Search

This article explores the earliest documented circulation of Shakespeare's Othello in Portugal in 1765. It discusses the broader trend of Anglophone communities in the 18th century reading English literature, as they sought to reconcile their Catholicism with Britain's Protestant society. The article also examines the presence of Shakespeare's works in Portugal before the 19th century, including translations and adaptations. It highlights the role of the English College in Lisbon in promoting Anglophone print culture and fostering an Anglo-Portuguese social community. The article delves into the shipment of books to the English College, including a diverse range of works intended for both English and Portuguese readers, such as Othello and The Funeral: or, Grief A-la-Mode. It also explores the relationship between the English College and the British state, as well as the reception of Shakespeare in Portugal. Overall, this article provides valuable insights into the reading habits and cultural exchange between England and Portugal during this period. [Extracted from the article]

IgG4-related disease (IgG4-RD) is an increasingly recognized immune-mediated fibroinflammatory disorder that promptly responds to glucocorticoids but commonly relapses during steroid tapering or after discontinuation. In the last few years, B-cell depletion therapy with rituximab (RTX) proved to be effective in the induction of remission and maintenance treatment of IgG4-RD, providing a new powerful tool in the management of this emerging condition. In this review, we outline the pathogenetic rationale for using B-cell depleting agents in IgG4-RD, we summarize available clinical experience with RTX in this disease, and we describe future possible therapies targeting B-lymphocytes that are now in the pipeline. [ABSTRACT FROM AUTHOR]

Understanding of the pathophysiology of immunoglobulin G4-related disease (IgG4-RD) over the last dozen years has opened the door to a variety of targeted treatment approaches. Glucocorticoids are an effective treatment for IgG4-RD if used at a sufficiently high dose, but disease flares are common during or after glucocorticoid tapers and these medications seldom lead to long-term, treatment-free remissions. Moreover, their long-term use in a disease that frequently affects middle-aged to elderly individuals and often causes major pancreatic damage leads to a narrow therapeutic index. Biological therapies offer the possibility of effective disease control with fewer treatment-associated side effects. Promising avenues of investigation include B-cell depletion, immunomodulation of B-cell subsets, interference with co-stimulation, Bruton's tyrosine kinase inhibition, and Signaling lymphocytic activation molecule F7-directed treatment. [ABSTRACT FROM AUTHOR]

Objective Tocilizumab plus prednisone induces sustained glucocorticoid-free remission in patients with GCA. However, its long-term benefits in new-onset vs relapsing disease are uncertain, and the value of weekly vs every-other-week dosing has not been evaluated. Methods In Giant-Cell Arteritis Actemra (GiACTA) part 1, patients with new-onset or relapsing GCA received blinded tocilizumab weekly (TCZ QW), tocilizumab every-other-week (TCZ Q2W) or placebo for 52 weeks, with a prednisone taper. In part 2 (open-label), patients were treated at investigator discretion for 104 weeks. In this analysis, patients were evaluated according to their original treatment assignments, and outcomes beyond 52 weeks were assessed. Outcomes of interest included time to first flare and cumulative glucocorticoid exposure over 3 years according to baseline disease status. Results Part 1 enrolled 250 patients; 215 entered part 2. At baseline, 48% had new-onset disease and 52% had relapsing disease. In patients with new-onset and relapsing disease, the median time to first flare in the TCZ QW group was 577 and 575 days, respectively, vs 479 and 428 days with TCZ Q2W and 179 and 224 days with placebo; the median cumulative glucocorticoid dose was 3068 mg and 2191 mg with TCZ QW, 4080 mg and 2353 mg with TCZ Q2W, and 4639 mg and 6178 mg with placebo. Conclusion TCZ QW delayed the time to flare and reduced the cumulative glucocorticoid dose in patients with relapsing GCA and new-onset GCA. These data support initiating TCZ QW as part of first-line therapy in all patients with active GCA. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT01791153. [ABSTRACT FROM AUTHOR]

The article presents a case report of a 67-year-old Caucasian female with abdominal pain due to biopsy-proven IgG4-RSM and the application of elotuzumab therapy. The patient's disease has remained stable for 9 months which suggests a therapeutic elotuzumab-induced effect with prevention of disease progression and an immunological response. Elotuzumab could be a therapeutic option in IgG4-related disease (IgG4-RD) and is being tested as of 2022.

