Dieci, Maria Vittoria; Orvieto, Enrico; Dominici, Massimo; Conte, PierFranco; Guarneri, Valentina
Breast cancer encompasses a collection of different diseases characterized by different biological and pathological features, clinical presentation, response to treatments, clinical behavior, and outcome. On the basis of cell morphology, growth, and architecture patterns, breast cancer can be classified in up to 21 distinct histological types. Breast cancer special types, including the classic lobular invasive carcinoma, represent 25% of all breast cancers. The histological diversity of breast carcinomas has relevant prognostic implications. Indeed, the rare breast cancer group includes subtypes with very different prognoses, ranging from the tubular carcinoma, associated with an indolent clinical course, to metaplastic cancer, whose outcome is generally unfavorable. New approaches based on gene expression profiling allow the identification of molecularly defined breast cancer classes, with distinct biological features and clinical behavior. In clinical practice, immunohistochemical classification based on the expression of human epidermal growth factor receptor 2 and Ki67 is applied as a surrogate of the intrinsic molecular subtypes. However, the identification of intrinsic molecular subtypes were almost completely limited to the study of ductal invasive breast cancer. Moreover, some good-prognosis triple-negative histotypes, on the basis of gene expression profiling, can be classified among the poor-prognosis group. Therefore, histopathological classification remains a crucial component of breast cancer diagnosis. Special histologies can be very rare, and the majority of information on outcome and treatments derives from small series and case reports. As a consequence, clear recommendations about clinical management are still lacking. In this review, we summarize current knowledge about rare breast cancer histologies.
Boxer, Paul; Tisak, Marie S.; Goldstein, Sara E.
Research in aggressive behavior development has distinguished between proactive (i.e., intended to achieve an instrumental goal) and reactive (i.e., emitted as an emotional response to provocation) subtypes of aggression. A similar distinction has not been made with regard to prosocial behavior. In this study, subtypes of both aggressive and…
Merritt, Melissa A; Cramer, Daniel W; Vitonis, Allison F; Titus, Linda J; Terry, Kathryn L
Inconsistent results for the role of dairy food intake in relation to ovarian cancer risk may reflect the potential adverse effects of lactose, which has been hypothesized to increase gonadotropin levels, and the beneficial antiproliferative effects of calcium and vitamin D. Using data from the New England case-control study (1,909 cases and 1,989 controls), we examined dairy foods and nutrients in relation to risk of ovarian cancer overall, histological subtypes and rapidly fatal versus less aggressive disease. We used logistic regression and polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). In models that were simultaneously adjusted for total (dietary plus supplements) calcium, total vitamin D and lactose, we observed a decreased overall risk of ovarian cancer with high intake of total calcium [Quartile 4 (Q4, >1,319 mg/day) vs. Quartile 1 (Q1, <655 mg/day), OR = 0.62, 95% CI = 0.49-0.79]; the inverse association was strongest for serous borderline and mucinous tumors. High intake of total vitamin D was not associated overall with ovarian cancer risk, but was inversely associated with risk of serous borderline (Q4, >559 IU/day vs. Q1, <164 IU/day, OR = 0.51, 95% CI = 0.34-0.76) and endometrioid tumors (Q4 vs. Q1, OR = 0.55, 95% CI = 0.39-0.80). We found no evidence that lactose intake influenced ovarian cancer risk or that risk varied by tumor aggressiveness in the analyses of intake of dairy foods and nutrients. The overall inverse association with high intake of calcium and the inverse associations of calcium and vitamin D with specific histological subtypes warrant further investigation.
McCullough, Marjorie L.; Franceschi, Silvia; Rinaldi, Sabina; Wolk, Alicja; Neta, Gila; Olov Adami, Hans; Anderson, Kristin; Andreotti, Gabriella; Beane Freeman, Laura E.; Bernstein, Leslie; Buring, Julie E.; Clavel-Chapelon, Francoise; De Roo, Lisa A.; Gao, Yu-Tang; Gaziano, J. Michael; Giles, Graham G.; Håkansson, Niclas; Horn-Ross, Pamela L.; Kirsh, Vicki A.; Linet, Martha S.; MacInnis, Robert J.; Orsini, Nicola; Park, Yikyung; Patel, Alpa V.; Purdue, Mark P.; Riboli, Elio; Robien, Kimberly; Rohan, Thomas; Sandler, Dale P.; Schairer, Catherine; Schneider, Arthur B.; Sesso, Howard D.; Shu, Xiao-Ou; Singh, Pramil N.; van den Brandt, Piet A.; Ward, Elizabeth; Weiderpass, Elisabete; White, Emily; Xiang, Yong-Bing; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Hartge, Patricia; Berrington de González, Amy
Background: Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality. Methods: This large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women) investigated thyroid cancer incidence associated with greater height, BMI at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models. Associations with thyroid cancer mortality were investigated in a subset of cohorts (578,922 men and 774,373 women) that contributed cause of death information. Results: During follow-up, 2996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric factors were positively associated with thyroid cancer incidence: hazard ratios (HR) [confidence intervals (CIs)] for height (per 5 cm) = 1.07 [1.04–1.10], BMI (per 5 kg/m2) = 1.06 [1.02–1.10], waist circumference (per 5 cm) = 1.03 [1.01–1.05], young-adult BMI (per 5 kg/m2) = 1.13 [1.02–1.25], and adulthood BMI gain (per 5 kg/m2) = 1.07 [1.00–1.15]. Associations for baseline BMI and waist circumference were attenuated after mutual adjustment. Baseline BMI was more strongly associated with risk in men compared with women (p = 0.04). Positive associations were observed for papillary, follicular, and anaplastic, but not medullary, thyroid carcinomas. Similar, but stronger, associations were observed for thyroid cancer mortality. Conclusion: The results suggest that greater height and excess adiposity throughout adulthood are associated with higher incidence of most major types of thyroid cancer, including the least common but
Cuellar-Partida, Gabriel; Lu, Yi; Dixon, Suzanne C; Fasching, Peter A; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan; Doherty, Jennifer Anne; Rossing, Mary Anne; Chang-Claude, Jenny; Rudolph, Anja; Wang-Gohrke, Shan; Goodman, Marc T; Bogdanova, Natalia; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B; Antonenkova, Natalia; Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M; Edwards, Robert P; Kelley, Joseph L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Cannioto, Rikki; Høgdall, Estrid; Høgdall, Claus; Jensen, Allan; Giles, Graham G; Bruinsma, Fiona; Kjaer, Susanne K; Hildebrandt, Michelle A T; Liang, Dong; Lu, Karen H; Wu, Xifeng; Bisogna, Maria; Dao, Fanny; Levine, Douglas A; Cramer, Daniel W; Terry, Kathryn L; Tworoger, Shelley S; Stampfer, Meir; Missmer, Stacey; Bjorge, Line; Salvesen, Helga B; Kopperud, Reidun K; Bischof, Katharina; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Brooks-Wilson, Angela; Olson, Sara H; McGuire, Valerie; Rothstein, Joseph H; Sieh, Weiva; Whittemore, Alice S; Cook, Linda S; Le, Nhu D; Blake Gilks, C; Gronwald, Jacek; Jakubowska, Anna; Lubiński, Jan; Kluz, Tomasz; Song, Honglin; Tyrer, Jonathan P; Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton; Lissowska, Jolanta; McLaughlin, John R; Narod, Steven A; Phelan, Catherine; Anton-Culver, Hoda; Ziogas, Argyrios; Eccles, Diana; Campbell, Ian; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J; Wu, Anna H; Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Timorek, Agnieszka; Szafron, Lukasz; Cunningham, Julie M; Fridley, Brooke L; Winham, Stacey J; Bandera, Elisa V; Poole, Elizabeth M; Morgan, Terry K; Goode, Ellen L; Schildkraut, Joellen M; Pearce, Celeste L; Berchuck, Andrew; Pharoah, Paul D P; Webb, Penelope M; Chenevix-Trench, Georgia; Risch, Harvey A; MacGregor, Stuart
Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ([Formula: see text] = 8.8 ± 1.1 %), endometrioid ([Formula: see text] = 3.2 ± 1.6 %), clear cell ([Formula: see text] = 6.7 ± 3.3 %) and all EOC ([Formula: see text] = 5.6 ± 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach.
Yeh, Michelle T.; Coccaro, Emil F.; Jacobson, Kristen C.
This study examined the genetic and environmental architecture underlying aggressive behavior measured by the Life History of Aggression Questionnaire (LHA; Coccaro et al. 1997a). Following preliminary phenotypic factor analysis procedures, multivariate behavioral genetics models were fit to responses from 2,925 adult twins from the PennTwins cohort on five LHA items assessing lifetime frequency of temper tantrums, indirect aggression, verbal aggression, fighting, and physical assault. The best-fitting model was a 2-factor common pathway model, indicating that these five aggressive behaviors are underpinned by two distinct etiological factors with different genetic and nonshared environmental influences. Although there was evidence of significant sex differences, the structure of the two factors appeared to be quite similar in males and females, where General Aggression and Physical Aggression factors emerged. Heritability of these factors ranged from .37 to .57, and nonshared environmental effects ranged from .43 to .63. The results of this study highlight the heterogeneous nature of the aggression construct and the need to consider differences in genetic and environmental influences on individual aggressive behaviors in a multivariate context. PMID:20432061
Yu, Mandi; Feuer, Eric J.; Cronin, Kathleen A.; Caporaso, Neil E.
Background Over the past several decades, advances in lung cancer research and practice have led to refinements of histological diagnosis of lung cancer. The differential use and subsequent alterations of non-specific morphology codes, however, may have caused artifactual fluctuations in the incidence rates for histologic subtypes, thus biasing temporal trends. Methods We developed a multiple imputation (MI) method to correct lung cancer incidence for non-specific histology using data from the Surveillance, Epidemiology, and End Results (SEER) Program during 1975–2010. Results For adenocarcinoma in men and squamous in both genders, the change to a increasing trend around 2005, after more than ten years of decreasing incidence, is apparently an artifact of the changes in histopathology practice and coding system. After imputation, the rates remained decreasing for adenocarcinoma and squamous in men, and became constant for squamous in women. Conclusions As molecular features of distinct histologies are increasingly identified by new technologies, accurate histological distinctions are becoming increasingly relevant to more effective 'targeted' therapies, and therefore, are important to track in patients. However, without incorporating the coding changes, the incidence trends estimated for histologic subtypes could be misleading. Impact The MI approach provides a valuable tool for bridging the different histology definitions, thus permitting meaningful inferences about the long-term trends of lung cancer by histological subtype. PMID:24855099
Pederson, Casey A; Fite, Paula J
The current study evaluated parenting behaviors (i.e., parental monitoring, inconsistent discipline, parental involvement, positive parenting, and corporal punishment) as moderators of the link between proactive and reactive aggression and oppositional defiant disorder (ODD) symptoms in a community sample of 89 children ranging from 9 to 12 years of age (M = 10.44, SD = 1.14; 56 % male). Reactive, but not proactive, aggression was uniquely positively associated with ODD symptoms. Additionally, inconsistent discipline moderated the association between proactive, but not reactive, aggression and ODD symptoms, such that proactive aggression was associated with ODD symptoms only when levels of inconsistent discipline were high. Findings appear to suggest that associations between these aggression subtypes and ODD symptoms are influenced by different factors, with inconsistent discipline indicated in the association between proactively aggressive behavior and ODD symptoms. Implications for intervention are discussed.
Hodgkin's disease (HD) incidence in whites is described by age, sex, Rye histologic subtype and time period for ten US locations, using recently available data with Rye histologic diagnoses for most cases. Some distinctive features of incidence in young persons - stable childhood rates, and high and increasing rates in young adults, particularly women - resulted from the elevated rates of the Nodular Sclerosis (NS) subtype. NS was the only histologic form with a rising incidence. Unexpectedly, among middle-aged and older persons rates of all subtypes declined during the 1970s. HD incidence varied little across study regions and became more geographically homogeneous with time, notably among women. HD rates were positively correlated with regional socio-economic levels. In areas with the highest young adult incidence, higher risk also affected a broader age range, including older children. Rates for young adults were positively associated with community socioeconomic status but did not covary with older adult rates. Rates for the NS and Lymphocyte Predominance subtypes were inversely correlated across areas. NS incidence increased with community economic levels. These features suggest the incidence of HD in a well-developed country is not static but evolves, characterized by higher rates of NS in an increasingly broad age range of young, particularly female, adults, rising with small increments in socioeconomic status, and occurring over the relatively short study interval. 27 figures, 50 tables.
Harir, Noria; Tou, Abdenacer; Medjamia, Miloud; Guenaoui, Khaira
Background Primary gastrointestinal (GI) lymphomas (GIL) are uncommon diseases that can involve the whole GI tract. Considerable variation exists in the literature with respect to incidence of the various histological subtypes and sites of involvement. This study was undertaken to establish the anatomic distribution, histological subtypes and sites of GI lymphomas of patients from Western Algeria. Methods The case records of 58 consecutive patients with GIL diagnosed at the Pathologies Departments of Algerian west region (the Military Hospital of Oran city and the Central University Hospital of Sidi Bel Abbes city) from January 2006 to December 2013 were retrospectively evaluated for epidemiology and histopathology report. All lymphomas were reclassified according to the WHO 2008 classification. Results A total of 58 patients (39 male, 19 female) with mean age of 61 years and a range of 20–89 years were included in this study. Stomach was the most common site involved (70.7%). The commonest histological subtype was mucosa-associated lymphoid tissue (MALT) B cell lymphoma (46.6%), followed by diffuse large B-cell lymphomas (DLBCL) (43.1%).The frequency of Helicobacter pylori (HP) positivity differ between gastric and intestinal location P=0.003 and correlates with the histological type P=0.01. Conclusions This retrospective study of patients with GI lymphoma from Western Algeria illustrates the pattern of distribution of various common and rare histological subtypes. More studies are necessary to find a potential cause, risk factor or genetic mutation that can explain these specific characteristics of GIL. PMID:28078126
Sugimoto, Kazutaka; Ideguchi, Makoto; Kimura, Tokuhiro; Kajiwara, Koji; Imoto, Hirochika; Sadahiro, Hirokazu; Ishii, Aya; Kawano, Hiroo; Ikeda, Eiji; Suzuki, Michiyasu
Epithelioid glioblastoma (GBM) and rhabdoid GBM are rare variants that are morphologically similar, but there is no consensus on the characteristics of each disease. These tumors have aggressive features of early recurrence and leptomeningeal dissemination and tend to develop in younger patients compared to typical GBM. The prognosis is normally worse than typical GBM, even with intensive chemoradiotherapy after surgical resection. Thus, accurate diagnosis and effective therapy for epithelioid/rhabdoid GBM are required. Four consecutive patients aged 16-48 years were diagnosed with epithelioid/rhabdoid GBM by pathological and immunohistochemical analysis at Yamaguchi University Hospital from 2006 to 2012. Two of these patients had relatively long-term survival (19 and 23 months after diagnosis). Two cases had a BRAF V600E mutation, whereas no ATRX mutation was present in any cases. All patients suffered leptomeningeal and/or spinal dissemination that worsened their prognosis. These results illustrate the need for a new therapeutic approach, such as molecular targeted drug therapy like BRAF inhibition, in addition to standard chemoradiotherapy for typical GBM.
Nemec, A; Murphy, B; Kass, P H; Verstraete, F J M
Several histological subtypes and grades of oral squamous cell carcinoma (SCC) are described in human literature and these subtypes have distinct morphological features and biological behaviour. This retrospective study (1990-2010) included 84 dogs diagnosed with SCC of the oral cavity and oropharynx, excluding the tonsils. Sixty-nine of the SCCs (82.1%) were further diagnosed as conventional SCC (CSCC) (33 [47.8%] well-differentiated, 31 [44.9%] moderately-differentiated and five [7.3%] poorly-differentiated), five (5.95%) each as papillary SCC and basaloid SCC, three (3.6%) as adenosquamous carcinoma and two (2.4%) as spindle cell carcinoma. Compared with the general hospital population, neutered female dogs, dogs aged 10 to <15 years, English springer spaniels and Shetland sheepdogs were overrepresented. The majority (78.1%) of SCCs were proliferative with or without associated ulceration, although no significant association was observed between the gross appearance and different SCC subtypes. 71.4% of SCCs were located in dentate jaws; however, well-differentiated CSCC more often affected the tongue and other non-dentate mucosal surfaces (P=0.0022). No significant association was found between any of the SCC subtypes and tumour-associated inflammation (TAI), perineural and lymphovascular invasion (PNI, LVI), or between gross appearance of the tumour and tumour location, PNI, LVI or TAI or PNI, LVI, TAI and tumour location.
Masugi-Tokita, Miwako; Flor, Peter J; Kawata, Mitsuhiro
Metabotropic glutamate receptor subtype 7 (mGluR7) is a member of group III mGluRs, which localize to the presynaptic active zones of the mammalian central nervous system. Although histological, genetic, and electrophysiological studies ensure the importance of mGluR7, its roles in behavior and physiology remain largely unknown. Using a resident–intruder paradigm, we found a severe reduction in intermale aggressive behavior in mGluR7 knockout (KO) mice. We also found alterations in other social behaviors in male mGluR7 KO mice, including sexual behavior toward male intruders. Because olfaction is critical for rodent social behavior, including aggression, we performed an olfaction test, finding that mGluR7 KO mice failed to show interest in the smell of male urine. To clarify the olfactory deficit, we then exposed mice to urine and analyzed c-Fos-immunoreactivity, discovering a remarkable reduction in neural activity in the bed nucleus of the stria terminalis (BNST) of mGluR7 KO mice. Finally, intra-BNST administration of the mGluR7-selective antagonist 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP) also reproduced the phenotype of mGluR7 KO mice, including reduced aggression and altered social interaction. Thus mGluR7 may work as an ‘enhancer of neural activity' in the BNST and is important for intermale aggression. Our findings demonstrate that mGluR7 is essential for social behavior and innate behavior. Our study on mGluR7 in the BNST will shed light on future therapies for emotional disorders in humans. PMID:26149357
Miao, Yingying; Zhang, Jianya; Zou, Jiawei; Zhu, Qingqing
Background Uncertainty remains on the association between image characteristics of the nodules in computed tomography (CT) scans and lung adenocarcinoma histopathologic subtypes. We aimed to estimate the correlation between preoperative high resolution computed tomography (HRCT) scan and postoperative histopathology of stage IA lung adenocarcinoma in East Asian Chinese population. Methods We retrospectively reviewed the clinical records and HRCT images of 190 patients (106 female and 84 male) with resected, preoperatively untreated stage IA adenocarcinomas. The relationship between image characteristics of nodules at preoperative HRCT and their histological subtypes after resection were analyzed. The one-way ANOVA, chi-square test and logistic regression were used for analysis. Results In 190 patients with stage IA lung adenocarcinoma, median tumor diameter was significantly lower in lepidic predominant invasive adenocarcinoma (LPA) (15.96±6.95 mm). Univariate analysis revealed that ground-glass opacity (GGO) proportion (P<0.001), margin (P<0.001), border definition (P=0.015), pleural retraction (P<0.001) and enhancement (P<0.001) had statistically significant differences in four histological subtypes. The multivariate analysis referenced for lepidic group which indicated that GGO proportion and pleural retraction were independent associated with acinar group (RR=4.221, 95% CI: 1.770–10.066, P=0.001; RR=0.380, 95% CI: 0.158–0.916, P=0.031, respectively). Male and whose nodule margin with spiculation or lobulation were prone to papillary predominant invasive adenocarcinoma (PPA) (RR=0.288, 95% CI: 0.090–0.920, P=0.036; RR=0.250, 95% CI: 0.070–0.887, P=0.032, respectively). GGO proportion and nodule margin were independent related factors in solid predominant invasive adenocarcinoma (SPA) (RR=13.338, 95% CI: 2.974–59.811, P=0.001; RR=0.097, 95% CI: 0.016–0.606, P=0.013, respectively). Conclusions Nodules with spiculation or lobulation and less GGO
Mencoboni, Manlio; Grosso, Federica; Ceresoli, Giovanni Luca; Lunardi, Francesca; Vuljan, Stefania Edith; Bertorelle, Roberta; Sacchetto, Valeria; Ciminale, Vincenzo; Rea, Federico; Favaretto, Adolfo; Conte, PierFranco; Calabrese, Fiorella
Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and limited treatment options. Sarcomatoid/biphasic mesotheliomas are characterized by more aggressive behaviour and a poorer prognosis compared with the epithelioid subtype. To date prognostic and tailored therapeutic biomarkers are lacking. The present study analyzed the expression levels of MDM2 and HIF1alpha in different histologic subtypes from chemonaive MPM patients. Diagnostic biopsies of MPM patients from four Italian cancer centers were centrally collected and analyzed. MDM2 and HIF1alpha expression levels were investigated through immunohistochemistry and RT-qPCR. Pathological assessment of necrosis, inflammation and proliferation index was also performed. Molecular markers, pathological features and clinical characteristics were correlated to overall survival (OS) and progression free survival (PFS). Sixty MPM patients were included in the study (32 epithelioid and 28 non-epithelioid). Higher levels of MDM2 (p < 0.001), HIF1alpha (p = 0.013), necrosis (p = 0.013) and proliferation index (p < 0.001) were seen mainly in sarcomatoid/biphasic subtypes. Higher levels of inflammation were significantly associated with epithelioid subtype (p = 0.044). MDM2 expression levels were correlated with HIF1alpha levels (p = 0.0001), necrosis (p = 0.008) and proliferation index (p = 0.009). Univariate analysis showed a significant correlation of non-epithelioid histology (p = 0.04), high levels of necrosis (p = 0.037) and proliferation index (p = 0.0002) with shorter PFS. Sarcomatoid/biphasic and epithelioid mesotheliomas showed different MDM2 and HIF1alpha expression levels and were characterized by different levels of necrosis, proliferation and inflammation. Further studies are warranted to confirm a prognostic and predictive role of such markers and features. PMID:26544728
Larrayoz, Marta; Pio, Ruben; Pajares, María J; Zudaire, Isabel; Ajona, Daniel; Casanovas, Oriol; Montuenga, Luis M; Agorreta, Jackeline
The vascular endothelial growth factor (VEGF) pathway is a clinically validated antiangiogenic target for non-small cell lung cancer (NSCLC). However, some contradictory results have been reported on the biological effects of antiangiogenic drugs. In order to evaluate the efficacy of these drugs in NSCLC histological subtypes, we analyzed the anticancer effect of two anti-VEGFR2 therapies (sunitinib and DC101) in chemically induced mouse models and tumorgrafts of lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Antiangiogenic treatments induced vascular trimming in both histological subtypes. In ADC tumors, vascular trimming was accompanied by tumor stabilization. In contrast, in SCC tumors, antiangiogenic therapy was associated with disease progression and induction of tumor proliferation. Moreover, in SCC, anti-VEGFR2 therapies increased the expression of stem cell markers such as aldehyde dehydrogenase 1A1, CD133, and CD15, independently of intratumoral hypoxia. In vitro studies with ADC cell lines revealed that antiangiogenic treatments reduced pAKT and pERK signaling and inhibited proliferation, while in SCC-derived cell lines the same treatments increased pAKT and pERK, and induced survival. In conclusion, this study evaluates for the first time the effect of antiangiogenic drugs in lung SCC murine models in vivo and sheds light on the contradictory results of antiangiogenic therapies in NSCLC. PMID:24500694
Hu, Hui-Di; Wan, Ming-Yue; Xu, Chun-Hua; Zhan, Ping; Zou, Jue; Zhang, Qian-Qian
Objective To explore the histological subtypes of solitary pulmonary nodules (SPNs) of invasive adenocarcinoma and their clinical relevance. Methods A total of 188 patients with pathologically confirmed invasive adenocarcinoma in our hospital from January 2007 to December 2011 were enrolled in this study. In accordance with the new classification of lung adenocarcinoma, all the histological sections were reviewed and classified, and the clinical data were collected and analyzed. Results Of these 188 patients who had been initially diagnosed as SPNs of adenocarcinoma, there were 6 cases of lepidic predominant adenocarcinoma (LPA), 71 cases of acinar predominant adenocarcinoma (APA), 74 cases of papillary predominant adenocarcinoma (PPA), 15 cases of micorpapillary predominant adenocarcinoma (MPA), and 22 cases of solid predominant adenocarcinoma (SPA) with mucin production. The incidence of lymph node metastasis was 80.0% and 81.8% in MPA and SPA, respectively, which was significantly higher than those in LPA, APA, and PPA (all P<0.01). The incidence of LPA was 83.3% (5/6) in women, which was significantly higher than that in men (P=0.037). Conclusions According to the new classification, MPA and SPA have high incidence of lymph node metastasis. LPA is more likely to occur in women. Sub-typing of the lung adenocarcinoma based on the newest international classification criteria is helpful to identify the clinical features of this disease. PMID:24409363
Ostrov, Jamie M; Kamper, Kimberly E; Hart, Emily J; Godleski, Stephanie A; Blakely-McClure, Sarah J
A short-term longitudinal study during early childhood (N = 301; 155 girls; M = 44.76 months old, SD = 8.20) investigated the prospective associations between peer victimization and aggression subtypes. Specifically, observations of relational and physical victimization as well as teacher reports of the forms (i.e., relational and physical) and functions (i.e., proactive and reactive) of aggression were collected at two time points during an academic year. Within- and between-group gender differences were examined as part of the preliminary analyses. In order to address key study questions, both directions of effect between peer victimization and aggression subtypes were examined. We found that teacher-reported proactive relational aggression predicted decreases in observed relational victimization over time, whereas reactive relational aggression predicted increases in observed relational victimization over time. Ways in which these and other findings extend the literature are discussed.
Roncati, Luca; Pusiol, Teresa; Piscioli, Francesco
Today, the scientific community is focusing on the prognostic significance of different histological subtypes of thin melanoma (1). The current staging system for melanoma of the American Joint Committee on Cancer (AJCC) uses Breslow thickness as the primary attribute: melanomas with up to 1 mm thickness is defined as thin, because they present a good prognosis after surgical excision, with a 10-year survival rate of 85-90% in case of a tumor-free margin ≥1 cm (2). There is a significant interaction between mitotic rate and Breslow depth, so the predictive value of the mitotic rate on sentinel lymph node (SLN) positivity can be dependent on Breslow thickness (3). Cutaneous melanoma generally evolves through three clearly discernible progression stages. At first, transformed melanocytes proliferate above the epidermal basement membrane (the in situ or epidermal radial growth phase); they then invade the papillary dermis (the micro-invasive radial growth phase); and subsequently acquire the capacity to grow as a well-known malignant tumor (the invasive vertical growth phase). More specifically, micro-invasive melanoma is a non-tumorigenic radial growth phase of cutaneous melanoma, which invades the superficial dermis without forming a tumor nodule or papule, in absence of regression (3). In contrast, the micro-invasive radial growth phase of cutaneous melanoma with regression will rarely metastasize and, for this reason, the lesion should be recognized and could also be categorized as a 'micro-invasive radial growth phase of uncertain tumorigenic potential' (4). The early vertical growth phase of tumorigenic melanoma is characterized by the presence of a cell cluster in the dermis that is larger than the largest cluster in the epidermis (5). This feature is typical of tumorigenicity, while the mitogenicity is documented by the observation of mitotic figures in dermal melanoma cells (5,6). The early vertical growth phase and the radial growth phase with regression
Ovarian cancer is one of the most common and most lethal cancers. For Bulgaria (2012) it occupies third place in the structure of gynecological malignancies with a share of 22.6 percent, while regarding mortality is at first place with 35.7 percent. New cases are 838 with crude incidence 22.3 x 10(5), and the deaths are 463 with crude mortality 12.3 x 10(5). Ovarian tumors, even when they are of the same histological type clearly differ in their cellular differentiation, molecular characteristiques and subsequently in their biological behavior. In this review, we discuss the frequency origin, morphology and molecular characteristiques of the five major subtypes of ovarian cancer--serous low and high grade, mucinous, endometroid and and clear cell. The role of different risk and prognostic factors for the efficiency of the treatment and control of disease been discussed.
Troche, Jose Ramon; Mayne, Susan T; Freedman, Neal D; Shebl, Fatma M; Abnet, Christian C
Alcohol is a carcinogen suspected of increasing lung cancer risk. Therefore, we prospectively evaluated the relationship between alcohol consumption and lung carcinoma in 492,902 persons from the National Institutes of Health-AARP Diet and Health Study. We used Cox models to calculate hazard ratios and 95% confidence intervals, adjusting for tobacco smoking and other potential confounders. Between 1995/1996 and December 31, 2006, there were 10,227 incident cases of lung carcinoma, classified as adenocarcinoma (n = 4,036), squamous cell carcinoma (n = 1,998), small cell carcinoma (n = 1,524), undifferentiated carcinoma (n = 559), and other (n = 2,110). Compared with nondrinking, alcohol consumption was associated with a modest nonlinear reduction in total lung carcinoma risk at lower levels of consumption (for 0.5-<1 drink/day, HR = 0.89, 95% confidence interval: 0.82, 0.96) but a modest increase in risk in the highest category (for ≥7 drinks/day, HR = 1.11, 95% confidence interval: 1.00, 1.24). Regarding histological type, alcohol was associated with a nonlinear reduction in squamous cell carcinoma that became attenuated as consumption increased and a modest increase in adenocarcinoma among heavier drinkers. Cubic spline models confirmed these findings. Our data suggest that the relationship between alcohol consumption and lung carcinoma differs by histological subtype.
Hyde, Luke W.; Burt, S. Alexandra; Shaw, Daniel S.; Donnellan, M. Brent; Forbes, Erika E.
Antisocial behavior (AB) in adolescence predicts problematic outcomes in adulthood. However, researchers have noted marked heterogeneity within the broad group of youth engaging in these destructive behaviors and have attempted to identify those with distinct etiologies and different trajectories of symptoms. In the present study, we evaluate three prominent AB subtyping approaches: age of onset, presence of callous-unemotional (CU) traits, and aggressive versus rule breaking symptoms. We examined the overlap of these subtypes and their predictive validity in a diverse sample of 268 low-income young men followed prospectively from adolescence into emerging adulthood. We found that those with early starting AB were uniquely high on aggressive symptoms but not on CU traits. Early starting AB and both aggression and rule breaking measured during adolescence predicted most subsequent psychiatric and AB outcomes in early adulthood in univariate models, whereas CU traits were only predictive of adolescent arrests, later substance dependence diagnosis, and later CU traits. Finally, after accounting for shared variance among predictor variables, we found that aggressive symptoms explained the most unique variance in predicting several later outcomes (e.g., antisocial personality disorder) over and above other subtyping approaches. Results are discussed in relation to of the utility of existing subtyping approaches to AB, noting that aggression and age of onset, but not CU traits, appear to be the best at predicting later negative outcome. PMID:25603360
Shi, Bing; Xie, Hongling
Using peer nominations of physical aggression and perceived popularity in the spring semester of fifth grade, we identified 54 popular aggressive and 42 nonpopular aggressive preadolescents in a diverse sample of 318 participants recruited from an urban school district. Physical aggression in the spring semester of sixth grade was included to…
Vitacco, Michael J; Van Rybroek, Gregory J; Rogstad, Jill E; Yahr, Laura E; Tomony, James D; Saewert, Emily
Accurately predicting inpatient aggression is an important endeavor. The current study investigated inpatient aggression over a six-month time period in a sample of 152 male forensic patients. We assessed constructs of psychopathy, anger, and active symptoms of mental illness and tested their ability to predict reactive and instrumental aggression. Across all levels of analyses, anger and active symptoms of mental illness predicted reactive aggression. Traits of psychopathy, which demonstrated no relationship to reactive aggression, were a robust predictor of instrumental aggression. This study (a) reestablishes psychopathy as a clinically useful construct in predicting inpatient instrumental aggression, (b) provides some validation for the reactive/instrumental aggression paradigm in forensic inpatients, and (c) makes recommendations for integrating risk assessment results into treatment interventions.
Strowd, Roy E.; Rodriguez, Fausto J.; McLendon, Roger E.; Vredenburgh, James J.; Chance, Aaron B.; Jallo, George; Olivi, Alessandro; Ahn, Edward S.; Blakeley, Jaishri O.
Although optic pathway gliomas are the most common brain tumors associated with neurofibromatosis type 1 (NF1), extra-optic gliomas occur and may behave more aggressively with outcomes that differ by age. A retrospective case-control study was designed to describe the clinical course of adult NF1 patients with progressive extra-optic pilocytic astrocytomas (PAs) and compare to a pediatric cohort. Data for patients treated at the Johns Hopkins Comprehensive Neurofibromatosis Center from 2003 to 2013 were reviewed to identify cases (adults, age >18) and controls (pediatric, age <18) with clinically or radiographically progressive extra-optic PAs. Demographic, clinical, histologic, and radiographic data were collected. Three adult NF1 cases and four pediatric NF1 controls were identified. Mean age was 32.3 ± 9.5 years, 66% male (cases); 12.8±4.2 years, 100% male (controls). Symptomatic progression occurred in two-of-three adults (67%) while the majority of pediatric patients presented with isolated radiographic progression (n=3, 75%). Onset tended to be more rapid in adults (4±1 vs. 14±8.3 months, P=0.10). Subtotal resection was the treatment for all pediatric patients. Radiotherapy (n=2), chemotherapy (n=2), and targeted, biologic agents (n=2) were administered in adults. Although all pediatric patients are living, outcomes were universally poor in adults with progression to death in all (median survival 17.1 months, range 6.6–30.3). In conclusion, despite grade I histology, all three adult NF1 patients with progressive extra-optic PAs suffered an aggressive clinical course which was not seen in pediatric patients. Clinicians should be aware of this clinico-histologic discrepancy when counseling and managing adult NF1 patients with progressive extra-optic PAs. PMID:26992069
Strowd, Roy E; Rodriguez, Fausto J; McLendon, Roger E; Vredenburgh, James J; Chance, Aaron B; Jallo, George; Olivi, Alessandro; Ahn, Edward S; Blakeley, Jaishri O
Although optic pathway gliomas are the most common brain tumors associated with neurofibromatosis type 1 (NF1), extra-optic gliomas occur and may behave more aggressively with outcomes that differ by age. A retrospective case-control study was designed to describe the clinical course of adult NF1 patients with progressive extra-optic pilocytic astrocytomas (PAs) and compare to a pediatric cohort. Data for patients treated at the Johns Hopkins Comprehensive Neurofibromatosis Center from 2003 to 2013 were reviewed to identify cases (adults, age >18) and controls (pediatric, age <18) with clinically or radiographically progressive extra-optic PAs. Demographic, clinical, histologic, and radiographic data were collected. Three adult NF1 cases and four pediatric NF1 controls were identified. Mean age was 32.3 ± 9.5 years, 66% male (cases); 12.8 ± 4.2 years, 100% male (controls). Symptomatic progression occurred in two-of-three adults (67%) while the majority of pediatric patients presented with isolated radiographic progression (n = 3, 75%). Onset tended to be more rapid in adults (4 ± 1 vs. 14 ± 8.3 months, P = 0.10). Subtotal resection was the treatment for all pediatric patients. Radiotherapy (n = 2), chemotherapy (n = 2), and targeted, biologic agents (n = 2) were administered in adults. Although all pediatric patients are living, outcomes were universally poor in adults with progression to death in all (median survival 17.1 months, range 6.6-30.3). In conclusion, despite grade I histology, all three adult NF1 patients with progressive extra-optic PAs suffered an aggressive clinical course which was not seen in pediatric patients. Clinicians should be aware of this clinico-histologic discrepancy when counseling and managing adult NF1 patients with progressive extra-optic PAs. © 2016 Wiley Periodicals, Inc.
Aarestrup, J; Gamborg, M; Ulrich, L G; Sørensen, T I A; Baker, J L
Background: Endometrial cancer risk factors include adult obesity and taller stature, but the influence of size earlier in life is incompletely understood. We examined whether childhood body mass index (BMI; kg m−2) and height were associated with histologic subtypes of endometrial cancer. Methods: From the Copenhagen School Health Records Register, 155 505 girls born 1930–1989 with measured weights and heights from 7 to 13 years were linked to health registers. BMI and height were transformed to age-specific z-scores. Hazard ratios (HRs) and 95% confidence intervals were estimated by Cox regressions. Results: A total of 1020 endometrial cancers were recorded. BMI was non-linearly associated with all endometrial cancers, oestrogen-dependent cancers and the subtype of endometrioid adenocarcinomas; associations were statistically significant and positive above a z-score=0 and non-significant below zero. Compared with a 7-year-old girl with a BMI z-score=0, an equally tall girl who was 3.6 kg heavier (BMI z-score=1.5) had a hazard ratio=1.53 (95% confidence interval: 1.29–1.82) for endometrioid adenocarcinoma. BMI was not associated with non-oestrogen-dependent cancers, except at the oldest childhood ages. Height at all ages was statistically significant and positively associated with all endometrial cancers, except non-oestrogen-dependent cancers. At 7 years, per ~5.2 cm (1 z-score), the risk of endometrioid adenocarcinoma was 1.18 (95% confidence interval: 1.09–1.28). Among non-users of unopposed oestrogens, associations between BMI and endometrioid adenocarcinoma strengthened, but no effects on height associations were observed. Conclusions: Endometrial carcinogenesis is linked to early-life body size, suggesting that childhood BMI and height may be useful indicators for the risk of later development of endometrial cancer and might aid in the early prevention of obesity-related endometrial cancers. PMID:27121254
Han, Baohui; Zhang, Jie; Zhao, Heng; Fang, Wentao; Luo, Qingquan; Yang, Jun; Yang, Yunhai; Zhu, Lei; Chen, Tianxiang; Cheng, Xinghua; Huang, Qingyuan; Wang, Yiyang; Zheng, Jiajie; Chen, Haiquan
Introduction This study investigated the correlation between histologic predominant pattern and postrecurrence survival (PRS), and identified the clinicopathologic factors influencing PRS in patients with completely resected stage I lung adenocarcinoma. Methods A total of 136 stage I lung adenocarcinoma patients who experienced tumor recurrence after completely resection were included in this study. To analysis the association between histologic predominant pattern and PRS, invasive adenocarcinomas with mixed histologic components were divided into 2 groups: solid and nonsolid group (including lepidic, acinar, papillary, micropapillary) based on the histologic predominant pattern. PRS was analyzed to identify the prognostic predictors using the Kaplan-Meier approach and multivariable Cox models. Results For all stage I invasive adenocarcinoma patients, the majority of postsurgical recurrences occurred within 2 years. Patients with solid predominant histological pattern were associated with unfavorable PRS (HR, 2.40; 95%CI 1.13-5.08, p=.022). There was a significant difference for poor PRS for patients who diagnosed tumor recurrence shorter than 12 months after surgery (HR, 2.34; 95%CI 1.12-4.90, p=.024). Extrathoracic metastasis was associated with poor media PRS in univariable analysis (p =.011), however, there was no significant PRS difference in multivariable analysis (HR, 1.56; 95%CI 0.65-3.73, p=.322) compared with intrathoracic metastasis. Conclusions Solid predominant histologic subtype and recurrence free interval less than 12 months predict worse PRS in patients with stage I lung adenocarcinoma. PMID:27732964
Chen, Ying-Bei; Xu, Jianing; Skanderup, Anders Jacobsen; Dong, Yiyu; Brannon, A. Rose; Wang, Lu; Won, Helen H.; Wang, Patricia I.; Nanjangud, Gouri J.; Jungbluth, Achim A.; Li, Wei; Ojeda, Virginia; Hakimi, A. Ari; Voss, Martin H.; Schultz, Nikolaus; Motzer, Robert J.; Russo, Paul; Cheng, Emily H.; Giancotti, Filippo G.; Lee, William; Berger, Michael F.; Tickoo, Satish K.; Reuter, Victor E.; Hsieh, James J.
Renal cell carcinomas with unclassified histology (uRCC) constitute a significant portion of aggressive non-clear cell renal cell carcinomas that have no standard therapy. The oncogenic drivers in these tumours are unknown. Here we perform a molecular analysis of 62 high-grade primary uRCC, incorporating targeted cancer gene sequencing, RNA sequencing, single-nucleotide polymorphism array, fluorescence in situ hybridization, immunohistochemistry and cell-based assays. We identify recurrent somatic mutations in 29 genes, including NF2 (18%), SETD2 (18%), BAP1 (13%), KMT2C (10%) and MTOR (8%). Integrated analysis reveals a subset of 26% uRCC characterized by NF2 loss, dysregulated Hippo–YAP pathway and worse survival, whereas 21% uRCC with mutations of MTOR, TSC1, TSC2 or PTEN and hyperactive mTORC1 signalling are associated with better clinical outcome. FH deficiency (6%), chromatin/DNA damage regulator mutations (21%) and ALK translocation (2%) distinguish additional cases. Altogether, this study reveals distinct molecular subsets for 76% of our uRCC cohort, which could have diagnostic and therapeutic implications. PMID:27713405
Useche, Ana Carolina; Sullivan, Amanda L.; Merk, Welmoet; Orobio de Castro, Bram
This study examines the concurrent and longitudinal relationships between reactive and proactive aggression and children's peer status. Participants were 94 Dutch elementary school-aged boys in self-contained special education classrooms for students with emotional/behavioral disorders (EBD) and 47 boys with no disabilities in general education…
Lynch, Rebecca J; Kistner, Janet A; Stephens, Haley F; David-Ferdon, Corinne
There is a growing body of research linking children's positively biased self-perceptions with higher levels of aggression. This study extended this area of research by examining prospective associations of positively biased self-perceptions of peer acceptance with overt and relational aggression. In addition, moderating effects of peer rejection were examined to test the "disputed overestimation hypothesis," which posits that the link between bias and aggression is limited to children who are rejected by their peers. Using a two-wave longitudinal design, measures of peer-rated and self-perceived peer acceptance and peer-rated overt and relational aggression were obtained for 712 children in 3rd through 5th grades (386 girls and 326 boys). Positively biased perceptions led to increases in relational, but not overt, aggression. This pattern was observed even when the effects of gender, race, peer rejection, and overt aggression on relational aggression were controlled. Contrary to the disputed overestimation hypothesis, the prospective associations between bias and aggression did not vary as a function of children's peer rejection status, thus supporting the view that positive bias predicts future aggressive behavior, regardless of social status. The results are discussed in terms of the comparability with previous findings and practical implications.
