical Association (JAMA). With this database, articles were categorized into medical subspecialties. We calculated the respective h-index and Radicchi index of each specialty. We found that the Radicchi index eliminated variability associated with publication and citation opportunity between different specialties when compared to the h-index. The Radicchi index is a useful measure of scientific impact and productivity that advances the h-index by allowing interspecialty comparisons. There remains a need to define a researcher's specialty designation especially if he/she conducts multidisciplinary research.

From the Historical Examples of Drs. Osler, Cushing, and Van Wagenen: Lessons on the Importance of Mentorship in Contemporary Neurosurgery.

Although the historical relationships between William Osler, Harvey Williams Cushing, and William Perine Van Wagenen are well known in the neurosurgical world, the nature of the mentor-mentee relationships that existed between these historical giants is not widely appreciated. In this historical vignette, we describe and exemplify such relationships, while at the same time extract important and applicable principles from them. We reviewed relevant primary and secondary sources that documented the interactions between Cushing, Osler, and Van Wagenen. In founding the field of neurological surgery, the brilliant yet volatile Dr. Harvey Cushing received guidance from his mentor, Dr. William Osler. Through our review, it is undeniable that Dr. Osler's personal and professional guidance was vital to young Dr. Cushing's success as the founder of modern neurosurgery. Likewise, Cushing's tutelage of Van Wagenen enabled Van Wagenen to become a leader of a second generation of neurosurgeons, thereby perpetuating the existence of Cushing's high neurosurgical standards. These historical mentor-mentee relationships were built on 4 primary components: accurate recognition of talent, guidance, arrangement of opportunity, and sustenance of mentorship-actions that are commonly implicated in effective mentorship in contemporary studies. Proper mentorship remains indispensable for the success of neurosurgical trainees.

Multi-parameter evaluation of the effect of processing conditions on meat protein modification.

Evaluating the interconnecting effects of pH, temperature and time on food proteins is of relevance to food processing, and food functionality. Here we describe a matrix-based approach in which meat proteins were exposed to combinations of these parameters, selected to cover coordinates in a realistic processing space, and analyzed using redox proteomics. Regions within the matrix showing high levels of protein modification were evaluated for oxidative and other modifications. Both pH and temperature, independently, had a significant effect on the oxidative modifications mostly detected in myofibrillar proteins such as myosin and troponin and also collagen. Heat induced pyroglutamic acid formation was exclusively observed in the myofibrillar proteins. Potential interdependencies between pH, temperature and exposure time were evaluated using a 3-way analysis of variance (ANOVA) on protein modification levels to better understand how industry relevant process parameters influence protein quality and function.

Development of a nude mouse model for the study of antlerogenesis--mechanism of tissue interactions and ossification pathway.

In a previous study (Li et al., 2001. J Exp Zool 290:18-30) a nude mouse model was established to investigate deer antler development. In that study we found nude mice could support the singularly implanted antlerogenic periosteum (AP) to form pedicle-like, but not antler-like, bony protuberances. To further develop the model and at the same time to use the updated model for the investigation of antler formation, three experiments were carried out in this study. The results showed that (1) antler-like protuberances were successfully induced on the nude mouse heads via subcutaneous co-transplantation of AP and deer skin, and subsequent exposure through wounding of the deer xenografts; (2) deer skin epidermis and its attached half thickness of dermis were sufficient to interact with the AP, and the interactions were capable of transforming adult scalp skin into velvet; (3) the putative initial inductive molecules were primarily derived from the AP cellular layer, rather than fibrous layer; (4) initiation of the ossification center in the avascular cartilage of each mouse "antler" took place via metaplasia, rather than classical endochondral ossification. Further research is required to identify means for effective stimulation of calcification of the "mouse antlers" in order to create the opportunity to investigate antler regeneration using the nude mouse model. Overall, the nude mouse model, once further developed, has the potential to become a powerful tool to study underlying mechanism of antlerogenesis and organogenesis/regeneration in general.

Cutaneous pseudolymphoma: an unusual presentation of a scalp mass.

The term cutaneous pseudolymphoma (CPL), an accumulation of lymphocytes in response to a foreign antigen or unknown stimuli lacks specificity, and has been used when neither cause nor mechanism for the lymphocytic proliferation has been identified. Cases of childhood CPL are rare and require extensive investigation because of their potential for malignant transformation. We report a case of a child with a scalp mass diagnosed as CPL.