Objective To evaluate the association between cigarette smoking and the odds of IgG4-related disease (IgG4-RD). Methods We performed a case–control study of patients with IgG4-RD compared in a 1:5 ratio with age-, race- and sex-matched controls. We included cases evaluated at the Massachusetts General Hospital, a hospital within the Mass General Brigham (MGB) System. Controls were identified from the MGB Biobank. Smoking status at the date of IgG4-RD diagnosis or corresponding index date was determined. Conditional logistic regression was used to estimate the association between cigarette smoking and the odds of having IgG4-RD. Results There were 234 IgG4-RD cases and 1170 controls. The mean age (59 years), sex (62% male) and race (75% white) were well balanced. IgG4-RD cases were more likely to be current smokers compared with controls [25 (11%) vs 70 (6%); odds ratio (OR) 1.79 (95% CI 1.08, 2.95)]. This association was strongest among female cases [13 (14%) vs 19 (4%);, OR 3.79 (95% CI 1.71, 8.39)] and those with retroperitoneal fibrosis [RPF; 13 (28%) vs 13 (6%);, OR 6.93 (95% CI 2.78, 17.26)] or normal IgG4 concentrations [21 (21%) vs 21 (4%); OR 6.22 (95% CI 3.09, 12.49)]. When RPF cases were excluded, there was no longer an association between current smoking and the odds of having IgG4-RD [12 (6%) vs 57 (6%); OR 0.95 (95% CI 0.49, 1.86)]. Conclusion Being a current smoker is associated with greater odds of having IgG4-RD, especially among women and those with RPF or normal IgG4 concentrations. Current smoking is the first recognized modifiable risk factor for IgG4-RD. [ABSTRACT FROM AUTHOR]

Objectives IgG4-related disease (IgG4-RD) is a systemic fibro-inflammatory disorder characterized by a dysregulated resolution of inflammation and wound healing response that might develop after an apoptotic insult induced by cytotoxic T lymphocytes (CTLs). Mer receptor tyrosine kinase (MerTK) and its ligand, protein S (ProS1), have a pivotal role in the resolution of inflammation, being implicated in the clearance of apoptotic cells, quenching of the immune response and development of tissue fibrosis. In the present work we aimed to investigate a possible involvement of the MerTK signalling pathway in the pathogenesis of IgG4-RD and development of tissue fibrosis. Methods MerTK and ProS1 expression patterns in IgG4-RD lesions were evaluated by immunohistochemistry and immunofluorescence studies. Circulating MerTK + monocytes, soluble Mer and MerTK ligands were measured in the peripheral blood of IgG4-RD patients and healthy controls by flow cytometry and ELISA, respectively. Results MerTK was highly expressed by macrophages infiltrating IgG4-RD lesions. MerTK+ macrophages were more abundant in IgG4-RD than in Sjögren's syndrome and interacted with apoptotic cells and ProS1-expressing T and B lymphocytes. Moreover, they expressed the pro-fibrotic cytokine TGF-β and their numbers declined following rituximab-induced disease remission. Circulating MerTK+ monocytes, soluble Mer and MerTK ligands were not increased in the peripheral blood of patients with IgG4-RD. Conclusions The MerTK–ProS1 axis is activated in IgG4-RD lesions, possibly leading to persistent stimulation of processes involved in the resolution of inflammation and tissue fibrosis. [ABSTRACT FROM AUTHOR]