Lynch, Rebecca J.; Kistner, Janet A.; Stephens, Haley F.; David-Ferdon, Corinne
There is a growing body of research linking children’s positively biased self-perceptions with higher levels of aggression. This study extended this area of research by examining prospective associations of positively biased self-perceptions of peer acceptance with overt and relational aggression. In addition, moderating effects of peer rejection were examined to test the “disputed overestimation hypothesis,” which posits that the link between bias and aggression is limited to children who are rejected by their peers. Using a two-wave longitudinal design, measures of peer-rated and self-perceived peer acceptance and peer-rated overt and relational aggression were obtained for 712 children in 3rd through 5th grades (386 girls and 326 boys). Positively biased perceptions led to increases in relational, but not overt, aggression. This pattern was observed even when the effects of gender, race, peer rejection, and overt aggression on relational aggression were controlled. Contrary to the disputed overestimation hypothesis, the prospective associations between bias and aggression did not vary as a function of children’s peer rejection status, thus supporting the view that positive bias predicts future aggressive behavior, regardless of social status. The results are discussed in terms of the comparability with previous findings and practical implications. PMID:26423823
Bergthold, Guillaume; Bandopadhayay, Pratiti; Hoshida, Yujin; Ramkissoon, Shakti; Ramkissoon, Lori; Rich, Benjamin; Maire, Cecile L.; Paolella, Brenton R.; Schumacher, Steven E.; Tabak, Barbara; Ferrer-Luna, Ruben; Ozek, Memet; Sav, Aydin; Santagata, Sandro; Wen, Patrick Yung; Goumnerova, Liliana C.; Ligon, Azra H.; Stiles, Charles; Segal, Rosalind; Golub, Todd; Grill, Jacques; Ligon, Keith L.; Chan, Jennifer A.; Kieran, Mark W.; Beroukhim, Rameen
Background Pediatric low-grade gliomas (PLGGs), the most frequent pediatric brain tumor, comprise a heterogeneous group of diseases. Recent genomic analyses suggest that these tumors are mostly driven by mitogene-activated protein kinase (MAPK) pathway alterations. However, little is known about the molecular characteristics inherent to their clinical and histological heterogeneity. Methods We performed gene expression profiling on 151 paraffin-embedded PLGGs from different locations, ages, and histologies. Using unsupervised and supervised analyses, we compared molecular features with age, location, histology, and BRAF genomic status. We compared molecular differences with normal pediatric brain expression profiles to observe whether those patterns were mirrored in normal brain. Results Unsupervised clustering distinguished 3 molecular groups that correlated with location in the brain and histological subtype. “Not otherwise specified” (NOS) tumors did not constitute a unified class. Supratentorial pilocytic astrocytomas (PAs) were significantly enriched with genes involved in pathways related to inflammatory activity compared with infratentorial tumors. Differences based on tumor location were not mirrored in location-dependent differences in expression within normal brain tissue. We identified significant differences between supratentorial PAs and diffuse astrocytomas as well as between supratentorial PAs and dysembryoplastic neuroepithelial tumors but not between supratentorial PAs and gangliogliomas. Similar expression patterns were observed between childhood and adolescent PAs. We identified differences between BRAF-duplicated and V600E-mutated tumors but not between primary and recurrent PLGGs. Conclusion Expression profiling of PLGGs reveals significant differences associated with tumor location, histology, and BRAF genomic status. Supratentorial PAs, in particular, are enriched in inflammatory pathways that appear to be tumor-related. PMID:25825052
Perry, Kristin J; Ostrov, Jamie M
This study assessed how the forms and functions of aggression fit into a higher order model of internalizing and externalizing behavior, for children in early childhood (N = 332, M age = 47.11 months, SD = 7.32). The lower order internalizing factors were depressed affect, anxious-fearfulness, and asocial behavior (i.e., social withdrawal) and the lower order externalizing factors were deception and hyperactivity. The forms and functions of aggression were crossed to create four factors: reactive relational, reactive physical, proactive relational, and proactive physical aggression. Seven confirmatory factor models were tested. Results supported a two-factor externalizing model where reactive and proactive relational aggression and deception loaded on one externalizing factor and reactive and proactive physical aggression and hyperactivity loaded on another externalizing factor.
Okudela, Koji; Woo, Tetsukan; Mitsui, Hideaki; Yazawa, Takuya; Shimoyamada, Hiroaki; Tajiri, Michihiko; Ogawa, Nobuo; Masuda, Munetaka; Kitamura, Hitoshi
We have established a concise sub-typing system suitable for predicting the postoperative outcome in cases of stage I lung adenocarcinoma (ADC), using morphometric profiling. The association between postoperative disease recurrence and a variety of morphological features including histological architecture, cell type, cytoplasmic color/internal structure, nuclear shape/size, chromatin pattern, and nucleoli count/remarkableness, was analyzed. Histological architecture had the most prognostic value and could be subdivided into low-grade (bronchioloalveolar, papillary and tubular: “tubular” in this paper is defined as a tubular or glandular structure lined with single-layered neoplastic cells) and high-grade (acinar and solid: “acinar” is defined as a tubular or glandular structure lined with poly-layered neoplastic cells or as a fused glandular structure such as the cribriform pattern) components. The subgroups separated based on a cut-off value, 71.5% of the high-grade component comprised by a tumor, which was calculated according to a relative operating characteristic curve, exhibited a significant difference in disease recurrence [estimated 5-year disease-free survival rate, 95.3% in the low-grade group versus 66.7% in the high-grade group, hazard ratio 7.35, Log-rank test p = 0.002]. The sub-grouping system is concise and suitable for practical use. It will improve the histological classification of ADC. PMID:20490327
Centrally necrotizing carcinoma is a rare subtype of breast carcinoma, which is characterized by an extensive central necrotic zone accounting for at least 70% of the cross-sectional area of the neoplasm. This central necrotic zone, in turn, is surrounded by a narrow rim of proliferative viable tumor cells. We report an unusual clinical situation in which a patient whose evident breast mass suggested an ipsilateral local recurrence and for which numerous attempts to confirm the histological diagnosis had failed. The patient was treated with a radical mastectomy based on clinical suspicion of breast cancer recurrence after an undesirable delay. In this case, the narrow rim of viable malignant tissue had a thickness of 0.5 to 8 mm, and the centrally necrotizing carcinoma had a central zone with a predominance of fibrosis. The special features of this case led to a misdiagnosis and to an evident clinical local recurrence. PMID:22852765
Dier, Usawadee; Shin, Dong-Hui; Hemachandra, L P Madhubhani P; Uusitalo, Larissa M; Hempel, Nadine
Epithelial ovarian cancer (EOC) is the most lethal of all gynecological cancers, and encompasses distinct histological subtypes that have specific genetic and tissues-of-origin differences. Ovarian clear cell carcinoma (OCCC) represents approximately 10% of cases and has been termed a stress responsive cancer. OCCC is characterized by increased expression of oxidative stress and glycolysis-related genes. In the present study, we hypothesized that bioenergetic profiling might uniquely distinguish OCCC from other EOC histological subtypes. Using an extracellular flux analyzer, OCCC lines (ES-2, TOV-21-G) were shown to be highly metabolically active, with high oxygen consumption rate (OCR) and high extracellular acidification rate (ECAR), indicative of enhanced mitochondrial oxidative phosphorylation and glycolytic rate, respectively. A high bioenergetics profile was associated with the cell lines' ability to form anchorage independent spheroids. Given their high glycolytic and mitochondrial activity, OCCC cells displayed strong sensitivity to 2-deoxy-D-glucose and Rotenone growth inhibition, although this chemosensitivity profile was not specific to only OCCC cells. Bioenergetic profiling also identified a non-OCCC cell line, OVCA420, to have severely compromised mitochondrial function, based on low OCR and a lack of stimulation of maximal respiration following application of the uncoupler FCCP. This was accompanied by mitochondrial morphology changes indicative of enhanced fission, increased expression of the mitochondrial fission protein Drp1, a loss of mitochondrial membrane potential and dependence on glycolysis. Importantly, this loss of mitochondrial function was accompanied by the inability of OVCA420 cells to cope with hypoxic stress, and a compromised ability to stabilize HIF-1α in response to 1% O2 hypoxia. This knowledge may be imperative for researchers planning to utilize this cell line for further studies of metabolism and hypoxia, and suggests that
Monuteaux, Michael C.; Biederman, Joseph; Doyle, Alysa E.; Mick, Eric; Faraone, Stephen V.
Four hundred forty-four subjects aged 6-55 years were evaluated to examine the role of COMT and SLC6A4 genes in the risk for conduct disorder and its symptomatic subtypes in the context of attention deficit hyperactivity disorder. No significant association is found between these genes and the risk for conduct disorder.
Park, Eunhyang; Park, Soo Young; Sun, Ping-Li; Jin, Yan; Kim, Ji Eun; Jheon, Sanghoon; Kim, Kwhanmien; Lee, Choon Taek
Cancer stem cells (CSCs) are a small subset of tumor cells that exhibit stem cell-like properties and contribute in treatment failure. To clarify the expression and prognostic significance of several CSC markers in non-small cell lung cancer, we retrospectively analyzed 368 patients with adenocarcinoma (n = 226) or squamous cell carcinoma (n = 142). We correlated the expression of six CSC markers – CD133, CD44, aldehyde dehydrogenase 1 (ALDH1), sex determining region Y-box 2 (SOX2), octamer binding transcription factor 4 (OCT4), and Nanog – with clinicopathologic and molecular variables and survival outcomes. In adenocarcinoma, CD133, ALDH1 and CD44 expression was associated with low pathologic stage and absence of lymphovascular invasion, while Nanog expression correlated with high histologic grade, lymphatic invasion and increased expression of Snail-1, a transcription factor associated with epithelial-mesenchymal transition. CSC marker expression was also associated with histologic subtypes in adenocarcinoma. Multivariate analysis showed that high Nanog expression was an independent factor associated with a poor prognosis in adenocarcinoma. CSC markers had no prognostic value in squamous cell carcinoma. These results suggest that Nanog is an independent negative prognostic factor that may be associated with epithelial-mesenchymal transition in lung adenocarcinoma. PMID:27285762
Travetti, Olga; di Giancamillo, Mauro; Stefanello, Damiano; Ferrari, Roberta; Giudice, Chiara; Grieco, Valeria; Saunders, Jimmy H
Feline injection-site sarcoma (FISS) may be a consequence of subcutaneous injection. In the present study, the medical records and the computed tomography (CT) features of 22 cats with a FISS, histopathological subtype fibrosarcoma, were used. The majority of the fibrosarcomas (45%) were located in the interscapular region. All fibrosarcomas, except one with mild enhancement, showed strong contrast uptake, characterised as ring (42%), heterogeneous (36%), homogeneous (9%), heterogeneous/ring (6.5%) or mixed heterogeneous/homogeneous enhancement (6.5%). The longest axis of the mass was in a cranio-caudal (68%) or dorso-ventral (32%) direction. The median volume calculated on CT was 7.57 cm(3). Common features were a marked local invasiveness of the musculature and heterogeneity of the tissue in the periphery of the neoplasia. When the fibrosarcoma was interscapular, performing an additional post-contrast scan with the forelimbs positioned caudally along the body, in addition to the standard protocol with the forelimbs extended cranially, allowed better evaluation of the actual relationship between the tumour and the surrounding tissues. The mean number of muscles involved with the tumour was 2.09 with extended and 1.95 with flexed forelimbs. When a lower number of structures was considered infiltrated through the double positioning, a less invasive surgical approach to underlying muscles and scapula was performed.
Trabert, B; Chen, J; Devesa, S S; Bray, F; McGlynn, K A
Incidence rates of testicular cancer in Northern European and North American countries have been widely reported, whereas rates in other populations, such as Eastern Europe, Central/South America, Asia, and Africa, have been less frequently evaluated. We examined testicular cancer incidence rates overall and by histologic type by calendar time and birth cohort for selected global populations 1973-2007. Age-standardized incidence rates over succeeding 5-year periods were calculated from volumes 4-9 of Cancer Incidence in Five Continents electronic database (CI5plus) and the newly released CI5X (volume 10) database. Annual percent change over the 35-year period was calculated using weighted least squares regression. Age-period-cohort analyses were performed and observed rates and fitted rate ratios presented by birth cohort. Incidence rates of testicular cancer increased between 1973-1977 and 2003-2007 in most populations evaluated worldwide. Of note, incidence rates in Eastern European countries rose rapidly and approached rates in Northern European countries. Rates in Central and South America also increased and are now intermediate to the high rates among men of European ancestry and low rates among men of Asian or African descent. Some heterogeneity in the trends in seminoma and nonseminoma were observed in Denmark, the United Kingdom, and among US whites, particularly in recent generations, with rapid and uniform increases in the incidence of both histologic types in Slovakia. Reasons for the rising incidence rates among European and American populations remain unexplained; however, changing distributions in the prevalence of risk factors for testicular cancer cannot be ruled out.
Ostrov, Jamie M.; Godleski, Stephanie A.
An integrative model is proposed for understanding the development of physical and relational aggression in early and middle childhood. The central goal was to posit a new theoretical framework that expands on existing social-cognitive and gender schema models (i.e., Social Information-Processing Model of Children's Adjustment [N. R. Crick & K. A.…
Lamm, Connie; Granic, Isabela; Zelazo, Philip David; Lewis, Marc D.
Emotion regulation is a key social skill and children who fail to master it are at risk for clinical disorders. Specific styles of emotion regulation have been associated with particular patterns of prefrontal activation. We investigated whether anxious aggressive children would reveal a different pattern of cortical activation than non-anxious…
Agarwal, Sonika; Schmeler, Kathleen M.; Ramirez, Pedro T.; Sun, Charlotte C.; Nick, Alpa; dos Reis, Ricardo; Brown, Jubilee; Frumovitz, Michael
Structured Abstract Introduction The most common types of cervical cancer are squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma, referred to here collectively as SA cervical cancer. Other types of cervical cancer, referred to here collectively as nonsquamous/nonadenocarcinoma (NSNA) cervical cancer, include neuroendocrine, small cell, clear cell, sarcomatoid, and serous tumors. Anecdotally, NSNA tumors seem to have a worse prognosis than their SA counterparts. We sought to determine whether patients with early-stage NSNA have a worse prognosis than those with early-stage SA cervical cancer. Methods We retrospectively reviewed charts of women with stage IA1-IB2 NSNA cervical cancer treated by radical hysterectomy and lymph node staging at MD Anderson Cancer Center from 1990 to 2006. NSNA patients were matched 1:2 to patients with grade 3 SA lesions on the basis of stage, age at diagnosis, tumor size, and date of diagnosis. Results Eighteen patients with NSNA primary cervical cancer subtypes [neuroendocrine (n=7), small cell (5), clear cell (4), papillary serous (1), and sarcomatoid (1)] were matched to 36 patients with grade 3 SA lesions. There were no differences between the 2 groups in age, body mass index, clinical stage, or lesion size. The 2 groups also did not differ with respect to number of nodes resected, lymphovascular space invasion, margin status, lymph node metastasis, or adjuvant radiation therapy or chemotherapy. At a median follow-up of 44 months, median progression-free and overall survivals had not been reached; however, both progression-free survival (p=0.018) and overall survival (p=0.028) were worse for the NSNA group. The 5-year progression-free and overall survival rates were 61.2% and 67.6%, respectively, for the NSNA group, compared to 90.1% and 88.3%, respectively, for the SA group. Conclusions Patients with early-stage NSNA cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy have a worse prognosis
Yang, TienYu Owen; Cairns, Benjamin J; Kroll, Mary E; Reeves, Gillian K; Green, Jane; Beral, Valerie
Risk of adult lymphoid malignancy is associated with recent adiposity. Some have reported apparent associations with adiposity in childhood or early adulthood, but whether these associations are independent of recent adiposity is unknown. Birth weight, body size at age 10 years, clothes size at age 20 years, and recent body mass index (BMI) were recorded in 745,273 UK women, mean age 60.1 (SD 4.9) at baseline, without prior cancer. They were followed for 11 years, during which time 5,765 lymphoid malignancies occurred. Using Cox regression, a higher risk of lymphoid malignancy was strongly associated with higher recent BMI (RR=1.33, 95%CI 1.17-1.51, for BMI 35+ vs <22.5 kg/m(2)), and this association remained essentially unchanged after adjustment for birth weight and body size at 10. Higher lymphoid malignancy risk was also associated with large size at birth, at age 10, and at age 20 years, but after adjustment for recent BMI, the significance of the associations with large size at birth and at age 10 years was sufficiently reduced that residual confounding by adult BMI could not be excluded; a weak association with large size at 20 years remained (adjusted RR =1.17, 95%CI 1.10-1.24 for large size at age 20 vs. medium or small size). We found no strong evidence of histological specificity in any of these associations. In conclusion, our findings suggest a possible role of adiposity throughout adulthood in the risk of lymphoid malignancy, but the independent contribution of body size at birth and during childhood appears to be small.
Cairns, Benjamin J.; Kroll, Mary E.; Reeves, Gillian K.; Green, Jane; Beral, Valerie
Risk of adult lymphoid malignancy is associated with recent adiposity. Some have reported apparent associations with adiposity in childhood or early adulthood, but whether these associations are independent of recent adiposity is unknown. Birth weight, body size at age 10 years, clothes size at age 20 years, and recent body mass index (BMI) were recorded in 745,273 UK women, mean age 60.1 (SD 4.9) at baseline, without prior cancer. They were followed for 11 years, during which time 5,765 lymphoid malignancies occurred. Using Cox regression, a higher risk of lymphoid malignancy was strongly associated with higher recent BMI (RR=1.33, 95%CI 1.17‐1.51, for BMI 35+ vs <22.5 kg/m2), and this association remained essentially unchanged after adjustment for birth weight and body size at 10. Higher lymphoid malignancy risk was also associated with large size at birth, at age 10, and at age 20 years, but after adjustment for recent BMI, the significance of the associations with large size at birth and at age 10 years was sufficiently reduced that residual confounding by adult BMI could not be excluded; a weak association with large size at 20 years remained (adjusted RR =1.17, 95%CI 1.10–1.24 for large size at age 20 vs. medium or small size). We found no strong evidence of histological specificity in any of these associations. In conclusion, our findings suggest a possible role of adiposity throughout adulthood in the risk of lymphoid malignancy, but the independent contribution of body size at birth and during childhood appears to be small. PMID:26888490
Ostrov, Jamie M; Godleski, Stephanie A
An integrative model is proposed for understanding the development of physical and relational aggression in early and middle childhood. The central goal was to posit a new theoretical framework that expands on existing social-cognitive and gender schema models (i.e., Social Information-Processing Model of Children's Adjustment [N. R. Crick & K. A. Dodge, 1994] and the Schematic-Processing Model of Sex Role Stereotyping [C. L. Martin & C. F. Halverson, 1981]). The proposed model suggests several individual- and group-level effects and the available evidence for each of these hypotheses is discussed. The ways in which the proposed model may guide future research in the field are presented.
Bechert, Charles; Kim, Jee-Yeon; Tramm, Trine; Tavassoli, Fattaneh A
In the USA alone, approximately 61,000 new diagnoses of ductal intraepithelial neoplasia 1c-3 (DIN) are made each year. Around 10-20 % of the patients develop a recurrence, about 50 % of which are invasive. Prior studies have shown that invasive breast carcinomas positive for p16 or p53 have a higher frequency of recurrence and a more aggressive course; however, the co-expression of these markers across the entire spectrum of DIN and its potential correlation with grade of the lesions has not been studied previously. Immunohistochemical staining for p16 and p53 was evaluated on 262 DIN lesions from 211 cases diagnosed between 1991 and 2008. The lesions ranged from DIN1b (atypical intraductal hyperplasia) to DIN3 (DCIS, grade 3) and included 45 cases with associated invasive carcinoma. Frequency of staining for both p16 and p53 increased with increasing grade of DIN. Strong co-expression was found exclusively in higher grade DIN lesions (DIN2 and DIN3) particularly those associated with periductal stromal fibrosis and lymphocytic infiltrate. Strong co-expression was seen in 8 of 12 DIN3 lesions (67 %) associated with invasive carcinoma. In conclusion, co-expression of p16 and p53 increases with advancing grade of DIN and is maximal in high grade DIN lesions associated with invasive carcinoma, indicating a more aggressive phenotype. A distinctive variant of DIN with periductal fibrosis and lymphocytic infiltrate invariably falls into the high-grade category, based on either morphology or marker expression. Co-expression of p16/p53 may be of help in distinguishing between high-grade and low-grade DIN lesions.
Jang, Sejin; Hong, Mineui; Shin, Mi Kyung; Kim, Byung Chun; Shin, Hyung-Sik; Yu, Eunsil; Hong, Seung-Mo; Kim, Jihun; Chun, Sung Min; Kim, Tae-Im; Choi, Kyung-Chan; Ko, Young Woong; Kim, Jeong Won
Tumor budding (TB) in colorectal carcinoma (CRC) is related to epithelial-mesenchymal transition (EMT) and has been recently characterized as an indicator of poor prognosis along with lymphovascular tumor emboli (LVE), perineural invasion (PNI), and an infiltrative growth pattern. Mutations in the genes of the Ras-MAPK and PI3K pathways are associated with EMT and an aggressive CRC phenotype and have been used in patient stratification for anti-EGF receptor therapies; however, the impact of these mutations on CRC morphology and behavior remains unclear. In this study, using a multi-gene panel, we detected KRAS, NRAS, BRAF, PIK3CA, TP53, and POLE mutations in 90 CRCs and investigated their associations with clinicopathological parameters, including TB. Our results showed that 21 of 34 tumors with high-grade TB had KRAS mutations (P=.001) and KRAS G12D and PIK3CA exon 9 variants were significantly associated with high-grade TB (P=.002 and .006, respectively); furthermore, tumors with KRAS mutations in exons 3 and 4 tended to have LVE and PNI (P=.044 and .049, respectively). PIK3CA exon 9 mutations indicated a tendency for shorter disease-free survival (P=.030), whereas BRAF mutations were associated with extracellular mucin deposition (P=.016). Our study revealed a correlation of KRAS mutations with high-grade TB, an association of certain KRAS and PIK3CA variants with aggressive clinicopathological features, as well as a possible relationship between BRAF mutations and mucin production in CRC.
Cheon, Dong-Joo; Li, Andrew J; Beach, Jessica A; Walts, Ann E; Tran, Hang; Lester, Jenny; Karlan, Beth Y; Orsulic, Sandra
ADAM metallopeptidase domain 12 (ADAM12) is a promising biomarker because of its low expression in normal tissues and high expression in a variety of human cancers. However, ADAM12 levels in ovarian cancer have not been well characterized. We previously identified ADAM12 as one of the signature genes associated with poor survival in high-grade serous ovarian carcinoma (HGSOC). Here, we sought to determine if high levels of the ADAM12 protein and/or messenger RNA (mRNA) are associated with clinical variables in HGSOC. We show that high protein levels of ADAM12 in banked preoperative sera are associated with shorter progression-free and overall survival. Tumor levels of ADAM12 mRNA were also associated with shorter progression-free and overall survival as well as with lymphatic and vascular invasion, and residual tumor volume following cytoreductive surgery. The majority of genes co-expressed with ADAM12 in HGSOC were transforming growth factor (TGF)β signaling targets that function in collagen remodeling and cell-matrix adhesion. In tumor sections, the ADAM12 protein and mRNA were expressed in epithelial cancer cells and surrounding stromal cells. In vitro data showed that ADAM12 mRNA levels can be increased by TGFβ signaling and direct contact between epithelial and stromal cells. High tumor levels of ADAM12 mRNA were characteristic of the mesenchymal/desmoplastic molecular subtype of HGSOC, which is known to have the poorest prognosis. Thus, ADAM12 may be a useful biomarker of aggressive ovarian cancer for which standard treatment is not effective.
Ujiie, Hideki; Kadota, Kyuichi; Chaft, Jamie E.; Buitrago, Daniel; Sima, Camelia S.; Lee, Ming-Ching; Huang, James; Travis, William D.; Rizk, Nabil P.; Rudin, Charles M.; Jones, David R.; Adusumilli, Prasad S.
Purpose To examine the significance of the proposed International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) histologic subtypes of lung adenocarcinoma for patterns of recurrence and, among patients who recur following resection of stage I lung adenocarcinoma, for postrecurrence survival (PRS). Patients and Methods We reviewed patients with stage I lung adenocarcinoma who had undergone complete surgical resection from 1999 to 2009 (N = 1,120). Tumors were subtyped by using the IASLC/ATS/ERS classification. The effects of the dominant subtype on recurrence and, among patients who recurred, on PRS were investigated. Results Of 1,120 patients identified, 188 had recurrent disease, 103 of whom died as a result of lung cancer. Among patients who recurred, 2-year PRS was 45%, and median PRS was 26.1 months. Compared with patients with nonsolid tumors, patients with solid predominant tumors had earlier (P = .007), more extrathoracic (P < .001), and more multisite (P = .011) recurrences. Multivariable analysis of primary tumor factors revealed that, among patients who recurred, solid predominant histologic pattern in the primary tumor (hazard ratio [HR], 1.76; P = .016), age older than 65 years (HR, 1.63; P = .01), and sublobar resection (HR, 1.6; P = .01) were significantly associated with worse PRS. Presence of extrathoracic metastasis (HR, 1.76; P = .013) and age older than 65 years at the time of recurrence (HR, 1.7; P = .014) were also significantly associated with worse PRS. Conclusion In patients with stage I primary lung adenocarcinoma, solid predominant subtype is an independent predictor of early recurrence and, among those patients who recur, of worse PRS. Our findings provide a rationale for investigating adjuvant therapy and identify novel therapeutic targets for patients with solid predominant lung adenocarcinoma. PMID:26261257
Carcinoma of the collecting ducts of Bellini and renal medullary carcinoma: clinicopathologic analysis of 52 cases of rare aggressive subtypes of renal cell carcinoma with a focus on their interrelationship.
Gupta, Ruta; Billis, Athanase; Shah, Rajal B; Moch, Holger; Osunkoya, Adeboye O; Jochum, Wolfram; Hes, Ondrej; Bacchi, Carlos E; de Castro, Marilia G; Hansel, Donna E; Zhou, Ming; Vankalakunti, Mahesha; Salles, Paulo G; Cabrera, Rafael A; Gown, Allen M; Amin, Mahul B
-confined small tumors were disease free beyond the median survival time. Differential clinical features between collecting duct carcinoma and renal medullary carcinoma included proclivity for younger male individuals of African ancestry with hemoglobin abnormalities and a shorter median survival of 17 weeks (vs. 44 wk for collecting duct carcinoma) for renal medullary carcinoma. The markedly overlapping clinical features, histology, immunophenotype, metastasis patterns, and uniformly aggressive outcome in collecting duct and renal medullary carcinomas suggest that renal medullary carcinoma is a distinctive clinicopathologic subtype within the entity of collecting duct carcinoma. The extremely poor prognosis and ongoing clinical trials with specific therapeutic protocols argue for their accurate distinction from other renal cell carcinoma subtypes.
Mujahid, Mahasin; Srinivas, Sandy; Keegan, Theresa H.M.
Purpose: Testicular cancer is the most common cancer among adolescent and young adult (AYA) men 15–39 years of age. This study aims to determine whether race/ethnicity and/or neighborhood socioeconomic status (SES) contribute independently to survival of AYAs with testicular cancer. Methods: Data on 14,249 eligible AYAs with testicular cancer diagnosed in California between 1988 and 2010 were obtained from the population-based California Cancer Registry. Multivariable Cox proportional hazards regression was used to examine overall and testicular cancer-specific survival and survival for the seminoma and nonseminoma histologic subtypes according to race/ethnicity, census-tract level neighborhood SES, and other patient and clinical characteristics. Results: Compared with White AYAs, Hispanic AYAs had worse overall and testicular cancer-specific survival (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.07–1.37) and Black AYAs had worse overall survival (HR, 1.41; 95% CI, 1.01–1.97), independent of neighborhood SES and other demographic and clinical factors. Racial/ethnic disparities in survival were more pronounced for nonseminoma than for seminoma. AYAs residing in middle and low SES neighborhoods experienced worse survival across both histologic subtypes independent of race/ethnicity and other factors, while improvements in survival over time were more pronounced for seminoma. Longer time to treatment was also associated with worse survival, particularly for AYAs with nonseminoma. Conclusion: Among AYAs, race/ethnicity, and neighborhood SES are independently associated with survival after testicular cancer. Variation in disparities by histologic type according to demographic factors, year of diagnosis, and time to treatment may reflect differences in prognosis and extent of treatment for the two histologies. PMID:26812451
Ali, Shihab; Olszewski, Adam J
We compared survival outcomes and rates of secondary non-Hodgkin lymphoma (NHL) in 28 323 patients with nodular lymphocyte predominant (NLPHL) and classical Hodgkin lymphoma (HL) from the Surveillance, Epidemiology and End Results database, diagnosed between 1995 and 2010. In a multivariate analysis NLPHL demonstrated a significantly better relative survival (5-year risk of lymphoma-related death 5.7%, hazard ratio [HR] 0.46, p < 0.0001) than the reference nodular sclerosis (NSHL) subtype (5-year risk 12.7%). Lymphocyte-rich classical HL had outcomes comparable to NSHL (5-year risk 14.3%, HR 0.84, p = 0.11). Exceptionally poor outcomes were observed in lymphocyte depleted HL (5-year risk 48.8%, HR 2.26, p < 0.0001). The risk of secondary NHL was increased in NLPHL (HR 2.81, p < 0.001) and lymphocyte-rich classical HL (HR 2.27, p = 0.002), but not in other subtypes compared with NSHL. In conclusion, the histologic classification retains a significant prognostic value in HL and the disparities between the subtypes warrant customized treatment and surveillance strategies.
This study examined the mediating roles of three types of child aggression in the relation between harsh parenting and Chinese early adolescents' peer acceptance as well as the moderating role of child gender on this indirect relation. 833 children (mean age=13.58, 352 girls) with their parents were recruited as participants from two junior high schools in Shandong Province, People's Republic of China. The results showed that paternal harsh parenting was only associated with boys' aggressive behaviors and maternal harsh parenting was only associated with boys' and girls' verbal aggression. Adolescents' verbal and relational aggressions were negatively associated with their peer acceptance. Verbal aggression was more strongly and negatively associated with girls' peer acceptance. The results imply that in the Chinese cultural context, paternal harsh parenting may compromise boys' peer acceptance through boys' verbal and relational aggression as mediators, whereas maternal harsh parenting may impair children's peer acceptance through children's verbal aggression as a mediator, especially for girls. These results provide a theoretical basis for ameliorating the negative effect of harsh parenting on early adolescents' peer acceptance by reducing their aggressive behaviors, with different strategies between boys and girls.
Ettekal, Idean; Ladd, Gary W.
This study examined the associations between children's co-occurring relational and physical aggression trajectories and their peer relations (i.e., peer rejection, peer acceptance, and reciprocated friendships) from late childhood (Grade 4; M[subscript age] = 10.0) to early adolescence (Grade 8; M[subscript age] = 13.9). Using a sample of 477…
Bowker, Julie C.; Markovic, Andrea; Cogswell, Alex; Raja, Radhi
Recent research has revealed significant heterogeneity in the peer difficulties associated with social withdrawal subtypes during early adolescence, but little is known about possible sources of that heterogeneity. This study of 194 Indian young adolescents (48% female; 90% Hindu; M age = 13.35 years) evaluated whether the peer adversity related…
Cho, Gene Young; Moy, Linda; Kim, Sungheon G.; Baete, Steven H.; Moccaldi, Melanie; Babb, James S.; Sodickson, Daniel K.; Sigmund, Eric E.
Purpose To examine heterogeneous breast cancer through intravoxel incoherent motion (IVIM) histogram analysis. Materials and methods This HIPAA-compliant, IRB-approved retrospective study included 62 patients (age 48.44±11.14 years, 50 malignant lesions and 12 benign) who underwent contrast-enhanced 3 T breast MRI and diffusion-weighted imaging. Apparent diffusion coefficient (ADC) and IVIM biomarkers of tissue diffusivity (Dt), perfusion fraction (fp), and pseudo-diffusivity (Dp) were calculated using voxel-based analysis for the whole lesion volume. Histogram analysis was performed to quantify tumour heterogeneity. Comparisons were made using Mann–Whitney tests between benign/malignant status, histological subtype, and molecular prognostic factor status while Spearman’s rank correlation was used to characterize the association between imaging biomarkers and prognostic factor expression. Results The average values of the ADC and IVIM biomarkers, Dt and fp, showed significant differences between benign and malignant lesions. Additional significant differences were found in the histogram parameters among tumour subtypes and molecular prognostic factor status. IVIM histogram metrics, particularly fp and Dp, showed significant correlation with hormonal factor expression. Conclusion Advanced diffusion imaging biomarkers show relationships with molecular prognostic factors and breast cancer malignancy. This analysis reveals novel diagnostic metrics that may explain some of the observed variability in treatment response among breast cancer patients. PMID:26615557
Andersen, Maja D; Kamper, Peter; Nielsen, Patricia S; Bendix, Knud; Riber-Hansen, Rikke; Steiniche, Torben; Hamilton-Dutoit, Stephen; Clausen, Michael; d'Amore, Francesco
The tumour microenvironment in classical Hodgkin's lymphoma (cHL) is characterised by a minor population of neoplastic Hodgkin and Reed-Sternberg cells within a heterogeneous background of non-neoplastic bystanders cells, including mast cells. The number of infiltrating mast cells in cHL has been reported to correlate with poor prognosis. We used immunohistochemistry to assess the degree of tumour-infiltrating mast cells in cHL tissue microarrays and correlated this with clinico-pathological features and prognosis in a cohort of homogeneously treated patients with Hodgkin's disease. A high degree of tumour mast cells was associated with nodular sclerosis (NS) subtype histology (P = 0.0002). Moreover, the number of mast cells was inversely correlated with the numbers of CD68+ and CD163+ macrophages (P = 0.0001 and P = 0.003, respectively) and with the number of granzyme+ cytotoxic cells (P = 0.004). The degree of mast cell infiltration was not a prognostic factor in cHL of nodular sclerosis subtype. In contrast, in mixed cellularity cHL a high number of intratumoral mast cells correlated with significantly poorer outcome both in terms of overall (P = 0.03) and event-free survival (P = 0.01). Further studies are warranted into the biological mechanisms underlying this adverse outcome and their possible therapeutic implications.
King, Sara; Waschbusch, Daniel A.; Pelham, William E.; Frankland, Bradley W.; Corkum, Penny V.; Jacques, Sophie
We examined aggressive behavior in 6- to 12-year-old children, including 20 children with attention deficit hyperactivity disorder (ADHD) on stimulant medication, 19 children with ADHD on placebo (n = 19), and 32 controls. Children completed a laboratory provocation task designed to measure hostile, instrumental, reactive, and proactive…
O'Brien, Michael J; Yang, Shi; Clebanoff, Jennifer L; Mulcahy, Elizabeth; Farraye, Francis A; Amorosino, Mark; Swan, Niall
We investigated the frequency of promoter region CpG island methylation (CIM) of hMLH1, MGMT, MINT1, MINT2, and p16 and K-ras mutations in a total of 79 hyperplastic (serrated) polyps (HPs) from 75 patients and correlated the molecular profiles to polyp location in the colorectum, histologic variation, and other factors. Methylation-specific PCR (MS-PCR) was used to assay CIM status. HPs that showed CIM of one or more or two or more of the genes assayed were classified as CpG island methylator phenotype (CIMP) and CIMP-high (CIMP-H), respectively. PCR restriction fragment length polymorphism was used to assay K-ras codon 12 and 13 mutations. Logistic regression indicated a statistically significant trend for increasing odds for CIMP (P = 0.002) and CIMP-H (P < 0.001) according to proximity to the cecum or distance from the rectum. Conversely, K-ras codon 12 mutation was present in 13 of 40 (32.5%) distally located HPs compared with 2 of 39 (5.1%) proximal HPs (P = 0.006). Histologic subtype distribution varied by proximal and distal locations. Frequency of CIMP in serrated polyps with abnormal proliferation (SPAPs), differed significantly from goblet cell serrated polyps (GCSPs) (24 of 26, 92.3% vs. 6 of 13, 46.2%) (P = 0.003) and microvesicular serrated polyps (MVSPs) (26 of 38, 68.4%) (P = 0.03). Frequency of K-ras mutation in GCSPs (7 of 13, 54%) differed from that of MVSPs (6 of 38, 16%) (P = 0.01) and SPAPs (2 of 26, 8%) (P = 0.003). Location in the colorectum and histologic subtype were major determinants of the molecular profile of HPs. The molecular findings of CIMP and K-ras mutations appear to encompass most if not all HPs; CIMP profiles suggest that SPAP is the most advanced morphologic variant. We postulate that MVSP and GCSP may be precursor lesions that, if proximally located or larger, can progress to SPAP. Frequent K-ras mutations and infrequent CIMP distinguish the distal GCSP variant.
Ghirelli, Cristina; Reyal, Fabien; Jeanmougin, Marine; Zollinger, Raphaël; Sirven, Philémon; Michea, Paula; Caux, Christophe; Bendriss-Vermare, Nathalie; Donnadieu, Marie-Hélène; Caly, Martial; Fourchotte, Virginie; Vincent-Salomon, Anne; Sigal-Zafrani, Brigitte; Sastre-Garau, Xavier; Soumelis, Vassili
Reciprocal interactions between tumor cells and their microenvironment vitally impact tumor progression. In this study, we show that GM-CSF produced by primary breast tumor cells induced the activation of plasmacytoid predendritic cells (pDC), a cell type critical to anti-viral immunity. pDC that expressed the GM-CSF receptor were increased in breast tumors compared with noninvolved adjacent breast tissue. Tumor-activated pDC acquired naïve CD4(+) T-cell stimulatory capacity and promoted a regulatory Th2 response. Finally, the concomitant increase of GM-CSF and pDC was significantly associated with relatively more aggressive breast cancer subtypes. Our results characterize the first tumor-derived factor that can activate pDC to promote a regulatory Th2 response, with implications for therapeutic targeting of a tumor-immune axis of growing recognition in its significance to cancer.
Molè, Daniela; Gentilin, Erica; Ibañez-Costa, Alejandro; Gagliano, Teresa; Gahete, Manuel D; Tagliati, Federico; Rossi, Roberta; Pelizzo, Maria Rosa; Pansini, Giancarlo; Luque, Raúl M; Castaño, Justo P; degli Uberti, Ettore; Zatelli, Maria Chiara
The truncated somatostatin receptor variant sst5TMD4 associates with increased invasiveness and aggressiveness in breast cancer. We previously found that sst5 activation may counteract sst2 selective agonist effects in a medullary thyroid carcinoma (MTC) cell line, the TT cells, and that sst5TMD4 is overexpressed in poorly differentiated thyroid cancers. The purpose of this study is to evaluate sst5TMD4 expression in a series of human MTC and to explore the functional role of sst5TMD4 in TT cells. We evaluated sst5TMD4 and sst5 expression in 36 MTC samples. Moreover, we investigated the role of sst5TMD4 in TT cells evaluating cell number, DNA synthesis, free cytosolic calcium concentration ([Ca(2+)]i), calcitonin and vascular endothelial growth factor levels, cell morphology, protein expression, and invasion. We found that in MTC the balance between sst5TMD4 and sst5 expression influences disease stage. sst5TMD4 overexpression in TT cells confers a greater growth capacity, blocks sst2 agonist-induced antiproliferative effects, modifies the cell phenotype, decreases E-cadherin and phosphorylated β-catenin levels, increases vimentin, total β-catenin and phosphorylated GSK3B levels (in keeping with the development of epithelial to mesenchymal transition), and confers a greater invasion capacity. This is the first evidence indicating that sst5TMD4 is expressed in human MTC cells, where it associates with more aggressive behavior, suggesting that sst5TMD4 might play a functionally relevant role.
