American Society of Biomechanics Journal of Biomechanics Award 2017: High-acceleration training during growth increases optimal muscle fascicle lengths in an avian bipedal model.

Sprinters have been found to possess longer muscle fascicles than non-sprinters, which is thought to be beneficial for high-acceleration movements based on muscle force-length-velocity properties. However, it is unknown if their morphology is a result of genetics or training during growth. To explore the influence of training during growth, thirty guinea fowl (Numida meleagris) were split into exercise and sedentary groups. Exercise birds were housed in a large pen and underwent high-acceleration training during their growth period (age 4-14 weeks), while sedentary birds were housed in small pens to restrict movement. Morphological analyses (muscle mass, PCSA, optimal fascicle length, pennation angle) of a hip extensor muscle (ILPO) and plantarflexor muscle (LG), which differ in architecture and function during running, were performed post-mortem. Muscle mass for both ILPO and LG was not different between the two groups. Exercise birds were found to have ∼12% and ∼14% longer optimal fascicle lengths in ILPO and LG, respectively, than the sedentary group despite having ∼3% shorter limbs. From this study we can conclude that optimal fascicle lengths can increase as a result of high-acceleration training during growth. This increase in optimal fascicle length appears to occur irrespective of muscle architecture and in the absence of a change in muscle mass. Our findings suggest high-acceleration training during growth results in muscles that prioritize adaptations for lower strain and shortening velocity over isometric strength. Thus, the adaptations observed suggest these muscles produce higher force during dynamic contractions, which is beneficial for movements requiring large power outputs.

Interferon-γ inhibits integrin-mediated extracellular signal-regulated kinase activation stimulated by fibronectin binding in thyroid cells.

Hashimoto's thyroiditis (HT) is an autoimmune disorder characterized by the presence of specific antibodies and by a lymphocytic infiltration of the thyroid secreting inflammatory cytokines. Macrophages, lymphocytes, and cytokines play a pivotal role in both development and progression of Th1-mediated autoimmune diseases, and a direct role in the destruction of thyroid follicles and follicular cell function in autoimmune thyroiditis. Integrins are integral membrane receptors involved in cell-extra-cellular matrix (ECM) interaction with both structural and signaling functions. The integrin- ECM interaction is necessary for the correct function and survival of thyroid follicular cells. The purpose of this study was to determine the effect of cytokine stimulation on integrin expression and signaling in the thyroid cell. Primary cultures from normal thyroids were treated with interferon-γ (IFN-γ), INF-α, tumor necrosis factor-α, interleukin 1a or these cytokines all together. Integrin expression, cell adhesion to fibronectin (FN) and FN-stimulated extracellular signal-regulated kinase (ERK) phosphorylation were determined after cytokine treatment. IFN-γ and IFN-α were the most effective, reducing the expression of the integrin αvß3 and slightly increasing the α3ß1. Cell treatment with IFN-γ strongly impaired cell adhesion to FN. At the same time, the treatment with IFN-γ dramatically inhibited the stimulation of ERK phosphorylation induced by cell adhesion to FN. In conclusion, IFN-γ inhibits the expression of the integrin αvß3, reducing the cell adhesion to FN and the following intracellular signaling in thyroid cells in culture. These results suggest that integrins may be a target of the infiltrating lymphocytes and have a role in the pathogenesis of autoimmune thyroiditis.

Progression of BRAF-induced thyroid cancer is associated with epithelial-mesenchymal transition requiring concomitant MAP kinase and TGFß signaling.

Mice with thyroid-specific expression of oncogenic BRAF (Tg-Braf) develop papillary thyroid cancers (PTCs) that are locally invasive and have well-defined foci of poorly differentiated thyroid carcinoma (PDTC). To investigate the PTC-PDTC progression, we performed a microarray analysis using RNA from paired samples of PDTC and PTC collected from the same animals by laser capture microdissection. Analysis of eight paired samples revealed a profound deregulation of genes involved in cell adhesion and intracellular junctions, with changes consistent with an epithelial-mesenchymal transition (EMT). This was confirmed by immunohistochemistry, as vimentin expression was increased and E-cadherin lost in PDTC compared with adjacent PTC. Moreover, PDTC stained positively for phospho-Smad2, suggesting a role for transforming growth factor (TGF)ß in mediating this process. Accordingly, TGFß-induced EMT in primary cultures of thyroid cells from Tg-Braf mice, whereas wild-type thyroid cells retained their epithelial features. TGFß-induced Smad2 phosphorylation, transcriptional activity and induction of EMT required mitogen-activated protein kinase (MAPK) pathway activation in Tg-Braf thyrocytes. Hence, tumor initiation by oncogenic BRAF renders thyroid cells susceptible to TGFß-induced EMT, through a MAPK-dependent process.