In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, viral load peaks early and declines quickly after symptom onset. Severe coronavirus disease 2019 (COVID-19) is marked by aberrant innate and adaptive immune responses with an abnormal cytokine profile and multiorgan system dysfunction that persists well after viral clearance. A purely antiviral treatment strategy may therefore be insufficient, and antiviral agents have not shown a benefit later in the illness course. A number of immunomodulatory strategies are being tested, including corticosteroids, cytokine and anticytokine therapies, small molecule inhibitors, and cellular therapeutics. To date, the only drug to show a mortality benefit for COVID-19 in a randomized, controlled trial is dexamethasone. However, there remains uncertainty about which patients may benefit most and about longer-term complications, including secondary infections. Here, we review the immune dysregulation of severe COVID-19 and the existing data behind various immunomodulatory strategies, and we consider future directions of study. [ABSTRACT FROM AUTHOR]

The article discusses the early modern English quartos included in the collection of the library of the Royal Scots College of Salamanca in Spain as of September 2020. Among the plays are "The Two Noble Kinsmen" by William Shakespeare and John Fletcher, "The Dumbe Knight" by Lewis Machin and Gervase Markham, and "The Raging Turke" by Thomas Goffe.

Objective The objective of this study was to evaluate causes of death in a contemporary inception cohort of ANCA-associated vasculitis patients, stratifying the analysis according to ANCA type. Methods We identified a consecutive inception cohort of patients newly diagnosed with ANCA-associated vasculitis from 2002 to 2017 in the Partners HealthCare System and determined vital status through the National Death Index. We determined cumulative mortality incidence and standardized mortality ratios (SMRs) compared with the general population. We compared MPO- and PR3-ANCA+ cases using Cox regression models. Results The cohort included 484 patients with a mean diagnosis age of 58 years; 40% were male, 65% were MPO-ANCA+, and 65% had renal involvement. During 3385 person-years (PY) of follow-up, 130 patients died, yielding a mortality rate of 38.4/1000 PY and a SMR of 2.3 (95% CI: 1.9, 2.8). The most common causes of death were cardiovascular disease (CVD; cumulative incidence 7.1%), malignancy (5.9%) and infection (4.1%). The SMR for infection was greatest for both MPO- and PR3-ANCA+ patients (16.4 and 6.5). MPO-ANCA+ patients had an elevated SMR for CVD (3.0), respiratory disease (2.4) and renal disease (4.5). PR3- and MPO-ANCA+ patients had an elevated SMR for malignancy (3.7 and 2.7). Compared with PR3-ANCA+ patients, MPO-ANCA+ patients had a higher risk of CVD death [hazard ratio 5.0 (95% CI: 1.2, 21.2]; P = 0.03]. Conclusion Premature ANCA-associated vasculitis mortality is explained by CVD, infection, malignancy, and renal death. CVD is the most common cause of death, but the largest excess mortality risk in PR3- and MPO-ANCA+ patients is associated with infection. MPO-ANCA+ patients are at higher risk of CVD death than PR3-ANCA+ patients. [ABSTRACT FROM AUTHOR]

Early diagnosis and treatment of GCA is essential to prevent complications of the disease, including permanent vision loss. Temporal artery biopsy has been intrinsically linked with the diagnosis of GCA for several decades. A negative predictive value of>90% has been reported for temporal artery biopsy; however, a negative result does not reliably indicate the absence of GCA because inflammation of the temporal artery is not always evident because of segmental involvement or other reasons. This is demonstrated by a case study of a patient hospitalized following acute vision loss to the right eye whose glucocorticoid treatment was suspended after temporal artery biopsy revealed no evidence of GCA. The patient subsequently lost sight in the left eye 6 weeks after stopping glucocorticoid therapy. The specificity of temporal artery biopsy for the diagnosis of GCA is variable and influenced by many factors, including length of biopsy specimens, vasculitis in vessels other than the temporal artery (ophthalmic, retinal and posterior ciliary vessels), unilateral versus bilateral biopsy, expertise of the surgeon, interpretation of histology, effects of treatment and confounding factors such as atherosclerosis or other non-GCA diseases that can affect the temporal artery. Considering the limitations of temporal artery biopsy, collaboration and education between the clinician, the pathologist and the patient, taking into account a thorough examination of patient history, recognizing signs and symptoms, and potentially involving newer imaging studies with trained technicians and physicians, are essential in confirming or eliminating diagnosis of GCA. [ABSTRACT FROM AUTHOR]