Moshiri, Ata S; Doumani, Ryan; Yelistratova, Lola; Blom, Astrid; Lachance, Kristina; Shinohara, Michi M; Delaney, Martha; Chang, Oliver; McArdle, Susan; Thomas, Hannah; Asgari, Maryam M; Huang, Meei-Li; Schwartz, Stephen M; Nghiem, Paul
Previous studies have reached conflicting conclusions regarding the proportion of Merkel cell carcinomas (MCCs) that contain the Merkel cell polyomavirus (MCPyV) and the clinical significance of tumor viral status. To address these controversies, we detected MCPyV large T antigen using immunohistochemistry with two distinct antibodies and MCPyV DNA using quantitative PCR. Tumors were called MCPyV-positive if two or more of these three assays indicated presence of this virus. A total of 53 of 282 (19%) MCC tumors in this cohort were virus-negative using this multimodal system. Immunohistochemistry with the CM2B4 antibody had the best overall performance (sensitivity = 0.882, specificity = 0.943) compared with the multimodal classification. Multivariate analysis including age, sex, and immunosuppression showed that, relative to MCC patients with virus-positive tumors, virus-negative MCC patients had significantly increased risk of disease progression (hazard ratio = 1.77, 95% confidence interval = 1.20-2.62) and death from MCC (hazard ratio = 1.85, 95% confidence interval = 1.19-2.89). We confirm that approximately 20% of MCCs are not driven by MCPyV and that such virus-negative MCCs, which can be quite reliably identified by immunohistochemistry using the CM2B4 antibody alone, represent a more aggressive subtype that warrants closer clinical follow-up.
Wu, Meei-Maan; Lee, Chih-Hung; Hsu, Ling-I; Cheng, Wen-Fang; Lee, Te-Chang; Wang, Yuang-Hung; Chiou, Hung-Yi; Chen, Chien-Jen
Heme oxygenase (HO)-1 is upregulated by many stressful stimuli, including arsenic. A GT-repeat ((GT)n) polymorphism in the HO-1 gene promoter inversely modulates the levels of HO-1 induction. Previous HO-1 (GT)n polymorphism studies in relation to cancer risk have shown disparate results. We prospectively investigated the associations between HO-1 (GT)n polymorphism and cancer risk related to arsenic from drinking water. Totally, 1,013 participants from community-based cohorts of arseniasis-endemic areas in Taiwan were followed for 13 years. Allelic polymorphisms were classified into long (L, ≥ 27 (GT)n) and short (S, <27 (GT)n). Newly developed cases were identified through linkage with National Cancer Registry of Taiwan. Multivariate Cox proportional hazard methods were used to evaluate effects of the HO-1 polymorphism alone or combined with arsenic exposure. Results showed that participants with the S/S genotype had an increased risk of Bowen's disease (HR = 10.49; 95% CI: 2.77-39.7), invasive skin cancer (HR = 2.99; 95% CI: 1.13-7.87), and lung squamous cell carcinoma (HR = 3.39; 95% CI: 1.15-9.95) versus those with L/S or L/L genotype. The S/S genotype combined with high arsenic exposure (>300 μg/L) had a greater risk of skin cancer compared to the genotype alone. Consistent with previous findings, participants with the S-allele had a reduced risk of lung adenocarcinoma (HR = 0.21; 95% CI: 0.03-0.68) versus those with L/L genotype. There were no significant differences in risk of urothelial carcinoma among the three genotypes. Associations of HO-1 (GT)n polymorphism with cancer risk differs by histological subtype and the polymorphism should be considered a modifier in the risk assessment of arsenic exposure.
Misemer, Benjamin S; Skubitz, Amy P N; Carlos Manivel, J; Schmechel, Stephen C; Cheng, Edward Y; Henriksen, Jonathan C; Koopmeiners, Joseph S; Corless, Christopher L; Skubitz, Keith M
Aggressive fibromatosis (AF) represents a group of tumors with a variable and unpredictable clinical course, characterized by a monoclonal proliferation of myofibroblastic cells. The optimal treatment for AF remains unclear. Identification and validation of genes whose expression patterns are associated with AF may elucidate biological mechanisms in AF, and aid treatment selection. This study was designed to examine the protein expression by immunohistochemistry (IHC) of four genes, ADAM12, FAP, SOX11, and WISP1, that were found in an earlier study to be uniquely overexpressed in AF compared with normal tissues. Digital image analysis was performed to evaluate inter- and intratumor heterogeneity, and correlate protein expression with histologic features, including a histopathologic assessment of tumor activity, defined by nuclear chromatin density ratio (CDR). AF tumors exhibited marked inter- and intratumor histologic heterogeneity. Pathologic assessment of tumor activity and digital assessment of average nuclear size and CDR were all significantly correlated. IHC revealed protein expression of all four genes. IHC staining for ADAM12, FAP, and WISP1 correlated with CDR and was higher, whereas SOX11 staining was lower in tumors with earlier recurrence following excision. All four proteins were expressed, and the regional variation in tumor activity within and among AF cases was demonstrated. A spatial correlation between protein expression and nuclear morphology was observed. IHC also correlated with the probability of recurrence following excision. These proteins may be involved in AF pathogenesis and the corresponding pathways could serve as potential targets of therapy.
Meijer, Tineke W H; de Geus-Oei, Lioe-Fee; Visser, Eric P; Oyen, Wim J G; Looijen-Salamon, Monika G; Visvikis, Dimitris; Verhagen, Ad F T M; Bussink, Johan; Vriens, Dennis
Purpose To assess whether dynamic fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET) has added value over static (18)F-FDG PET for tumor delineation in non-small cell lung cancer (NSCLC) radiation therapy planning by using pathology volumes as the reference standard and to compare pharmacokinetic rate constants of (18)F-FDG metabolism, including regional variation, between NSCLC histologic subtypes. Materials and Methods The study was approved by the institutional review board. Patients gave written informed consent. In this prospective observational study, 1-hour dynamic (18)F-FDG PET/computed tomographic examinations were performed in 35 patients (36 resectable NSCLCs) between 2009 and 2014. Static and parametric images of glucose metabolic rate were obtained to determine lesion volumes by using three delineation strategies. Pathology volume was calculated from three orthogonal dimensions (n = 32). Whole tumor and regional rate constants and blood volume fraction (VB) were computed by using compartment modeling. Results Pathology volumes were larger than PET volumes (median difference, 8.7-25.2 cm(3); Wilcoxon signed rank test, P < .001). Static fuzzy locally adaptive Bayesian (FLAB) volumes corresponded best with pathology volumes (intraclass correlation coefficient, 0.72; P < .001). Bland-Altman analyses showed the highest precision and accuracy for static FLAB volumes. Glucose metabolic rate and (18)F-FDG phosphorylation rate were higher in squamous cell carcinoma (SCC) than in adenocarcinoma (AC), whereas VB was lower (Mann-Whitney U test or t test, P = .003, P = .036, and P = .019, respectively). Glucose metabolic rate, (18)F-FDG phosphorylation rate, and VB were less heterogeneous in AC than in SCC (Friedman analysis of variance). Conclusion Parametric images are not superior to static images for NSCLC delineation. FLAB-based segmentation on static (18)F-FDG PET images is in best agreement with pathology volume and could be
Gahete, Manuel D.; Serrano-Somavilla, Ana; Villa-Osaba, Alicia; Adrados, Magdalena; Ibáñez-Costa, Alejandro; Martín-Pérez, Elena; Culler, Michael D.
Purpose Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and heterogeneous tumors, and their biological behavior is not well known. We studied the presence and potential functional roles of somatostatin receptors (sst1-5), focusing particularly on the truncated variants (sst5TMD4, sst5TMD5) and on their relationships with the angiogenic system (Ang/Tie-2 and VEGF) in human GEP-NETs. Experimental Design We evaluated 42 tumor tissue samples (26 primary/16 metastatic) from 26 patients with GEP-NETs, and 30 non-tumoral tissues (26 from adjacent non-tumor regions and 4 from normal controls) from a single center. Expression of sst1-5, sst5TMD4, sst5TMD5, Ang1-2, Tie-2 and VEGF was analyzed using real-time qPCR, immunofluorescence and immunohistochemistry. Expression levels were associated with tumor characteristics and clinical outcomes. Functional role of sst5TMD4 was analyzed in GEP-NET cell lines. Results sst1 exhibited the highest expression in GEP-NET, whilst sst2 was the most frequently observed sst-subtype (90.2%). Expression levels of sst1, sst2, sst3, sst5TMD4, and sst5TMD5 were significantly higher in tumor tissues compared to their adjacent non-tumoral tissue. Lymph-node metastases expressed higher levels of sst5TMD4 than in its corresponding primary tumor tissue. sst5TMD4 was also significantly higher in intestinal tumor tissues from patients with residual disease of intestinal origin compared to those with non-residual disease. Functional assays demonstrated that the presence of sst5TMD4 was associated to enhanced malignant features in GEP-NET cells. Angiogenic markers correlated positively with sst5TMD4, which was confirmed by immunohistochemical/fluorescence studies. Conclusions sst5TMD4 is overexpressed in GEP-NETs and is associated to enhanced aggressiveness, suggesting its potential value as biomarker and target in GEP-NETs. PMID:26673010
McQuade, Julia D; Breaux, Rosanna P; Gómez, Angelina F; Zakarian, Rebecca J; Weatherly, Julia
This study expands on prior research suggesting that children who either over- or under-estimate their social competence relative to others' reports are more likely to be aggressive. Linear and curvilinear associations between biased social self-perceptions and forms (physical vs. relational) and functions (proactive vs. reactive) of aggression were tested along with three moderators (peer rejection, social dominance goals, and child sex). Children in the fifth through eight grade (N = 167) completed self-reports of perceived social competence and social dominance goals. Teachers completed ratings of children's social competence, peer rejection, and reactive and proactive physical and relational aggression. Bias in self-perceived social competence was quantified as the residual difference between child and teacher ratings of the child's social competence. There was a significant interaction between quadratic bias and peer rejection predicting reactive physical aggression; rejected children with a positive bias or a negative bias were highest in reactive physical aggression. The interaction between linear bias, social dominance goals, and the sex of the child was also significant when predicting proactive physical aggression. Among girls who highly valued social dominance, a positive bias predicted greater proactive physical aggression. Results are discussed in terms of implications for aggression theory and intervention. Aggr. Behav. 42:498-509, 2016. © 2016 Wiley Periodicals, Inc.
Said, Jonathan W
Aggressive B-cell lymphomas are diverse group of neoplasms that arise at different stages of B-cell development and by various mechanisms of neoplastic transformation. The aggressive B-cell lymphomas include many types, subtypes and variants of diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), mantle cell lymphoma and its blastoid variant, and B lymphoblastic lymphoma. Differences in histology, cytogenetic and molecular abnormalities, as well as the relationship with the tumor microenvironment, help define characteristic signatures for these neoplasms, and in turn dictate potential therapeutic targets. Rather than survey the entire spectrum of aggressive B-cell lymphomas, this report aims to identify and characterize important clinically aggressive subtypes of DLBCL, and explore the relationship of DLBCL to BL and the gray zone between them (B-cell lymphoma unclassifiable with features intermediate between DLBCL and BL). PMID:23154748
Impact of histological subtype on survival in patients with locally advanced cervical cancer that were treated with definitive radiotherapy: adenocarcinoma/adenosquamous carcinoma versus squamous cell carcinoma
Kuroda, Hiromasa; Kimura, Tadashi
Objective To compare the survival outcomes of patients with cervical squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) among patients with locally advanced cervical cancer that were treated with definitive radiotherapy. Methods The baseline characteristics and outcome data of patients with locally advanced cervical cancer who were treated with definitive radiotherapy between November 1993 and February 2014 were collected and retrospectively reviewed. A Cox proportional hazards regression model was used to investigate the prognostic significance of AC/ASC histology. Results The patients with AC/ASC of the cervix exhibited significantly shorter overall survival (OS) (p=0.004) and progression-free survival (PFS) (p=0.002) than the patients with SCC of the cervix. Multivariate analysis showed that AC/ASC histology was an independent negative prognostic factor for PFS. Among the patients who displayed AC/ASC histology, larger tumor size, older age, and incomplete response to radiotherapy were found to be independent prognostic factors. PFS was inversely associated with the number of poor prognostic factors the patients exhibited (the estimated 1-year PFS rates; 100.0%, 77.8%, 42.8%, 0.0% for 0, 1, 2, 3 factors, respectively). Conclusion Locally advanced cervical cancer patients with AC/ASC histology experience significantly worse survival outcomes than those with SCC. Further clinical studies are warranted to develop a concurrent chemoradiotherapy (CCRT) protocol that is specifically tailored to locally advanced cervical AC/ASC. PMID:28028992
Zaric, Bojan; Stojsic, Vladimir; Panjkovic, Milana; Tegeltija, Dragana; Stepanov, Vanesa; Kovacevic, Tomi; Sarcev, Tatjana; Radosavljevic, Davorin; Milovancev, Aleksandar; Adamidis, Vasilis; Zarogoulidis, Paul; Hohenforst-Schmidt, Wolfgang; Trakada, Georgia; Rapti, Aggeliki; Perin, Branislav
Introduction: The incidence of echinoderm microtubule-associated protein-like4-anaplastic lymphoma kinase (EML4-ALK) mutation among surgically treated patients with adenocarcinoma of the lung of the Eastern European ethnicity is underreported. The aim of this trial was the determination of EML4-ALK mutation frequency in investigated population, and the evaluation of correlations between lung adenocarcinoma subtype and clinical characteristics with mutation status. Patients and methods: This was a prospective trial which included 195 patients with adenocarcinoma of the lung who underwent surgical treatment. ALK mutation screening was performed by immunohistochemistry (IHC). IHC scores of 2+ and 3+ were regarded as positive. Confirmatory FISH was performed in all IHC positive and in 2:1 ratio in negative patients. Results: Overall ALK mutation rate established by IHC was 6.2%, while FISH confirmed rate of 5.1%. The FISH confirmed ALK positivity in 7.6% Hungarians, 5.5% Serbians, and 6.6% Slovakians. Acinar subtype of adenocarcinoma of the lung was significantly (p=0.02) related to EML4-ALK positive mutation status. Most of the patients were males (56.9%), smokers (50.8%), or former smokers (28.7%) with acinar (55.4%) or solid (35.9%) adenocarcinoma of the lung. Sensitivity and specificity of IHC were 100% and 98.9% respectively. Conclusions: ALK mutation rate in surgically treated patients with adenocarcinoma of the lung was found to be 6.2% by IHC and 5.1% by FISH. Acinar subtype of the adenocarcinoma of the lung was significantly related to ALK positive mutation. PMID:27994656
Relationship of epidermal growth factor receptor activating mutations with histologic subtyping according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society 2011 adenocarcinoma classification and their impact on overall survival
Maturu, Venkata Nagarjuna; Singh, Navneet; Bal, Amanjit; Gupta, Nalini; Das, Ashim; Behera, Digambar
Background: There is limited Indian data on epidermal growth factor receptor (EGFR) gene activating mutations (AMs) prevalence and their clinicopathologic associations. The current study aimed to assess the relationship between EGFR AM and histologic subtypes and their impact on overall survival (OS) in a North Indian cohort. Patients and Methods: Retrospective analysis of nonsmall cell lung cancer patients who underwent EGFR mutation testing (n = 186) over 3 years period (2012–2014). EGFR mutations were tested using polymerase chain reaction amplification and direct sequencing. Patients were classified as EGFR AM, EGFR wild type (WT) or EGFR unknown (UKN). Histologically adenocarcinomas (ADC) were further categorized as per the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society-2011 classification. Results: Overall EGFR AM prevalence was 16.6%. The ratio of exon 19 deletions to exon 21 L858R mutations was 3.17:1. Female sex (P = 0.002), never smoking status (P = 0.002), metastatic disease (P = 0.032), and nonsolid subtype of ADC (P = 0.001) were associated with EGFR AM on univariate logistic regression analysis (LRA). On multivariate LRA, solid ADC was negatively associated with EGFR AM. Median OS was higher in patients with EGFR AM (750 days) as compared to EGFR-WT (459 days) or EGFR-UKN (291 days) for the overall population and in patients with Stage IV disease (750 days vs. 278 days for EGFR-WT, P = 0.024). On univariate Cox proportional hazard (CPH) analysis, smoking, poor performance status (Eastern Cooperative Oncology Group ≥ 2), EGFR-UKN status, and solid ADC were associated with worse OS while female sex and lepidic ADC had better OS. On multivariate CPH analysis, lepidic ADC (hazard ratio [HR] =0.12) and EGFR-WT/EGFR-UKN (HR = 2.39 and HR = 3.30 respectively) were independently associated with OS in separate analyses. Conclusions: Histologic subtyping of ADC performed on small biopsies is
Urbano-Ispizua, Alvaro; Pavletic, Steven Z; Flowers, Mary E; Klein, John P; Zhang, Mei-Jie; Carreras, Jeanette; Montoto, Silvia; Perales, Miguel-Angel; Aljurf, Mahmoud D; Akpek, Görgün; Bredeson, Christopher N; Costa, Luciano J; Dandoy, Christopher; Freytes, César O; Fung, Henry C; Gale, Robert Peter; Gibson, John; Hamadani, Mehdi; Hayashi, Robert J; Inamoto, Yoshihiro; Inwards, David J; Lazarus, Hillard M; Maloney, David G; Martino, Rodrigo; Munker, Reinhold; Nishihori, Taiga; Olsson, Richard F; Rizzieri, David A; Reshef, Ran; Saad, Ayman; Savani, Bipin N; Schouten, Harry C; Smith, Sonali M; Socié, Gérard; Wirk, Baldeep; Yu, Lolie C; Saber, Wael
The purpose of this study was to analyze the impact of graft-versus-host disease (GVHD) on the relapse rate of different lymphoma subtypes after allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients with a diagnosis of Hodgkin lymphoma, diffuse large B cell lymphoma, follicular lymphoma (FL), peripheral T cell lymphoma, or mantle cell lymphoma (MCL) undergoing HLA-identical sibling or unrelated donor hematopoietic cell transplantation between 1997 and 2009 were included. Two thousand six hundred eleven cases were included. A reduced-intensity conditioning (RIC) regimen was used in 62.8% of the transplantations. In a multivariate analysis of myeloablative cases (n = 970), neither acute (aGVHD) nor chronic GVHD (cGVHD) were significantly associated with a lower incidence of relapse/progression in any lymphoma subtype. In contrast, the analysis of RIC cases (n = 1641) showed that cGVHD was associated with a lower incidence of relapse/progression in FL (risk ratio [RR], .51; P = .049) and in MCL (RR, .41; P = .019). Patients with FL or MCL developing both aGVHD and cGVHD had the lowest risk of relapse (RR, .14; P = .007; and RR, .15; P = .0019, respectively). Of interest, the effect of GVHD on decreasing relapse was similar in patients with sensitive disease and chemoresistant disease. Unfortunately, both aGVHD and cGVHD had a deleterious effect on treatment-related mortality and overall survival (OS) in FL cases but did not affect treatment-related mortality, OS or PFS in MCL. This study reinforces the use of RIC allo-HCT as a platform for immunotherapy in FL and MCL patients.
Urbano-Ispizua, Alvaro; Pavletic, Steven Z.; Flowers, Mary E.; Klein, John P.; Zhang, Mei-Jie; Carreras, Jeanette; Montoto, Silvia; Perales, Miguel-Angel; Aljurf, Mahmoud D.; Akpek, Görgün; Bredeson, Christopher N.; Costa, Luciano J.; Dandoy, Christopher; Freytes, César O.; Fung, Henry C.; Gale, Robert Peter; Gibson, John; Hamadani, Mehdi; Hayashi, Robert J.; Inamoto, Yoshihiro; Inwards, David J.; Lazarus, Hillard M.; Maloney, David G.; Martino, Rodrigo; Munker, Reinhold; Nishihori, Taiga; Olsson, Richard F.; Rizzieri, David A.; Reshef, Ran; Saad, Ayman; Savani, Bipin N.; Schouten, Harry C.; Smith, Sonali M.; Socié, Gérard; Wirk, Baldeep; Yu, Lolie C.; Saber, Wael
Purpose To analyze the impact of graft versus host disease (GVHD) on the relapse rate of different lymphoma subtypes after allogeneic hematopoietic cell transplantation (allo-HCT). Patients and Methods Adult patients with a diagnosis of Hodgkin lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), peripheral T-cell lymphoma (PTCL), or mantle cell lymphoma (MCL) undergoing HLA-identical sibling or unrelated donor HCT between 1997 and 2009 were included. Results Two thousand six hundred and eleven cases were included. Reduced-intensity conditioning (RIC) regimen was used in 62.8% of the transplants. In a multivariate analysis of myeloablative cases (n=970), neither acute (aGVHD) nor chronic GVHD (cGVHD) were significantly associated with a lower incidence of relapse/progression in any lymphoma subtype. In contrast, the analysis of RIC cases (n=1641) showed that cGVHD was associated with a lower incidence of relapse/progression in FL (RR 0.51, p=0.049) and in MCL (RR 0.41, p=0.019). Patients with FL or MCL developing both aGVHD and cGVHD had the lowest risk of relapse (RR 0.14, p=0.007; and RR 0.15, p=0.0019, respectively). Of interest, the effect of GVHD on decreasing relapse was similar in patients with sensitive disease and chemoresistant disease. Unfortunately, both aGVHD and cGVHD had a deleterious effect on treatment related mortality (TRM) and overall survival (OS) in FL cases, and did not impact TRM, OS or PFS in MCL. Conclusion This study reinforces the use of RIC allo-HCT as a platform for immunotherapy in follicular and mantle cell lymphoma patients. PMID:25981509
Cowin, Prue A.; Johnstone, Cameron N.; House, Colin M.; Sheppard, Karen E.; Etemadmoghadam, Dariush; Melnyk, Nataliya; Rustgi, Anil K.; Phillips, Wayne A.; Johnsen, Hilde; Holm, Ruth; Kristensen, Gunnar B.; Birrer, Michael J.; Pearson, Richard B.; Børresen-Dale, Anne-Lise; Huntsman, David G.; deFazio, Anna; Creighton, Chad J.; Smyth, Gordon K.; Bowtell, David D. L.
Molecular subtypes of serous ovarian cancer have been recently described. Using data from independent datasets including over 900 primary tumour samples, we show that deregulation of the Let-7 pathway is specifically associated with the C5 molecular subtype of serous ovarian cancer. DNA copy number and gene expression of HMGA2, alleles of Let-7, LIN28, LIN28B, MYC, MYCN, DICER1, and RNASEN were measured using microarray and quantitative reverse transcriptase PCR. Immunohistochemistry was performed on 127 samples using tissue microarrays and anti-HMGA2 antibodies. Fluorescence in situ hybridisation of bacterial artificial chromosomes hybridized to 239 ovarian tumours was used to measure translocation at the LIN28B locus. Short interfering RNA knockdown in ovarian cell lines was used to test the functionality of associations observed. Four molecular subtypes (C1, C2, C4, C5) of high-grade serous ovarian cancers were robustly represented in each dataset and showed similar pattern of patient survival. We found highly specific activation of a pathway involving MYCN, LIN28B, Let-7 and HMGA2 in the C5 molecular subtype defined by MYCN amplification and over-expression, over-expression of MYCN targets including the Let-7 repressor LIN28B, loss of Let-7 expression and HMGA2 amplification and over-expression. DICER1, a known Let-7 target, and RNASEN were over-expressed in C5 tumours. We saw no evidence of translocation at the LIN28B locus in C5 tumours. The reported interaction between LIN28B and Let-7 was recapitulated by siRNA knockdown in ovarian cancer cell lines. Our results associate deregulation of MYCN and downstream targets, including Let-7 and oncofetal genes, with serous ovarian cancer. We define for the first time how elements of an oncogenic pathway, involving multiple genes that contribute to stem cell renewal, is specifically altered in a molecular subtype of serous ovarian cancer. By defining the drivers of a molecular subtype of serous ovarian cancers we
Yüksel, Mehmet Onur; Gürbüz, Mehmet Sabri; Tanrıverdi, Osman; Özmen, Sevilay Akalp
Lipomatous meningiomas are extremely rare subtypes of benign meningiomas and are classified as metaplastic meningioma in the World Health Organization classification. We present a 77-year-old man presented with the history of a gradually intensifying headache for the last 3 months. A right frontoparietal mass was detected on his cranial magnetic resonance imaging. The patient was operated on via a right frontoparietal craniotomy, and histopathological diagnosis was lipomatous meningioma. Distinctive characteristics of lipomatous meningiomas were discussed with special emphasis to importance of immunohistochemical examinations, particularly for its differentiation from the tumors showing similar histology though having more aggressive character. PMID:28149104
Groheux, David; Mankoff, David; Espié, Marc; Hindié, Elif
Early assessment of response to neoadjuvant chemotherapy (NAC) might be helpful in avoiding the toxicity of ineffective chemotherapy and allowing refinement of treatment. We conducted a review of the literature regarding the applicability of (18)F-FDG PET/CT to the prediction of an early pathological response in different subgroups of breast cancer. Clinical research in this field has intensified in the last few years. Early studies by various groups have shown the potential of (18)F-FDG PET/CT in the early assessment of response to NAC. However, interim PET/CT in breast cancer has not yet gained wide acceptance compared to its use in other settings such as lymphomas. This is in part due to a lack of consensus that early evaluation of response can be used to direct change in therapy in the neoadjuvant breast cancer setting, and only limited data showing that response-adaptive therapy leads to improved outcomes. However, one major element that has hampered the use of (18)F-FDG PET/CT in directing neoadjuvant therapy is its evaluation in populations with mixed subtypes of breast cancer. However, major improvements have occurred in recent years. Pilot studies have highlighted the need for considering breast cancer subtype and the type of treatment, and have offered criteria for the use of PET/CT for the early prediction of response in specific settings. (18)F-FDG PET/CT has considerable potential for the early prediction of pathological complete response to NAC in aggressive subtypes such as triple-negative or HER2-positive breast cancers. The results of a multicentre trial that used early metabolic response on (18)F-FDG PET/CT as a means to select poor responders to adapt neoadjuvant treatment have recently been published. Other trials are ongoing or being planned.
Background To study the expression of D2R, MGMT and VEGF for clinical significance in pituitary adenomas, and to predict the potential curative medical therapy of dopamine agonists, temozolomide and bevacizumab on pituitary adenomas. Methods Immunohistochemistry and western blot were performed to detect the expression of expression of D2R, MGMT and VEGF in pituitary adenoma tissue samples. The ratio of high expression of D2R, MGMT or VEGF in different subtypes of PA was compared by the use of chi-squared tests. The relationships between D2R, MGMT and VEGF expression were assessed by the Spearman rank correlation test. The association between their expression and clinical parameters was analyzed using a chi-squared test, or Fisher's exact probability test when appropriate. Results The data showed that in 197 different histological subtypes of pituitary adenomas (PAs), 64.9% of them were D2R high expression, 86.3% were MGMT low expression and 58.9% were VEGF high expression. D2R high expression existed more frequently in PRL- and GH- secreting PAs. MGMT low expression existed in all PA subtypes. VEGF high expression existed more frequently in PRL, ACTH, FSH secreting and non-functioning PAs. The data of western blot also support the results. Spearman's rank correlation analysis showed that expression of MGMT was positively associated with D2R (r = 0.154, P = 0.031) and VEGF (r = 0.161, P = 0.024) in PAs, but no correlation was showed between D2R and VEGF expression (r = −0.025, P = 0.725 > 0.05). The association between their expression and clinical parameters was analyzed using a chi-squared test, or Fisher's exact probability test when appropriate, but the result showed no significant association. Conclusions PRL-and GH-secreting PAs exist high expression of D2R, responding to dopamine agonists; Most PAs exist low expression of MGMT and high expression of VEGF, TMZ or bevacizumab treatment could be applied under the premise of
DeMarco, Sebastian S; Vos, Paul; Green, Harris; Defazio, Jennifer; Davis, Natalie; Fiz, Lindsey; Phillips, Charles
The results of skin biopsies over a 10 year period were reviewed from the outpatient dermatology clinic at the Brody School of Medicine in Greenville, North Carolina. This research was conducted because there are very few studies that characterize this information over a long-term horizon. The biopsy rate per patient encounter, the clinical reason for the biopsy, the biopsy outcomes, the distribution of cutaneous malignancies per encounter, and the distribution of the subtypes of basal cell carcinoma, squamous cell carcinoma, and melanoma were analyzed. Biopsy logs from January 1, 2001 to December 31, 2010 were reviewed. Our investigation found that 20% of patient encounters resulted in a biopsy. Of these biopsies, 87.9% were performed to rule out malignancy and 12.1% were completed on patients suspected of having inflammatory skin conditions. The basal cell carcinomas diagnosed in Greenville, NC have more aggressive histologic subtypes compared to other studies, whereas the squamous cell carcinomas and melanomas were less aggressive.
Lim, Sang Min; Jeong, Yujeong; Lee, Suhyun; Im, Honggu; Tae, Hyun Seop; Kim, Byung Gyu; Park, Hee Dong; Park, Jonghoon; Hong, Sungwoo
The treatment of activated B cell-like DLBCL (ABC-DLBCL) is one of the urgent unmet medical needs because it is the most resistant DLBCL subtype to current therapies eagerly awaiting effective therapeutic strategies. Recently, the paracaspase MALT1 has emerged as a promising therapeutic target for the treatment of ABC-DLBCL. Herein, we report a new class of MALT1 inhibitors developed by high-throughput screening and structure-based drug design. The original hit, 4-amino-1,2-naphthoquinone series inhibited MALT1 activity but suffered from poor cellular activity. The extensive pharmacophore search led to the discovery of structurally similar β-lapachone that is a direct inhibitor of MALT1 and possesses favorable physicochemical properties. Molecular simulation studies suggested the possibility of the formation of a covalent bond between MALT1 and β-lapachone, which was corroborated by experimental wash-out studies. Inspired by this, we explored the structure-activity relationships by incorporating electron-withdrawing substituents at C8 position of β-lapachone. These MALT1 inhibitors exhibited potent antiproliferative activity to OCI-LY3 cell line and inhibited the cleavage of CYLD mediated MALT1.
Shen, Yao-An; Liu, Chang-Sheng; Chang, Yen-Hou; Chen, Po-Hung; He, Chun-Lin; Wu, Han-Chung; Chuang, Chi-Mu
Currently, epithelial ovarian cancer is viewed as a heterogeneous disease with five major histological subtypes. Clear cell carcinoma represents a specific histological subtype of epithelial ovarian cancer that demonstrates more aggressive clinical behavior and drug resistance compared with other subtypes. Nevertheless, clear cell carcinoma is treated in the same manner as the other subtypes without any particular consideration to its unique clinical characteristics. To improve the therapeutic efficacy of the current liposomal doxorubicin approach for the treatment of clear cell carcinoma, we aimed to develop a novel peptide-conjugated liposomal doxorubicin to actively target this subtype. Two phage clones (OC-6 and OC-26) that specifically bound to clear cell carcinoma were isolated from a phage peptide display library after biopanning procedures. The peptide sequences were translated and aligned (OCSP-6 for OC-6, and OCSP-26 for OC-26, respectively). Peptide-conjugated nanoparticles demonstrated better tumor endocytosis and time-dependent gradual increase of intracellular drug uptake than non-targeting liposomal nanoparticles. Furthermore, peptide-conjugated liposomal doxorubicin better controlled tumors than did non-targeting liposomal doxorubicin. The current work may pave a new way for the development of drugs that target each subtype of epithelial ovarian cancer in the future.
Gentile, Douglas A.; Mathieson, Lindsay C.; Crick, Nicki R.
Although the association between media violence exposure (MVE) and physical aggression (PA) has been well studied, few studies have examined the link between MVE and other subtypes of aggression. The purpose of this study was to examine the relation between MVE and reactive and proactive subtypes of both PA and relational aggression (RA). Six…
Wachter, David L.; Hartmann, Arndt; Beckmann, Matthias W.; Fasching, Peter A.; Hein, Alexander; Bayer, Christian M.; Agaimy, Abbas
Background. Carcinomas of the breast with neuroendocrine features are incorporated in the World Health Organization classification since 2003 and include well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas/small cell carcinomas, and invasive breast carcinomas with neuroendocrine differentiation. Neuroendocrine differentiation is known to be more common in certain low-grade histologic special types and has been shown to mainly cluster to the molecular (intrinsic) luminal A subtype. Methods. We analyzed the frequency of neuroendocrine differentiation in different molecular subtypes of breast carcinomas of no histologic special type using immunohistochemical stains with specific neuroendocrine markers (chromogranin A and synaptophysin). Results. We found neuroendocrine differentiation in 20% of luminal B-like carcinomas using current WHO criteria (at least 50% of tumor cells positive for synaptophysin or chromogranin A). In contrast, no neuroendocrine differentiation was seen in luminal A-like, HER2 amplified and triple-negative carcinomas. Breast carcinomas with neuroendocrine differentiation presented with advanced stage disease and showed aggressive behavior. Conclusions. We conclude that neuroendocrine differentiation is more common than assumed in poorly differentiated luminal B-like carcinomas. Use of specific neuroendocrine markers is thus encouraged in this subtype to enhance detection of neuroendocrine differentiation and hence characterize the biological and therapeutic relevance of this finding in future studies. PMID:24701575
Dykman, Roscoe A.; Ackerman, Peggy T.
This article reviews research on three behavioral subtypes of attention deficit disorder (ADD): (1) without hyperactivity (ADD/WO), (2) with hyperactivity, and (3) with hyperactivity and aggression (ADDHA). Children with ADDHA appear to be at increased risk of having oppositional and conduct disorders, whereas children with ADD/WO show symptoms…
Ferris, Craig F
Vasopressin/oxytocin and related peptides comprise a phylogenetically old superfamily of chemical signals in both vertebrates and invertebrates. Each peptide isoform has its own distinct receptor subtype and specific cellular action. The conservation and dispersion of vasopressin/oxytocin signalling systems across the animal kingdom attests to their functional significance in evolution. Indeed, they are involved in the physiology of fluid balance, carbohydrate metabolism, thermoregulation, immunity and reproduction. In addition, these peptides evolved a role in social behaviours related to aggression and affiliation. The focus of this chapter is the role of vasopressin/oxytocin as chemical signals in the brain altering aggressive responding in a context- and species-dependent manner. There is compelling evidence from several mammalian species including humans that vasopressin enhances aggression. The activity of the vasopressin appears linked to the serotonin system providing a mechanism for enhancing and suppressing aggressive behaviour.
... Listen Español Text Size Email Print Share Aggressive Behavior Page Content Article Body My child is sometimes very aggressive. What is the best ... once they are quiet and still reinforces this behavior, so your child learns that time out means “quiet and still.” ...
van Staaden, Moira J; Searcy, William A; Hanlon, Roger T
From psychological and sociological standpoints, aggression is regarded as intentional behavior aimed at inflicting pain and manifested by hostility and attacking behaviors. In contrast, biologists define aggression as behavior associated with attack or escalation toward attack, omitting any stipulation about intentions and goals. Certain animal signals are strongly associated with escalation toward attack and have the same function as physical attack in intimidating opponents and winning contests, and ethologists therefore consider them an integral part of aggressive behavior. Aggressive signals have been molded by evolution to make them ever more effective in mediating interactions between the contestants. Early theoretical analyses of aggressive signaling suggested that signals could never be honest about fighting ability or aggressive intentions because weak individuals would exaggerate such signals whenever they were effective in influencing the behavior of opponents. More recent game theory models, however, demonstrate that given the right costs and constraints, aggressive signals are both reliable about strength and intentions and effective in influencing contest outcomes. Here, we review the role of signaling in lieu of physical violence, considering threat displays from an ethological perspective as an adaptive outcome of evolutionary selection pressures. Fighting prowess is conveyed by performance signals whose production is constrained by physical ability and thus limited to just some individuals, whereas aggressive intent is encoded in strategic signals that all signalers are able to produce. We illustrate recent advances in the study of aggressive signaling with case studies of charismatic taxa that employ a range of sensory modalities, viz. visual and chemical signaling in cephalopod behavior, and indicators of aggressive intent in the territorial calls of songbirds.
aggressiveness including histologic analysis, Ki-67 proliferative assays, lactate dehydrogenase (LDH) activity, LDH-A expression, cellularity, and micro...assay determinations of cancer aggressiveness including histologic analysis, Ki-67 proliferative assays, lactate dehydrogenase (LDH) activity, LDH-A...distinguish aggressive prostate cancers from indolent disease based on up- regulated lactate - dehydrogenase (LDH) conversion of HP-pyruvate to lactate and
Li, Shaoying; Lin, Pei; Fayad, Luis E; Lennon, Patrick A; Miranda, Roberto N; Yin, C Cameron; Lin, E; Medeiros, L Jeffrey
B-cell lymphomas with MYC/8q24 rearrangement and IGH@BCL2/t(14;18)(q32;q21), also known as double-hit or MYC/BCL2 B-cell lymphomas, are uncommon neoplasms. We report our experience with 60 cases: 52 MYC/BCL2 B-cell lymphomas and 8 tumors with extra MYC signals plus IGH@BCL2 or MYC rearrangement plus extra BCL2 signals/copies. There were 38 men and 22 women with a median age of 55 years. In all, 10 patients had antecedent/concurrent follicular lymphoma. Using the 2008 World Health Organization classification, there were 33 B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (henceforth referred to as unclassifiable, aggressive B-cell lymphoma), 23 diffuse large B-cell lymphoma, 1 follicular lymphoma grade 3B, 1 follicular lymphoma plus diffuse large B-cell lymphoma, 1 B-lymphoblastic lymphoma, and 1 composite diffuse large B-cell lymphoma with B-lymphoblastic lymphoma. Using older classification systems, the 33 unclassifiable, aggressive B-cell lymphomas most closely resembled Burkitt-like lymphoma (n=24) or atypical Burkitt lymphoma with BCL2 expression (n=9). Of 48 cases assessed, 47 (98%) had a germinal center B-cell immunophenotype. Patients were treated with standard (n=23) or more aggressive chemotherapy regimens (n=34). Adequate follow-up was available for 57 patients: 26 died and 31 were alive. For the 52 patients with MYC/BCL2 lymphoma, the median overall survival was 18.6 months. Patients with antecedent/concurrent follicular lymphoma had median overall survival of 7.8 months. Elevated serum lactate dehydrogenase level, ≥2 extranodal sites, bone marrow or central nervous system involvement, and International Prognostic Index >2 were associated with worse overall survival (P<0.05). Morphological features did not correlate with prognosis. Patients with neoplasms characterized by extra MYC signals plus IGH@BCL2 (n=6) or MYC rearrangement with extra BCL2 signals (n=2) had overall survival
Kuppens, Sofie; Grietens, Hans; Onghena, Patrick; Michiels, Daisy
The present study examined specialized associations between parental control and child aggression in a sample of 600 8- to 10-years old children. Parental control dimensions and aggression subtypes were assessed using multiple informants (i.e. children, mothers, fathers, peers, and teachers). In line with expectations, parental physical punishment…
Ludwig, Nicole; Kim, Yoo-Jin; Mueller, Sabine C.; Backes, Christina; Werner, Tamara V.; Galata, Valentina; Sartorius, Elke; Bohle, Rainer M.; Keller, Andreas; Meese, Eckart
Background Micro (mi)RNAs are key regulators of gene expression and offer themselves as biomarkers for cancer development and progression. Meningioma is one of the most frequent primary intracranial tumors. As of yet, there are limited data on the role of miRNAs in meningioma of different histological subtypes and the affected signaling pathways. Methods In this study, we compared expression of 1205 miRNAs in different meningioma grades and histological subtypes using microarrays and independently validated deregulation of selected miRNAs with quantitative real-time PCR. Clinical utility of a subset of miRNAs as biomarkers for World Health Organization (WHO) grade II meningioma based on quantitative real-time data was tested. Potential targets of deregulated miRNAs were discovered with an in silico analysis. Results We identified 13 miRNAs deregulated between different subtypes of benign meningiomas, and 52 miRNAs deregulated in anaplastic meningioma compared with benign meningiomas. Known and putative target genes of deregulated miRNAs include genes involved in epithelial-to-mesenchymal transition for benign meningiomas, and Wnt, transforming growth factor–β, and vascular endothelial growth factor signaling for higher-grade meningiomas. Furthermore, a 4-miRNA signature (miR-222, -34a*, -136, and -497) shows promise as a biomarker differentiating WHO grade II from grade I meningiomas with an area under the curve of 0.75. Conclusions Our data provide novel insights into the contribution of miRNAs to the phenotypic spectrum in benign meningiomas. By deregulating translation of genes belonging to signaling pathways known to be important for meningioma genesis and progression, miRNAs provide a second in line amplification of growth promoting cellular signals. MiRNAs as biomarkers for diagnosis of aggressive meningiomas might prove useful and should be explored further in a prospective manner. PMID:25681310
Ostrov, Jamie M.; Ries, Emily E.; Stauffacher, Kirstin; Godleski, Stephanie A.; Mullins, Adam D.