Sexually active adolescents and young adults: a high-risk group for Chlamydia trachomatis infection.

BACKGROUND: The importance of travel as a risk factor for Chlamydia trachomatis infection was evaluated among a series of young people consecutively tested. METHODS: We studied 130 sexually active young subjects, aged 14-25 years, all living in the Rome, Italy, urban area. Ninety-eight females and 32 males attended hospital-based clinics or were the partners of an infected female. About half of these subjects had traveled abroad either for pleasure or for work, mostly to Europe, but also to North America or to Asia, where they admitted to having had casual sex. We used two "gold standard" methods to diagnose infection with C. trachomatis: culture on McCoy cells grown in shell vial, and direct immunofluorescence with monoclonal antibodies. Subjects were considered infected when at least one test was positive. RESULTS: Thirty-nine of 130 (30%) subjects were asymptomatic, and 27/130 (20.8%) subjects were infected with Chlamydia trachomatis, of whom 6/25 (24%) asymptomatic females and 3/14 (21.4%) asymptomatic males were infected. Among teen-aged (ages 14-19) youngsters with more than one sex partner, international travel was an additional significant risk factor for C. trachomatis infection (p<.02; OR 20; 95% CI 1.47-40%). Urethritis/cystitis and vaginal pathology/discharge were the prevalent manifestations of illness among the females, while urethritis was the only clinical condition found in the males. CONCLUSION: In a series of young subjects, travel abroad, sex with more than one partner, and teen age, combined together, were significant risk factors for the acquisition of Chlamydia trachomatis genitourinary infection.

Time trends of consumption and costs of drugs in a cancer referral centre.

This study is a descriptive analysis of the consumption and the costs of antineoplastic chemotherapeutic agents and of the major groups of drugs used for supportive therapy during the 1990-1995 period, at the National Cancer Institute of Naples, Italy. Increasing consumption trends were observed for methotrexate, vinorelbine, oxazophorines (cyclophosphamide + ifosfamide), epirubicin, dacarbazine and 5-fluorouracil; stable trends for etoposide, mitomycin C, bleomycin, vincristine + vindesine, and platinum compounds (cisplatin + carboplatin); decreasing trends in procarbazine, nitrosoureas, mitozantrone and vinblastine consumption. Among BRM's, since 1992-1993, a decrease in consumption was observed both for immunomodulators and interferons; Cr-CSF consumption has increased during the last 3 years. Starting in 1992, among antiemetic drugs there was a decrease in alizapride and methoclopramide consumption contemporarily with the launch on the market of 5-HT3 antagonists; for the tatter drugs, a plateau seemed to have been reached in 1995. In 1992 the highest value of costs was reached (almost 2 billion Italian lire). Since 1993 the reduction in interferons and immunomodulator agents has paralleled the reduction in total costs, reaching about 1.5 billion in 1994. In 1995 the increasing consumption of G-CSF and taxol induced an increase in total costs. Reported data could reliably reflect the reality of Italian cancer referral centres; further reports from other European institutions could be beneficial to a more extensive debate.

Noninvasive monitoring of ovarian cancer: improved results using CT with intraperitoneal contrast combined with immunocytology.