Aims Investigators have proposed that cardiovascular magnetic resonance (CMR) should have restrictions similar to those of ionizing imaging techniques. We aimed to investigate the acute effect of 1.5 T CMR on leucocyte DNA integrity, cell counts, and function in vitro, and in a large cohort of patients in vivo. Methods and results In vitro study: peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers, and histone H2AX phosphorylation (γ-H2AX) expression, leucocyte counts, and functional parameters were quantified using flow cytometry under the following conditions: (i) immediately following PBMC isolation, (ii) after standing on the benchside as a temperature and time control, (iii) after a standard CMR scan. In vivo study: blood samples were taken from 64 consecutive consenting patients immediately before and after a standard clinical scan. Samples were analysed for γ-H2AX expression and leucocyte counts. CMR was not associated with a significant change in γ-H2AX expression in vitro or in vivo, although there were significant inter-patient variations. In vitro cell integrity and function did not change with CMR. There was a significant reduction in circulating T cells in vivo following CMR. Conclusion 1.5 T CMR was not associated with DNA damage in vitro or in vivo. Histone H2AX phosphorylation expression varied markedly between individuals; therefore, small studies using γ-H2AX as a marker of DNA damage should be interpreted with caution. Cardiovascular magnetic resonance was not associated with loss of leucocyte viability or function in vitro. Cardiovascular magnetic resonance was associated with a statistically significant reduction in viable leucocytes in vivo. [ABSTRACT FROM AUTHOR]

Background. Donor kidneys contain a large reservoir of passenger leucocytes that contribute to acute rejection via direct alloantigen presentation and pro-inflammatory cytokine secretion. However, the early contribution of these cells following revascularization has not previously been described. We performed a secondary, high-volume preservation flush following cold storage to characterize the inflammatory contribution of the donor kidney upon reperfusion. Methods. Porcine kidneys were retrieved using a protocol analogous to current UK clinical practice. Following 2 h of cold static preservation, kidneys underwent a secondary flush with Ringer's solution. The venous effluent was collected and leucocytes phenotyped via flow cytometry. Inflammatory mediators, including cytokines and cell-free DNA, were then assessed to determine the inflammatory contribution of the donor kidney. Results. Upon reperfusion, a significant population of donorderived CD45þ leucocytes mobilized from the renal vasculature via the renal vein [mean 4.738×108 (SD 1.348×108)]. Within this population, T cells were dominant, representing >60% of the leucocyte repertoire. Granulocytes, monocytes and natural killer cells were also identified, but in comparatively lower numbers. Significant concentrations of cytokines and cell-free DNA were also eluted upon reperfusion. Conclusions. The donor kidney contains a significant immune load that rapidly mobilizes following reperfusion. Performing a secondary preservation flush prior to implantation may reduce this inflammatory burden via diversion of donor leucocytes and inflammatory mediators from entry into the recipient circulation. This may modulate direct presentation and reduce the inflammatory contribution of the donor kidney following transplantation. [ABSTRACT FROM AUTHOR]