A short-term longitudinal study examined relational and physical aggression and deceptive behavior among 120 preschool-aged children (M = 44.36 months old, SD = 11.07). Multiple informants and methods (i.e., observational, teacher reports) were used. Evidence for discriminant validity of the observations of aggression subtypes was found. For…
Barry, Tammy D; Thompson, Alice; Barry, Christopher T; Lochman, John E; Adler, Kristy; Hill, Kwoneathia
The present study examined the importance of psychopathy-linked narcissism in predicting proactive and reactive aggression and conduct problems in a group of 160 moderately to highly aggressive children (mean age of 10 years, 9 months). Children's self-report of self-esteem and parent and teacher report of dimensions of psychopathy [narcissism, callous-unemotional (CU) traits, and impulsivity], proactive and reactive aggression, and conduct problems were collected. Composites of parent and teacher ratings of children's behavior were used. Consistent with the study's hypotheses, narcissism predicted unique variance in both proactive and reactive aggression, even when controlling for other dimensions of psychopathy, demographic variables associated with narcissism, and the alternative subtype of aggression. As hypothesized, impulsivity was significantly associated with only reactive aggression. CU traits were not related to proactive or reactive aggression once the control variables were entered. All dimensions of psychopathy predicted unique variance in conduct problems. Consistent with prediction, narcissism was not significantly related to general self-esteem, providing support that narcissism and self-esteem are different constructs. Furthermore, narcissism and self-esteem related differentially to proactive aggression, reactive aggression, and conduct problems. Furthermore, narcissism but not self-esteem accounted for unique variance in aggression and conduct problems. The importance of narcissism in the prediction of aggressive behaviors and clinical implications are discussed.
Kuppens, Sofie; Grietens, Hans; Onghena, Patrick; Michiels, Daisy
The present study examined specialized associations between parental control and child aggression in a sample of 600 8- to 10-years old children. Parental control dimensions and aggression subtypes were assessed using multiple informants (i.e. children, mothers, fathers, peers, and teachers). In line with expectations, parental physical punishment was positively associated with overt aggression, whereas parental psychological control was positively associated with relational aggression in both girls and boys. In addition, this study demonstrated that if both parents employed similar parenting strategies, it appeared to have a cumulative effect on child aggressive behaviour. Associations involving overt aggression were more pronounced for boys than girls, whereas associations involving relational aggression were not moderated by gender. Overall, the present study contributes to an emerging research field by supporting the hypothesis of specialized associations between parental control and child aggression.
Farmer, Cristan A.; Aman, Michael G.
Little is known about the manifestation of aggressive behavior in children with autism, although it is commonly cited as a significant problem. Existing reports in autism do not emphasize subtypes of aggression, whereas distinguishing forms of aggression is commonplace in the typically developing literature. This study compared a sample of 121…
Whitaker, Regina Navonne
Previous research has indicated that preschoolers identified for aggressive behavior would benefit from family, group, or individual therapy. However, there remains an important gap in the current literature regarding treatments for aggressive behavior based on the subtype of aggression. The purpose of this pilot study was to examine if 2…
Estell, David B.; Farmer, Thomas W.; Pearl, Ruth; Van Acker, Richard; Rodkin, Philip C.
Recent studies have found distinct subtypes of aggressive youth, marked by either high social status or social marginalization, and that various measures of status differentially associate with aggression. The majority of these studies, however, focused on boys, adolescents, and/or relational aggression in girls. The current research examined how…
In a sample of 244 first graders, we identified four subtypes of children based on multi-informant measures of victimization by peers and aggression toward peers: aggressive victims (AV), non-victimized aggressors, non-aggressive victims, and non-aggressive, non-victimized (i.e., normative) children. We examined the differences between the…
Bronsveld, Heleen K.; Jensen, Vibeke; Vahl, Pernille; De Bruin, Marie L.; Cornelissen, Sten; Sanders, Joyce; Auvinen, Anssi; Haukka, Jari; Andersen, Morten; Vestergaard, Peter; Schmidt, Marjanka K.
Background Women with diabetes have a worse survival after breast cancer diagnosis compared to women without diabetes. This may be due to a different etiological profile, leading to the development of more aggressive breast cancer subtypes. Our aim was to investigate whether insulin and non-insulin treated women with diabetes develop specific clinicopathological breast cancer subtypes compared to women without diabetes. Methods and Findings This cross-sectional study included randomly selected patients with invasive breast cancer diagnosed in 2000–2010. Stratified by age at breast cancer diagnosis (≤50 and >50 years), women with diabetes were 2:1 frequency-matched on year of birth and age at breast cancer diagnosis (both in 10-year categories) to women without diabetes, to select ~300 patients with tumor tissue available. Tumor MicroArrays were stained by immunohistochemistry for estrogen and progesterone receptor (ER, PR), HER2, Ki67, CK5/6, CK14, and p63. A pathologist scored all stains and revised morphology and grade. Associations between diabetes/insulin treatment and clinicopathological subtypes were analyzed using multivariable logistic regression. Morphology and grade were not significantly different between women with diabetes (n = 211) and women without diabetes (n = 101), irrespective of menopausal status. Premenopausal women with diabetes tended to have more often PR-negative (OR = 2.44(95%CI:1.07–5.55)), HER2-negative (OR = 2.84(95%CI:1.11–7.22)), and basal-like (OR = 3.14(95%CI:1.03–9.60) tumors than the women without diabetes, with non-significantly increased frequencies of ER-negative (OR = 2.48(95%CI:0.95–6.45)) and triple negative (OR = 2.60(95%CI:0.88–7.67) tumors. After adjustment for age and BMI, the associations remained similar in size but less significant. We observed no evidence for associations of clinicopathological subtypes with diabetes in postmenopausal women, or with insulin treatment in general. Conclusions We found no
Ben Salha, Imen; Zaidi, Shane; Noujaim, Jonathan; Miah, Aisha B.; Fisher, Cyril; Jones, Robin L.; Thway, Khin
Dedifferentiated liposarcoma (DDL) is a histologically pleomorphic sarcoma, traditionally defined as well-differentiated liposarcoma with abrupt transition to high grade, non-lipogenic sarcoma. It can occur as part of recurrent well-differentiated liposarcoma, or may arise de novo. DDL most frequently occurs within the retroperitoneum, and while it is prone to local recurrence, it usually has a lower rate of metastasis than other pleomorphic sarcomas. We describe a case of retroperitoneal dedifferentiated liposarcoma in a 63-year-old male, who showed MDM2 amplification with fluorescence in situ hybridization, which displayed unusually aggressive behavior, with brain, lung and subcutaneous soft tissue metastases. As previous reports of metastatic liposarcoma have largely grouped DDL in with other (genetically and clinically distinct) liposarcoma subtypes, we highlight and discuss the rare occurrence of brain metastasis in MDM2-amplified retroperitoneal liposarcoma. PMID:27746879
Poirier, John T.; Gardner, Eric E.; Connis, Nick; Moreira, Andre L.; de Stanchina, Elisa; Hann, Christine L.; Rudin, Charles M.
Small cell lung cancer (SCLC) is an aggressive malignancy characterized by early metastasis, rapid development of resistance to chemotherapy, and genetic instability. This study profiles DNA methylation in SCLC, patient-derived xenografts (PDXs) and cell lines at single nucleotide resolution. DNA methylation patterns of primary samples are distinct from those of cell lines, while PDXs maintain a pattern closely consistent with primary samples. Clustering of DNA methylation and gene expression of primary SCLC revealed distinct disease subtypes among histologically indistinguishable primary patient samples with similar genetic alterations. SCLC is notable for dense clustering of high-level methylation in discrete promoter CpG islands, in a pattern clearly distinct from other lung cancers and strongly correlated with high expression of the E2F target and histone methyltransferase gene EZH2. Pharmacologic inhibition of EZH2 in a SCLC PDX markedly inhibited tumor growth. PMID:25746006
Poirier, J T; Gardner, E E; Connis, N; Moreira, A L; de Stanchina, E; Hann, C L; Rudin, C M
Small cell lung cancer (SCLC) is an aggressive malignancy characterized by early metastasis, rapid development of resistance to chemotherapy and genetic instability. This study profiles DNA methylation in SCLC, patient-derived xenografts (PDX) and cell lines at single-nucleotide resolution. DNA methylation patterns of primary samples are distinct from those of cell lines, whereas PDX maintain a pattern closely consistent with primary samples. Clustering of DNA methylation and gene expression of primary SCLC revealed distinct disease subtypes among histologically indistinguishable primary patient samples with similar genetic alterations. SCLC is notable for dense clustering of high-level methylation in discrete promoter CpG islands, in a pattern clearly distinct from other lung cancers and strongly correlated with high expression of the E2F target and histone methyltransferase gene EZH2. Pharmacologic inhibition of EZH2 in a SCLC PDX markedly inhibited tumor growth.
Beckers, Leif; Petermann, Franz
A precondition of an appropriate treatment of aggressive children and youth is a specific diagnosis. The Reactive-Proactive-Aggression-Questionnaire for 5-10 Graders (RPA 5-10) assesses reactive and proactive aggression and different facets of the subtypes such as angry-aggression, defensive attribution of aggression, obtaining of resources and power/domination-aggression. This study proves the validity of the questionnaire by differential correlates based on a sample of 9 to 17 year-old students (N = 250). The scales of the RPA 5-10 were associated with anger, physical aggression, verbal aggression, conduct problems and decreased prosocial behaviour. Reactive aggression but not proactive aggression was related to hostility, emotional symptoms and peer relationship problems. The relations between reactive aggression and anger and emotional symptoms are based on angry-aggression. Contrary to predictions hyperactivity/inattention was associated with reactive but also with proactive aggression.
Gentile, Douglas A; Coyne, Sarah; Walsh, David A
Many studies have shown that media violence has an effect on children's subsequent aggression. This study expands upon previous research in three directions: (1) by examining several subtypes of aggression (verbal, relational, and physical), (2) by measuring media violence exposure (MVE) across three types of media, and (3) by measuring MVE and aggressive/prosocial behaviors at two points in time during the school year. In this study, 430 3rd-5th grade children, their peers, and their teachers were surveyed. Children's consumption of media violence early in the school year predicted higher verbally aggressive behavior, higher relationally aggressive behavior, higher physically aggressive behavior, and less prosocial behavior later in the school year. Additionally, these effects were mediated by hostile attribution bias. The findings are interpreted within the theoretical framework of the General Aggression Model.
Cleverley, Kristin; Szatmari, Peter; Vaillancourt, Tracy; Boyle, Michael; Lipman, Ellen
Objective: Two common subtypes of aggression (physical and indirect) have been shown to develop concurrently throughout childhood and to uniquely predict maladjustment. However, nothing is known about psychiatric outcomes of joint trajectories of physical aggression (PA) and indirect aggression (IA) in emerging adulthood. Method: Trajectories of…
Takahashi, Aki; Quadros, Isabel M.; de Almeida, Rosa M. M.; Miczek, Klaus A.
Serotonin (5-HT) has long been considered as a key transmitter in the neurocircuitry controlling aggression. Impaired regulation of each subtype of 5-HT receptor, 5-HT transporter, synthetic and metabolic enzymes has been linked particularly to impulsive aggression. The current summary focuses mostly on recent findings from pharmacological and genetic studies. The pharmacological treatments and genetic manipulations or polymorphisms of a specific target (e.g., 5-HT1A receptor) can often result in inconsistent results on aggression, due to “phasic” effects of pharmacological agents vs “trait”-like effects of genetic manipulations. Also, the local administration of a drug using the intracranial microinjection technique has shown that activation of specific subtypes of 5-HT receptors (5-HT1A and 5-HT1B) in mesocorticolimbic areas can reduce species-typical and other aggressive behaviors, but the same receptors in the medial prefrontal cortex or septal area promote escalated forms of aggression. Thus, there are receptor populations in specific brain regions that preferentially modulate specific types of aggression. Genetic studies have shown important gene × environment interactions; it is likely that the polymorphisms in the genes of 5-HT transporters (e.g., MAO A) or rate-limiting synthetic and metabolic enzymes of 5-HT determine the vulnerability to adverse environmental factors that escalate aggression. We also discuss the interaction between the 5-HT system and other systems. Modulation of 5-HT neurons in the dorsal raphe nucleus by GABA, glutamate, and CRF profoundly regulate aggressive behaviors. Also, interactions of the 5-HT system with other neuropeptides (arginine vasopressin, oxytocin, neuropeptide Y, opioid) have emerged as important neurobiological determinants of aggression. Studies of aggression in genetically modified mice identified several molecules that affect the 5-HT system directly (e.g., Tph2, 5-HT1B, 5-HT transporter, Pet1, MAOA) or
Shaw, Phyllis A; Friedman, Erica S
Providing a context for learning information and requiring learners to teach specific content has been demonstrated to enhance knowledge retention. To enhance students' appreciation of the role of science and specifically histology in clinical reasoning, disease diagnosis, and treatment, a new teaching format was created to provide clinical context, promote integration and application of science knowledge, and to foster peer teaching and learning: the Clinico-Histologic Conference (CHC) for the Mount Sinai School of Medicine Histology course. Teams of six students were each assigned specific disease processes and were charged with creating oral presentations and handouts that taught their classmates about the clinical manifestations, etiopathogeneses, diagnoses, and treatments of the assigned processes, along with comparisons of normal histology to the pathology of the disease. Each team also created four questions, some of which were used on Histology written examinations. The physician facilitator evaluated the presentation and handouts. About two-thirds of students agreed the CHC enhanced appreciation of the importance of histology, provided a context for integration and application of basic science to patient care and enhanced their ability to teach their peers. Student feedback demonstrated that the CHCs were successful in promoting teamwork, peer teaching, and the application of histology to diagnose diseases. The authors believe that teaching basic science content in this new format enhanced student learning and application of medical knowledge, and that this new teaching format can be adopted by other medical school courses.
Gao, Yu; Tuvblad, Catherine; Schell, Anne; Baker, Laura; Raine, Adrian
Autonomic fear conditioning deficits have been linked to child aggression and adult criminal behavior. However, it is unknown if fear conditioning deficits are specific to certain subtypes of aggression, and longitudinal research is rare. In the current study, reactive and proactive aggression were assessed in a sample of males and females when aged 10, 12, 15, and 18 years old. Skin conductance fear conditioning data were collected when they were 18 years old. Individuals who were persistently high on proactive aggression measures had significantly poorer conditioned responses at 18 years old when compared to others. This association was not found for reactive aggression. Consistent with prior literature, findings suggest that persistent antisocial individuals have unique neurobiological characteristics and that poor autonomic fear conditioning is associated with the presence of increased instrumental aggressive behavior.
Gao, Yu; Tuvblad, Catherine; Schell, Anne; Baker, Laura; Raine, Adrian
Autonomic fear conditioning deficits have been linked to child aggression and adult criminal behavior. However, it is unknown if fear conditioning deficits are specific to certain subtypes of aggression, and longitudinal research is rare. In the current study, reactive and proactive aggression were assessed in a sample of males and females when aged 10, 12, 15, and 18 years old. Skin conductance fear conditioning data were collected when they were 18 years old. Individuals who were persistently high on proactive aggression measures had significantly poorer conditioned responses at 18 years old when compared to others. This association was not found for reactive aggression. Consistent with prior literature, findings suggest that persistent antisocial individuals have unique neurobiological characteristics and that poor autonomic fear conditioning is associated with the presence of increased instrumental aggressive behavior. PMID:25174802
Muglia, Valdair F; Prando, Adilson
Renal cell carcinoma (RCC) is the seventh most common histological type of cancer in the Western world and has shown a sustained increase in its prevalence. The histological classification of RCCs is of utmost importance, considering the significant prognostic and therapeutic implications of its histological subtypes. Imaging methods play an outstanding role in the diagnosis, staging and follow-up of RCC. Clear cell, papillary and chromophobe are the most common histological subtypes of RCC, and their preoperative radiological characterization, either followed or not by confirmatory percutaneous biopsy, may be particularly useful in cases of poor surgical condition, metastatic disease, central mass in a solitary kidney, and in patients eligible for molecular targeted therapy. New strategies recently developed for treating renal cancer, such as cryo and radiofrequency ablation, molecularly targeted therapy and active surveillance also require appropriate preoperative characterization of renal masses. Less common histological types, although sharing nonspecific imaging features, may be suspected on the basis of clinical and epidemiological data. The present study is aimed at reviewing the main clinical and imaging findings of histological RCC subtypes.
Newman, Brenda; Hu, Weimin; Nigro, Kelly; Gilliam, Anita C
Histiocytoses are a heterogeneous group of disorders that are characterized by the proliferation and accumulation of reactive or neoplastic histiocytes. Three classes of histiocytoses have been defined: class I, Langerhans cell disease; class II, non-Langerhans cell histiocytic disease without features of malignancy; and class III, malignant histiocytic disorders. Although the disorders in classes I and II usually have a benign appearance on histology and are commonly non-aggressive and self-healing, some can cause debilitating or even fatal outcomes. Such cases beg the question: what stimulates aggressive behavior of a classically benign disease? New molecular information may now provide insight into the driving force behind many of the aggressive histiocytoses. In this article, we review Langerhans cell disease and seven aggressive histiocytoses that can involve skin, discuss histologic features that may forecast a poor prognosis, and discuss the molecular findings that help to explain the pathophysiology of these aggressive histiocytic disorders.
Burt, S Alexandra; Donnellan, M Brent
There is converging evidence that physical aggression, rule-breaking, and social aggression constitute meaningfully distinct, if somewhat overlapping, components of the broader construct of antisocial behavior. Indeed, these subtypes appear to have different developmental trajectories, demographic correlates, and personological underpinnings. They also demonstrate important etiological distinctions. One potential limitation to accumulating additional scientific insights into the correlates and origins of these three types of antisocial behavior is the lack of an efficient self-report assessment in the public domain. We developed the 32-item Subtypes of Antisocial Behavior Questionnaire (STAB) to fill this gap. Our goal was to develop a brief measure that could reliably and validly assess each of the three major subtypes of antisocial behavior and that would be freely available for other researchers. The present series of studies provides initial evidence of the factorial validity, internal consistency, and criterion-related validity of the STAB scales. In short, it appears that the STAB is a brief and useful measure that can be used to differentiate and assess physically aggressive, rule-breaking, and socially aggressive forms of antisocial behavior.
Jambroes, Tijs; Jansen, Lucres M C; Vermeiren, Robert R J M; Doreleijers, Theo A H; Colins, Olivier F; Popma, Arne
In DSM 5, conduct disorder (CD) has been expanded with a new specifier 'with Limited Prosocial Emotions' (LPE) in addition to the age-of-onset (AoO) subtyping, and is thought to identify a severe antisocial subgroup of CD. However, research in clinical practice has been scarce. Therefore, the current study will examine differences in clinical symptoms between subtypes of CD, based on both subtyping schemes. Subsequently, it will investigate whether the LPE specifier explains unique variance in aggression, added to the AoO subtyping. A sample of 145 adolescents with CD (51 % male, mean age 15.0) from a closed treatment institution participated in this study. CD diagnoses and AoO subtype were assessed using a structured diagnostic interview. The LPE specifier was assessed using the callous-unemotional dimension of the Youth Psychopathy Traits Inventory (YPI). Self-reported proactive and reactive aggression, rule-breaking behavior and internalizing problems within the subtypes were compared. Youth with childhood-onset CD and LPE showed significantly more aggression than adolescent-onset CD without LPE (proactive aggression: F = 3.1, p < 0.05, reactive aggression: F = 3.7, p < 0.05). Hierarchical regression revealed that the LPE specifier uniquely explained 7 % of the variance in reactive aggression, additionally to the AoO subtyping. For proactive aggression, the interaction between AoO and the LPE added 4.5 % to the explained variance. Although the LPE specifier may help to identify a more aggressive subtype of CD in adolescents, the incremental utility seems to be limited. Therefore, clinical relevance of the LPE specifier in high-risk adolescent samples still needs to be investigated thoroughly.
Rousseaux, Sophie; Debernardi, Alexandra; Jacquiau, Baptiste; Vitte, Anne-Laure; Vesin, Aurélien; Nagy-Mignotte, Hélène; Moro-Sibilot, Denis; Brichon, Pierre-Yves; Lantuejoul, Sylvie; Hainaut, Pierre; Laffaire, Julien; de Reyniès, Aurélien; Beer, David G.; Timsit, Jean-François; Brambilla, Christian; Brambilla, Elisabeth; Khochbin, Saadi
Activation of normally silent tissue-specific genes and the resulting cell “identity crisis” are the unexplored consequences of malignant epigenetic reprogramming. We designed a strategy for investigating this reprogramming, which consisted of identifying a large number of tissue-restricted genes that are epigenetically silenced in normal somatic cells and then detecting their expression in cancer. This approach led to the demonstration that large-scale “off-context” gene activations systematically occur in a variety of cancer types. In our series of 293 lung tumors, we identified an ectopic gene expression signature associated with a subset of highly aggressive tumors, which predicted poor prognosis independently of the TNM (tumor size, node positivity, and metastasis) stage or histological subtype. The ability to isolate these tumors allowed us to reveal their common molecular features characterized by the acquisition of embryonic stem cell/germ cell gene expression profiles and the down-regulation of immune response genes. The methodical recognition of ectopic gene activations in cancer cells could serve as a basis for gene signature–guided tumor stratification, as well as for the discovery of oncogenic mechanisms, and expand the understanding of the biology of very aggressive tumors. PMID:23698379
Campara, Zoran; Spasic, Aleksandar; Aleksic, Predrag; Milev, Bosko
Introduction: Aggressive fibromatosis (AF) is a heterogeneous group of mesenchymal tumors that have locally infiltrative growth and a tendency to relapse. The clinical picture is often conditioned by the obstruction of the ureter or small intestine. Diagnosis is based on clinical, radiological and histological parameters. A case report: We report a case of male patient, aged 35 years, with the retroperitoneal fibromatosis. He reported to the physician because of frequent urination with the feeling of pressure and pain. Computed tomography revealed the tumor mass on the front wall of the bladder with diameter of 70mm with signs of infiltration of the musculature of the anterior abdominal wall. Endoscopic transurethral biopsy showed proliferative lesion binders by type of fibromatosis. The tumor was surgically removed in a classical way. The patient feels well and has no recurrence thirty-six months after the operative procedure. Conclusion: The complete tumor resection is the therapeutic choice for the primary tumor as well as for a relapse. PMID:27147794
Becker, Stephen P.; Luebbe, Aaron M.; Stoppelbein, Laura; Greening, Leilani; Fite, Paula J.
Competing hypotheses for explaining the role of anxiety in the relation between attention-deficit/hyperactivity disorder (ADHD) symptoms and childhood aggression were evaluated. Two studies tested whether anxiety exacerbated, attenuated, or had no effect on the relation between ADHD and aggression subtypes among psychiatrically hospitalized…
Fite, Paula J.; Hendrickson, Michelle; Rubens, Sonia L.; Gabrielli, Joy; Evans, Spencer
Background: There is substantial evidence to suggest that aggressive behavior is associated with poor academic performance in school-aged children. However, less is known about how different subtypes of aggression are related to academic performance and what variables may account for this association. Objective: The current study examined unique…
Greening, Leilani; Stoppelbein, Laura; Luebbe, Aaron; Fite, Paula J.
Two subtypes of aggression--reactive and proactive--were examined to see how they relate to suicidal behaviors among young children admitted for acute psychiatric inpatient care. The children and their parents completed self-report questionnaires/interviews. Regression analyses revealed that depressed girls who scored higher on reactive aggression…
Fite, Paula J.; Vitulano, Michael; Wynn, Porche'; Wimsatt, Amber; Gaertner, Alden; Rathert, Jamie
The current study examined associations between perceived neighborhood safety and proactive and reactive subtypes of aggression while also considering peer delinquency and poor parental monitoring in a community recruited sample of 89 children (56% male) ranging from 9 to 12 years of age (M=10.44, SD=1.14). In addition, neighborhood safety was…
Hubbard, S.M.; Chabner, B.A.; DeVita, V.T., Jr.; Simon, R.; Berard, C.W.; Jones, R.B.; Garvin, A.J.; Canellos, G.P.; Osborne, C.K.; Young, R.C.
The clinical course and biopsy specimens from 515 consecutive non-Hodgkin's lymphoma patients was evaluated retrospectively in an attempt to determine the clinical importance of documented changes in histology over time. Two-hundred and five of these patients has an initial diagnosis of nodular lymphoma and were reviewed for this anaysis. Sixty-three underwent a repeat biopsy greater than 6 mo after initial diagnosis. In 23 patients, these repeat biopsies revealed a change in histology to a diffuse pattern and/or a change to a larger ''histiocytic'' cell type, while repeat biopsies for the other 40 (63%) disclosd persistence of a nodular pattern and no clear change in basic cell type. Progression from nodular lymphoma to diffuse histiocytic, mixed, or undifferentiated types of lymphomas of Rappaport was found in repeate biopsies obtained from 19 patients (30%). Prognosis for survival following a biopsy that demonstrated histologic change was related to the histology demonstrated at the most recent biopsy and to the response to subsequent drug treatment. Survival following repeat biopsy for these 19 patients was significantly shorter than for the 40 patients whose histology remained nodular (p < 0.001). However, attainment of a complete remission with intensive combination chemotherapy was associated with prolonged survival in eight patients and prolonged disease-free survival in one patient. Since prior treatment may compromise the ability to achieve a complete response to chemotherapy in patients with nodular lymphoma who develop an aggressive diffuse histology, the likelihood of histologic progression must be considered in the design of future clinical trials in nodular lymphoma. Histologic progression does not preclude attainment of a complete response to intensive chemotherapy.
Vachon, David D.; Bagby, R. Michael
Although pathological gambling (PG) is regarded in the 4th edition of the "Diagnostic and Statistical Manual of Mental Disorders" (American Psychiatric Association, 1994) as a unitary diagnostic construct, it is likely composed of distinct subtypes. In the current report, the authors used cluster analyses of personality traits with a…
Shaw, Phyllis A.; Friedman, Erica S.
Providing a context for learning information and requiring learners to teach specific content has been demonstrated to enhance knowledge retention. To enhance students' appreciation of the role of science and specifically histology in clinical reasoning, disease diagnosis, and treatment, a new teaching format was created to provide clinical…
Reviews the acute effects of alcohol on aggressive responding. From experimental studies that use human subjects, it is concluded that a moderate dose of alcohol does not increase aggression if subjects are unprovoked. Under provocative situations, aggression is increased as a function of alcohol intoxication, provided that subjects are restricted…
Fossati, Andrea; Borroni, Serena; Eisenberg, Nancy; Maffei, Cesare
In recent years, there has been increasing acknowledgment of the multidimensionality of narcissism and that different types of narcissism may relate differently to other domains of functioning. Similarly, aggression-a frequently discussed correlate of narcissism-is a heterogeneous construct. In this study, the relations of proactive and reactive aggression with overt and covert manifestations of narcissism were examined in a sample of 674 Italian high school students (mean age=15.5 years, SD=2.1 years). Overt narcissism was positively related to both proactive and reactive subtypes of aggression, whereas covert narcissism related only to reactive aggression. Vanity, Authority, Exhibitionism, and Exploitativeness were the components of overt narcissism related to Proactive Aggression (all remained unique correlates when controlling for Reactive Aggression), whereas Reactive Aggression was associated with the Exhibitionism, Superiority, and Entitlement subscales (only the latter was uniquely related when controlling for Proactive Aggression).
Estell, David B; Farmer, Thomas W; Pearl, Ruth; Van Acker, Richard; Rodkin, Philip C
Recent studies have found distinct subtypes of aggressive youth, marked by either high social status or social marginalization, and that various measures of status differentially associate with aggression. The majority of these studies, however, focused on boys, adolescents, and/or relational aggression in girls. The current research examined how the kind of status measured and the social ecology affect the association between overt aggression and social status in a sample of 187 3rd grade girls. Cluster analysis uncovered aggressive-popular, aggressive-unpopular, and prosocial-popular configurations. Although likeability was related solely to prosocial behavior, other measures of status co-occurred with both prosocial and aggressive behavior. Peer-group behavior complemented that of individuals, though peer-group and classroom acceptance of aggression were not related to cluster prevalence.
Versteven, Marijke; Vanden Broeck, Lies; Geurten, Bart; Zwarts, Liesbeth; Decraecker, Lisse; Beelen, Melissa; Göpfert, Martin C; Heinrich, Ralf; Callaerts, Patrick
Aggression is a universal social behavior important for the acquisition of food, mates, territory, and social status. Aggression in Drosophila is context-dependent and can thus be expected to involve inputs from multiple sensory modalities. Here, we use mechanical disruption and genetic approaches in Drosophila melanogaster to identify hearing as an important sensory modality in the context of intermale aggressive behavior. We demonstrate that neuronal silencing and targeted knockdown of hearing genes in the fly's auditory organ elicit abnormal aggression. Further, we show that exposure to courtship or aggression song has opposite effects on aggression. Our data define the importance of hearing in the control of Drosophila intermale aggression and open perspectives to decipher how hearing and other sensory modalities are integrated at the neural circuit level.
Stanojevic, Maja; Papa, Anna; Papadimitriou, Evagelia; Zerjav, Sonja; Jevtovic, Djordje; Salemovic, Dubravka; Jovanovic, Tanja; Antoniadis, Antonis
To gain insight concerning the genetic diversity of HIV-1 viruses associated with the HIV-1 epidemic in Yugoslavia, 45 specimens from HIV-1-infected individuals were classified into subtypes by sequence-based phylogenetic analysis of the polymerase (pol) region of the viral genome. Forty-one of 45 specimens (91.2%) were identified as pol subtype B, 2 of 45 as subtype C (4.4%), 1 of 45 as CRF01_AE (2.2%), and 1 as CRF02_AG recombinant (2.2%). Nucleotide divergence among subtype B sequences was 4.8%. Results of this study show that among HIV-1-infected patients in Yugoslavia subtype B predominates (91.5%), whereas non-B subtypes are present at a low percentage, mostly related to travel abroad.
Elkourashy, Sarah A.; Nashwan, Abdulqadir J.; Alam, Syed I.; Ammar, Adham A.; El Sayed, Ahmed M.; Omri, Halima El; Yassin, Mohamed A.
Extranodal lymphoma (ENL) occurs in approximately 30%–40% of all patients with non-Hodgkin lymphoma and has been described in almost all organs and tissues. However, diffuse large B-cell lymphoma is the most common histological subtype of non-Hodgkin lymphoma, primarily arising in the retroperitoneal region. In this article, we report a rare case of an adult male diagnosed with primary diffuse large B-cell lymphoma of the gluteal and adductor muscles with aggressive bone involvement. All appropriate radiological and histopathological studies were done for diagnosis and staging. After discussion with the lymphoma multidisciplinary team, it was agreed to start on R-CHOP protocol (rituximab, cyclophosphamide, doxorubicin (Adriamycin), vincristine (Oncovin®), and prednisone) as the standard of care, which was later changed to R-CODOX-M/R-IVAC protocol (rituximab, cyclophosphamide, vincristine (Oncovin®), doxorubicin, and high-dose methotrexate alternating with rituximab, ifosfamide, etoposide, and high-dose cytarabine) due to inadequate response. Due to the refractory aggressive nature of the disease, subsequent decision of the multidisciplinary team was salvage chemotherapy and autologous stem cell transplant. The aim of this case report was to describe and evaluate the clinical presentation and important radiological features of extranodal lymphoma affecting the musculoskeletal system. PMID:27398038
Fossati, Andrea; Borroni, Serena; Eisenberg, Nancy; Maffei, Cesare
In recent years, there has been increasing acknowledgement of the multidimensionality of narcissism and that different types of narcissism may relate differently to other domains of functioning. Similarly, aggression—a frequently discussed correlate of narcissism--is a heterogeneous construct. In the present study, the relations of proactive and reactive aggression with overt and covert manifestations of narcissism were examined in a sample of 674 Italian high school students (mean age = 15.5 years, SD = 2.1 years). Overt narcissism was positively related to both proactive and reactive subtypes of aggression, whereas covert narcissism related only to reactive aggression. Vanity, Authority, Exhibitionism, and Exploitativeness were the components of overt narcissism related to Proactive Aggression (all remained unique correlates when controlling for Reactive Aggression), whereas Reactive Aggression was associated with the Exhibitionism, Superiority, and Entitlement subscales (only the latter was uniquely related when controlling for Proactive Aggression). PMID:19918915
Ballance, W A; Mendelsohn, G; Carter, J R; Abdul-Karim, F W; Jacobs, G; Makley, J T
A distinctly different entity from the now well-delineated malignant fibrous histiocytoma (MFH) of bone is the MFH histopathologic subtype of osteogenic sarcoma. Although uncommon, recently the authors have encountered six cases of this neoplasm, in each of which the soft tissue component was devoid of bone elements and was microscopically indistinguishable from MFH of bone or soft tissue. Neoplastic osteoid and woven bone were present in the osseous component of each tumor, however. Radiologically, the lesions generally were osteoblastic but focally osteolytic with features typical of osteogenic sarcoma. Pain was the most common presenting symptom. There was no age or sex predilection. Immunocytochemical staining showed strong positivity with alpha-1-antichymotrypsin within malignant bizarre giant cells and occasional neoplastic osteoblasts in five cases. The biological behavior followed a very aggressive course. Four of the six patients developed pulmonary metastases 6 to 12 months after initial surgery; one patient presented initially with pulmonary metastases. Adequate tumor sampling as well as optimal correlation with clinical and radiographic information are required to distinguish the MFH subtype of osteogenic sarcoma from MFH of bone, both being high-grade neoplasms, however.
Mavrogenis, Andreas F; Angelini, Andrea; Panagopoulos, Georgios N; Pala, Elisa; Calabrò, Teresa; Igoumenou, Vasilios G; Katzouraki, Galatia; Megaloikonomos, Panayiotis D; Pneumaticos, Spyros G; Papagelopoulos, Panayiotis J; Ruggieri, Pietro
The authors reviewed the files of all patients with chordomas who were admitted and treated at their institutions from 1975 to 2012. Patients were categorized by early local recurrence and metastasis. Aggressive clinical behavior was defined as local recurrence and metastasis within 24 months of diagnosis and adequate treatment (wide en bloc resection with microscopically negative tumor margins). According to these criteria, 13 patients (14.3%) had aggressive chordomas, including 7 men and 6 women, with mean age of 54 years (range, 37-65 years) at diagnosis and treatment. All patients had preoperative tumor biopsy, followed by resection with partial (7 patients) or total sacrectomy (6 patients). In all cases, biopsy and histologic analysis of resected tumor specimens showed conventional chordomas. Resection margins were wide (grossly negative) in 6 patients and wide contaminated in 7 patients. Mean maximum tumor diameter was 11.8 cm (range, 5-21 cm). Mean follow-up was 43 months (range, 8-131 months). Rates of local recurrence, metastasis, and death were evaluated. At the last follow-up, all patients had local recurrence at a mean of 13 months (range, 5-22 months). Histologic examination of recurrent tumors showed a dedifferentiated chordoma with a fibrosarcoma component in 2 patients and no histologic change in the remaining patients. In addition, 8 patients had metastases at a mean of 13 months (range, 4-24 months) and died of their disease. All histologic findings of metastatic lesions were similar to those of primary tumors. Early diagnosis of aggressive tumors requires close follow-up of patients with chordomas. Metastasis is common, with resultant poor survival. [Orthopedics. 2017; 40(2):e248-e254.].
Kimbung, Siker; Kovács, Anikó; Danielsson, Anna; Bendahl, Pär-Ola; Lövgren, Kristina; Stolt, Marianne Frostvik; Tobin, Nicholas P.; Lindström, Linda; Bergh, Jonas; Einbeigi, Zakaria; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid
The relevance of the intrinsic subtypes for clinical management of metastatic breast cancer is not comprehensively established. We aimed to evaluate the prevalence and prognostic significance of drifts in tumor molecular subtypes during breast cancer progression. A well-annotated cohort of 304 women with advanced breast cancer was studied. Tissue microarrays of primary tumors and synchronous lymph node metastases were constructed. Conventional biomarkers were centrally assessed and molecular subtypes were assigned following the 2013 St Gallen guidelines. Fine-needle aspirates of asynchronous metastases were transcriptionally profiled and subtyped using PAM50. Discordant expression of individual biomarkers and molecular subtypes was observed during tumor progression. Primary luminal-like tumors were relatively unstable, frequently adopting a more aggressive subtype in the metastases. Notably, loss of ER expression and a luminal to non-luminal subtype conversion was associated with an inferior post-recurrence survival. In addition, ER and molecular subtype assessed at all tumor progression stages were independent prognostic factors for post-recurrence breast cancer mortality in multivariable analyses. Our results demonstrate that drifts in tumor molecular subtypes may occur during tumor progression, conferring adverse consequences on outcome following breast cancer relapse. PMID:26375671
Amann, Birgit H.
Abstract Objective: This article examines the characteristics of impulsive aggression (IA) as a comorbidity in children and adolescents with attention-deficit/hyperactivity disorder (ADHD), focusing on its incidence, impact on ADHD outcomes, need for timely intervention, and limitations of current treatment practices. Methods: Relevant literature was retrieved with electronic searches in PubMed and PsycINFO using the search strategy of “ADHD OR attention deficit hyperactivity disorder” AND “impulsive aggression OR reactive aggression OR hostile aggression OR overt aggression” AND “pediatric OR childhood OR children OR pre-adolescent OR adolescent” with separate searches using review OR clinical trial as search limits. Key articles published before the 2007 Expert Consensus Report on IA were identified using citation analysis. Results: More than 50% of preadolescents with ADHD combined subtype reportedly display clinically significant aggression, with impulsive aggression being the predominant subtype. Impulsive aggression is strongly predictive of a highly unfavorable developmental trajectory characterized by the potential for persistent ADHD, increasing psychosocial burden, accumulating comorbidities, serious lifelong functional deficits across a broad range of domains, delinquency/criminality, and adult antisocial behavior. Impulsive aggression, which triggers peer rejection and a vicious cycle of escalating dysfunction, may be a key factor in unfavorable psychosocial outcomes attributed to ADHD. Because severe aggressive behavior does not remit in many children when treated with primary ADHD therapy (i.e., stimulants and behavioral therapy), a common practice is to add medication of a different class to specifically target aggressive behavior. Conclusions: Impulsive aggression in children and adolescents with ADHD is a serious clinical and public health problem. Although adjunctive therapy with an aggression-targeted agent is widely recommended when
Gentile, Douglas A.; Linder, Jennifer R.; Walsh, David A.
Many studies have shown that media violence has an effect on children's subsequent aggression. This study expands upon previous research in three directions: (1) by examining several subtypes of aggression (verbal, relational, and physical); (2) by measuring media violence exposure across three types of media (television, movies/videos, and video…
Studies comparing aggressive and nonaggressive prisoners show higher testosterone levels among the former. While there is limited evidence for a strong association between aggressiveness and testosterone during adolescence, other studies indicate that testosterone levels are responsive to influences from the social environment, particularly those…
Underwood, Marion K.