The purpose of this study was to evaluate whether CT with intraperitoneal contrast (ipc/CT) in combination with immunocytochemical (ICC) tests could improve the diagnostic accuracy over conventional methods in the follow-up of ovarian carcinoma. Forty-five clinically disease-free ovarian cancer patients eligible for a second-look laparotomy were given an intraperitoneal infusion of positive contrast material followed by pelvic and abdominal CT. After the radiographic examination, the contrast fluid was collected by paracentesis and processed for morphological as well as for immunocytochemical analysis employing a panel of monoclonal antibodies identifying distinct ovarian tumor-associated antigens. While ipc/CT correctly detected the presence of peritoneal recurrences in 22 of 45 (49%) patients, the immunocytochemical tests demonstrated the presence of otherwise undiagnosed microscopic disease in an additional 8 patients (18%). Our results demonstrate that the combination of radiological and immunological methods may represent a more accurate, noninvasive means of monitoring ovarian cancer, thus reducing the need for a second-look laparotomy.

Chlamydia trachomatis in neonatal respiratory distress of very preterm babies: biphasic clinical picture.

We observed 12 very preterm infants (10 males) with a peculiar respiratory syndrome characterized by early onset soon after birth and by a biphasic course. The severe first phase was characterized by a clinical pattern mimicking the idiopathic respiratory distress syndrome of prematurity. Gradually, respiratory symptoms decreased and assisted ventilation with oxygen therapy was reduced. In the second phase, a significant worsening of respiratory signs and the appearance of apneic spells were observed. Chest X-ray showed hypoexpansion of the lungs and the prevalence of a fine reticular pattern. Chlamydia trachomatis was identified in this second phase in conjunctival and pharyngeal swabs and/or on tracheal aspirates. Our data suggest that in the very preterm infants, chlamydial infection shows different clinical and laboratory features if compared with Chlamydia trachomatis pneumonia of infants born at term.

Selected monoclonal antibodies can increase the accuracy of cytodiagnosis of neoplastic effusions of cryptic origin expanded in a short term culture.

The use of a selected panel of monoclonal antibodies (MoAb) to tumor associated antigens (TAA) in immunocytochemical (IIC) tests has been shown, in a preliminary study, to be a powerful diagnostic tool for the identification of the primary solid tumor causing metastatic effusion. Despite this improvement in a minority of neoplastic fluids a number of different causes may still determine false negative (FN) immunocytochemical diagnoses. The aim of the present study was to confirm the diagnostic accuracy of this panel of MoAb. This was done by analyzing in IIC tests a larger number of effusions and by evaluating whether the expansion in short term culture of those fluids with an uncertain malignant morphology could provide an adequate cellular substrate for immunocytodiagnosis. The analysis of 314 effusions confirmed the results of the pilot study and demonstrated that the combination of short term culture and immunocytochemical assays can further increase the sensitivity of this novel diagnostic procedure from 84.3% to 95.3%.

The use of a panel of monoclonal antibodies can lower false-negative diagnoses of peritoneal washings in ovarian tumors.

A correct surgical staging of ovarian carcinoma and the identification of persistent microscopic disease at second-look surgery largely rely on the cytologic examination of peritoneal washings (PW). Nevertheless, the morphologic analysis of these fluids frequently provides false-negative findings. As shown in other areas of cytodiagnosis, monoclonal antibodies (MoAb) to tumor-associated antigens may be a useful adjunct to overcome the limitations of conventional cytopathologic examination of PW. To evaluate this question, immunocytochemical tests were done using a panel of four MoAb to ovarian carcinoma-associated antigens (B72.3, MOv18, MOv19, and OC-125) to analyze 117 PW sampled during initial surgical staging and 121 PW harvested at second-look operations. The results of this study showed that immunocytochemical tests using the combination of the four reagents could improve cytodiagnosis more than 15% in both groups of PW. Thus a significant fraction of patients could be correctly staged and treated or become potentially curable by second-line salvage therapy.

The role of immunocytochemical assays in the diagnosis of stereotactic biopsies from intracranial tumors.

A selected panel of monoclonal antibodies (MoAbs) directed to distinct tumor associated antigens (TAA) has been tested to define the capability of these reagents to differentiate among metastatic carcinoma, lymphoma and primary brain tumor on cytologic specimens obtained with stereotactic techniques. Results obtained on 50 patients bearing either single or multiple brain lesions demonstrated that immunocytochemical (ICC) methods can distinguish between primary brain tumor and brain metastasis suggesting, in 90% of patients with cryptic primary neoplasia, the site of origin of the tumor.