Objectives: To report the clinicopathologic features of monotypic immunoglobulin G4+ (IgG4+) lymphoid and plasmacytic proliferations.Methods: Cases were identified from the pathology files. Pathology and clinical materials were reviewed.Results: Eleven cases of monotypic IgG4+ proliferations were identified at nodal, orbital, or salivary sites. Six cases (three men, three women; age, 57-94 years) met criteria for lymphoma or plasma cell neoplasia. Most contained frequent Mott cells. Five cases (three men, two women; age, 40-80 years) had restricted proliferations of atypical/monotypic IgG4+ plasma cells in a background of reactive lymphoid hyperplasia or inflammation.Conclusions: Monotypic IgG4+ proliferations include lymphomas, plasmacytic neoplasms, and a previously uncharacterized group of proliferations not meeting criteria for conventional hematolymphoid neoplasia. Distinct features included prominent Mott cells and/or monotypic plasma cells within follicles. The proliferations were infrequently associated with IgG4-related disease (IgG4-RD). Our findings raise questions regarding the relationship between clonal IgG4+ proliferations, reactive/inflammatory processes, and IgG4-RD. [ABSTRACT FROM AUTHOR]

Objective: A series of destructive and tumefactive lesions of the midline structures have been recently added to the spectrum of IgG4-related disease (IgG4-RD). We examined the clinical, serological, endoscopic, radiological, and histological features that might be of utility in distinguishing IgG4-RD from other forms of inflammatory conditions with the potential to involve the sinonasal area and the oral cavity. Methods: We studied 11 consecutive patients with erosive and/or tumefactive lesions of the midline structures referred to our tertiary care center. All patients underwent serum IgG4 measurement, flow cytometry for circulating plasmablast counts, nasal endoscopy, radiological studies, and histological evaluation of tissue specimens. The histological studies included immunostaining studies to assess the number of IgG4 + plasma cells/HPF for calculation of the IgG4+/IgG + plasma cell ratio. Results: Five patients with granulomatosis with polyangiitis (GPA), three with cocaine-induced midline destructive lesions (CIMDL), and three with IgG4-RD were studied. We found no clinical, endoscopic, or radiological findings specific for IgG4-RD. Increased serum IgG4 and plasmablasts levels were not specific for IgG4-RD. Rather, all 11 patients had elevated blood plasmablast concentrations, and several patients with GPA and CIMDL had elevated serum IgG4 levels. Storiform fibrosis and an IgG4+/IgG + plasma cell ratio 420% on histological examination, however, were observed only in patients with IgG4-RD. Conclusions: Histological examination of bioptic samples from the sinonasal area and oral cavity represents the mainstay for the diagnosis of IgG4-RD involvement of the midline structures. [ABSTRACT FROM AUTHOR]

Summary NanoShaper is a program specifically aiming the construction and analysis of the molecular surface of nanoscopic systems. It uses ray-casting for parallelism and it performs analytical computations whenever possible to maximize robustness and accuracy of the approach. Among the other features, NanoShaper provides volume, surface area, including that of internal cavities, for any considered molecular system. It identifies pockets via a very intuitive definition based on the concept of probe radius, intrinsic to the definition of the solvent excluded surface. We show here that, with a suitable choice of the parameters, the same approach can also permit the visualisation of molecular channels. NanoShaper has now been interfaced with the widely used molecular visualization software VMD, further enriching its already well furnished toolset. Availability and implementation VMD is available at http://www.ks.uiuc.edu/Research/vmd/. NanoShaper, its documentation, tutorials and supporting programs are available at http://concept.iit.it/downloads. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Objective. IgG4-related disease (IgG4-RD) is a relapsing-remitting condition responsible for fibroinflam-matory lesions that can lead to organ damage and life-threatening complications at nearly any anatomical site. The duration of remission following treatment varies and predictors of relapse are unclear. The objectives of this study were to review our experience with rituximab as remission induction in IgG4-RD, to clarify the duration of efficacy and to identify predictors of flare following treatment. Methods. In this retrospective cohort study, all patients were treated with two doses of rituximab (1 g) separated by 15 days. Clinical, radiographic and laboratory data pertaining to rituximab response and disease relapse were collected from the electronic medical record. Kaplan-Meier curves were constructed to estimate the time to disease relapse. Log-rank analyses were performed to compare times to relapse among subgroups. Potential relapse predictors were evaluated with Cox regression analysis. Results. Fifty-seven of 60 patients (95%) had clinical responses to rituximab. Forty-one patients (68%) were treated without glucocorticoids. Twenty-one patients (37%) experienced relapses following treatment at a median time from the first infusion of 244 days. Baseline concentrations of serum IgG4, IgE and circulating eosinophils predicted subsequent relapses, with hazard ratios of 6.2 (95% CI: 1.2, 32.0), 8.2 (95% CI: 1.4, 50.0) and 7.9 (95% CI: 1.8, 34.7), respectively. The higher the baseline values, the greater the risk of relapse and the shorter the time to relapse. Only 10% of the patients had elevations of all three major risk factors, underscoring the importance of measuring all three at baseline. Conclusion. Baseline elevations in serum IgG4, IgE and blood eosinophil concentrations all predict IgG4-RD relapses independently. [ABSTRACT FROM AUTHOR]