Noting recent interest in girls' social or "relational" aggression, this volume offers a balanced, scholarly analysis of scientific knowledge in this area. The book integrates current research on emotion regulation, gender, and peer relations, to examine how girls are socialized to experience and express anger and aggression from infancy…
Lane, Scott D.; Kjome, Kimberly L.; Moeller, F. Gerard
Synopsis Aggression is a serious medical problem that can place both the patient and the health care provider at risk. Aggression can result from medical, neurologic and or psychiatric disorders. A comprehensive patient evaluation is needed. Treatment options include pharmacotherapy as well as non-pharmacologic interventions, both need to be individualized to the patient. PMID:21172570
Barrick, Ann Louise; And Others
Although humor is an important phenomenon in human interactions, it has rarely been studied in the elderly. An understanding of responses to humor in aggressive cartoons as a function of advancing age would provide information regarding both the development of humor and the negative (aggressive) emotional experiences of the elderly. This study was…
Brown, Serena-Lynn; And Others
Decreased serotonin function has consistently been shown to be highly correlated with impulsive aggression across a number of different experimental paradigms. Such lowered serotonergic indices appear to correlate with the dimension of aggression dyscontrol and/or impulsivity rather than with psychiatric diagnostic categories per se. Implications…
Buesa, René J
An analysis of histology salaries from the last 4 national surveys conducted by the American Society of Clinical Pathologists is presented. The regional variations within and between years for histology salaries presented in the last 4 national surveys of medical laboratory specialties are not statistically significant. Local variations greater than the national variations reflect the preponderant effect of local supply and demand over regional characteristics. Salaries by hospitals are significantly different only between 2 size categories and the supervisors' salary. There is no correlation between the salary increase for any histology position in any one year and the vacancy level in the previous year. On the other hand, the correlation between histotechnicians' salaries and both the cost of living and the median income are significant, as well as between the latter and the supervisors' salary. The histotechnologists' salaries are significantly correlated with the consumer price index but not with the inflation rate. A survey of histology salaries in foreign countries was also undertaken and compared with salaries in the United States. National salaries rank close to the general average for 10 foreign countries when expressed as ratios with the personal gross domestic product or with the countries' minimum wage. For the midpoint salary ranges, the United States ranks fourth after Canada, the United Kingdom, and Australia, the latter 3 countries with structured pay rates adjusted to local costs of living in contrast with United States' salary characteristics. Histology salaries rest on negotiations within each employer's salary structure and fluctuate according to license level, documented studies, special training(s), years of experience, references, and the ability to negotiate, where each side tries to take advantage of the other. The result is a heterogeneous and chaotic salary situation driven by personal and local needs, where the histology worker usually
AWARD NUMBER: W81XWH-14-1-0223 TITLE: Genetic and Epigenetic Determinants of Lung Cancer Subtype: Adenocarcinoma to Small Cell Conversion...COVERED 1Aug2014 - 31Jul2015 4. TITLE AND SUBTITLE Genetic and Epigenetic Determinants of Lung Cancer Subtype: 5a. CONTRACT NUMBER W81XWH-14-1-0223...histologies of lung cancer is made difficult in part because of the extensive genetic and epigenetic changes that occur in lung carcinogenesis, the
Nitta, Masayuki; Muragaki, Yoshihiro; Maruyama, Takashi; Ikuta, Soko; Komori, Takashi; Maebayashi, Katsuya; Iseki, Hiroshi; Tamura, Manabu; Saito, Taiichi; Okamoto, Saori; Chernov, Mikhail; Hayashi, Motohiro; Okada, Yoshikazu
OBJECT There is no standard therapeutic strategy for low-grade glioma (LGG). The authors hypothesized that adjuvant therapy might not be necessary for LGG cases in which total radiological resection was achieved. Accordingly, they established a treatment strategy based on the extent of resection (EOR) and the MIB-1 index: patients with a high EOR and low MIB-1 index were observed without postoperative treatment, whereas those with a low EOR and/or high MIB-1 index received radiotherapy (RT) and/or chemotherapy. In the present retrospective study, the authors reviewed clinical data on patients with primarily diagnosed LGGs who had been treated according to the above-mentioned strategy, and they validated the treatment policy. Given their results, they will establish a new treatment strategy for LGGs stratified by EOR, histological subtype, and molecular status. METHODS One hundred fifty-three patients with diagnosed LGG who had undergone resection or biopsy at Tokyo Women's Medical University between January 2000 and August 2010 were analyzed. The patients consisted of 84 men and 69 women, all with ages ≥ 15 years. A total of 146 patients underwent surgical removal of the tumor, and 7 patients underwent biopsy. RESULTS Postoperative RT and nitrosourea-based chemotherapy were administered in 48 and 35 patients, respectively. Extent of resection was significantly associated with both overall survival (OS; p = 0.0096) and progression-free survival (PFS; p = 0.0007) in patients with diffuse astrocytoma but not in those with oligodendroglial subtypes. Chemotherapy significantly prolonged PFS, especially in patients with oligodendroglial subtypes (p = 0.0009). Patients with a mutant IDH1 gene had significantly longer OS (p = 0.034). Multivariate analysis did not identify MIB-1 index or RT as prognostic factors, but it did identify chemotherapy as a prognostic factor for PFS and EOR as a prognostic factor for OS and PFS. CONCLUSIONS The findings demonstrated that EOR was
Nistal, Manuel; Calvo, Enrique; Madero, Rosario; Díaz, Esther; Camafeita, Emilio; de Castro, Javier; López, Juan Antonio; González-Barón, Manuel; Espinosa, Enrique; Fresno Vara, Juan Ángel
Background Proteomics is expected to play a key role in cancer biomarker discovery. Although it has become feasible to rapidly analyze proteins from crude cell extracts using mass spectrometry, complex sample composition hampers this type of measurement. Therefore, for effective proteome analysis, it becomes critical to enrich samples for the analytes of interest. Despite that one-third of the proteins in eukaryotic cells are thought to be phosphorylated at some point in their life cycle, only a low percentage of intracellular proteins is phosphorylated at a given time. Methodology/Principal Findings In this work, we have applied chromatographic phosphopeptide enrichment techniques to reduce the complexity of human clinical samples. A novel method for high-throughput peptide profiling of human tumor samples, using Parallel IMAC and MALDI-TOF MS, is described. We have applied this methodology to analyze human normal and cancer lung samples in the search for new biomarkers. Using a highly reproducible spectral processing algorithm to produce peptide mass profiles with minimal variability across the samples, lineal discriminant-based and decision tree–based classification models were generated. These models can distinguish normal from tumor samples, as well as differentiate the various non–small cell lung cancer histological subtypes. Conclusions/Significance A novel, optimized sample preparation method and a careful data acquisition strategy is described for high-throughput peptide profiling of small amounts of human normal lung and lung cancer samples. We show that the appropriate combination of peptide expression values is able to discriminate normal lung from non-small cell lung cancer samples and among different histological subtypes. Our study does emphasize the great potential of proteomics in the molecular characterization of cancer. PMID:19890392
de Anda-Jáuregui, Guillermo; Velázquez-Caldelas, Tadeo E; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique
Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes. In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach. We use 493 samples of primary breast cancer tissue classified in four molecular subtypes: Luminal A, Luminal B, Basal and HER2-enriched. For comparison, a network for non-tumoral mammary tissue (61 samples) is also inferred and analyzed. Transcriptional networks present particular architectures in each breast cancer subtype as well as in the non-tumor breast tissue. We find substantial differences between the non-tumor network and those networks inferred from cancer samples, in both structure and gene composition. More importantly, we find specific network architectural features associated to each breast cancer subtype. Based on breast cancer networks' centrality, we identify genes previously associated to the disease, either, generally (i.e., CNR2) or to a particular subtype (such as LCK). Similarly, we identify LUZP4, a gene barely explored in breast cancer, playing a role in transcriptional networks with subtype-specific relevance. With this approach we observe architectural differences between cancer and non-cancer at network level, as well as differences between cancer subtype networks which might be associated with breast cancer heterogeneity. The centrality measures of these networks allow us to identify genes with potential biomedical implications to breast cancer.
de Anda-Jáuregui, Guillermo; Velázquez-Caldelas, Tadeo E.; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique
Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes. In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach. We use 493 samples of primary breast cancer tissue classified in four molecular subtypes: Luminal A, Luminal B, Basal and HER2-enriched. For comparison, a network for non-tumoral mammary tissue (61 samples) is also inferred and analyzed. Transcriptional networks present particular architectures in each breast cancer subtype as well as in the non-tumor breast tissue. We find substantial differences between the non-tumor network and those networks inferred from cancer samples, in both structure and gene composition. More importantly, we find specific network architectural features associated to each breast cancer subtype. Based on breast cancer networks' centrality, we identify genes previously associated to the disease, either, generally (i.e., CNR2) or to a particular subtype (such as LCK). Similarly, we identify LUZP4, a gene barely explored in breast cancer, playing a role in transcriptional networks with subtype-specific relevance. With this approach we observe architectural differences between cancer and non-cancer at network level, as well as differences between cancer subtype networks which might be associated with breast cancer heterogeneity. The centrality measures of these networks allow us to identify genes with potential biomedical implications to breast cancer. PMID:27920729
Rugge, Massimo; Pennelli, Gianmaria; Pilozzi, Emanuela; Fassan, Matteo; Ingravallo, Giuseppe; Russo, Valentina M; Di Mario, Francesco
Gastritis is defined as inflammation of the gastric mucosa. In histological terms, it is distinguishable into two main categories, i.e. non-atrophic and atrophic. In the gastric mucosa, atrophy is defined as the loss of appropriate glands. There are several etiological types of gastritis, their different etiology being related to different clinical manifestations and pathological features. Atrophic gastritis (resulting mainly from long-standing Helicobacter pylori infection) is a major risk factor for the onset of (intestinal type) gastric cancer. The extent and site of the atrophic changes correlate significantly with the cancer risk. The current format for histology reporting in cases of gastritis fails to establish an immediate link between gastritis phenotype and risk of malignancy. Building on current knowledge of the biology of gastritis, an international group of pathologists [Operative Link for Gastritis Assessment (OLGA)] has proposed a system for reporting gastritis in terms of its stage (the OLGA Staging System): this system places the histological phenotypes of gastritis on a scale of progressively increasing gastric cancer risk, from the lowest (Stage 0) to the highest (Stage IV). The aim of this tutorial is to provide unequivocal information on how to standardize histology reports on gastritis in diagnostic practice.
Perry, Arie; Wesseling, Pieter
Gliomas form a heterogeneous group of tumors of the central nervous system (CNS) and are traditionally classified based on histologic type and malignancy grade. Most gliomas, the diffuse gliomas, show extensive infiltration in the CNS parenchyma. Diffuse gliomas can be further typed as astrocytic, oligodendroglial, or rare mixed oligodendroglial-astrocytic of World Health Organization (WHO) grade II (low grade), III (anaplastic), or IV (glioblastoma). Other gliomas generally have a more circumscribed growth pattern, with pilocytic astrocytomas (WHO grade I) and ependymal tumors (WHO grade I, II, or III) as the most frequent representatives. This chapter provides an overview of the histology of all glial neoplasms listed in the WHO 2016 classification, including the less frequent "nondiffuse" gliomas and mixed neuronal-glial tumors. For multiple decades the histologic diagnosis of these tumors formed a useful basis for assessment of prognosis and therapeutic management. However, it is now fully clear that information on the molecular underpinnings often allows for a more robust classification of (glial) neoplasms. Indeed, in the WHO 2016 classification, histologic and molecular findings are integrated in the definition of several gliomas. As such, this chapter and Chapter 6 are highly interrelated and neither should be considered in isolation.
Ortigo, Kile M; Westen, Drew; Bradley, Bekh
Research into personality factors related to suicidality suggests substantial variability among suicide attempters. A potentially useful approach that accounts for this complexity is personality subtyping. As part of a large sample looking at personality pathology, this study used Q-factor analysis to identify subtypes of 311 adult suicide attempters using Shedler-Westen Assessment Procedure-II personality profiles. Identified subtypes included internalizing, emotionally dysregulated, dependent, hostile-isolated, psychopathic, and anxious somatizing. Subtypes differed in hypothesized ways on criterion variables that address their construct validity, including adaptive functioning, Axis I and II comorbidity, and etiology-related variables (e.g., history of abuse). Furthermore, dimensional ratings of the subtypes predicted adaptive functioning above DSM-based diagnoses and symptoms.
Asherson, Philip; Cormand, Bru
Aggression, an overt behaviour with the intention to inflict damage, is a physiological trait with important roles throughout evolution, both in defence and predation. However, when expressed in humans in the wrong context, aggression leads to social maladjustment and crime. This special issue is about the genetic and neurobiological basis for aggression. Most of the 12 works presented here have been prepared by members of five international consortia established under the auspice of the FP7 and H2020 programs of the European Union to investigate different aspects of aggression and related behavioural phenotypes, including delineation of subtypes, aetiological mechanisms, neurobiology, neuroimaging, biomarkers, animal models and development and assessment of new treatments. Research on human aggression has largely focused on the societal causes of violent behaviour with relatively little focus on the underlying neuroscientific basis. However, interesting findings are emerging which suggest that by identifying distinct pathways to aggression, better targeting of social, psychological and medical treatments, can lead to improved outcomes for individuals and society. This issue represents a state of the art review of current neurobiological understanding of human aggression and a starting point for concerted efforts to move the field towards the development of new strategies for prevention and treatment. © 2016 Wiley Periodicals, Inc.
Verhaak, Roel GW; Hoadley, Katherine A; Purdom, Elizabeth; Wang, Victoria; Qi, Yuan; Wilkerson, Matthew D; Miller, C Ryan; Ding, Li; Golub, Todd; Mesirov, Jill P; Alexe, Gabriele; Lawrence, Michael; O'Kelly, Michael; Tamayo, Pablo; Weir, Barbara A; Gabriel, Stacey; Winckler, Wendy; Gupta, Supriya; Jakkula, Lakshmi; Feiler, Heidi S; Hodgson, J Graeme; James, C David; Sarkaria, Jann N; Brennan, Cameron; Kahn, Ari; Spellman, Paul T; Wilson, Richard K; Speed, Terence P; Gray, Joe W; Meyerson, Matthew; Getz, Gad; Perou, Charles M; Hayes, D Neil; Network, The Cancer Genome Atlas Research
The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefit in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.
Yarur, Andres J.; Strobel, Sebastian G.; Deshpande, Amar R.
Inflammatory bowel disease comprises a group of conditions characterized by idiopathic inflammation of the gastrointestinal tract. The natural course of disease can range from an indolent course with prolonged periods of remission to aggressive, incapacitating disease. Predicting which patients are more susceptible to developing severe disease is important, especially when choosing therapeutic agents and treatment strategies. This paper reviews current evidence on the main demographic, clinical, endoscopic, histologic, serologic, and genetic markers that predict aggressive inflammatory bowel disease. In ulcerative colitis, we considered disease to be aggressive when patients had a high relapse rate, need for admission and/or surgery, development of colon cancer, or extraintestinal manifestations. We defined aggressive Crohn's disease as having a high relapse rate, development of penetrating disease, need for repeat surgery, or multiple admissions for flares. In Crohn's disease, involvement of the upper gastrointestinal tract and ileum, penetrating disease, early age at diagnosis, smoking, extensive ulceration of the mucosa, high titers of serum antibodies, and mutations of the NOD2 gene are markers of aggressive disease. In ulcerative colitis, patients with more extensive involvement of the colon (pancolitis) have more symptomatology and are at higher risk for needing a colectomy and developing colon cancer. Also, plasmocytic infiltration of the colonic mucosa and crypt atrophy predict treatment failure. As with diagnosis, no single method can predict disease aggressiveness. Multiple serologic and genetic tests are being developed to refine the accuracy of prediction. Endoscopic findings can also predict the future course of disease. At present, clinical manifestations are the most useful way to make therapeutic decisions. PMID:22298958
Burton, Robert W
Viewing aggression in its healthy form, in contrast to its extreme and inappropriate versions, and sport as a health-promoting exercise in psychological development and maturation may allow participants and spectators alike to retain an interest in aggression and sport and derive further enjoyment from them. In addition, it will benefit all involved with sport to have a broader understanding of human aggression. Physicians, mental health professionals, and other health care providers can be influential in this process, and should be willing to get involved and speak out when issues and problems arise.
Kim, Hark Kyun; Kim, In-Hoo
With the advent of targeted agents, it has become clinically important to distinguish histologic types of non-small cell lung cancers (NSCLCs) using biopsy samples. We investigated whether direct tissue matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) analysis on lipid may classify histology of NSCLCs. Twentyone pairs of frozen, resected NSCLCs were analyzed using histology-directed, MALDI MS. 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument. Squamous cell carcinomas and adenocarcinomas, two major histologic types of NSCLC, were found to have different lipid profiles. Discriminatory lipids correctly classified the histology of 80.4% of independent NSCLC surgical tissue samples (41 out of 51) in validation set, suggesting that lipid profiles can classify NSCLCs according to the histologic type. We also found that protein and lipid MALDI MS profiles can classify 30 breast cancers according to the intrinsic subtypes. Immunohistochemistry-defined, luminal, HER2+, and triple-negative tumors demonstrated different protein and lipid profiles, as evidenced by cross validation P values < 0.01. Discriminatory proteins and lipids classified tumors according to the intrinsic subtype with median prediction accuracies of 80.0-81.3% in 100 random test sets. Potential advantages of this label-free approach may include small tissue requirement, relatively rapid procedure, and low reagent cost. Day-today variation of this technology is also acceptable, with the Pearson correlation of 0.95. Taken together, these results suggest the possible clinical utility of histology-directed, lipid and protein MALDI MS.
Molnár, István Artúr; Molnár, Béla Ákos; Vízkeleti, Laura; Fekete, Krisztina; Tamás, Judit; Deák, Péter; Szundi, Csilla; Székely, Borbála; Moldvay, Judit; Vári-Kakas, Stefan; Szász, Marcell A; Ács, Balázs; Kulka, Janina; Tőkés, Anna-Mária
The aim of our retrospective study was to analyze patterns of subtype specific metastatic spread and to identify the time course of distant metastases. A consecutive series of 490 patients with breast cancer who underwent surgery and postoperative treatment at Semmelweis University, Hungary, and diagnosed between the years 2000 and 2007 was identified from the archives of the 2nd Department of Pathology, Hungary. Molecular subtypes were defined based on the 2011 St. Gallen recommendations. Statistical analysis was performed with SPSS Statistics for Windows, Version 22.0. Distant metastasis free survival (DMFS) was defined as the time elapsed between the first pathological diagnosis of the tumor and the first distant metastasis detection. Distant metastases were detected in 124 patients. Mean time to develop metastasis was 29 months (range 0-127 months). The longest DMFS was observed in the Luminal A (LUMA) subtype (mean 39 months) whereas the shortest was seen in the HER2-positive (HER2+) subtype (mean 21 months; p = 0.012). We confirmed that HER2+ tumors carry a higher risk for distant metastases (42.1%). LUMA-associated metastases were found to be solitary in 59% of cases, whereas HER2+ tumors showed multiple metastases in 79.2% of cases. LUMA tumors showed a preference for bone-only metastasis as compared with HER2+ and triple negative breast cancer (TNBC) cases, which exhibited a higher rate of brain metastasis. The most frequent second metastatic sites of hormone receptor (HR) positive tumors were the lung and liver, whereas the brain was the most affected organ in HR-negative (HR-) cases. Tumor subtypes differ in DMFS and in pattern of distant metastases. HER2+ tumors featured the most aggressive clinical course. Further identification of subtype-specific factors influencing prognosis might have an impact on clinical care and decision-making.
Fehr, Karla K.; Russ, Sandra W.
Research Findings: Pretend play is an essential part of child development and adjustment. However, parents, teachers, and researchers debate the function of aggression in pretend play. Different models of aggression predict that the expression of aggression in play could either increase or decrease actual aggressive behavior. The current study…
Figarella-Branger, D; Colin, C; Coulibaly, B; Quilichini, B; Maues De Paula, A; Fernandez, C; Bouvier, C
Gliomas are the most frequent tumors of the central nervous system. The WHO classification, based on the presumed cell origin, distinguishes astrocytic, oligodendrocytic and mixed gliomas. A grading system is based on the presence of the following criteria: increased cellular density, nuclear atypias, mitosis, vascular proliferation and necrosis. The main histological subtype of grade I gliomas are pilocytic astrocytomas, which are benign. Diffuse astrocytomas, oligodendrogliomas and oligoastrocytomas are low-grade (II) or high-grade (III and IV) tumors. Glioblastomas correspond to grade IV astrocytomas. C. Daumas-Duport et al. have proposed another classification based on histology and imaging data, which distinguishes oligodendrogliomas and mixed gliomas of grade A (without endothelial proliferation and/or contrast enhancement), oligodendrogliomas and mixed gliomas of grade B (with endothelial proliferation or contrast enhancement), glioblastomas and glioneuronal malignant tumors. Both classifications lack reproducibility. Many studies have searched for a molecular classification. Recurrent abnormalities in gliomas have been found. They encompassed recurrent chromosomal alterations, such as lost of chromosome 10, gain of chromosome 7, deletion of chromosome 1p and 19q, but also activation of the Akt pathway (amplification of EGFR), dysregulation of the cell cycle (deletion of p16, p53). These studies have enabled the description of two molecular subtypes for glioblastomas. De novo glioblastomas, which occur in young patients without of a prior history of brain tumor and harbor frequent amplification of EGFR, deletion of p16 and mutation of PTEN while mutation of p53 is infrequent. Secondary glioblastomas occur in the context of a preexisting low-grade glioma and are characterized by more frequent mutation of p53. On the other side, combined complete deletion of 1p and 19q as the result of the translocation t(1;19)(q10;p10) is highly specific of oligodendrogliomas
Coyne, Sarah M; Nelson, David A; Carroll, Jason S; Smith, Nathan J; Yang, Chongming; Holmgren, Hailey G; Johnson, Chad
Relational aggression occurs in many different contexts, including in romantic relationships. The current study examined associations between two subtypes of relational aggression (love withdrawal and social sabotage) and marital quality over a 5-year time period. Participants consisted of 311 married couples who completed a number of questionnaires on relational aggression and relationship quality once a year over a 5-year period. Results revealed that relational aggression was highly stable over time and that women used more relational aggression than men. Men's use of social sabotage and love withdrawal were bidirectionally related to both partners' perceptions of poor marital quality over time. Conversely, only women's use of love withdrawal was related to her own perceptions of poor marital quality over time. Collectively, these results suggest that relational aggression by men may be less common, though particularly toxic in a marital relationship. Couples are encouraged to find healthier ways of coping with problems in relationships. (PsycINFO Database Record
Ostrov, Jamie M
A multi-informant and multi-measure short-term longitudinal study of the association between subtypes of aggression and peer victimization was conducted in an early childhood sample (M = 44.36 months; SD = 11.07; N = 120). Observational and teacher report measures demonstrated appropriate reliability and validity as well as stability across an academic year. Concurrent associations revealed that observed relational aggression was uniquely associated with teacher reported relational victimization and observed physical aggression was uniquely associated with teacher reported physical victimization. Prospective findings indicated that observed relational aggression predicted increases in teacher reported relational victimization for girls only, controlling for the variance associated with physical aggression, prosocial behavior, physical victimization, and gender. Peer rejection partially mediated the association between observed relational aggression at time 1 and teacher reported relational victimization at time 2. Ways in which these and other prospective findings extend the extant literature are discussed.
Ostrov, Jamie M.; Houston, Rebecca J.
A sample of 679 (341 women) emerging adults (M = 18.90 years; SD = 1.11; range = 18.00-22.92) participated in a study on the utility of forms (i.e., physical and relational) and functions (i.e., proactive and reactive) of aggression. We examined the link between these four subtypes of aggression and personality pathology (i.e., psychopathic…
Acerbi, I; Cassereau, L; Dean, I; Shi, Q; Au, A; Park, C; Chen, YY; Liphardt, J; Hwang, ES; Weaver, VM
Tumors are stiff and data suggest that the extracellular matrix stiffening that correlates with experimental mammary malignancy drives tumor invasion and metastasis. Nevertheless, the relationship between tissue and extracellular matrix stiffness and human breast cancer progression and aggression remains unclear. We undertook a biophysical and biochemical assessment of stromal-epithelial interactions in noninvasive, invasive and normal adjacent human breast tissue and in breast cancers of increasingly aggressive subtype. Our analysis revealed that human breast cancer transformation is accompanied by an incremental increase in collagen deposition and a progressive linearization and thickening of interstitial collagen. The linearization of collagen was visualized as an overall increase in tissue birefringence and was most striking at the invasive front of the tumor where the stiffness of the stroma and cellular mechanosignaling were the highest. Amongst breast cancer subtypes we found that the stroma at the invasive region of the more aggressive Basal-like and Her2 tumor subtypes was the most heterogeneous and the stiffest when compared to the less aggressive Luminal A and B subtypes. Intriguingly, we quantified the greatest number of infiltrating macrophages and the highest level of TGF beta signaling within the cells at the invasive front. We also established that stroma stiffness and the level of cellular TGF beta signaling positively correlated with each other and with the number of infiltrating tumor-activated, macrophages, which was highest in the more aggressive tumor subtypes. These findings indicate that human breast cancer progression and aggression, collagen linearization and stromal stiffening are linked and implicate tissue inflammation and TGF beta. PMID:25959051
Arena, F; Nicotina, P A; Cruccetti, A; Centonze, A; Arena, S; Romeo, G
The aim of this study was to review the histology of the upper pole segment in patients with duplex ectopic ureterocele to verify if a less aggressive surgery is justified in the prenatally diagnosed patients. We reviewed the histology of the upper pole segment of 15 consecutive patients with duplex system ectopic ureterocele treated between 1991 and 1999 at the Paediatric Surgery Unit of University Hospital of Messina. The diagnosis of duplex system ectopic ureterocele was made according to the criteria of the Section on Urology of the American Academy of Paediatrics. The histology specimens were assessed for dysplastic, inflammatory and obstructive changes. All 15 patients with duplex system ectopic ureterocele were surgically treated with heminephro-ureterectomy and the surgical specimens were histologically examined. Nine of the 15 patients were prenatally diagnosed. The histology of the upper pole segment of the 9 prenatally diagnosed showed in all patients segmental renal microcystic dysplasia, chondroid metaplasic islands and an inflammatory tubulo-interstitial nephropathy in 6 patients (66.6%) and in 2 (22.2%) nephroblastomatosis. The histology of six the postnatal postnatally diagnosed patients showed in all patients segmental multicystic renal dysplasia, inflammatory tubulo-interstitial nephropathy and segmental parenchymal scars. The upper pole histology of the patients with duplex ectopic ureterocele diagnosed prenatally did not show any evidence of reversible histological change. Considering the histology and the good outcome of patients treated with upper pole nephroureterectomy a less aggressive surgery with preservation of the upper pole does not seem justified.
Shojaii, Rushin; Karavardanyan, Tigran; Yaffe, Martin; Martel, Anne L.
The aim of this paper is to validate an image registration pipeline used for histology image alignment. In this work a set of histology images are registered to their correspondent optical blockface images to make a histology volume. Then multi-modality fiducial markers are used to validate the alignment of histology images. The fiducial markers are catheters perfused with a mixture of cuttlefish ink and flour. Based on our previous investigations this fiducial marker is visible in medical images, optical blockface images and it can also be localized in histology images. The properties of this fiducial marker make it suitable for validation of the registration techniques used for histology image alignment. This paper reports on the accuracy of a histology image registration approach by calculation of target registration error using these fiducial markers.
Ostrov, Jamie M.; Woods, Kathleen E.; Jansen, Elizabeth A.; Casas, Juan F.; Crick, Nicki R.
A semi-structured observational study investigated gender differences in delivered and received relational, physical, verbal, and nonverbal aggression in a young preschool sample (N=60). Findings revealed that gender differences in subtypes of aggression may be apparent as early as 3 years of age. Specifically, girls were found to deliver and…
Buesa, René J; Peshkov, Maxim V
After the hazardous effects of xylene became indisputable in the 1970s, many potential substitutes became available, some with as many if not more hazards. This article discusses the inadequacy of 5 vegetable oils as substitutes, as well as the characteristics of 22 D-limonene-based substitutes, all less effective in their chemical role, some capable of inducing health problems, and costing more than twice as much as xylene. Some of the 35 alkane-based substitutes discussed are effective for tissue processing, less toxic, with a cost about the same as xylene, but are not very effective for dewaxing and other staining tasks. Isopropanol (2-propanol) alone or mixed with molten paraffin is a technically acceptable and cost-effective substitute for xylene for tissue processing, but in this study, we demonstrate that the best clearing agents from the sectioning quality and diagnostic value point of view, with automated or manual protocols, are mixtures of 5:1 and 2:1 isopropanol and mineral oil, followed by undiluted mineral oil, all at 50 degrees C, making them a safer and cheaper substitute than xylene. Using a 1.7% dishwasher soap aqueous solution at 90 degrees C to dewax before staining and oven drying the stained sections before coverslipping will eliminate xylene from the staining tasks. Tissue processors retorts and conduits can be dewaxed with a 2% solution of a strong glassware laboratory detergent. These 4 methodologies will make the histology laboratory xylene-free but, due to the natural resistance to change, many histotechs will be reluctant to adopt them if they think that their technical expertise could be jeopardized, and the only way these changes will succeed is if the pathologists, as stewards of the histology laboratory, commit to their implementation.
Eron, Leonard D.; Huesmann, L. Rowell
As indicated by multiple measures (including overt criminal behavior), stability of aggressive behavior was investigated across 22 years for males and females in a variety of situations. Originally, subjects included the entire population enrolled in the third grade in a semi-rural county in New York State. The sample included approximately 870…
Vaaland, Grete Sorensen; Idsoe, Thormod; Roland, Erling
This study aims to conceptualize disobedient pupil behavior within the more general framework of antisocial behavior and to reveal how two forms of aggressiveness are related to disobedience. Disobedience, in the context of this article, covers disruptive pupil behavior or discipline problems when the pupil is aware of breaking a standard set by…
Huesmann, L. Rowell; Yarmel, Patty Warnick
Using data from a broader longitudinal study, this investigation explores within-subject and cross-generational stability of intellectual competence and the relationship of such stability to aggressive behavior. Data were gathered three times (when subjects' modal age was 8, 19, and 30 years). Initially, subjects included the entire population…
Young, Ellie L.; Nelson, David A.; Hottle, America B.; Warburton, Brittney; Young, Bryan K.
"Relational aggression" refers to harm within relationships caused by covert bullying or manipulative behavior. Examples include isolating a youth from his or her group of friends (social exclusion), threatening to stop talking to a friend (the silent treatment), or spreading gossip and rumors by email. This type of bullying tends to be…
Mills, Shari; Raine, Adrian
Brain imaging research allows direct assessment of structural and functional brain abnormalities, and thereby provides an improved methodology for studying neurobiological factors predisposing to violent and aggressive behavior. This paper reviews 20 brain imaging studies using four different types of neuroimaging techniques that were conducted in…
Brown, Gerald L.; Goodwin, Frederick K
The central nervous system transmitter serontonin may be altered in aggressive/impulsive and suicidal behaviors in humans. These reports are largely consistent with animal data, and constitute one of the most highly replicated set of findings in biological psychiatry. Suggests that some suicidal behavior may be a special kind of aggressive…
Duman, Sarah; Margolin, Gayla
This study examined children's aggressive and assertive solutions to hypothetical peer scenarios in relation to parents' responses to similar hypothetical social scenarios and parents' actual marital aggression. The study included 118 children ages 9 to 10 years old and their mothers and fathers. Children's aggressive solutions correlated with…
Page, Angela; Smith, Lisa F.
Both physical and relational aggression are characterised by the intent to harm another. Physical aggression includes direct behaviours such as hitting or kicking; relational aggression involves behaviours designed to damage relationships, such as excluding others, spreading rumours, and delivering threats and verbal abuse. This study extended…
Background Breast cancer is one of the leading causes of cancer deaths. Triple-negative breast cancer (TNBC), an immunophenotype defined by the absence of immunolabeling for estrogen receptor (ER), progesterone receptor (PR) and HER2 protein, has a highly aggressive behavior. A subpopulation of TNBCs exhibit a basal-like morphology with immunohistochemical positivity for cytokeratins 5/6 (CK5/6) and/or epidermal growth factor receptor (EGFR), and have a high incidence of BRCA (breast cancer susceptibility) mutations. Feline mammary adenocarcinomas (FMAs) are highly malignant and share a similar basal-like subtype. The purpose of this study was to classify FMAs according to the current human classification of breast cancer that includes evaluation of ER, PR and HER2 status and expression of basal CK 5/6 and EGFR. Furthermore, we selected triple negative, basal-like FMAs to screen for BRCA mutations similar to those described in human TNBC. Methods Twenty four FMAs were classified according to the current human histologic breast cancer classification including immunohistochemistry (IHC) for ER, PR HER2, CK5/6 and EGFR. Genetic alteration and loss of heterozygosity of BRCA1 and BRCA2 genes were analyzed in triple negative, basal-like FMAs. Results IHC for ER, PR and HER2 identified 14 of the 24 (58%) FMAs as a triple negative. Furthermore, 11of these 14 (79%) triple negative FMAs had a basal-like subtype. However, no genetic abnormalities were detected in BRCA1 and BRCA2 by direct sequencing and loss of heterozygosity analysis. Conclusion FMAs are highly aggressive neoplasms that are commonly triple negative and exhibit a basal-like morphology. This is similar to human TNBC that are also commonly classified as a basal-like subtype. While sequencing of a select number of triple negative, basal-like FMAs and testing for loss of heterozygosity of BRCA1 and BRCA2 did not identify mutations similar to those described in human TNBC, further in-depth evaluation is required
Lee, Jonguk; Jin, Long; Park, Daihee; Chung, Yongwha
Aggression among pigs adversely affects economic returns and animal welfare in intensive pigsties. In this study, we developed a non-invasive, inexpensive, automatic monitoring prototype system that uses a Kinect depth sensor to recognize aggressive behavior in a commercial pigpen. The method begins by extracting activity features from the Kinect depth information obtained in a pigsty. The detection and classification module, which employs two binary-classifier support vector machines in a hierarchical manner, detects aggressive activity, and classifies it into aggressive sub-types such as head-to-head (or body) knocking and chasing. Our experimental results showed that this method is effective for detecting aggressive pig behaviors in terms of both cost-effectiveness (using a low-cost Kinect depth sensor) and accuracy (detection and classification accuracies over 95.7% and 90.2%, respectively), either as a standalone solution or to complement existing methods. PMID:27144572
Xu, Yiyuan; Farver, Jo Ann M; Zhang, Zengxiu
This study examined the additive and interactive effects of temperament and harsh and indulgent parenting on Chinese children's proactive and reactive aggression. Participants were 401 children (M age = 9.29 years, 203 girls) and their parents who were recruited from 2 elementary schools in Shanghai, People's Republic of China. The results showed that children's sensation seeking was associated with proactive aggression, whereas anger/frustration was associated with reactive aggression. Both subtypes of aggression were negatively related to children's effortful control but positively related to harsh parenting. Significant Temperament x Temperament and Parenting x Temperament interactions were also found. The findings point to similarities and differences between proactive and reactive aggression in relation to children's temperament and harsh and indulgent parenting in the Chinese context.
Lee, Jonguk; Jin, Long; Park, Daihee; Chung, Yongwha
Aggression among pigs adversely affects economic returns and animal welfare in intensive pigsties. In this study, we developed a non-invasive, inexpensive, automatic monitoring prototype system that uses a Kinect depth sensor to recognize aggressive behavior in a commercial pigpen. The method begins by extracting activity features from the Kinect depth information obtained in a pigsty. The detection and classification module, which employs two binary-classifier support vector machines in a hierarchical manner, detects aggressive activity, and classifies it into aggressive sub-types such as head-to-head (or body) knocking and chasing. Our experimental results showed that this method is effective for detecting aggressive pig behaviors in terms of both cost-effectiveness (using a low-cost Kinect depth sensor) and accuracy (detection and classification accuracies over 95.7% and 90.2%, respectively), either as a standalone solution or to complement existing methods.
Serotonin (5-HT) regulates aggressive behavior in animals. This study examined if 5-HT regulation of aggressiveness is gene-dependent. Chickens from two divergently selected lines KGB and MBB (Kind Gentle Birds and Mean Bad Birds displaying low and high aggressiveness, respectively) and DXL (Dekalb ...
Vennewald, Irina; Schönlebe, J; Klemm, E
Fungal infections of the ear are mostly described as mycoses of the auditory canal. The aim of our investigations was to find out how fungi colonize the ear in immunocompetent patients. In the years from 1993 to 2000, 128 patients suspected of having otomycosis were examined. Of these 115 patients suffered from chronic otitis media with persisting tympanum perforation and otorrhea. A further 13 patients had clinical signs of otitis externa only. In 54 out of 139 samples, fungi were found in the auditory canal, in five on the tympanic membrane, and in five in the middle ear. Two-thirds were isolated as moulds and one-third as yeasts. Dominating species were Aspergillus niger and Candida parapsilosis. Samples of 15 patients suspected of having mastoiditis or cholesteatoma were examined histologically. Fungal hyphae were observed in the middle ear cavity and/or between horny lamellae of cholesteatoma in 4 patients. In the middle ear of immunocompetent patients chronic-hyperplastic (polypous) inflammation was detected with increased production of mucus, which probably promotes the colonization with pathogenic fungi as in the middle ear just like in the auditory canal.
Flynn, Jane M.; And Others
The construct validity of Boder's typology of dyslexia was investigated using quantified electroencephalography with 39 children (ages 7-11) during a reading task and at rest. Results supported beta frequency differences in anticipated regions by dyslexia subtype during the reading task. However, the direction of difference hypothesis was not…
A comprehensive analysis of 1,122 diffuse glioma samples from The Cancer Genome Atlas has revealed two new subtypes of this common brain cancer, with molecular and clinical features that diverge from the norm. The study findings also support the use of DNA methylation profiles to improve glioma classification and treatment.
Gutzler, Stephanie J; Karom, Mary; Erwin, W D; Albers, H E
Arginine-vasopressin (AVP) is critical for the expression of a variety of social behaviors in many species. Previous studies have demonstrated that AVP regulates behaviors such as social communication and aggression in Syrian hamsters through the V1a receptor subtype. In male hamsters, AVP injected into the anterior hypothalamus (AH) stimulates aggression, while injection of a V1a receptor antagonist inhibits the behavior. The purpose of the present studies was to determine whether AVP influences aggression by its action in the AH in female hamsters. In the first experiment, we were surprised to find that injection of the V1a receptor antagonist, Manning compound, into the AH of intact female hamsters increased aggression. The second experiment confirmed the ability of the V1a receptor antagonist to increase aggression and found that the largest effects of the antagonist occurred at intermediate concentrations of the compound. The next experiment found that injection of AVP into the AH significantly reduced the latency to attack and the duration of aggression. Finally, we examined whether the effects of AVP and the V1a receptor antagonist on aggression differed in hamsters exposed to long 'summer-like' photoperiods or short 'winter-like' photoperiods, and found that their effects on aggression were not photoperiod dependent. In summary, contrary to what is observed in males, these data suggest that AVP in the AH may play an inhibitory role on aggression in female Syrian hamsters.
saturation bands (six for fat and two for water) were used to minimize lipid/water contamination to the VOI. The 2D MRSI sequence details are: TR/TE... fat as measured by in-vivo imaging using proton magnetic resonance spectroscopy imaging in the prediction of prostate disease aggressiveness...histology, in-vivo intraprostatic fat as measured by 1H MRSI, metabolic signatures of lipid oxidation and metabolism, and prostate cancer
Stodulski, Dominik; Majewska, Hanna; Skálová, Alena; Mikaszewski, Bogusław; Biernat, Wojciech; Stankiewicz, Czesław
Reassessment of histological specimens of salivary gland carcinomas is associated with a change of primary diagnosis in a significant number of patients. The authors evaluated the relation between reclassification/verification of histological diagnosis and the clinical course of parotid gland carcinomas. Histological and immunohistochemical examinations of 111 specimens of parotid gland carcinomas operated on during the years 1992-2010 were revised and in some cases supplemented with cytogenetic tests (FISH), to verify the diagnosis and potentially reclassify the tumours. Analysis of the clinical documentation and follow-up data of patients whose diagnosis was changed was then carried out. The prognostic factors taken into account in the evaluation of the clinical course included the T and N stage, the tumour grade and the extent of resection. The primary diagnosis was changed on review in 28 patients (25.2 %). In 16 patients, the change involved a different histological type of cancer. In six cases, what was thought to be a primary salivary gland cancer was reclassified as a secondary tumour. In four other cases, the change was made from a malignant to a benign tumour and in one case to a non-neoplastic lesion (necrotizing sialometaplasia). Additionally, in two patients with carcinoma ex pleomorphic adenoma, the malignant component was found to be of in situ type. A potentially atypical clinical course was observed in 4 out of 28 patients whose diagnosis was changed. In the case of 2 patients, the course of disease was more aggressive (dissemination, death) than predicted and less aggressive in rest of the patients. Histological reclassification/verification of parotid gland carcinomas can explain the cause of an atypical clinical course in some patients and sometimes enables doctors to implement a change in therapy.
Tang, Catherine So-Kum; And Others
Compared sexual and aggressive motives for sexual aggression in Chinese college students. Male undergraduates (N=146) completed self-report measures. Results suggest that sex guilt and aggressive guilt acted as inhibitors for their respective drives and sexual aggression resulted from aggressive, rather than sexual, motives. Sexual aggression may…
de Boer, S F; Olivier, B; Veening, J; Koolhaas, J M
Experimental studies aimed at understanding the neurobiology of aggression started in the early 20th century, and by employing increasingly sophisticated tools of functional neuroanatomy (i.e., from electric/chemical lesion and stimulation techniques to neurochemical mapping and manipulations) have provided the important framework for the functional brain circuit organization of aggressive behaviors. Recently, newly emerging technologies for mapping,measuring and manipulating neural circuitry at the level of molecular and genetically defined neuronal subtypes promise to further delineate the precise neural microcircuits mediating the initiation and termination of aggressive behavior, and characterize its dynamic neuromolecular functioning. This paper will review some of the behavioral, neuroanatomical and neurochemical evidence in support of a modular view of the neurobiology of offensive aggressive behavior. Although aggressive behavior likely arises from a specific concerted activity within a distributed neural network across multiple brain regions, emerging opto- and pharmacogenetic neuronal manipulation studies make it clear that manipulation of molecularly-defined neurons within a single node of this global interconnected network seems to be both necessary and sufficient to evoke aggressive attacks. However, the evidence so far also indicates that in addition to behavior-specific neurons there are neuronal systems that should be considered as more general behavioral control modules. The answer to the question of behavioral specificity of brain structures at the level of individual neurons requires a change of the traditional experimental setup. Studies using c-fos expression mapping usually compare the activation patterns induced by for example aggression with a home cage control. However, to reveal the behavioral specificity of this neuronal activation pattern, a comparison with other social and non-social related behaviors such as mating, defensive burying
Arena, F; Nicotina, A; Cruccetti, A; Centonze, A; Arena, S; Romeo, G
The aim of this study was to review the histology of the upper-pole segment in patients with duplex-system ectopic ureterocele (DEU) to determine if less aggressive surgery is justified in prenatally-diagnosed cases. The study included 15 consecutive patients with DEU treated between 1991 and 1999. The diagnosis was made according to the criteria of the Section on Urology of the American Academy of Pediatrics. The histology specimens were assessed for dysplastic, inflammatory, and obstructive changes. All 15 patients were surgically treated by heminephro-ureterectomy and the surgical specimens were histologically examined. Nine cases were diagnosed prenatally; the histology of the upper-pole segment in these patients showed segmental renal microcystic dysplasia, chondroid metaplasic islands, and an inflammatory tubulointerstitial nephropathy in 6 (66.6%) and nephroblastomatosis in 2 (22.2%). The histology of the 6 postnatally-diagnosed patients showed segmental multicystic renal dysplasia, inflammatory tubulo-interstitial nephropathy, and segmental parenchymal scars. The upper-pole histology of the prenatally-diagnosed patients did not show any evidence of reversible histologic changes. Considering this findings and the good outcome of patients treated with upper-pole nephroureterectomy, less aggressive surgery with preservation of the upper pole does not seem justified.