Background: Evidence implicates the amount and location of fat in aging-related loss of muscle function; however, whether intramyocellular lipids affect muscle contractile capacity is unknown.Methods: We compared both in vivo knee extensor muscle strength, power, and quality and in vitro mechanical properties of vastus lateralis single-muscle fibers between normal weight (NW) and obese older adults and determined the relationship between muscle lipid content (both intramuscular adipose tissue and intramyocellular lipids) and in vivo and in vitro muscle function in NW and obese individuals.Results: The obese group had a greater percentage of type-I fibers compared to the NW group. The cross-sectional area of type-I fibers was greater in obese compared to NW; however, maximal shortening velocity of type-I fibers in the obese was slower compared to NW. Type-I and type-IIa fibers from obese group produced lower specific force than that of type-I and type-IIa fibers from the NW group. Normalized power was also substantially lower (~50%) in type-I fibers from obese adults. The intramyocellular lipids data showed that total lipid droplet area, number of lipid droplets, and area fraction were about twofold greater in type-I fibers from the obese compared to the NW group. Interestingly, a significant inverse relationship between average number of lipid droplets and single-fiber unloaded shortening velocity, maximal velocity, and specific power was observed in obese participants. Additionally, muscle echointensity correlated with single-fiber specific force.Conclusions: These data indicate that greater intramyocellular lipids are associated with slower myofiber contraction, force, and power development in obese older adults. [ABSTRACT FROM AUTHOR]

In physical therapy, there is increasing focus on the need at the community level to promote health, eliminate disparities in health status, and ameliorate risk factors among underserved minorities. Community-based participatory research (CBPR) is the most promising paradigm for pursuing these goals. Community-based participatory research stresses equitable partnering of the community and investigators in light of local social, structural, and cultural elements. Throughout the research process, the CBPR model emphasizes coalition and team building that joins partners with diverse skills/expertise, knowledge, and sensitivities. This article presents core concepts and principles of CBPR and the rationale for its application in the management of health issues at the community level. Community-based participatory research is now commonly used to address public health issues. A literature review identified limited reports of its use in physical therapy research and services. A published study is used to illustrate features of CBPR for physical therapy. The purpose of this article is to promote an understanding of how physical therapists could use CBPR as a promising way to advance the profession's goals of community health and elimination of health care disparities, and social responsibility. Funding opportunities for the support of CBPR are noted. [ABSTRACT FROM AUTHOR]