Choi, Woonyoung; Czerniak, Bogdan; Ochoa, Andrea; Su, Xiaoping; Siefker-Radtke, Arlene; Dinney, Colin; McConkey, David J
Whole-genome analyses have revealed that muscle-invasive bladder cancers (MIBCs) are heterogeneous and can be grouped into basal and luminal subtypes that are highly reminiscent of those found in breast cancer. Basal MIBCs are enriched with squamous and sarcomatoid features and are associated with advanced stage and metastatic disease at presentation. Like basal breast cancers, basal bladder tumours contain a claudin-low subtype that is enriched with biomarkers characteristic of epithelial-to-mesenchymal transition. The stem cell transcription factor ΔNp63α controls basal MIBC gene expression, just as it does in basal breast cancers. Luminal MIBCs are enriched with activating FGFR3 and ERBB3 mutations and ERBB2 amplifications, and their gene expression profiles are controlled by peroxisome proliferator activator receptor γ (PPARγ) and possibly also by oestrogen receptor activation. Luminal bladder cancers can be further subdivided into two subtypes, p53-like and luminal, which can be distinguished from one another by different levels of biomarkers that are characteristic of stromal infiltration, cell cycle progression, and proliferation. Importantly, basal bladder cancers are intrinsically aggressive, but are highly sensitive to cisplatin-based combination chemotherapy. Although the luminal subtypes are not as intrinsically aggressive as basal cancers, p53-like tumours are resistant to chemotherapy and might, therefore, represent a problem for treated patients.
Sargen, Michael R.; Kanetsky, Peter A.; Newton-Bishop, Julia; Hayward, Nicholas K.; Mann, Graham J.; Gruis, Nelleke A.; Tucker, Margaret A.; Goldstein, Alisa M.; Bianchi-Scarra, Giovanna; Puig, Susanna; Elder, David E.
Background Inherited susceptibility genes have been associated with histopathologic characteristics of tumors. Objective To identify associations between histology of melanomas and CDKN2A genotype. Methods Case-control study design comparing 28 histopathologic tumor features among individuals with sporadic melanomas (N=81) and cases from melanoma families with (N=123) and without (N=120) CDKN2A germline mutations. Results Compared with CDKN2A-negative cases, mutation carriers tended to have histologic features of superficial spreading melanoma subtype including higher pigmentation (ptrend=0.02) and increased pagetoid scatter (ptrend=0.07) after adjusting for age at diagnosis, sex, and AJCC thickness category. Similar associations were observed when comparing mutation carriers to a combined group of CDKN2A-negative (wild type) and sporadic melanomas. The presence of spindle cell morphology in the vertical growth phase was also an important predictor of genotype. Of the fifteen cases with this phenotype, none were observed to harbor a CDKN2A mutation. Limitations Our study examined rare mutations and may have been underpowered to detect small, but biologically significant associations between histology and genotype. Conclusion Familial melanomas with CDKN2A mutations preferentially express a histologic phenotype of dense pigmentation, high pagetoid scatter, and a non-spindle cell morphology in the vertical growth phase. PMID:25592620
Pereira, Pedro; Melo Abreu, Elisa; Cunha, Teresa Margarida; Rolim, Inês
A 45-year-old woman with a history of total hysterectomy with adnexal preservation for uterine leiomyomas presented to our hospital with a right gluteal palpable mass, which she first noticed 6 months before and had progressively enlarged since then.Radiological studies revealed a 14 cm lesion with translevator growth that displaced rather than invaded adjacent structures, with a peculiar whorled pattern on T2-weighted MRI, which enhanced following gadolinium administration. CT-guided biopsy was performed, and in conjunction with imaging features the diagnosis of an aggressive angiomyxoma was assumed and confirmed following surgical excision.
Drake, Penelope M; Schilling, Birgit; Niles, Richard K; Prakobphol, Akraporn; Li, Bensheng; Jung, Kwanyoung; Cho, Wonryeon; Braten, Miles; Inerowicz, Halina D; Williams, Katherine; Albertolle, Matthew; Held, Jason M; Iacovides, Demetris; Sorensen, Dylan J; Griffith, Obi L; Johansen, Eric; Zawadzka, Anna M; Cusack, Michael P; Allen, Simon; Gormley, Matthew; Hall, Steven C; Witkowska, H Ewa; Gray, Joe W; Regnier, Fred; Gibson, Bradford W; Fisher, Susan J
We used a lectin chromatography/MS-based approach to screen conditioned medium from a panel of luminal (less aggressive) and triple negative (more aggressive) breast cancer cell lines (n=5/subtype). The samples were fractionated using the lectins Aleuria aurantia (AAL) and Sambucus nigra agglutinin (SNA), which recognize fucose and sialic acid, respectively. The bound fractions were enzymatically N-deglycosylated and analyzed by LC-MS/MS. In total, we identified 533 glycoproteins, ∼90% of which were components of the cell surface or extracellular matrix. We observed 1011 glycosites, 100 of which were solely detected in ≥3 triple negative lines. Statistical analyses suggested that a number of these glycosites were triple negative-specific and thus potential biomarkers for this tumor subtype. An analysis of RNaseq data revealed that approximately half of the mRNAs encoding the protein scaffolds that carried potential biomarker glycosites were up-regulated in triple negative vs luminal cell lines, and that a number of genes encoding fucosyl- or sialyltransferases were differentially expressed between the two subtypes, suggesting that alterations in glycosylation may also drive candidate identification. Notably, the glycoproteins from which these putative biomarker candidates were derived are involved in cancer-related processes. Thus, they may represent novel therapeutic targets for this aggressive tumor subtype.
Human aggression is viewed from four explanatory perspectives, derived from the ethological tradition. The first consists of its adaptive value, which can be seen throughout the animal kingdom, involving resource competition and protection of the self and offspring, which has been viewed from a cost-benefit perspective. The second concerns the phylogenetic origin of aggression, which in humans involves brain mechanisms that are associated with anger and inhibition, the emotional expression of anger, and how aggressive actions are manifest. The third concerns the origin of aggression in development and its subsequent modification through experience. An evolutionary approach to development yields conclusions that are contrary to the influential social learning perspective, notably that physical aggression occurs early in life, and its subsequent development is characterized by learned inhibition. The fourth explanation concerns the motivational mechanisms controlling aggression: approached from an evolutionary background, these mechanisms range from the inflexible reflex-like responses to those incorporating rational decision-making.
Dickson, Daniel J; Richmond, Ashley D; Brendgen, Mara; Vitaro, Frank; Laursen, Brett; Dionne, Ginette; Boivin, Michel
The present study examined sibling influence over reactive and proactive aggression in a sample of 452 same-sex twins (113 male dyads, 113 female dyads). Between and within siblings influence processes were examined as a function of relative levels of parental coercion and hostility to test the hypothesis that aggression contagion between twins occurs only among dyads who experience parental coerciveness. Teacher reports of reactive and proactive aggression were collected for each twin in kindergarten (M = 6.04 years; SD = 0.27) and in first grade (M = 7.08 years; SD = 0.27). Families were divided into relatively low, average, and relatively high parental coercion-hostility groups on the basis of maternal reports collected when the children were 5 years old. In families with relatively high levels of parental coercion-hostility, there was evidence of between-sibling influence, such that one twin's reactive aggression at age 6 predicted increases in the other twin's reactive aggression from ages 6 to 7, and one twin's proactive aggression at age 6 predicted increases in the other twin's proactive aggression from ages 6 to 7. There was also evidence of within-sibling influence such that a child's level of reactive aggression at age 6 predicted increases in the same child's proactive aggression at age 7, regardless of parental coercion-hostility. The findings provide new information about the etiology of reactive and proactive aggression and individual differences in their developmental interplay.
Harris, M B
For 416 college students, questioned about their experiences with aggression and television viewing, only very weak correlations between preference for violent shows and aggression were observed. Black males watched significantly more television than other respondents. These findings suggest that the frequently reported correlation between viewing televised violence and aggression may not appear when sex, ethnicity, and education are controlled in a sample of young adults.
Lanza, Giovanni; Messerini, Luca; Gafà, Roberta; Risio, Mauro
Epithelial colorectal tumors are common pathologic entities. Their histology report should be comprehensive of a series of pathologic parameters essential for the correct clinical management of the patients. Diagnostic histologic criteria of adenomatous, serrated, inflammatory, and hamartomatous polyps and of polyposis syndromes are discussed. In addition, the pathologic features of early and advanced colorectal cancer are described and a checklist is given. Finally, molecular prognostic and predictive factors currently employed in the treatment of colorectal cancer are discussed.
Logan-Greene, Patricia; Semanchin Jones, Annette
Neglect is the most common form of maltreatment in the United States, yet its impact on development remains understudied, especially for chronic neglect. Chronic neglect is also one of the most costly burdens on child welfare systems. This study examines the effects of chronic neglect, including two subtypes (Failure to Provide and Lack of Supervision) on adolescent aggression and delinquency using a diverse longitudinal sample of youth. Chronic neglect and chronic failure to provide (ages 0-12) predicted aggression/delinquency (age 14) even after controlling for the effects of other maltreatment (ages 0-12). Chronic lack of supervision, however, did not. Gender significantly moderated these effects, suggesting that males are more likely to respond to neglect by becoming aggressive/delinquent. Finally, social problems (age 12) partially mediated for boys, and fully mediated for girls, the connections between chronic neglect and aggression/delinquency, bolstering theorizing that neglect impairs social functioning broadly. Implications include the need for further research on chronic neglect, especially in providing guidance for child welfare systems. Interventions for chronically neglected youth should include social skill development.
Shen, Hui; Fridley, Brooke L.; Song, Honglin; Lawrenson, Kate; Cunningham, Julie M.; Ramus, Susan J.; Cicek, Mine S.; Tyrer, Jonathan; Stram, Douglas; Larson, Melissa C.; Köbel, Martin; Ziogas, Argyrios; Zheng, Wei; Yang, Hannah P.; Wu, Anna H.; Wozniak, Eva L.; Woo, Yin Ling; Winterhoff, Boris; Wik, Elisabeth; Whittemore, Alice S.; Wentzensen, Nicolas; Weber, Rachel Palmieri; Vitonis, Allison F.; Vincent, Daniel; Vierkant, Robert A.; Vergote, Ignace; Van Den Berg, David; Van Altena, Anne M.; Tworoger, Shelley S.; Thompson, Pamela J.; Tessier, Daniel C.; Terry, Kathryn L.; Teo, Soo-Hwang; Templeman, Claire; Stram, Daniel O.; Southey, Melissa C.; Sieh, Weiva; Siddiqui, Nadeem; Shvetsov, Yurii B.; Shu, Xiao-Ou; Shridhar, Viji; Wang-Gohrke, Shan; Severi, Gianluca; Schwaab, Ira; Salvesen, Helga B.; Rzepecka, Iwona K.; Runnebaum, Ingo B.; Rossing, Mary Anne; Rodriguez-Rodriguez, Lorna; Risch, Harvey A.; Renner, Stefan P.; Poole, Elizabeth M.; Pike, Malcolm C.; Phelan, Catherine M.; Pelttari, Liisa M.; Pejovic, Tanja; Paul, James; Orlow, Irene; Omar, Siti Zawiah; Olson, Sara H.; Odunsi, Kunle; Nickels, Stefan; Nevanlinna, Heli; Ness, Roberta B.; Narod, Steven A.; Nakanishi, Toru; Moysich, Kirsten B.; Monteiro, Alvaro N.A.; Moes-Sosnowska, Joanna; Modugno, Francesmary; Menon, Usha; McLaughlin, John R.; McGuire, Valerie; Matsuo, Keitaro; Adenan, Noor Azmi Mat; Massuger, Leon F.A. G.; Lurie, Galina; Lundvall, Lene; Lubiński, Jan; Lissowska, Jolanta; Levine, Douglas A.; Leminen, Arto; Lee, Alice W.; Le, Nhu D.; Lambrechts, Sandrina; Lambrechts, Diether; Kupryjanczyk, Jolanta; Krakstad, Camilla; Konecny, Gottfried E.; Kjaer, Susanne Krüger; Kiemeney, Lambertus A.; Kelemen, Linda E.; Keeney, Gary L.; Karlan, Beth Y.; Karevan, Rod; Kalli, Kimberly R.; Kajiyama, Hiroaki; Ji, Bu-Tian; Jensen, Allan; Jakubowska, Anna; Iversen, Edwin; Hosono, Satoyo; Høgdall, Claus K.; Høgdall, Estrid; Hoatlin, Maureen; Hillemanns, Peter; Heitz, Florian; Hein, Rebecca; Harter, Philipp; Halle, Mari K.; Hall, Per; Gronwald, Jacek; Gore, Martin; Goodman, Marc T.; Giles, Graham G.; Gentry-Maharaj, Aleksandra; Garcia-Closas, Montserrat; Flanagan, James M.; Fasching, Peter A.; Ekici, Arif B.; Edwards, Robert; Eccles, Diana; Easton, Douglas F.; Dürst, Matthias; du Bois, Andreas; Dörk, Thilo; Doherty, Jennifer A.; Despierre, Evelyn; Dansonka-Mieszkowska, Agnieszka; Cybulski, Cezary; Cramer, Daniel W.; Cook, Linda S.; Chen, Xiaoqing; Charbonneau, Bridget; Chang-Claude, Jenny; Campbell, Ian; Butzow, Ralf; Bunker, Clareann H.; Brueggmann, Doerthe; Brown, Robert; Brooks-Wilson, Angela; Brinton, Louise A.; Bogdanova, Natalia; Block, Matthew S.; Benjamin, Elizabeth; Beesley, Jonathan; Beckmann, Matthias W.; Bandera, Elisa V.; Baglietto, Laura; Bacot, François; Armasu, Sebastian M.; Antonenkova, Natalia; Anton-Culver, Hoda; Aben, Katja K.; Liang, Dong; Wu, Xifeng; Lu, Karen; Hildebrandt, Michelle A.T.; Schildkraut, Joellen M.; Sellers, Thomas A.; Huntsman, David; Berchuck, Andrew; Chenevix-Trench, Georgia; Gayther, Simon A.; Pharoah, Paul D.P.; Laird, Peter W.; Goode, Ellen L.; Pearce, Celeste Leigh
HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR) = 1.13, P = 3.1 × 10−10) and clear cell (rs11651755 OR = 0.77, P = 1.6 × 10−8) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome. Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes. These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes. PMID:23535649
Shen, Hui; Fridley, Brooke L; Song, Honglin; Lawrenson, Kate; Cunningham, Julie M; Ramus, Susan J; Cicek, Mine S; Tyrer, Jonathan; Stram, Douglas; Larson, Melissa C; Köbel, Martin; Ziogas, Argyrios; Zheng, Wei; Yang, Hannah P; Wu, Anna H; Wozniak, Eva L; Woo, Yin Ling; Winterhoff, Boris; Wik, Elisabeth; Whittemore, Alice S; Wentzensen, Nicolas; Weber, Rachel Palmieri; Vitonis, Allison F; Vincent, Daniel; Vierkant, Robert A; Vergote, Ignace; Van Den Berg, David; Van Altena, Anne M; Tworoger, Shelley S; Thompson, Pamela J; Tessier, Daniel C; Terry, Kathryn L; Teo, Soo-Hwang; Templeman, Claire; Stram, Daniel O; Southey, Melissa C; Sieh, Weiva; Siddiqui, Nadeem; Shvetsov, Yurii B; Shu, Xiao-Ou; Shridhar, Viji; Wang-Gohrke, Shan; Severi, Gianluca; Schwaab, Ira; Salvesen, Helga B; Rzepecka, Iwona K; Runnebaum, Ingo B; Rossing, Mary Anne; Rodriguez-Rodriguez, Lorna; Risch, Harvey A; Renner, Stefan P; Poole, Elizabeth M; Pike, Malcolm C; Phelan, Catherine M; Pelttari, Liisa M; Pejovic, Tanja; Paul, James; Orlow, Irene; Omar, Siti Zawiah; Olson, Sara H; Odunsi, Kunle; Nickels, Stefan; Nevanlinna, Heli; Ness, Roberta B; Narod, Steven A; Nakanishi, Toru; Moysich, Kirsten B; Monteiro, Alvaro N A; Moes-Sosnowska, Joanna; Modugno, Francesmary; Menon, Usha; McLaughlin, John R; McGuire, Valerie; Matsuo, Keitaro; Adenan, Noor Azmi Mat; Massuger, Leon F A G; Lurie, Galina; Lundvall, Lene; Lubiński, Jan; Lissowska, Jolanta; Levine, Douglas A; Leminen, Arto; Lee, Alice W; Le, Nhu D; Lambrechts, Sandrina; Lambrechts, Diether; Kupryjanczyk, Jolanta; Krakstad, Camilla; Konecny, Gottfried E; Kjaer, Susanne Krüger; Kiemeney, Lambertus A; Kelemen, Linda E; Keeney, Gary L; Karlan, Beth Y; Karevan, Rod; Kalli, Kimberly R; Kajiyama, Hiroaki; Ji, Bu-Tian; Jensen, Allan; Jakubowska, Anna; Iversen, Edwin; Hosono, Satoyo; Høgdall, Claus K; Høgdall, Estrid; Hoatlin, Maureen; Hillemanns, Peter; Heitz, Florian; Hein, Rebecca; Harter, Philipp; Halle, Mari K; Hall, Per; Gronwald, Jacek; Gore, Martin; Goodman, Marc T; Giles, Graham G; Gentry-Maharaj, Aleksandra; Garcia-Closas, Montserrat; Flanagan, James M; Fasching, Peter A; Ekici, Arif B; Edwards, Robert; Eccles, Diana; Easton, Douglas F; Dürst, Matthias; du Bois, Andreas; Dörk, Thilo; Doherty, Jennifer A; Despierre, Evelyn; Dansonka-Mieszkowska, Agnieszka; Cybulski, Cezary; Cramer, Daniel W; Cook, Linda S; Chen, Xiaoqing; Charbonneau, Bridget; Chang-Claude, Jenny; Campbell, Ian; Butzow, Ralf; Bunker, Clareann H; Brueggmann, Doerthe; Brown, Robert; Brooks-Wilson, Angela; Brinton, Louise A; Bogdanova, Natalia; Block, Matthew S; Benjamin, Elizabeth; Beesley, Jonathan; Beckmann, Matthias W; Bandera, Elisa V; Baglietto, Laura; Bacot, François; Armasu, Sebastian M; Antonenkova, Natalia; Anton-Culver, Hoda; Aben, Katja K; Liang, Dong; Wu, Xifeng; Lu, Karen; Hildebrandt, Michelle A T; Schildkraut, Joellen M; Sellers, Thomas A; Huntsman, David; Berchuck, Andrew; Chenevix-Trench, Georgia; Gayther, Simon A; Pharoah, Paul D P; Laird, Peter W; Goode, Ellen L; Pearce, Celeste Leigh
HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR)=1.13, P=3.1 × 10(-10)) and clear cell (rs11651755 OR=0.77, P=1.6 × 10(-8)) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome. Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes. These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes.
Pederson, Casey A; Rathert, Jamie L; Fite, Paula J; Stoppelbein, Laura; Greening, Leilani
Psychiatric inpatient hospitalization is a costly intervention for youth. With rates of hospitalization rising, efforts to refine prevention and intervention are necessary. Aggression often precedes severe internalizing behaviors, and proactive and reactive functions of aggression are differentially associated with internalizing symptomatology. Thus, further understanding of the links between functions of aggression and internalizing symptomatology could aid in the improvement of interventions for hospitalized youth. The current study examined parenting styles, gender, and age as potential moderators of the relations between proactive and reactive aggression and internalizing symptoms. Participants included 392 children, 6-12 years of age admitted consecutively to a psychiatric inpatient unit. Reactive aggression was uniquely associated with anxiety symptoms. However, proactive aggression was associated with internalizing problems only when specific parenting styles and demographic factors were present. Although both proactive and reactive subtypes of aggression were associated with internalizing symptoms, differential associations were evident. Implications of findings are discussed.
Cryptosporidium parvum subtype IIaA21G1R1 oocysts were used to infect dexamethasone immunosuppressed N: NIH Swiss mice. Histology showed developmental stages in the duodenum, proximal and distal jejunum, ileum, cecum and colon, with the small intestine remaining infected until day 35 post infection....
Xu, Yiyuan; Raine, Adrian; Yu, Lidong; Krieg, Alexander
Abundant research conducted in Western contexts has shown that biological risk factors such as low resting heart rate (HR) might be related to childhood aggression. However, it was unclear (1) how resting HR, as well as other markers of cardiac functions such as resting vagal tone, may be related to subtypes of aggression such as reactive and proactive aggression, and (2) whether the HR-aggression relation can be replicated in non-Western contexts. Therefore, this study examined the concurrent and prospective relations between resting HR, vagal tone, and Chinese children's reactive and proactive aggression. Participants were 183 children (M age=7.64 years, 91 girls) recruited from an elementary school in Zhenjiang, PRC. Children's resting HR and vagal tone were assessed in the second grade (T1). Teachers rated children's reactive and proactive aggression in the second (T1) and fourth grade (T2). Results showed that lower resting HR at T1 was associated with higher reactive and proactive aggression at T1 and T2, and higher vagal tone was associated with lower HR, which in turn was related to higher reactive and proactive aggression at T1 and T2. Lower vagal tone was directly related to higher reactive but not proactive aggression at T1 and T2, whereas lower HR was related to higher reactive aggression at T2 for children with low or moderate vagal tone but was not for children with high vagal tone. These psychophysiological findings from a non-Western context add additional support for both similarities and differences between reactive and proactive aggression in childhood.
Takahashi, Aki; Quadros, Isabel M.; de Almeida, Rosa M. M.; Miczek, Klaus A.
Rationale Recent findings have shown a complexly regulated 5-HT system as it is linked to different kinds of aggression. Objective We focus on (1) phasic and tonic changes of 5-HT and (2) state and trait of aggression, and emphasize the different receptor subtypes, their role in specific brain regions, feed-back regulation and modulation by other amines, acids and peptides. Results New pharmacological tools differentiate the first three 5-HT receptor families and their modulation by GABA, glutamate and CRF. Activation of 5-HT1A, 5-HT1B and 5-HT2A/2C receptors in mesocorticolimbic areas, reduce species-typical and other aggressive behaviors. In contrast, agonists at 5-HT1A and 5-HT1B receptors in the medial prefrontal cortex or septal area can increase aggressive behavior under specific conditions. Activation of serotonin transporters reduce mainly pathological aggression. Genetic analyses of aggressive individuals have identified several molecules that affect the 5-HT system directly (e.g., Tph2, 5-HT1B, 5-HT transporter, Pet1, MAOA) or indirectly (e.g., Neuropeptide Y, αCaMKII, NOS, BDNF). Dysfunction in genes for MAOA escalates pathological aggression in rodents and humans, particularly in interaction with specific experiences. Conclusions Feedback to autoreceptors of the 5-HT1 family and modulation via heteroreceptors are important in the expression of aggressive behavior. Tonic increase of the 5-HT2 family expression may cause escalated aggression, whereas the phasic increase of 5-HT2 receptors inhibits aggressive behaviors. Polymorphisms in the genes of 5-HT transporters or rate-limiting synthetic and metabolic enzymes of 5-HT modulate aggression, often requiring interaction with the rearing environment. PMID:20938650
Ullrich, Simone; Coid, Jeremy
There have been criticisms that the criteria for antisocial personality disorder (ASPD) are over-dependent on criminal behavior. This study aimed to identify unrelated criteria of social and behavioral problems and instability, and to investigate their associations in a representative household sample of adults in the UK. Approximately one third of adults with ASPD did not fulfill any of the criteria for instability. They were less aggressive and involved in illegal activities but expressed less remorse for their behaviors. Instability in ASPD was mediated primarily through comorbid anxiety disorders and borderline personality disorder. The concept of Secondary Psychopathy, which has not generally been applied to ASPD, demonstrated many similarities to the unstable subtype.
Bertucci, François; Finetti, Pascal; Birnbaum, Daniel; Mamessier, Emilie
Analysis of PDL1 mRNA expression in ∼5,500 breast cancers showed PDL1 upregulation in 38% of basal tumors and 38% of inflammatory breast cancers (IBC). Upregulation, associated with signs of strong cytotoxic local immune response, was associated with a better survival in the basal or triple-negative subtypes, and with a better pathological response to chemotherapy in these subtypes and IBC. Reactivation of dormant tumor-infiltrating lymphocytes (TILs) by PD1/PDL1-inhibitors represents a promising strategy in these aggressive tumors.
Bertucci, François; Finetti, Pascal; Birnbaum, Daniel; Mamessier, Emilie
ABSTRACT Analysis of PDL1 mRNA expression in ∼5,500 breast cancers showed PDL1 upregulation in 38% of basal tumors and 38% of inflammatory breast cancers (IBC). Upregulation, associated with signs of strong cytotoxic local immune response, was associated with a better survival in the basal or triple-negative subtypes, and with a better pathological response to chemotherapy in these subtypes and IBC. Reactivation of dormant tumor-infiltrating lymphocytes (TILs) by PD1/PDL1-inhibitors represents a promising strategy in these aggressive tumors. PMID:27141340
Discusses what may be considered aggressive behavior, what motivates aggressive students, and possible teacher responses to aggressive behavior. Describes four points on which teachers can focus to diminish the attractiveness of aggression and ensure that it is not rewarded. Identifies learning activities which provide aggressive students with the…
Stacy, Lauri L.
This document reviews existing empirical research on the effect of pornography on aggressive behavior. Two types of pornography are distinguished: aggressive pornography and non-aggressive pornography. Conclusions drawn from the research review are presented, including: (1) aggressive pornograpy consistently increases aggressive attitudes and…
Chaux, Alcides; Lezcano, Cecilia; Cubilla, Antonio L; Tamboli, Pheroze; Ro, Jae; Ayala, Alberto
There is a worldwide geographical variation in the incidence of penile squamous cell carcinoma (PSCC); some subtypes are HPV-related (warty, basaloid) while others (keratinizing variants) are not. The aims of this study were to compare the distribution of different histological subtypes of PSCC from regions of low (Paraguay, 144 cases) and high (USA, 157 cases) incidence and to identify and compare tumors with and without warty and/or basaloid morphology. The distribution of subtypes in the Paraguayan and the American series was: usual, 49.3 and 46.5%; verrucous, 8.3 and 7.6%; papillary NOS, 7.6 and 5.7%; warty, 6.9 and 8.3%; basaloid, 4.2 and 7.0%; sarcomatoid, 0.7 and 0.6%; adenosquamous, 3.5 and 0.6%; and mixed, 19.4 and 23.6%, respectively. The distribution of mixed PSCC was: warty-basaloid, 50.0 and 59.5%; usual-verrucous, 21.4 and 21.6%; usual-warty, 14.3 and 8.1%; usual-basaloid, 7.1 and 0.0%; usual-papillary, 3.6 and 5.4%; and others, 3.6 and 5.4%, respectively. In conclusion, we found no geographical difference in the incidence of histological subtypes (p = 0.6501), mixed PSCC (p = 0.5937) or HPV-related tumors (p = 0.2505). Geographical variation may be the result of staging variation at clinical presentation or of pathological diagnosis. The identification of similar histological subtypes in both series validates this classification approach for penile cancer. The tendency for typical SCC to mix with verrucous and papillary carcinomas and of the basaloid to preferentially mix with benign condyloma and condylomatous (warty) carcinomas would support the hypothesis of the existence of an etiologically different dual population of penile tumors.
Papadopoulos, Nikolaos G; Guibas, George V
Rhinitis is often seen as posing a small burden. However, rhinitis is a complex disease that is underpinned by a plethora of different mechanisms and causes. Rhinitis is frequently associated with other comorbid conditions but, by itself, is a source of considerable morbidity for patients and creates a significant financial burden on health systems worldwide. This article approaches this condition from both a phenotypic and mechanistic standpoint, focusing on the complexity of characterizing these subtypes. Developing a clearer demarcation of the currently obscure rhinitis phenotypes and endotypes will substantially improve their future prevention and treatment.
Russell, Gordon W.; Dua, Manjula
Used league records of all Canadian hockey games (N=426) played during a season to test a lunar-aggression hypothesis. Despite the use of multiple measures of lunar phase and interpersonal aggression, support for lunar influence was not forthcoming. Supplemental data revealed that beliefs in lunar influence are fairly common. (JAC)
Persons who have suffered traumatic injury to the brain may subsequently display aggressive behavior. Three main syndromes of aggression following traumatic brain injury are described: (1) episodic dyscontrol; (2) frontal lobe disinhibition; and (3) exacerbation of premorbid antisociality. The neuropsychological substrates of these syndromes are…
Blair, Robert J R
This selective review provides a model of the neurobiology of impulsive aggression from a cognitive neuroscience perspective. It is argued that prototypical cases of impulsive aggression, those associated with anger, involve the recruitment of the acute threat response system structures; that is, the amygdala, hypothalamus, and periaqueductal gray. It is argued that whether the recruitment of these structures results in impulsive aggression or not reflects the functional roles of ventromedial frontal cortex and dorsomedial frontal and anterior insula cortex in response selection. It is also argued that impulsive aggression may occur because of impaired decision making. The aggression may not be accompanied by anger, but it will reflect disrupted evaluation of the rewards/benefits of the action.
Abstract This selective review provides a model of the neurobiology of impulsive aggression from a cognitive neuroscience perspective. It is argued that prototypical cases of impulsive aggression, those associated with anger, involve the recruitment of the acute threat response system structures; that is, the amygdala, hypothalamus, and periaqueductal gray. It is argued that whether the recruitment of these structures results in impulsive aggression or not reflects the functional roles of ventromedial frontal cortex and dorsomedial frontal and anterior insula cortex in response selection. It is also argued that impulsive aggression may occur because of impaired decision making. The aggression may not be accompanied by anger, but it will reflect disrupted evaluation of the rewards/benefits of the action. PMID:26465707
Laney, Cara; Takarangi, Melanie K T
Can people develop false memories for committing aggressive acts? How does this process compare to developing false memories for victimhood? In the current research we used a simple false feedback procedure to implant false memories for committing aggressive acts (causing a black eye or spreading malicious gossip) or for victimhood (receiving a black eye). We then compared these false memories to other subjects' true memories for equivalent events. False aggressive memories were all too easy to implant, particularly in the minds of individuals with a proclivity towards aggression. Once implanted, the false memories were indistinguishable from true memories for the same events, on several dimensions, including emotional content. Implications for aggression-related memory more generally as well as false confessions are discussed.
Sigre-Leirós, Vera; Carvalho, Joana; Nobre, Pedro J
Although the role of interpersonal factors on sexual offending is already recognized, there is a need for further investigation on the psychosocial correlates of pedophilic behavior. This study aimed to examine the relationship between adult interpersonal features and subtypes of sexual offending. The study involved the participation of a total of 164 male convicted offenders namely 50 rapists, 63 child molesters (20 pedophilic and 43 nonpedophilic), and 51 nonsexual offenders. All participants were assessed using the Adult Attachment Scale, the Interpersonal Behavior Survey, the Brief Symptom Inventory, and the Socially Desirable Response Set Measure. Results from sets of multinomial logistic regression analyses showed that pedophilic offenders were more likely to present anxiety in adult relationships compared to nonsex offenders. Likewise, nonpedophilic child molesters were less likely to be generally aggressive compared to rapists and nonsex offenders, as well as less generally assertive than rapists. Overall, findings indicated that certain interpersonal features characterized subtypes of offenders, thus providing some insight on their particular therapeutic needs. Further replications with larger samples particularly of pedophilic child molesters are required.
Fernandes, Samuel Raimundo; Baldaia, Cilénia; Pinto Marques, Hugo; Tortosa, Francisco; Ramalho, Fernando
Clear-cell cholangiocarcinoma is a very uncommon variant of cholangiocarcinoma with a largely unknown natural history and prognosis. We report a case of a 51-year-old previously healthy woman presenting with a large liver nodule found on routine imaging. Needle biopsy of the lesion suggested a non-hepatocellular carcinoma. After extensive workup for other primary neoplasms, the patient underwent a partial hepatectomy. Histopathology was compatible with a moderately differentiated clear-cell cholangiocarcinoma. There was no evidence of liver disease in the remaining tissue. The patient underwent chemotherapy and remains in clinical remission after two years.
Levinson, Cheri A; Giancola, Peter R; Parrott, Dominic J
The goal of this investigation was to determine whether permissive beliefs about aggression moderate the relation between acute alcohol intoxication and aggression in two large experiments. Participants in Study 1 were 328 (163 men and 165 women) social drinkers and those in Study 2 were 518 (252 men and 266 women) social drinkers. Beliefs about aggression were assessed using a well-validated self-report measure. Following the consumption of either an alcohol or a placebo beverage, participants were tested on a laboratory task in which electric shocks were received from, and administered to, a fictitious opponent under the guise of a competitive reaction-time task. Aggression was operationalized as the combined mean responses for shock intensity and duration across all trials. Our central finding was that alcohol increased aggression in persons with more approving beliefs about aggression than in those who did not hold such beliefs. Our results are discussed within the context of Huesmann's (1988) cognitive script model of aggression. Suggestions for violence prevention efforts are put forth as well.
Examines the effects of aggressive-erotic stimuli on male aggression toward females. Male subjects' deliveries of electric shocks to males or females after viewing either a neutral, erotic, or aggressive-erotic film were measured. (Author/SS)
Yukawa, S; Yoshida, F
This study investigated whether cognitions and emotions elicited by media violence mediate aggressive behavior. Eighty undergraduates, 40 men and 40 women, participated in the experiment. First, subjects were exposed to one of four violent videos which varied in levels of violence and entertainment. Subjects' heart rate and eyeblink rate were continuously recorded while they watched the video. After watching it, subjects described their thoughts which occurred while watching it and rated their affective reactions to it. Finally, their aggressive behavior was measured. Results showed that (1) videos high in violence elicited more aggressive thoughts, more thoughts of negative affect, stronger negative affects, and stronger empty-powerless affects, whereas videos high in entertainment elicited stronger positive affects; (2) no significant differences were found among the videos in terms of physiological reactions and aggressive behavior; and (3) cognitions and emotions elicited by media violence did not mediate aggressive behavior.
Dickson, Daniel J.; Richmond, Ashley; Brendgen, Mara; Vitaro, Frank; Laursen, Brett; Dionne, Ginette; Boivin, Michel
The present study examined sibling influence over reactive and proactive aggression in a sample of 452 same-sex twins (113 male dyads, 113 female dyads). Between and within siblings influence processes were examined as a function of relative levels of parental coercion and hostility to test the hypothesis that aggression contagion between twins occurs only among dyads who experience parental coerciveness. Teacher reports of reactive and proactive aggression were collected for each twin in kindergarten (M = 6.04 years; SD = 0.27) and in first grade (M = 7.08 years; SD = 0.27). Families were divided into relatively low, average, and relatively high parental coercion-hostility groups on the basis of maternal reports collected when the children were 5 years old. In families with relatively high levels of parental coercion-hostility, there was evidence of between-sibling influence, such that one twin’s reactive aggression at age 6 predicted increases in the other twin’s reactive aggression from ages 6 to 7, and one twin’s proactive aggression at age 6 predicted increases in the other twin’s proactive aggression from ages 6 to 7. There was also evidence of within-sibling influence such that a child’s level of reactive aggression at age 6 predicted increases in the same child’s proactive aggression at age 7, regardless of parental coercion-hostility. The findings provide new information about the etiology of reactive and proactive aggression and individual differences in their developmental interplay. PMID:25683448
Mrevlje, Gorazd V
Psychology has a long tradition of considering human creativity as a distinct human characteristic and a special kind of human activity. After explaining the key motives for such an attitude, the author discusses those forms of healthy aggressiveness that stand out as necessary and constitutive elements of the creative process. Taking the well-known statement of C. G. Jung's 'The person who does not build (create), will demolish and destroy' as a starting point, the author compares the basic premises for understanding the process of human creativity, at the same time drawing on Freud's psychology of the individual and Jung's principle of the collective unconscious as well as his notion of 'complexes'. In doing so, the author somewhat boldly paraphrases Jung's dictum: 'In order to be creative, rather than just constructive, one must occasionally also destroy'. With reference to Wallas, Taylor and Neumann (Wallas 1926; Taylor 1959;;Neumann 2001), the author goes on to explore those concepts which help us to investigate the phenomenon of human creativity, drawing distinctions between emergent, expressive, productive, inventive and innovative creativity. The second part of the article discusses the importance of intelligence, originality, nonconformity, subversiveness and free-mindedness for the creative process of human beings. The author concludes with a further explanation of Erich Neumann's argument that human creativity cannot be understood solely as a result of sociogenetic factors, and argues that it is only by taking into consideration Jung's perception of creativity that a global ontological understanding of these processes can be achieved.
McCauley, C; Woods, K; Coolidge, C; Kulick, W
Independent rankings of humor and aggressiveness were obtained for sets of cartoons drawn randomly from two different magazines. The correlation of median humor and median aggressiveness rankings ranged from .49 to .90 in six studies involving six different sets of cartoons and six different groups of subjects, including children and adults, high and low socioeconomic status (SES) individuals, and native- and foreign-born individuals. This correlation is consistent with Freudian, arousal, and superiority theories of humor. Another prediction of Freudian theory, that high-SES subjects should be more appreciative of aggressive humor than low-SES subjects, was not supported.
Barling, Julian; Dupré, Kathryne E; Kelloway, E Kevin
Consistent with the relative recency of research on workplace aggression and the considerable media attention given to high-profile incidents, numerous myths about the nature of workplace aggression have emerged. In this review, we examine these myths from an evidence-based perspective, bringing greater clarity to our understanding of the predictors of workplace aggression. We conclude by pointing to the need for more research focusing on construct validity and prevention issues as well as for methodologies that minimize the likelihood of mono-method bias and that strengthen the ability to make causal inferences.
In redesigning the preclinical curriculum and shifting from a discipline-based approach to an organ system-based approach, faculty at the University of Arizona College of Medicine in Tucson took the opportunity to restructure the sequence of introductory histology content to make it more engaging and relevant. In this article, the author describes…
Knieper, P; Rochels, R; Nover, A
The authors examined four cases of keratoglobus and report here on the histological changes found: degenerative alterations of the epithelium, characteristic changes of Bowman's membrane, such as thinning, detachment and wrinkling, alterations of the stroma and secondary alterations of the Descemet's membrane. These results indicate that keratoglobus is nearly an extreme variant of keratoconus.
Low, Gavin; Huang, Guan; Fu, Winnie; Moloo, Zaahir; Girgis, Safwat
Representing 2%-3% of adult cancers, renal cell carcinoma (RCC) accounts for 90% of renal malignancies and is the most lethal neoplasm of the urologic system. Over the last 65 years, the incidence of RCC has increased at a rate of 2% per year. The increased incidence is at least partly due to improved tumor detection secondary to greater availability of high-resolution cross-sectional imaging modalities over the last few decades. Most RCCs are asymptomatic at discovery and are detected as unexpected findings on imaging performed for unrelated clinical indications. The 2004 World Health Organization Classification of adult renal tumors stratifies RCC into several distinct histologic subtypes of which clear cell, papillary and chromophobe tumors account for 70%, 10%-15%, and 5%, respectively. Knowledge of the RCC subtype is important because the various subtypes are associated with different biologic behavior, prognosis and treatment options. Furthermore, the common RCC subtypes can often be discriminated non-invasively based on gross morphologic imaging appearances, signal intensity on T2-weighted magnetic resonance images, and the degree of tumor enhancement on dynamic contrast-enhanced computed tomography or magnetic resonance imaging examinations. In this article, we review the incidence and survival data, risk factors, clinical and biochemical findings, imaging findings, staging, differential diagnosis, management options and post-treatment follow-up of RCC, with attention focused on the common subtypes. PMID:27247714
Pompili, E; Carlone, C; Silvestrini, C; Nicolò, G
This work aims to define the aggression in all its forms, with notes on management and rapid tranquilization. The pathological aggression is described as a non-homogeneous phenomenon, it is variable in according to social, psychological and biological agents. The distinction of violence between affective aggression and predatory aggression can be functional to the prediction of outcome of any treatment. In general, a pattern of predatory violence tend to match with patients unresponsive and not compliant to treatment, a low probability to predict future violence and, therefore, a difficulty in managing risk. The affective aggressor, however, shows increased probability of treatment response, with more predictability of violent actions in reaction to situations perceived as threatening and, therefore, greater management of future violence risk. Those who act affective violence tend to show a wide range of emotional and cognitive problems, while those who act with predatory patterns show greater inclination to aggression and antisocial behavior. Aggression that occurs in psychiatry mostly appears to be affective, therefore susceptible to modulation through treatments.