Objective: The morbidity and mortality of hospitalized GCA patients have been unexplored. The aim of this study was to analyse inpatient complications experienced by patients with GCA. Methods: We used the Nationwide Inpatient Sample database to study a large group of patients admitted for pneumonia, myocardial infarction (MI), ischaemic stroke and femoral neck fracture. Patients were divided into two groups based on whether or not they had a diagnosis of GCA upon admission. Outcomes evaluated included inpatient mortality and the occurrence of adrenal insufficiency, deep vein thrombosis, pulmonary embolism and delirium. Results: From 2008 to 2011, 8203447 patients ≥50 years of age were discharged from US hospitals after admission with pneumonia, MI, stroke and femoral neck fracture. Among these patients, 9311 (0.11%) had GCA. Admissions for pneumonia, stroke and hip fracture were more frequent in GCA patients compared with those without GCA, accounting for 41.5% vs 39.4%, 24.9% vs 19.8% and 15.4% vs 14.2% of hospitalizations, respectively (P ≤ 0.001). Admissions for MI were more common in non-GCA patients (26.6% vs 18.2%, P< 0.001). During hospitalization, 4.1% of the GCA patients died, compared with 4.8% of those without GCA [odds ratio (OR) 0.73, P< 0.001). The GCA population suffered significantly more often from deep vein thrombosis (OR 2.08, P< 0.001), pulmonary embolism (OR 1.58, P< 0.001), delirium (OR 1.60, P< 0.001) and adrenal insufficiency (OR 4.95, P< 0.001). Conclusion: Hospitalized GCA patients have lower mortality compared with the general inpatient population but greater risk of venous thromboembolism, delirium and adrenal insufficiency. [ABSTRACT FROM AUTHOR]

The article describes the case of a 78-year-old male with severe valvular heart disease requiring multiple valve replacements and repairs. Topics discussed include findings on transesophageal echocardiogram, his treatment of prednisone followed by rituximab following a lung biopsy showing chronic pneumonitis and interstitial fibrosis with dense IgG4-positive plasmacytic infiltration, and clinical characteristics of IgG4-related disease.

Little is known about how age influences the ways in which cardiac fibroblasts interact with the extracellular matrix. We investigated the deformation of collagen substrates by neonatal and adult rat cardiac fibroblasts in monolayer and three-dimensional (3D) cultures, and quantified the expression of three collagen receptors [discoidin domain receptor (DDR)1, DDR2, and β1 integrin] and the contractile protein alpha smooth muscle actin (α-SMA) in these cells. We report that adult fibroblasts contracted 3D collagen substrates significantly less than their neonate counterparts, whereas no differences were observed in monolayer cultures. Adult cells had lower expression of β1 integrin and α-SMA than neonate cultures, and we detected significant correlations between the expression of α-SMA and each of the collagen receptors in neonate cells but not in adult cells. Consistent with recent work demonstrating age-dependent interactions with myocytes, our results indicate that interactions between cardiac fibroblasts and the extracellular matrix change with age. [ABSTRACT FROM AUTHOR]

This paper examines the relationship between feeding a diet rich in protease inhibitors and the reduction of mammary cancer induced by x-irradiation in Sprague-Dawley rats. Of a total of 145 irradiated animals, 44% of the 45 rats fed a raw soybean diet containing a high concentration of protease inhibitor developed mammary tumors as compared to 74% of 50 rats fed a casein diet containing no protease inhibitor. Animals fed Purina rat chow which contained low levels of protease inhibitor exhibited a 70% mammary tumor incidence. No spontaneous neoplasms were found in any of the non-irradiated animals on the raw soybean diet whereas about 10% of the animals on the protease-free diet developed tumors. Thus, soybeans which are rich in protease inhibitors reduced the induction of mammary cancer in x-irradiated rats. This work suggests that diets rich in protease inhibitors may contribute to reducing cancer incidence in man. [ABSTRACT FROM PUBLISHER]

An introduction to the journal is presented that focuses on studies related to the clinical challenges of diagnosing and managing giant cell arteritis (GCA) including a review of large-vessel GCA that draws on the finest evidence available, the broad physiological implications of excess IL-6 states, and a study on GCA at the tissue level for an updated description of disease pathophysiology.