Gene sequencing and RT-PCR based methods are the molecular alternative to serology for the identification of influenza virus hemagglutinin and neuraminidase antigenic subtypes. Compared to serology both RT-PCR and sequencing are preferred subtyping methods because of the number of reference reagents...
Reports an error in "Parsing the heterogeneity of psychopathy and aggression: Differential associations across dimensions and gender" by Lisa K. Hecht, Joanna M. Berg, Scott O. Lilienfeld and Robert D. Latzman (Personality Disorders: Theory, Research, and Treatment, 2016[Jan], Vol 7, 2-14). In the article, there was an error in Table 3 and in the fifth paragraph of the Results. The correct information has been provided. (The following abstract of the original article appeared in record 2015-29370-001.) Psychopathy is a multidimensional construct that is broadly associated with both reactive (RA) and proactive (PA) aggression. Nevertheless, a consistent pattern of associations between psychopathy and these 2 aggression subtypes has yet to emerge because of methodological differences across studies. Moreover, research has yet to examine gender differences in the relation between dimensions of psychopathy and RA/PA. Accordingly, we examined the associations between psychopathy dimensions, as operationalized by 2 self-report instruments, and subtypes of aggression within a diverse sample of undergraduates (N = 1,158). Results confirmed that psychopathy is broadly associated with PA, as well as RA, with dimensions of psychopathy evidencing common and distinct associations with both raw and residual RA and PA scores. In both models of psychopathy, PA was significantly and positively associated with all dimensions, whereas RA was significantly negatively associated with interpersonal and affective dimensions, and significantly positively associated with dimensions related to an antisocial and impulsive lifestyle. Gender significantly moderated associations among dimensions of psychopathy and RA/PA, such that the antisocial/behavioral dimension of psychopathy was positively associated with PA for males, whereas the antisocial/behavioral dimension was positively associated with RA for females. Results suggest both generality and specificity of psychopathy dimensions as
Feldmeyer, Laurence; Prieto, Victor G; Ivan, Doina; Nagarajan, Priyadharsini; Tetzlaff, Michael T; Curry, Jonathan L; Bell, Diana; Moon, Bryan S; Torres-Cabala, Carlos A; Aung, Phyu P
Aggressive digital papillary adenocarcinoma (ADPA) is a rare and often misdiagnosed malignant tumor of the sweat glands, most commonly encountered on the extremities. Due to the relatively high metastatic potential of the tumor, aggressive surgical treatment, including amputation, is generally recommended. We present a case of a 36-year-old male with an over 10-year history of a skin lesion on the right hand in the web space between the index and the middle finger. Histologically, the lesion revealed a malignant epithelioid neoplasm with features consistent with ADPA. The lesion was treated with 5-weeks preoperative radiation (total 5000 cGy) followed by surgical resection. There was no evidence of residual disease confirmed by pathological study of re-excision specimen as well as imaging studies. This is, to the best of knowledge, the first report of complete regression of an ADPA after radiotherapy.
Lacourse, Eric; Baillargeon, Raymond; Dupere, Veronique; Vitaro, Frank; Romano, Elisa; Tremblay, Richard
Background: Investigating the latent structure of conduct disorder (CD) can help clarify how symptoms related to aggression, property destruction, theft, and serious violations of rules cluster in individuals with this disorder. Discovering homogeneous subtypes can be useful for etiologic, treatment, and prevention purposes depending on the…
Teles, Magda C; Oliveira, Rui F
Aggression is a complex behavior that influences social relationships and can be seen as adaptive or maladaptive depending on the context and intensity of expression. A model organism suitable for genetic dissection of the underlying neural mechanisms of aggressive behavior is still needed. Zebrafish has already proven to be a powerful vertebrate model organism for the study of normal and pathological brain function. Despite the fact that zebrafish is a gregarious species that forms shoals, when allowed to interact in pairs, both males and females express aggressive behavior and establish dominance hierarchies. Here, we describe two protocols that can be used to quantify aggressive behavior in zebrafish, using two different paradigms: (1) staged fights between real opponents and (2) mirror-elicited fights. We also discuss the methodology for the behavior analysis, the expected results for both paradigms, and the advantages and disadvantages of each paradigm in face of the specific goals of the study.
This paper briefly reviews some of the research areas which indicate a correlation between environmental factors and initiation of aggressive behavior. Environmental factors including lunar influences, month of birth, climate and the effects of crowding and certain chemicals are discussed.
Feddersen-Petersen, D U
The science of ethology is concerned with the way external stimuli and internal events cause animals to fight in a particular way. The classification of dog breeds with respect to their relative danger to humans makes no sense, as both, the complex antecedent conditions in which aggressive behaviour occurs, and its ramifying consequences in the individual dog's ecological and social environment, are not considered. From a biological point of view, environmental and learning effects are always superimposed upon genetic influences. Based on the recent developments in the study of ethology, aggression of wolves (Canis lupus L.) and domesticated dogs (Canis lupus f. familiaris) was put into context with respect to other aspects of the lifestyle of wild and domestic canids. Aggressive behaviour does not occur in a biological vacuum. This is also true for domestic dogs and their relationship to human partners. Individual dogs can become highly aggressive and dangerous. Their development and social situation will be presented and discussed in case studies. Finally, there is the question about defining "normal aggression" versus symptoms for maladaptive aggression resp. danger to humans as conspecifics. It is possible to protect the safety of the public and at the the same time practise animal care. Effective animal control legislation must focus on responsible ownership and socialisation of pups f.e. Problems are not unique to some breeds.
Chen, Meng-Jinn; Miller, Brenda A.; Grube, Joel W.; Waiters, Elizabeth D.
Objective This study investigated whether young people’s substance use and aggressive behaviors are related to their listening to music containing messages of substance use and violence. Method Data were collected using self-administered questionnaires and from a sample of community college students aged 15-25 (N = 1056; 43% male). A structural equation modeling method was used to simultaneously assess the associations between listening to various genres of music, alcohol use, illicit drug use, and aggressive behaviors, taking into account respondents’ age, gender, race/ethnicity, and level of sensation seeking. Results Listening to rap music was significantly and positively associated with alcohol use, problematic alcohol use, illicit drug use, and aggressive behaviors when all other variables were controlled. Additionally, alcohol and illicit drug use were positively associated with listening to musical genres of techno and reggae. Control variables such as sensation seeking, age, gender and race/ethnicity were significantly related to substance use and aggressive behaviors. Conclusion The findings suggest that young people’s substance use and aggressive behaviors may be related to their frequent exposure to music containing references to substance use and violence. Conversely, music listening preference may reflect some personal predispositions or lifestyle preferences. Alternatively, substance use, aggression and music preference are independent constructs, but share common “third factors.” PMID:16608146
Björklund, Gunilla M
A sample of 98 drivers responded to a Swedish version of the UK Driving Anger Scale [UK DAS; [Lajunen, T., Parker, D., Stradling, S.G., 1998. Dimensions of driver anger, aggressive and highway code violations and their mediation by safety orientation in UK drivers. Transport. Res. Part F 1, 107-121]. The results indicated that the Swedish version, like the British original, measures three sources of driver irritation: "progress impeded", "reckless driving", and "direct hostility". Structural equation modelling was used to investigate the relationships between the three sources of self-reported driver irritation, aggressive actions, speed, sex, age, and annual mileage. The models suggested a positive relationship between the amount of driver irritation and frequency of aggressive actions for all three sources of irritation. Female drivers tended to become more irritated than male drivers, while the male drivers tended to act aggressively more often. Surprisingly, drivers who reported that they enjoy fast speeds did not become more irritated than slower drivers when obstructed. The important conclusions are that experienced irritation often leads to openly aggressively actions, and that expression of aggressive behaviours may be a cause of other drivers' feeling of irritation.
Wright, Michelle F; Li, Yan
This longitudinal study examined normative beliefs about aggression (e.g., face-to-face, cyber) in relation to the engagement in cyber aggression 6 months later among 126 (69 women) young adults. Participants completed electronically administered measures assessing their normative beliefs, face-to-face and cyber aggression at Time 1, and cyber aggression 6 months later (Time 2). We found that men reported more cyber relational and verbal aggression when compared to women. After controlling for each other, Time 1 face-to-face relational aggression was positively related to Time 2 cyber relational aggression, whereas Time 1 face-to-face verbal aggression was positively related to Time 2 cyber verbal aggression. Normative beliefs regarding cyber aggression was positively related to both forms of cyber aggression 6 months later, after controlling for normative beliefs about face-to-face aggression. Furthermore, a significant two-way interaction between Time 1 cyber relational aggression and normative beliefs about cyber relational aggression was found. Follow-up analysis showed that Time 1 cyber relational aggression was more strongly related to Time 2 cyber relational aggression when young adults held higher normative beliefs about cyber relational aggression. A similar two-way interaction was found for cyber verbal aggression such that the association between Time 1 and Time 2 cyber verbal aggression was stronger at higher levels of normative beliefs about cyber verbal aggression. Results are discussed in terms of the social cognitive and behavioral mechanisms associated with the engagement of cyber aggression.
Gravendeel, Lonneke A M; Kloosterhof, Nanne K; Bralten, Linda B C; van Marion, Ronald; Dubbink, Hendrikus Jan; Dinjens, Winand; Bleeker, Fonnet E; Hoogenraad, Casper C; Michiels, Erna; Kros, Johan M; van den Bent, Martin; Smitt, Peter A E Sillevis; French, Pim J
Mutations in the gene encoding the isocitrate dehydrogenase 1 gene (IDH1) occur at a high frequency (up to 80%) in many different subtypes of glioma. In this study, we have screened for IDH1 mutations in a cohort of 496 gliomas. IDH1 mutations were most frequently observed in low grade gliomas with c.395G>A (p.R132H) representing >90% of all IDH1 mutations. Interestingly, non-p.R132H mutations segregate in distinct histological and molecular subtypes of glioma. Histologically, they occur sporadically in classic oligodendrogliomas and at significantly higher frequency in other grade II and III gliomas. Genetically, non-p.R132H mutations occur in tumors with TP53 mutation, are virtually absent in tumors with loss of heterozygosity on 1p and 19q and accumulate in distinct (gene-expression profiling based) intrinsic molecular subtypes. The IDH1 mutation type does not affect patient survival. Our results were validated on an independent sample cohort, indicating that the IDH1 mutation spectrum may aid glioma subtype classification. Functional differences between p.R132H and non-p.R132H mutated IDH1 may explain the segregation in distinct glioma subtypes.
Ben Sasson, Dvora; Somech, Anit
Purpose: Despite growing research on school aggression, significant gaps remain in the authors' knowledge of team aggression, since most studies have mainly explored aggression on the part of students. The purpose of this paper is to focus on understanding the phenomenon of workplace aggression in school teams. Specifically, the purpose of the…
The focus of this article is the anatomy and histology of the anal canal, and its clinical relevance to anal cancers. The article also highlights the recent histological and anatomical changes to the traditional terminology of the anal canal. The terminology has been adopted by the American Joint Committee on Cancer, separating the anal region into the anal canal, the perianal region and the skin. This paper describes the gross anatomy of the anal canal, along with its associated blood supply, venous and lymphatic drainage, and nerve supply. The new terminology referred to in this article may assist clinicians and health care providers to identify lesions more precisely through naked eye observation and without the need for instrumentation. Knowledge of the regional anatomy of the anus will also assist in management decisions.
Beaufort, Corine M.; Helmijr, Jean C. A.; Piskorz, Anna M.; Hoogstraat, Marlous; Ruigrok-Ritstier, Kirsten; Besselink, Nicolle; Murtaza, Muhammed; van IJcken, Wilfred F. J.; Heine, Anouk A. J.; Smid, Marcel; Koudijs, Marco J.; Brenton, James D.; Berns, Els M. J. J.; Helleman, Jozien
Epithelial ovarian cancer is a highly heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Therapeutic approaches need to account for inter-patient and intra-tumoural heterogeneity and detailed characterization of in vitro models representing the different histological and molecular ovarian cancer subtypes is critical to enable reliable preclinical testing. There are approximately 100 publicly available ovarian cancer cell lines but their cellular and molecular characteristics are largely undescribed. We have characterized 39 ovarian cancer cell lines under uniform conditions for growth characteristics, mRNA/microRNA expression, exon sequencing, drug response for clinically-relevant therapeutics and collated all available information on the original clinical features and site of origin. We tested for statistical associations between the cellular and molecular features of the lines and clinical features. Of the 39 ovarian cancer cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type. Three morphological subtypes: Epithelial (n = 21), Round (n = 7) and Spindle (n = 12) were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes in the Spindle subtype. Comparison with the original clinical data showed association of the spindle-like tumours with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the expression profiles of Spindle, Round and Epithelial morphologies clustered with the previously described C1-stromal, C5-mesenchymal and C4 ovarian subtype expression profiles respectively. Comprehensive profiling of 39 ovarian cancer cell lines under controlled, uniform conditions demonstrates clinically relevant cellular and genomic characteristics. This data provides a rational basis for selecting models to develop specific treatment
Buesa, René J
Histology laboratories (histolabs) can increase productivity and reduce turnaround time and errors by using any one of several available management tools. After a few years of operation, all histolabs develop workflow problems. Histology laboratories handling more than 20,000 cases per year benefit the most from implementing management tools, as occurred in the 25 facilities summarized in this article. Discontinuous workflow, lack of "pulling" between steps, accepting unavoidable waiting times while working with small batches within work cells, and a workflow with an uneven rate of completion, are some of the adaptations required by the Lean system when it is used in histology because 70% of the tasks are manual and the flow has to be interrupted to add value to the pieces of tissue during tissue processing, no matter how short that step is. After all these adaptations are incorporated, the histolab becomes as "Lean" as it can be, and the qualifier is also a recognition of the effort and personnel involvement in the implementation. Given its service nature, productivity increments do not expand the histolab customer base and could lead to staffing reductions. This is one of the causes of reluctance by some employees for implementing these techniques which are mostly driven by cost reductions sought by insurance companies and administrators, and not necessarily because of a real medical need to reduce the turnaround time. Finally, any histolab wanting to improve its workflow can follow some easy steps presented here as a guide to accomplish that objective. These steps stress the need for the supervisors to insure that the personnel in the histology laboratory are being paid at a comparable rate as other histolabs in the area.
Background To compare the distribution of the intrinsic molecular subtypes of breast cancer based on immunohistochemical profile in the five major geographic regions of Brazil, a country of continental dimension, with a wide racial variation of people. Methods The study was retrospective observational. We classified 5,687 invasive breast cancers by molecular subtype based on immunohistochemical expression of estrogen-receptor (ER), progesterone-receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 proliferation index. Cases were classified as luminal A (ER and/or PR positive and HER2 negative, Ki-67 < 14%), luminal B (ER and/or PR positive, HER2 negative, and Ki-67 > 14%), triple-positive (ER and/or PR positive and HER2 positive), HER2-enriched (ER and PR negative, and HER2- positive), and triple-negative (TN) (ER negative, PR negative, and HER2- negative). Comparisons of the ages of patients and molecular subtypes between different geographic regions were performed. Results South and Southeast regions with a higher percentage of European ancestry and higher socioeconomic status presented with the highest proportion of luminal tumors. The North region presented with more aggressive subtypes (HER2-enriched and triple-negative), while the Central-West region predominated triple-positive carcinomas. The Northeast—a region with a high African influence—presented intermediate frequency of the different molecular subtypes. The differences persisted in subgroups of patients under and over 50 years. Conclusions The geographic regions differ according to the distribution of molecular subtypes of breast cancer. However, other differences, beside those related to African ancestry, such as socioeconomic, climatic, nutritional, and geographic, have to be considered to explain our results. The knowledge of the differences in breast cancer characteristics among the geographic regions may help to organize healthcare programs in large countries
Improved biomarker tests are required to minimize overdiagnosis and overtreatment of breast cancers. A number of pathologic criteria have been established to differentiate indolent or aggressive behavior, such as Nottingham grade of cancer cells. However, the effects of the tumor microenvironment on patient outcomes have not been integrated into pathologic criteria. In the current study, the Reactive subtype of breast cancer, identified by reverse-phase protein arrays, was demonstrated to indicate a favorable outcome.
van Lier, Pol; Boivin, Michel; Dionne, Ginette; Vitaro, Frank; Brendgen, Mara; Koot, Hans; Tremblay, Richard E.; Perusse, Daniel
Objective: To examine whether kindergarten children's genetic liability to physically aggress moderates the contribution of friends' aggression to their aggressive behaviors. Method: Teacher and peer reports of aggression were available for 359 6-year-old twin pairs (145 MZ, 212 DZ) as well as teacher and peer reports of aggression of the two best…
Parker, Gordon B
The concept of atypical depression has evolved over the past several decades, yet remains inadequately defined. As currently defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), the main criterion of atypical depression is the presence of mood reactivity in combination with at least 2 of 4 secondary criteria (hypersomnia, hyperphagia and weight gain, leaden paralysis, and oversensitivity to criticism and rejection). The focus on mood reactivity as the primary distinguishing criterion remains questionable among researchers who have been unable to verify the primacy of this symptom in relation to the other diagnostic criteria for atypical depression. A model challenging the DSM-IV-TR definition of atypical depression has been developed, redefining the disorder as a dimensional nonmelancholic syndrome in which individuals with a personality subtype of "interpersonal rejection sensitivity" have a tendency toward the onset of anxiety disorders and depression, thereby exhibiting a variety of dysregulated emotional and self-consolatory responses. This reformulated definition of atypical depression (in arguing for the primacy of a personality style or rejection sensitivity as against mood reactivity) may lead to a better understanding and recognition of the disorder and its symptoms as well as other "spectrum" disorders within the scope of major depression.
Chiavarina, Barbara; Nokin, Marie-Julie; Durieux, Florence; Bianchi, Elettra; Turtoi, Andrei; Peulen, Olivier; Peixoto, Paul; Irigaray, Philippe; Uchida, Koji; Belpomme, Dominique; Delvenne, Philippe; Castronovo, Vincent; Bellahcène, Akeila
Metabolic syndrome and type 2 diabetes are associated with increased risk of breast cancer development and progression. Methylglyoxal (MG), a glycolysis by-product, is generated through a non-enzymatic reaction from triose-phosphate intermediates. This dicarbonyl compound is highly reactive and contributes to the accumulation of advanced glycation end products. In this study, we analyzed the accumulation of Arg-pyrimidine, a MG-arginine adduct, in human breast adenocarcinoma and we observed a consistent increase of Arg-pyrimidine in cancer cells when compared with the non-tumoral counterpart. Further immunohistochemical comparative analysis of breast cancer subtypes revealed that triple negative lesions exhibited low accumulation of Arg-pyrimidine compared with other subtypes. Interestingly, the activity of glyoxalase 1 (Glo-1), an enzyme that detoxifies MG, was significantly higher in triple negative than in other subtype lesions, suggesting that these aggressive tumors are able to develop an efficient response against dicarbonyl stress. Using breast cancer cell lines, we substantiated these clinical observations by showing that, in contrast to triple positive, triple negative cells induced Glo-1 expression and activity in response to MG treatment. This is the first report that Arg-pyrimidine adduct accumulation is a consistent event in human breast cancer with a differential detection between triple negative and other breast cancer subtypes.
Fertig, Elana J.; Lee, Esak; Pandey, Niranjan B.; Popel, Aleksander S.
Breast cancer is a heterogeneous disease, having multiple subtypes with different malignant phenotypes. The triple-negative breast cancer, or basal breast cancer, is highly aggressive, metastatic, and difficult to treat. Previously, we identified that key molecules (IL6, CSF2, CCL5, VEGFA, and VEGFC) secreted by tumor cells and stromal cells in basal breast cancer can promote metastasis. It remains to assess whether these molecules function similarly in other subtypes of breast cancer. Here, we characterize the relative gene expression of the five secreted molecules and their associated receptors (GP130, GMRA, GMRB, CCR5, VEGFR2, NRP1, VEGFR3, NRP2) in the basal, HER2 (human epidermal growth factor receptor 2) positive, luminal A, and luminal B subtypes using high throughput data from tumor samples in The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). IL6 and CCL5 gene expression are basal breast cancer specific, whereas high gene expression of GP130 was observed in luminal A/B. VEGFA/C and CSF2 mRNA are overexpressed in HER2 positive breast cancer, with VEGFA and CSF2 also overexpressed in basal breast cancer. Further study of the specific protein function of these factors within their associated cancer subtypes may yield personalized biomarkers and treatment modalities. PMID:26173622
Lan, Chunyan; Heindl, Andreas; Huang, Xin; Xi, Shaoyan; Banerjee, Susana; Liu, Jihong; Yuan, Yinyin
Concerted efforts in genomic studies examining RNA transcription and DNA methylation patterns have revealed profound insights in prognostic ovarian cancer subtypes. On the other hand, abundant histology slides have been generated to date, yet their uses remain very limited and largely qualitative. Our goal is to develop automated histology analysis as an alternative subtyping technology for ovarian cancer that is cost-efficient and does not rely on DNA quality. We developed an automated system for scoring primary tumour sections of 91 late-stage ovarian cancer to identify single cells. We demonstrated high accuracy of our system based on expert pathologists’ scores (cancer = 97.1%, stromal = 89.1%) as well as compared to immunohistochemistry scoring (correlation = 0.87). The percentage of stromal cells in all cells is significantly associated with poor overall survival after controlling for clinical parameters including debulking status and age (multivariate analysis p = 0.0021, HR = 2.54, CI = 1.40–4.60) and progression-free survival (multivariate analysis p = 0.022, HR = 1.75, CI = 1.09–2.82). We demonstrate how automated image analysis enables objective quantification of microenvironmental composition of ovarian tumours. Our analysis reveals a strong effect of the tumour microenvironment on ovarian cancer progression and highlights the potential of therapeutic interventions that target the stromal compartment or cancer-stroma signalling in the stroma-high, late-stage ovarian cancer subset. PMID:26573438
Background Colon cancer patients with the same stage show diverse clinical behavior due to tumor heterogeneity. We aimed to discover distinct classes of tumors based on microarray expression patterns, to analyze whether the molecular classification correlated with the histopathological stages or other clinical parameters and to study differences in the survival. Methods Hierarchical clustering was performed for class discovery in 88 colon tumors (stages I to IV). Pathways analysis and correlations between clinical parameters and our classification were analyzed. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the main subtype was generated using the 3-Nearest-Neighbor method. Coincidences with other prognostic predictors were assesed. Results Hierarchical clustering identified four robust tumor subtypes with biologically and clinically distinct behavior. Stromal components (p < 0.001), nuclear β-catenin (p = 0.021), mucinous histology (p = 0.001), microsatellite-instability (p = 0.039) and BRAF mutations (p < 0.001) were associated to this classification but it was independent of Dukes stages (p = 0.646). Molecular subtypes were established from stage I. High-stroma-subtype showed increased levels of genes and altered pathways distinctive of tumour-associated-stroma and components of the extracellular matrix in contrast to Low-stroma-subtype. Mucinous-subtype was reflected by the increased expression of trefoil factors and mucins as well as by a higher proportion of MSI and BRAF mutations. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the Low-stroma-subtype distinguished low risk patients from high risk patients in the external cohort (Dukes B and C:HR = 8.56(2.53-29.01); Dukes B,C and D:HR = 1.87(1.07-3.25)). Eight different reported survival gene signatures segregated our tumors into two groups the Low-stroma-subtype and
Lehmann, Anja; Ittel, Angela
Studies concerning inmate psychopathy (as measured by Psychopathy-Checklist-Revised, PCL-R; Hare, 1991) have predominantly been concerned with male inmates. This study was the first to look into psychopathy using the PCL-R with the whole required procedure in German prisons with female inmates. The aims of the present study were to gain data about the prevalence of psychopathy in this sample and to examine potential relations between the types and motive of aggression, prosocial behavior and scores on the PCL-R. Sixty female inmates were examined. We obtained a prevalence rate of psychopathy of 17% (N=10, with a cut-off score of 25). Considering a wide range of subtypes of aggressive behaviors, we found that physical proactive, and relational reactive aggression as well as age predicted high scores of psychopathy. However, prosocial or helping behavior was not associated with psychopathy. Implications for diagnostic issues in forensics concerning female prisoners are discussed.
Barón Duarte, F J; Rodríguez Calvo, M S; Amor Pan, J R
Aggressiveness criteria proposed in the scientific literature a decade ago provide a quality judgment and are a reference in the care of patients with advanced cancer, but their use is not generalized in the evaluation of Oncology Services. In this paper we analyze the therapeutic aggressiveness, according to standard criteria, in 1.001 patients with advanced cancer who died in our Institution between 2010 and 2013. The results seem to show that aggressiveness at the end of life is present more frequently than experts recommend. About 25% of patients fulfill at least one criterion of aggressiveness. This result could be explained by a liquid Oncology which does not prioritize the patient as a moral subject in the clinical appointment. Medical care is oriented to necessities and must be articulated in a model focused on dignity and communication. Its implementation through Advanced Care Planning, consideration of patient's values and preferences, and Limitation of therapeutic effort are ways to reduce aggressiveness and improve clinical practice at the end of life. We need to encourage synergic and proactive attitudes, adding the best of cancer research with the best clinical care for the benefit of human being, moral subject and main goal of Medicine.
Hirko, Kelly A; Willett, Walter C; Hankinson, Susan E; Rosner, Bernard A; Beck, Andrew H; Tamimi, Rulla M; Eliassen, A Heather
We examined associations between dietary quality indices and breast cancer risk by molecular subtype among 100,643 women in the prospective Nurses' Health Study (NHS) cohort, followed from 1984 to 2006. Dietary quality scores for the Alternative Healthy Eating Index (AHEI), alternate Mediterranean diet (aMED), and Dietary Approaches to Stop Hypertension (DASH) dietary patterns were calculated from semi-quantitative food frequency questionnaires collected every 2-4 years. Breast cancer molecular subtypes were defined according to estrogen receptor (ER), progesterone receptor, human epidermal growth factor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor status from immunostained tumor microarrays in combination with histologic grade. Cox proportional hazards models, adjusted for age and breast cancer risk factors, were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). Competing risk analyses were used to assess heterogeneity by subtype. We did not observe any significant associations between the AHEI or aMED dietary patterns and risk of breast cancer by molecular subtype. However, a significantly reduced risk of HER2-type breast cancer was observed among women in 5th versus 1st quintile of the DASH dietary pattern [n = 134 cases, Q5 vs. Q1 HR (95 % CI) = 0.44 (0.25-0.77)], and the inverse trend across quintiles was significant (p trend = 0.02). We did not observe any heterogeneity in associations between AHEI (p het = 0.25), aMED (p het = 0.71), and DASH (p het = 0.12) dietary patterns and breast cancer by subtype. Adherence to the AHEI, aMED, and DASH dietary patterns was not strongly associated with breast cancer molecular subtypes.
Wo, Jennifer Y.; Taghian, Alphonse G.; Nguyen, Paul L.; Raad, Rita Abi; Sreedhara, Meera B.A.; Bellon, Jennifer R.; Wong, Julia S.; Gadd, Michele A.; Smith, Barbara L.; Harris, Jay R.
Purpose: To evaluate the risk of isolated regional nodal failure (RNF) among women with invasive breast cancer treated with breast-conserving surgery (BCS) and radiation therapy (RT) and to determine factors, including biological subtype, associated with RNF. Methods and Materials: We retrospectively studied 1,000 consecutive women with invasive breast cancer who received breast-conserving surgery and RT from 1997 through 2002. Ninety percent of patients received adjuvant systemic therapy; none received trastuzumab. Sentinel lymph node biopsy was done in 617 patients (62%). Of patients with one to three positive nodes, 34% received regional nodal irradiation (RNI). Biological subtype classification into luminal A, luminal B, HER-2, and basal subtypes was based on estrogen receptor status-, progesterone receptor status-, and HER-2-status of the primary tumor. Results: Median follow-up was 77 months. Isolated RNF occurred in 6 patients (0.6%). On univariate analysis, biological subtype (p = 0.0002), lymph node involvement (p = 0.008), lymphovascular invasion (p = 0.02), and Grade 3 histology (p = 0.01) were associated with significantly higher RNF rates. Compared with luminal A, the HER-2 (p = 0.01) and basal (p = 0.08) subtypes were associated with higher RNF rates. The 5-year RNF rate among patients with one to three positive nodes treated with tangents alone was 2.4%; we could not identify a subset of these patients with a substantial risk of RNF. Conclusions: Isolated RNF is a rare occurrence after breast-conserving therapy. Patients with the HER-2 (not treated with trastuzumab) and basal subtypes appear to be at higher risk of developing RNF although this risk is not high enough to justify the addition of RNI. Low rates of RNF in patients with one to three positive nodes suggest that tangential RT without RNI is reasonable in most patients.
Hirko, Kelly A.; Willett, Walter C.; Hankinson, Susan E.; Rosner, Bernard A.; Beck, Andrew H.; Tamimi, Rulla M.; Eliassen, A. Heather
Purpose We examined associations between dietary quality indices and breast cancer risk by molecular subtype among 100,643 women in the prospective Nurses' Health Study (NHS) cohort, followed from 1984 to 2006. Methods Dietary quality scores for the Alternative Healthy Eating Index (AHEI), alternate Mediterranean diet (aMED), and Dietary Approaches to Stop Hypertension (DASH) dietary patterns were calculated from semi-quantitative food frequency questionnaires collected every 2-4 years. Breast cancer molecular subtypes were defined according to estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR) status from immunostained tumor microarrays in combination with histologic grade. Cox proportional hazards models, adjusted for age and breast cancer risk factors, were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Competing risk analyses were used to assess heterogeneity by subtype. Results We did not observe any significant associations between the AHEI or aMED dietary patterns and risk of breast cancer by molecular subtype. However, a significant reduced risk of HER2-type breast cancer was observed among women in 5th vs. 1st quintile of the DASH dietary pattern (n=134 cases, Q5 vs. Q1 HR (95%CI) =0.44(0.25-0.77)), and the inverse trend across quintiles was significant (p-trend=0.02). We did not observe any heterogeneity in associations between AHEI (phet =0.25), aMED (phet =0.71) and DASH (phet =0.12) dietary patterns and breast cancer by subtype. Conclusions Adherence to the AHEI, aMED, and DASH dietary patterns was not strongly associated with breast cancer molecular subtypes. PMID:26872903
Gisselbrecht, C; Gaulard, P; Lepage, E; Coiffier, B; Brière, J; Haioun, C; Cazals-Hatem, D; Bosly, A; Xerri, L; Tilly, H; Berger, F; Bouhabdallah, R; Diebold, J
Peripheral T-cell lymphomas (PTCL) have been generally reported to have a worse prognosis than B-cell lymphomas (BCL). Because of their heterogeneity and scarcity, the outcomes of the different histological subtypes have not been compared. From October 1987 to March 1993, 1,883 patients with diffuse aggressive non-Hodgkin's lymphomas (NHL) included in the LNH87 protocol could be assessed for both morphology and immunophenotyping. Among them, 288 (15%) had PTCL and 1,595 (85%) had BCL. According to the Kiel classification, most PTCL were classified as angioimmunoblastic (AIL; 23%), pleomorphic medium and large T-cell (PML; 49%), or anaplastic large cell (ALCL; 20%) lymphomas. Comparing PTCL with BCL patients, the former had more disseminated disease (78% v 58%), B symptoms (57% v 40%), bone marrow involvement (31% v 17%), skin involvement (21% v 4%), and increased beta2-microglobulin (50% v 34%), whereas BCL patients had more bulky disease (41% v 26%). According to the International Prognostic Index (IPI), PTCL and BCL scores were, respectively: 0 factors, 13% and 15%; 1 factor, 17% and 22%; 2 factors, 24% and 25%; >/=3 factors, 45% and 37% (P = .09). For BCL and PTCL, respectively, complete remission rates were 63% and 54% (P = .004); the 5-year overall survival (OS) rates were 53% and 41% (P = .0004) and event-free survival (EFS) rates were 42% and 33% (P < . 0001). Comparison of the different histological subtypes of lymphoma showed that the 5-year OS rate for T-ALCL (64%) was superior to those of other PTCL (35%) as well as diffuse large B-cell (53%) NHL. When multivariate analysis was applied using the IPI score as one factor, nonanaplastic PTCL remained an independent parameter (P = . 0004). Although the poor prognosis of non-ALCL PTCL could be due in part to the presence of adverse prognostic factors at diagnosis, this study shows that the T-cell phenotype is an independent significant factor, which should be incorporated into the definition of prognostic
Villanacci, Vincenzo; Ceppa, Paola; Tavani, Enrico; Vindigni, Carla; Volta, Umberto
To this day intestinal biopsy is justly considered the "gold standard" for the diagnosis of coeliac disease (CD). The aim of the authors in setting up these guidelines was to assist pathologists in formulating a more precise morphological evaluation of a duodenal biopsy in the light of clinical and laboratory data, to prepare histological samples with correctly oriented biopsies and in the differential diagnosis with other pathological entities and complications of the disease. A further intention was to promote the conviction for the need of a close collaborative relationship between different specialists namely the concept of a "multidisciplinary team".
Doglioni, Claudio; Ponzoni, Maurilio; Ferreri, Andrés J M; Savio, Antonella
The diagnosis of gastric MALT lymphoma is frequently difficult for the general histopathologist. During recent years there have been relevant changes in the therapeutic approach to gastric MALT lymphoma and our knowledge about its pathogenesis has greatly improved. The management of this disease actually requires a close cooperation between the histopathologist and the clinicians. The histology report of biopsies of a newly diagnosed or of an already treated case implies information of clinical and therapeutical relevance. This paper aims at giving the histopathologist a general knowledge about the state of art of this disease and its management. The diagnostic process leading to a complete and competent report is then described step by step.
Sivrikoz, O N; Doganay, L; Sivrikoz, U K; Karaarslan, S; Sanal, S M
Chemokine receptor 4 (CXCR4) and γ-catenin are known to play an important role in development of metastasis in breast cancer. However, there is not enough information about these biological markers' distribution in different breast cancer subtypes, or their relationship to lymph node metastases in each subtype. In this study, staining characteristics of CXCR4 and γ-catenin were analyzed in each breast cancer subtype and their relationship to lymph node involvement explored. There was a statistically significant relationship between CXCR4 and certain tumor subtypes (p < 0.05). Basal-like and HER2 enriched tumors showed strong CXCR4 positivity (45.7%). Furthermore, a significant correlation was discovered between CXCR4 positivity and lymph node involvement (p < 0.05). Among tumor subtypes staining positively with CXCR4, 80% of basal-like, 90% of HER2 enriched, and 78.5% of luminal A showed axillary lymph node involvement. In general, there was a positive relationship between histological grade and CXCR4 expression (p = 0.004). A statistically significant correlation existed between HER2 positivity and γ-catenin expression (p < 0.05). Basal-like and HER2 enriched breast cancer subtypes express CXCR4 staining more often than the other subtypes. Additionally, there is also a positive relationship between lymph node involvement and CXCR4 staining of these subtypes.
Sentürk, S; Yalçin, E; Pentürk, S
Serum lipids and lipoprotein concentrations have been associated with dominance aggression in humans. The aim of this study was to investigate the link between serum lipids, including cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) to HDL-C ratio and dominance aggression in dogs. Levels of serum TC, triglyceride and HDL-C were significantly lower in dogs with dominance aggression compared with non-aggressive dogs (P < 0.001). These results suggest that a relationship exists between serum lipid profile and dominance aggression in dogs, and hypocholesterolaemia exists in dogs with dominance aggression.
Zwarts, Liesbeth; Versteven, Marijke; Callaerts, Patrick
Aggressive behavior is widely present throughout the animal kingdom and is crucial to ensure survival and reproduction. Aggressive actions serve to acquire territory, food, or mates and in defense against predators or rivals; while in some species these behaviors are involved in establishing a social hierarchy. Aggression is a complex behavior, influenced by a broad range of genetic and environmental factors. Recent studies in Drosophila provide insight into the genetic basis and control of aggression. The state of the art on aggression in Drosophila and the many opportunities provided by this model organism to unravel the genetic and neurobiological basis of aggression are reviewed. PMID:22513455
Smith, M.P.; Sansom, I.J.; Repetski, J.E.
THE first description of Anatolepis Bockelie & Fortey was from early Ordovician sediments of Ny Friesland, Spitsbergen1,2, but the genus is now known from many localities in North America and Greenland, ranging in age from the Late Cambrian period to the Early Ordovician3-6. Although initially interpreted as an agnathan fish2,3 that predated other representatives7, this has been widely disputed because the available histological data were unconvincing6,8-10 and the scales fell outside the known morphological range of other accepted early vertebrates9-11. Further doubt was cast upon the vertebrate affinity of Anatolepis when specimens from East Greenland were interpreted as the cuticular fragments of aglaspid arthropods6, although this interpretation has also been refuted12. Here we report on the morphology and histology of large collections of Anatolepis, and demonstrate the presence of dentine, a tissue unique to vertebrates, confirming that the taxon is both a vertebrate and the oldest known fish.
Yun, Rebecca J; Stern, Barry L; Lenzenweger, Mark F; Tiersky, Lana A
The current Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic system for Axis II disorders continues to be characterized by considerable heterogeneity and poor discriminant validity. Such problems impede accurate personality disorder (PD) diagnosis. As a result, alternative assessment tools are often used in conjunction with the DSM. One popular framework is the object relational model developed by Kernberg and his colleagues (J. F. Clarkin, M. F. Lenzenweger, F. Yeomans, K. N. Levy, & O. F. Kernberg, 2007, An object relations model of borderline pathology, Journal of Personality Disorders, Vol. 21, pp. 474-499; O. F. Kernberg, 1984, Severe Personality Disorders, New Haven, CT: Yale University Press; O. F. Kernberg & E. Caligor, 2005, A psychoanalytic theory of personality disorders, in M. F. Lenzenweger & J. F. Clarkin, Eds., Major Theories of Personality Disorder, New York, NY: Guilford Press). Drawing on this model and empirical studies thereof, the current study attempted to clarify Kernberg's (1984) PD taxonomy and identify subtypes within a sample with varying levels of personality pathology using finite mixture modeling. Subjects (N = 141) were recruited to represent a wide range of pathology. The finite mixture modeling results indicated that 3 components were harbored within the variables analyzed. Group 1 was characterized by low levels of antisocial, paranoid, and aggressive features, and Group 2 was characterized by elevated paranoid features. Group 3 revealed the highest levels across the 3 variables. The validity of the obtained solution was then evaluated by reference to a variety of external measures that supported the validity of the identified grouping structure. Findings generally appear congruent with previous research, which argued that a PD taxonomy based on paranoid, aggressive, and antisocial features is a viable supplement to current diagnostic systems. Our study suggests that Kernberg's object relational model offers a
Fatima, Kiran; Majeed, Hammad; Irshad, Humayun
Meningioma subtypes classification is a real-world multiclass problem from the realm of neuropathology. The major challenge in solving this problem is the inherent complexity due to high intra-class variability and low inter-class variation in tissue samples. The development of computational methods to assist pathologists in characterization of these tissue samples would have great diagnostic and prognostic value. In this article, we proposed an optimized evolutionary framework for the classification of benign meningioma into four subtypes. This framework investigates the imperative role of RGB color channels for discrimination of tumor subtypes and compute structural, statistical and spectral phenotypes. An evolutionary technique, Genetic Algorithm, in combination with Support Vector Machine is applied to tune classifier parameters and to select the best possible combination of extracted phenotypes that improved the classification accuracy (94.88%) on meningioma histology dataset, provided by the Institute of Neuropathology, Bielefeld. These statistics show that computational framework can robustly discriminate four subtypes of benign meningioma and may aid pathologists in the diagnosis and classification of these lesions.
West, C.B. Jr.; Shagets, F.W.; Mansfield, M.J. )
Aggressive fibromatosis is a poorly defined, locally aggressive, yet histologically benign fibroblastic proliferative lesion that may occur in the head and neck. The lesion is highly cellular and locally infiltrative and has a propensity to invade and erode bone, compromising vital structures within the head and neck. However, it is not a true malignancy because it does not have malignant cytologic characteristics nor does it metastasize. We present two cases of aggressive fibromatosis occurring in young adult men. The first case involved a rapidly enlarging mass of the anterior maxilla that involved the upper lip, nasal alae, nasal septum, inferior turbinates, and hard palate. The patient underwent incisional biopsy to confirm the diagnosis. Because of difficulty in determining the actual margins of this extensive lesion and the significant morbidity that would have resulted from surgical resection, we elected to treat this patient with chemotherapy and radiation therapy. The second case was an extensive lesion involving the right temporal bone, pterygomaxillary space, and infratemporal, temporal, and middle cranial fossae. Incisional biopsy confirmed the diagnosis. Because of the lack of functional and cosmetic deficits and the unavoidable morbidity of a surgical resection, this patient was treated with radiation therapy. Although wide field resection is the most satisfactory form of treatment, in situations in which this modality would result in unacceptable morbidity or if surgical margins are positive, then radiation therapy and chemotherapy should be considered. Support for these therapeutic modalities is found in larger series of cases outside the head and neck.
Clark, Danielle; Febbraio, Maria; Levin, Liran
Aggressive periodontal disease is an oral health mystery. Our current understanding of this disease is that specific bacteria invade the oral cavity and the host reacts with an inflammatory response leading to mass destruction of the alveolar bone. Aggressive periodontal disease is typically observed in a population under the age of 30 and occurs so rapidly that it is difficult to treat. Unfortunately, the consequence of this disease frequently involves tooth extractions. As a result, the aftermath is chewing disability and damage to self-esteem due to an altered self-image. Furthermore, patients are encumbered by frequent dental appointments which have an economic impact in regards to both personal financial strain and absent days in the workplace. Aggressive periodontal disease has a tremendous effect on patients' overall quality of life and needs to be investigated more extensively in order to develop methods for earlier definitive diagnosis and effective treatments. One of the mysteries of aggressive periodontal disease is the relatively nominal amount of plaque present on the tooth surface in relation to the large amount of bone loss. There seems to be a hidden factor that lies between the response by the patient's immune system and the bacterial threat that is present. A better mechanistic understanding of this disease is essential to provide meaningful care and better outcomes for patients.
Horrigan, Joseph P.; Barnhill, L. Jarrett
In this study, 11 males with autism and mental retardation were administered risperidone. Substantial clinical improvement was noted almost immediately; patients with aggression, self-injury, explosivity, and poor sleep hygiene were most improved. The modal dose for optimal response was 0.5 mg bid. Weight gain was a significant side effect.…
Bryan, Clifford; Horton, Robert
Several hypotheses are developed regarding fans and their behavior based upon a review of the literature. An exploratory study is then described, in which participant observers at a university sports arena observed cases of aggressive behavior among the spectators. Based upon the literature review and the findings of the study, four…
Foster, Hilliard G., Jr.; Spitz, Reuben T.
Examines biochemical measures in a population of forensic psychiatric inpatients. Regression equations utilizing chemical and biological variables were developed and evaluated to determine their value in predicting the severity and frequency of aggression. Findings strongly suggest the presence of specific biochemical alteration among those…
Nesdale, Drew; Pickering, Kaye
Drawing on social schema theory (Fiske & Taylor, 1991) and social identity theory (Tajfel & Turner, 1979), this study examined the impact on teachers' reactions to children's aggression of three variables, two of which were related to the aggressors and one was related to the teachers. Experienced female elementary school teachers (N=90) each read…
Arriaga, Ximena B; Capezza, Nicole M; Daly, Christine A
What determines whether people tolerate partner aggression? This research examined how norms, relationship experiences, and commitment predict personal standards for judging aggressive acts by a partner. Studies 1a and 1b (n = 689) revealed that experiencing aggression in a current relationship and greater commitment predicted greater tolerance for common partner aggression. Study 2 longitudinally tracked individuals who had never experienced partner aggression (n = 52). Once aggression occurred, individuals adopted more tolerant standards, but only if they were highly committed. Study 3 involved experimentally manipulating the relevance of partner aggression among individuals who reported current partner aggression (n = 73); they were more tolerant of aggressive acts imagined to occur by their partner (vs. the same acts by a stranger), but only if they were highly committed. Personal standards for judging partner aggression are dynamic. They shift toward greater tolerance when committed people experience aggression in a current relationship.
Henkel, James S; Tepp, William H; Przedpelski, Amanda; Fritz, Robert B; Johnson, Eric A; Barbieri, Joseph T
Botulinum neurotoxins (BoNT) are classified into 7 serotypes (A-G) based upon neutralization by serotype-specific anti-sera. Several recombinant serotype-specific subunit BoNT vaccines have been developed, including a subunit vaccine comprising the receptor binding domain (HCR) of the BoNTs. Sequencing of the genes encoding BoNTs has identified variants (subtypes) that possess up to 32% primary amino acid variation among different BoNT serotypes. Studies were conducted to characterize the ability of the HCR of BoNT/A to protect against challenge by heterologous BoNT/A subtypes (A1-A3). High dose vaccination with HCR/A subtypes A1-A4 protected mice from challenge by heterologous BoNT/A subtype A1-A3, while low dose HCR vaccination yielded partial protection to heterologous BoNT/A subtype challenge. Absolute IgG titers to HCRs correlated to the dose of HCR used for vaccination, where HCR/A1 elicited an A1 subtype-specific IgG response, which was not observed with HCR/A2 vaccination. Survival of mice challenged to heterologous BoNT/A2 following low dose HCR/A1 vaccination correlated with elevated IgG titers directed to the denatured C-terminal sub-domain of HCR/A2, while survival of mice to heterologous BoNT/A1 following low dose HCR/A2 vaccination correlated to elevated IgG titers directed to native HCRc/A1. This implies that low dose vaccinations with HCR/A subtypes elicit unique IgG responses, and provides a basis to define how the host develops a neutralizing immune response to BoNT intoxication. These results may provide a reference for the development of pan-BoNT vaccines.
Ireland, Jane L; Adams, Christine
The current study explores associations between implicit and explicit aggression in young adult male prisoners, seeking to apply the Reflection-Impulsive Model and indicate parity with elements of the General Aggression Model and social cognition. Implicit cognitive aggressive processing is not an area that has been examined among prisoners. Two hundred and sixty two prisoners completed an implicit cognitive aggression measure (Puzzle Test) and explicit aggression measures, covering current behaviour (DIPC-R) and aggression disposition (AQ). It was predicted that dispositional aggression would be predicted by implicit cognitive aggression, and that implicit cognitive aggression would predict current engagement in aggressive behaviour. It was also predicted that more impulsive implicit cognitive processing would associate with aggressive behaviour whereas cognitively effortful implicit cognitive processing would not. Implicit aggressive cognitive processing was associated with increased dispositional aggression but not current reports of aggressive behaviour. Impulsive implicit cognitive processing of an aggressive nature predicted increased dispositional aggression whereas more cognitively effortful implicit cognitive aggression did not. The article concludes by outlining the importance of accounting for implicit cognitive processing among prisoners and the need to separate such processing into facets (i.e. impulsive vs. cognitively effortful). Implications for future research and practice in this novel area of study are indicated.
O’Brien, Katie M.; Cole, Stephen R.; Tse, Chiu-Kit; Perou, Charles M.; Carey, Lisa A.; Foulkes, William D.; Dressler, Lynn G.; Geradts, Joseph; Millikan, Robert C.
Purpose Previous research identified differences in breast cancer-specific mortality across four "intrinsic" tumor subtypes: luminal A, luminal B, basal-like, and human epidermal growth factor receptor 2 positive/estrogen receptor negative (HER2+/ER−). Experimental Design We used immunohistochemical markers to subtype 1149 invasive breast cancer patients (518 African American, 631 white) in the Carolina Breast Cancer Study, a population-based study of women diagnosed with breast cancer. Vital status was determined through 2006 using the National Death Index, with median follow-up of 9 years. Results Cancer subtypes luminal A, luminal B, basal-like and HER2+/ER- were distributed as 64%, 11%, 11% and 5% for whites, and 48%, 8%, 22% and 7% for African Americans, respectively. Breast cancer mortality was higher for patients with HER2+/ER- and basal-like breast cancer compared to luminal A and B. African Americans had higher breast-cancer specific mortality than whites, but the effect of race was statistically significant only among women with luminal A breast cancer. However, when compared to the luminal A subtype within racial categories, mortality for patients with basal-like breast cancer was higher among whites (HR=2.0, 95% CI: 1.2, 3.4) than African Americans (HR=1.5, 95% CI: 1.0, 2.4), with the strongest effect seen in postmenopausal white women (HR=3.9, 95% CI: 1.5, 10.0). Conclusions Our results confirm the association of basal-like breast cancer with poor prognosis, and suggest that basal-like breast cancer is not an inherently more aggressive disease in African American women compared to whites. Additional analyses are needed in populations with known treatment profiles to understand the role of tumor subtypes and race in breast cancer mortality, and in particular our finding that among women with luminal A breast cancer, African Americans have higher mortality than whites. PMID:21169259
Grizenko, Natalie; Paci, Michael; Joober, Ridha
Objective: To compare the ADHD combined/hyperactive subtype (ADHD/CH) to the ADHD inattentive subtype (ADHD/I) on the level of comorbidity, treatment response, and possible etiological factors. Method: A total of 371 clinically referred children diagnosed with ADHD aged between 6 and 12 years are recruited for a double-blind, placebo-controlled…
Warrick, Joshua I.; Walter, Vonn; Yamashita, Hironobu; Chung, Eunah; Shuman, Lauren; Amponsa, Vasty Osei; Zheng, Zongyu; Chan, Wilson; Whitcomb, Tiffany L.; Yue, Feng; Iyyanki, Tejaswi; Kawasawa, Yuka I.; Kaag, Matthew; Guo, Wansong; Raman, Jay D.; Park, Joo-Seop; DeGraff, David J.
Discrete bladder cancer molecular subtypes exhibit differential clinical aggressiveness and therapeutic response, which may have significant implications for identifying novel treatments for this common malignancy. However, research is hindered by the lack of suitable models to study each subtype. To address this limitation, we classified bladder cancer cell lines into molecular subtypes using publically available data in the Cancer Cell Line Encyclopedia (CCLE), guided by genomic characterization of bladder cancer by The Cancer Genome Atlas (TCGA). This identified a panel of bladder cancer cell lines which exhibit genetic alterations and gene expression patterns consistent with luminal and basal molecular subtypes of human disease. A subset of bladder cancer cell lines exhibit in vivo histomorphologic patterns consistent with luminal and basal subtypes, including papillary architecture and squamous differentiation. Using the molecular subtype assignments, and our own RNA-seq analysis, we found overexpression of GATA3 and FOXA1 cooperate with PPARɣ activation to drive transdifferentiation of a basal bladder cancer cells to a luminial phenotype. In summary, our analysis identified a set of human cell lines suitable for the study of molecular subtypes in bladder cancer, and furthermore indicates a cooperative regulatory network consisting of GATA3, FOXA1, and PPARɣ drive luminal cell fate. PMID:27924948
Beaven, Anne W; Samsa, Greg; Zimmerman, Sheryl; Smith, Sophia K
Differences in quality of life (QOL) of long-term survivors of aggressive or indolent subtypes of non-Hodgkin lymphoma (NHL) have not been frequently evaluated. We assessed these differences by analyzing results of a large QOL survey of long-term NHL survivors. We hypothesized that the incurable nature of indolent NHL would relate to worse QOL in long-term survivors while the potentially cured long-term survivors of aggressive lymphoma would have better QOL. We found that QOL was similar between the two groups. Results suggest that patients with indolent NHL are coping well with their disease, yet experience some overall feelings of life threat.
Watanabe, Yukihiro; Okamoto, Kojun; Okada, Katsuya; Aikawa, Masayasu; Koyama, Isamu; Yamaguchi, Hiroshi
Solid pseudopapillary neoplasms (SPNs) may have an aggressive clinical course, but clinical predictors of this condition have not been thoroughly evaluated. We performed a retrospective study of 11 cases of SPN managed in our hospital between January 2007 and April 2015. Of these 11 cases, we encountered a single case with an aggressive clinical course. Histological, immunohistochemical, and clinical features were compared to identify predictors of poor prognosis. The 11 patients comprised four women and seven men with a median age of 41 years (range, 26-58 years). Clinical symptoms were nonspecific and the median tumor size was 4.6 cm (range, 1.4-18 cm). The patient with an aggressive clinical course developed multiple liver metastases within three months and died seven months after surgery. Pathological features of the tumor in this case included lymph node metastases, a diffuse growth pattern, extensive tumor necrosis, high mitotic rate, and immunohistochemistry. These features were not observed in patients who survived without recurrence at a median follow-up of 25 months (range, 6-82 months). Characteristic pathological features and a high proliferative index, as assessed by Ki-67 staining, may predict poor outcome in cases of SPN.
... fullstory_163824.html Gene Therapy Shows Promise for Aggressive Lymphoma Over one-third of patients appeared disease- ... 2017 (HealthDay News) -- An experimental gene therapy for aggressive non-Hodgkin lymphoma beat back more than a ...
Dupré, Kathryne E; Barling, Julian
The authors examined factors that lead to and prevent aggression toward supervisors at work using two samples: doctoral students and correctional service guards. The results supported that perceived interpersonal injustice mediates the relationship between perceptions of supervisory control over work performance and psychological aggression directed at supervisors, and further that psychological aggression toward supervisors is positively associated with physical acts of aggression directed at supervisors, supporting the notion of an escalation of aggressive workplace behaviors. Moreover, employees' perceptions of organizational sanctions (i.e., negative consequences for disobeying organizational policies) against aggression appear to play an important role in the prevention of workplace aggression by moderating the relationship between injustice and aggression targeting supervisors.
Burt, S Alexandra; Donnellan, M Brent; Iacono, William G; McGue, Matt
There are two common approaches to sub-typing the well-documented heterogeneity within antisocial behavior: age-of-onset (i.e., childhood-onset versus adolescence-onset; see Moffitt 1993) and behavioral (i.e., physical aggression versus non-aggressive rule-breaking). These approaches appear to be associated, such that aggression is more characteristic of childhood-onset antisocial behavior whereas rule-breaking is linked to both child- and adolescence-onset antisocial behavior. However, it remains unclear which approach, if either, better explains the heterogeneity within antisocial behavior. We examined this question in a prospective sample of male twins, assessed at the ages of 11, 14, 17, and 24 years. Although the age-of-onset subtypes predicted adult antisocial behavior in the expected direction when analyzed alone, this association dissipated once we controlled for aggression and rule-breaking. Such findings suggest that the behavioral sub-types of antisocial behavior may be a stronger predictor of later antisocial outcomes than is its age-of-onset.
Burt, S. Alexandra; Donnellan, M. Brent; Iacono, William G.; McGue, Matt
There are two common approaches to sub-typing the well-documented heterogeneity within antisocial behavior: age-of-onset (i.e., childhood-onset versus adolescence-onset; see Moffitt, 1993) and behavioral (i.e., physical aggression versus non-aggressive rule-breaking). These approaches appear to be associated, such that aggression is more characteristic of childhood-onset antisocial behavior whereas rule-breaking is linked to both child- and adolescence-onset antisocial behavior. However, it remains unclear which approach, if either, better explains the heterogeneity within antisocial behavior. We examined this question in a prospective sample of male twins, assessed at the ages of 11, 14, 17, and 24 years. Although the age-of-onset subtypes predicted adult antisocial behavior in the expected direction when analyzed alone, this association dissipated once we controlled for aggression and rule-breaking. Such findings suggest that the behavioral sub-types of antisocial behavior may be a stronger predictor of later antisocial outcomes than is their age-of-onset. PMID:21298333
Freedman, Joshua R; Greene, Ryan M; Green, Jeremy B
By utilizing resurfacing lasers, physicians can significantly improve the appearance of sun-damaged skin, scars, and more. The carbon dioxide and erbium:yttrium-aluminum-garnet lasers were the first ablative resurfacing lasers to offer impressive results although these earlier treatments were associated with significant downtime. Later, nonablative resurfacing lasers such as the neodymium:yttrium-aluminum-garnet laser proved effective, after a series of treatments with less downtime, but with more modest results. The theory of fractional photothermolysis has revolutionized resurfacing laser technology by increasing the safety profile of the devices while delivering clinical efficacy. A review of the histologic and molecular consequences of the resurfacing laser-tissue interaction allows for a better understanding of the devices and their clinical effects.
Machiela, Mitchell J; Lan, Qing; Slager, Susan L; Vermeulen, Roel C H; Teras, Lauren R; Camp, Nicola J; Cerhan, James R; Spinelli, John J; Wang, Sophia S; Nieters, Alexandra; Vijai, Joseph; Yeager, Meredith; Wang, Zhaoming; Ghesquières, Hervé; McKay, James; Conde, Lucia; de Bakker, Paul I W; Cox, David G; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R; De Roos, Anneclaire J; Brooks-Wilson, Angela R; Giles, Graham G; Melbye, Mads; Gu, Jian; Jackson, Rebecca D; Kane, Eleanor; Purdue, Mark P; Vajdic, Claire M; Albanes, Demetrius; Kelly, Rachel S; Zucca, Mariagrazia; Bertrand, Kimberly A; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M; Link, Brian K; Novak, Anne J; Dogan, Ahmet; Asmann, Yan W; Liebow, Mark; Thompson, Carrie A; Ansell, Stephen M; Witzig, Thomas E; Tilly, Hervé; Haioun, Corinne; Molina, Thierry J; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans-Olov; Roos, Göran; Bracci, Paige M; Riby, Jacques; Smith, Martyn T; Holly, Elizabeth A; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M; Severson, Richard K; Tinker, Lesley F; North, Kari E; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J; Villano, Danylo J; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R; Turner, Jenny; Southey, Melissa C; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Boeing, Heiner; Tjønneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; De Vivo, Immaculata; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Liang, Liming; Park, Ju-Hyun; Chung, Charles C; Weisenburger, Dennis D; Fraumeni, Joseph F; Salles, Gilles; Glenn, Martha; Cannon-Albright, Lisa; Curtin, Karen; Wu, Xifeng; Smedby, Karin E; de Sanjose, Silvia; Skibola, Christine F; Berndt, Sonja I; Birmann, Brenda M; Chanock, Stephen J; Rothman, Nathaniel
Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82,P-value = 8.5 × 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51,P-value = 4.0 × 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.
Irshad, Shazia; Bansal, Mukesh; Guarnieri, Paolo; Davis, Hayley; Zen, Ayman Al Haj; Baran, Brygida; Pinna, Claudia Maria Assunta; Rahman, Haseeb; Biswas, Sujata; Bardella, Chiara; Jeffery, Rosemary; Wang, Lai Mun; East, James Edward; Lewis, Annabelle; Tomlinson, Ian; Leedham, Simon John
The functional role of Bone Morphogenetic Protein (BMP) signalling in colorectal cancer (CRC) is poorly defined, with contradictory results in cancer cell line models reflecting the inherent difficulties of assessing a signalling pathway that is context dependent and subject to genetic constraints. By assessing the transcriptional response of a diploid human colonic epithelial cell line to BMP ligand stimulation we generated a prognostic BMP signalling signature, which was applied to multiple CRC datasets to investigate BMP heterogeneity across CRC molecular subtypes. We linked BMP and Notch signalling pathway activity and function in human colonic epithelial cells, and normal and neoplastic tissue. BMP induced Notch through a γ-secretase independent interaction, regulated by the SMAD proteins. In homeostasis, BMP/Notch co-localisation was restricted to cells at the top of the intestinal crypt, with more widespread interaction in some human CRC samples. BMP signalling was downregulated in the majority of CRC, but was conserved specifically in mesenchymal subtype tumours, where it interacts with Notch to induce an EMT phenotype. In intestinal homeostasis, BMP-Notch pathway crosstalk is restricted to differentiating cells through stringent pathway segregation. Conserved BMP activity and loss of signalling stringency in mesenchymal subtype tumours promotes synergistic BMP/Notch interaction, and this correlates with poor patient prognosis. BMP signalling heterogeneity across CRC subtypes and cell lines can account for previous experimental contradictions. Crosstalk between the BMP and Notch pathways will render mesenchymal subtype CRC insensitive to γ-secretase inhibition unless BMP activation is concomitantly addressed.
Ose, Jennifer; Poole, Elizabeth M; Schock, Helena; Lehtinen, Matti; Arslan, Alan A; Zeleniuch-Jacquotte, Anne; Visvanathan, Kala; Helzlsouer, Kathy J; Buring, Julie E; Lee, I-Min; Tjønneland, Anne; Dossus, Laure; Trichopoulou, Antonia; Masala, Giovanna; Onland-Moret, N Charlotte; Weiderpass, Elisabete; Duell, Eric J; Idahl, Annika; Travis, Ruth C; Rinaldi, Sabina; Merritt, Melissa A; Trabert, Britton; Wentzensen, Nicolas; Tworoger, Shelley S; Kaaks, Rudolf; Fortner, Renée T
Invasive epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. The etiology of EOC remains elusive; however, experimental and epidemiologic data suggest a role for hormone-related exposures in ovarian carcinogenesis and risk factor differences by histologic phenotypes and developmental pathways. Research on pre-diagnosis androgen concentrations and EOC risk has yielded inconclusive results, and analyses incorporating EOC subtypes are sparse. We conducted a pooled analysis of 7 nested case-control studies in the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis circulating androgens (testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS)), sex hormone binding globulin (SHBG), and EOC risk by tumor characteristics (i.e. histology, grade, and stage). The final study population included 1,331 EOC cases and 3,017 matched controls. Multivariable conditional logistic regression was used to assess risk associations in pooled individual data. Testosterone was positively associated with EOC risk (all subtypes combined, Odds Ratio (OR)log2=1.12 [95% Confidence Interval (CI) 1.02-1.24]); other endogenous androgens and SHBG were not associated with overall risk. Higher concentrations of testosterone and androstenedione associated with an increased risk in endometrioid and mucinous tumors (e.g., testosterone, endometrioid tumors, ORlog2=1.40 [1.03-1.91]), but not serous or clear cell. An inverse association was observed between androstenedione and high grade serous tumors (ORlog2=0.76 [0.60-0.96]). Our analyses provide further evidence for a role of hormone-related pathways in EOC risk, with differences in associations between androgens and histologic subtypes of EOC.
Koshiyama, Masafumi; Matsumura, Noriomi; Konishi, Ikuo
Ovarian cancer is the foremost cause of gynecological cancer death in the developed world, as it is usually diagnosed at an advanced stage. In this paper we discuss current issues, the efficacy and problems associated with ovarian cancer screening, and compare the characteristics of ovarian cancer subtypes. There are two types of ovarian cancer: Type I carcinomas, which are slow-growing, indolent neoplasms thought to arise from a precursor lesion, which are relatively common in Asia; and Type II carcinomas, which are clinically aggressive neoplasms that can develop de novo from serous tubal intraepithelial carcinomas (STIC) and/or ovarian surface epithelium and are common in Europe and the USA. One of the most famous studies on the subject reported that annual screening using CA125/transvaginal sonography (TVS) did not reduce the ovarian cancer mortality rate in the USA. In contrast, a recent study in the UK showed an overall average mortality reduction of 20% in the screening group. Another two studies further reported that the screening was associated with decreased stage at detection. Theoretically, annual screening using CA125/TVS could easily detect precursor lesions and could be more effective in Asia than in Europe and the USA. The detection of Type II ovarian carcinoma at an early stage remains an unresolved issue. The resolving power of CA125 or TVS screening alone is unlikely to be successful at resolving STICs. Biomarkers for the early detection of Type II carcinomas such as STICs need to be developed. PMID:28257098
Keramidas, Evangelos G; Miller, Gavin; Revelos, Kyriakos; Kitsanta, Panagiota; Page, Robert E
Aggressive digital papillary adenocarcinoma and aggressive digital papillary adenoma are rare tumours of the sweat glands. They are most common in the most distal part of the fingers and are locally aggressive with a 50% local recurrence rate; 14% of tumours metastasize. We present two cases.
Russell, Gordon W.; de Graaf, Jane P.
Tested lunar-aggression hypothesis using the aggressive penalties awarded in ice hockey over a season of competition. Interpersonal aggression was found to be unrelated to either the synodic or anomalistic cycles. Discussion centers on the persistence of lunar beliefs and their links to the literature on selective exposure and interpersonal…
Levy, Karyn; Hunt, Caroline; Heriot, Sandra
Objective: The aim of the study was to evaluate the effectiveness of an intervention that targeted both anxious and aggressive behaviors in children with anxiety disorders and comorbid aggression by parent report. Method: The effects of a cognitive-behavioral therapy intervention targeting comorbid anxiety and aggression problems were compared…
Martins, Nicole; Wilson, Barbara J.
A survey was conducted with over 500 children in grades K-5 to examine whether exposure to socially aggressive content was related to children's use of social aggression. The results of the survey revealed a significant relationship between exposure to televised social aggression and increased social aggression at school, but only for girls and…
Hadley, Jade; Mowbray, Tony; Jacobs, Nicky
Proactive aggression (PA) is goal-directed, hostile social behavior that has been linked to detrimental outcomes. It has been theorized that adolescents who believe aggression is a normal and acceptable social response (approval of aggression) are more likely to show PA. Confidence in one's ability to behave aggressively (self-efficacy about…
Salehinejad, Jahanshah; Gholami, Mahdi; Eshghpour, Majid; Mehri, Tahere
Adenoid ameloblastoma with dentinoid is a rare odontogenic tumor. Granular cell ameloblastoma also is a less common histological subtype of ameloblastoma. In this report, the patient was a 31-year-old male. The lesion was located in the right mandible and was unicystic with well-defined borders. The tumor tissue was showing a combination of follicular, plexiform, and desmoplastic patterns of ameloblastoma with wide areas of granular cells, fibrous stroma, glandular pattern, and dentinoid calcified. Very few cases of distinct forms of ameloblastoma that show the formation of dentinoid has been reported. However, there are no cases of adenoid granular cell ameloblastoma with dentinoid reported. PMID:27605998
Andrade Bitar, Renata; da Silva Martinho, Herculano; Zambelli Ramalho, Leandra Náira; dos Santos Junior, Arnaldo Rodrigues; Silva Ramalho, Fernando; Raniero, Leandro; Martin, Airton A.
Although there are many articles focused on in vivo or ex vivo Raman analysis for cancer diagnosis, to the best of our knowledge its potential to predict the aggressiveness of tumor has not been fully explored yet. In this work Raman spectra in the finger print region of ex vivo breast tissues of both healthy mice (normal) and mice with induced mammary gland tumors (abnormal) were measured and associated to matrix metalloproteinase-19 (MMP-19) immunohistochemical exam. It was possible to verify that normal breast, benign lesions, and adenocarcinomas spectra, including the subtypes (cribriform, papillary and solid) could have their aggressiveness diagnosed by vibrational Raman bands. By using MMP- 19 exam it was possible to classify the samples by malignant graduation in accordance to the classification results of Principal Component Analysis (PCA). The spectra NM /MH were classified correctly in 100% of cases; CA/CPA group had 60 % of spectra correctly classified and for PA/AS 54% of the spectra were correctly classified.
Derogatis, L R; Schmidt, C W; Fagan, P J; Wise, T N
Seventy-six women who presented with a principal complaint of anorgasmia were partitioned into four distinct subtypes on the basis of psychosexual and psychological symptoms using hierarchical cluster analysis, a mathematical taxonomic method. The classification was accomplished with data from the Derogatis Sexual Functioning Inventory (DSFI) and the Brief Symptom Inventory (BSI). Comparisons involving age, race, marital status, and social class demonstrated no significant differences between the four subtypes; however, statistical analyses of psychosexual, psychological symptom, and chart-review variables (including psychiatric diagnosis) revealed very significant distinctions between the four groups. From the resulting typology, anorgasmic subtypes were presumptively identified as "low desire" (n = 21), "histrionic/marital conflict" (n = 20) "psychiatric disorder" (n = 12) and "constitutional" (n = 16). Implications of the typology for etiologic and optimal treatment decisions concerning anorgasmia are discussed.
Chiu, A.T.; Herblin, W.F.; McCall, D.E.; Ardecky, R.J.; Carini, D.J.; Duncia, J.V.; Pease, L.J.; Wong, P.C.; Wexler, R.R.; Johnson, A.L.; )
We have demonstrated the existence of two distinct subtypes of the angiotensin II receptor in the rat adrenal gland using radioligand binding and tissue section autoradiography. The identification of the subtypes was made possible by the discovery of two structurally dissimilar, nonpeptide compounds, DuP 753 and EXP655, that show reciprocal selectivity for the two subtypes. In the rat adrenal cortex, DuP 753 inhibited 80% of the total AII binding with an IC50 value on the sensitive sites of 2 x 10(-8) M, while EXP655 displaced only 20%. In the rat adrenal medulla, EXP655 gave 90% inhibition of AII binding with an IC50 value of 3.0 x 10(-8) M, while DuP 753 was essentially inactive. The combination of the two compounds completely inhibited AII binding in both tissues.
Stockdale, Laura A; Coyne, Sarah M; Nelson, David A; Padilla-Walker, Laura M
Although there have been hundreds of studies on media violence, few have focused on literature, with none examining novels. Accordingly, the aim of the current study was to examine whether reading physical and relational aggression in books was associated with aggressive behavior in adolescents. Participants consisted of 223 adolescents who completed a variety of measures detailing their media use and aggressive behavior. A non-recursive structural equation model revealed that reading aggression in books was positively associated with aggressive behavior, even after controlling for exposure to aggression in other forms of media. Associations were only found for congruent forms of aggression. Implications regarding books as a form of media are discussed.
Gyawali, Rajesh; Bhattarai, Bhagabat
Aggressive periodontitis is a type of periodontitis with early onset and rapid progression and mostly affecting young adults who occupy a large percentage of orthodontic patients. The role of the orthodontist is important in screening the disease, making a provisional diagnosis, and referring it to a periodontist for immediate treatment. The orthodontist should be aware of the disease not only before starting the appliance therapy, but also during and after the active mechanotherapy. The orthodontic treatment plan, biomechanics, and appliance system may need to be modified to deal with the teeth having reduced periodontal support. With proper force application and oral hygiene maintenance, orthodontic tooth movement is possible without any deleterious effect in the tooth with reduced bone support. With proper motivation and interdisciplinary approach, orthodontic treatment is possible in patients with controlled aggressive periodontitis.
Aggressive periodontitis is a type of periodontitis with early onset and rapid progression and mostly affecting young adults who occupy a large percentage of orthodontic patients. The role of the orthodontist is important in screening the disease, making a provisional diagnosis, and referring it to a periodontist for immediate treatment. The orthodontist should be aware of the disease not only before starting the appliance therapy, but also during and after the active mechanotherapy. The orthodontic treatment plan, biomechanics, and appliance system may need to be modified to deal with the teeth having reduced periodontal support. With proper force application and oral hygiene maintenance, orthodontic tooth movement is possible without any deleterious effect in the tooth with reduced bone support. With proper motivation and interdisciplinary approach, orthodontic treatment is possible in patients with controlled aggressive periodontitis. PMID:28299350
McLemore, Monica R
The June 2005 Clinical Journal of Oncology Nursing editorial titled "Communication: Whose Problem Is It?" (Griffin-Sobel, 2005) was written to begin a dialogue about a phenomenon frequently experienced yet rarely discussed: workplace aggression, also known as disruptive behavior. Prompted by a groundbreaking study published in the American Journal of Nursing by Rosenstein and O'Daniel (2005), the editorial challenged oncology nurses to begin to fix problems of communication. After reflecting on both of the articles and considering my own experience as a nurse manager, clinician, and scholar, I decided to explore the topic as it relates to nurse-to-nurse workplace aggression. The following is a summary of interviews with nurse managers, nurse practitioners, and nurse scientists about root causes and effective strategies to manage these sometimes complicated situations. This article is meant to continue the dialogue about the very sensitive issue. Confidentiality has been maintained, and I welcome your comments.
Kim, Hyun-Soo; Yoon, Gun; Jang, Hye-In; Song, Sang Yong; Kim, Byoung-Gie
Carcinoid tumor of the ovary is uncommon. We herein report a very rare case of primary ovarian carcinoid tumor with aggressive histology and an unusual immunophenotype. A 21-year-old woman presented with a palpable abdominal mass. Computed tomographic scan revealed a large, extensively necrotic solid mass in the left ovary. The patient underwent a left salpingo-oophorectomy. Grossly, the left adnexa showed a large, vaguely lobulated ovarian tumor measuring 22×15×13 cm. Histologically, the tumor had a readily identifiable neuroendocrine growth pattern, but some areas showed solid growth pattern associated with mild nuclear pleomorphism and multiple foci of punctate necrosis. Furthermore, mitotic figures were recognized in 8 per 10 high-power fields, and a few foci of large coagulative tumor necrosis were also noted. In addition, the tumor tissue exhibited uniform, strong nuclear β-catenin immunoreactivity, indicating the nuclear accumulation of β-catenin in the individual tumor cells. In summary, we described the first case of primary ovarian carcinoid tumor with loss of neuroendocrine growth pattern, increased mitotic activity and large areas of coagulative tumor necrosis. According to the WHO classification of pulmonary carcinoid tumor, this case may be classified as "atypical" carcinoid. However, currently, no primary ovarian atypical carcinoid exists in the classification system. Due to its rarity, there are no established diagnostic criteria and clinical data on patient outcomes for ovarian carcinoid tumors with aggressive histology. Additional reports are clearly necessary. We also showed for the first time the nuclear accumulation of β-catenin in carcinoid tumor cells, suggestive of a role for β-catenin in the tumorigenesis of ovarian atypical carcinoid tumor or its aggressive histology.
Hecker, Sydney P.; Jamplis, Robert W.; Mitchell, Sidney P.
In analysis of the results of treatment of 48 episodes of spontaneous pneumothorax, aggressive treatment by means of closed intercostal drainage with constant suction was found to achieve the aims of therapy more effectively than conservative measures of bed rest with or without needle aspiration. In general, full expansion of the lung was more quickly restored, recurrence was of lesser incidence, the period in hospital was shorter and the time away from work was reduced. ImagesFigure 1. PMID:13905846
Zhu, Shan; Wu, Juan; Li, Xiang; Liu, Qian; Wei, Wen; Sun, Shengrong
Background & Aims Substantial controversy exists regarding the differences in tumor subtypes between male breast cancer (MBC) and female breast cancer (FBC). This is the largest population-based study to compare MBC and FBC patients. Methods Using data obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010-2012, a retrospective, population-based cohort study was conducted to investigate tumor subtype-specific differences in various characteristics, overall survival (OS) and breast cancer-specific mortality (BCSM) between males and females. Results In all, 181,814 BC patients (1,516 male and 180,298 female) were eligible for this study. The male patients were more likely to be black, older, and have lower histological grades, more advanced stages, larger tumors, more lymph node and distant metastases and human epidermal growth factor receptor 2 (HER2)-negative tumors (each p<0.05). A matched analysis showed that the 2-year OS was 91.2% and 93.7% and that the BCSM was 2.2% and 2.5% for male and female patients, respectively. The univariate analysis showed that male triple-negative (TN), hormone receptor (HoR)-positive/HER2-positive and HoR-positive/HER2-negative patients had poorer OS (p <0.01). Meanwhile, the HoR-positive/HER2-positive and TN subtypes were associated with a higher BCSM in MBC patients (p<0.01). The multivariate analysis revealed that TN MBC patients had poorer OS and BCSM (p<0.05). Simultaneously, the results showed that male patients in the HoR-positive/HER2-negative subgroup were less likely to die of BC when adjusting for other factors (p<0.05). Conclusions The analysis of 2-year OS and BCSM among the BC subtypes showed clear differences between MBC and FBC patients with the TN subtype; these differences warrant further investigation PMID:27655704
Bowen, Natasha K; Wretman, Christopher J
Structural equation modeling with latent variables was used to evaluate the direct and mediated effects of a neighborhood risk factor (negative teen behaviors) on the parent-report aggressive behavior of 213 students in grades 3 through 5 attending a school in a low-income, rural community. Contagion and social control hypotheses were examined as well as hypotheses about whether the neighborhood served as a microsystem or exosystem for rural pre-adolescents. Analyses took into account the clustering of students and ordinal nature of the data. Findings suggest that rural neighborhoods may operate as both a microsystem and exosystem for children, with direct contagion effects on their aggressive behaviors as well as indirect social control effects through parenting practices. Direct effects on aggression were also found for parenting practices and child reports of friends' negative behaviors. Pre-adolescence may be a transitional stage, when influences of the neighborhood on child behavior begin to compete with influences of caregivers. Findings can inform the timing and targets of violence prevention in rural communities.
Coyne, Sarah M; Archer, John; Eslea, Mike
Numerous studies have shown that viewing violence in the media can influence an individual's subsequent aggression, but none have examined the effect of viewing indirect aggression. This study examines the immediate effect of viewing indirect and direct aggression on subsequent indirect aggression among 199 children ages 11 to 14 years. They were shown an indirect, direct, or no-aggression video and their subsequent indirect aggression was measured by negative evaluation of a confederate and responses to a vignette. Participants viewing indirect or direct aggression gave a more negative evaluation of and less money to a confederate than participants viewing no-aggression. Participants viewing indirect aggression gave less money to the confederate than those viewing direct aggression. Participants viewing indirect aggression gave more indirectly aggressive responses to an ambiguous situation and participants viewing direct aggression gave more directly aggressive responses. This study provides the first evidence that viewing indirect aggression in the media can have an immediate impact on subsequent aggression.
Giancola, Peter R; Levinson, Cheri A; Corman, Michelle D; Godlaski, Aaron J; Morris, David H; Phillips, Joshua P; Holt, Jerred C D
The purpose of this study was to examine the acute effects of alcohol on aggressive behavior in men and women in a laboratory setting. Participants were 526 (261 men and 265 women) healthy social drinkers between 21 and 35 years of age. They were randomly assigned to either an alcohol or a placebo group. Aggression was measured using a modified version of the Taylor Aggression Paradigm in which electric shocks are received from, and delivered to, a same gender fictitious opponent during a supposed competitive interpersonal task. Aggression was operationalized as the intensity and duration of shocks that participants administered to their "opponent." Overall, men were more aggressive than women. Alcohol increased aggression for both men and women but this effect was stronger for men. This is one of the first laboratory studies to demonstrate that alcohol increases aggression in women.
Itil, T M
In the treatment of violent-aggressive behavior, four major groups of drugs emerged: 1. Major tranquilizers in the treatment of aggressive-violent behavior associated with psychotic syndromes. 2. Anti-epileptic drugs such as diphenylhydantoin and barbiturates in the treatment of aggressive-violent behavior within the epileptic syndrome. 3. Psychostimulants in the treatment of aggressive behavior of adolescents and children within behavior disturbances. 4. Anti-male hormones such as cyproterone acetate in the treatment of violent-aggressive behavior associated with pathological sexual hyperactivity. Whereas each category of drug is predominantly effective in one type of aggressive syndrome, it may also be effective in other conditions as well. Aggression as a result of a personality disorder is most difficult to treat with drugs.
Margolin, Gayla; Ramos, Michelle C.; Timmons, Adela C.; Miller, Kelly F.; Han, Sohyun C.
Children who grow up in aggressive households are at risk of having problems with physiological regulation, but researchers have not investigated physiology as a mechanism in the intergenerational transmission of aggression. In this article, we posit that physiological regulation, particularly during stressful interpersonal interactions, may shed light on sensitivity to conflict, It can also inform our understanding of associations between childhood exposure to aggression in families of origin and aggression against partners in adolescence or adulthood. In support of this model, we highlight findings showing that childhood exposure to family aggression relates to physiological regulation across the life span, and that reactions to physiological stress concurrently relate to aggression against intimate partners. Emerging evidence from research on biological processes during stressful interpersonal interactions raises questions about what is adaptive for individuals from aggressive families, particularly as past family experiences intersect with the challenges of new relationships. PMID:26929773
Wendroth, Scott M; Mentrikoski, Mark J; Wick, Mark R
GATA3 is a transcription factor, which is involved in the growth and differentiation of several human tissues. Immunohistochemical staining for this marker has proven to be useful in recognizing a number of tumors, most notably those in the urinary tract and breasts. To date, no study has specifically assessed the distribution of GATA3 among different histomorphologic subtypes of breast carcinoma. The surgical pathology archive at our institution was searched, to retrieve cases of breast carcinomas of the following microscopic types-ductal, lobular, mucinous, metaplastic, medullary, apocrine, signet-ring cell, and micropapillary. Tissue microarrays were created, with four 0.6-mm punch specimens from each case. The tissue microarrays were cut at a 5-μm thickness and stained with monoclonal antibodies to GATA3 (Biocare Medical Inc, Concord, CA), mammaglobin (Dako, Carpinteria, CA), and gross cystic disease fluid protein 15 (Dako). Tumors were considered to be positive for those markers if more than 5% of the cells were labeled. Of 55 ductal adenocarcinomas, 51 (92.7%) expressed GATA3. All 4 GATA3-negative tumors were Nottingham grade III lesions that were also nonreactive for estrogen receptor protein. GATA3 was present in 28 (96.6%) of 29 lobular adenocarcinomas, 10 (90.9%) of 11 apocrine adenocarcinomas, 10 (83.3%) of 12 medullary carcinomas, 5 (55.5%) of 9 metaplastic carcinomas, and 1 of 2 signet-ring cell carcinomas. Mucinous carcinomas (23 cases) and micropapillary carcinomas (12 cases) uniformly and strongly labeled for GATA3. GATA3 equaled or surpassed the sensitivity of mammaglobin and gross cystic disease fluid protein 15 in all histologic subgroups of breast cancer in the study. Although most ductal adenocarcinomas were labeled for GATA3, it was absent in high-grade tumors that also lacked estrogen receptor protein. Favorable prognosis types of breast carcinoma (eg, mucinous carcinoma) and aggressive variants such as micropapillary carcinoma were equally
Higuchi, Hiroshi; Kobayashi, Yasukazu; Kobayashi, Atsushi; Hatayama, Kazuhisa; Kimura, Masashi
Bone marrow signal changes on magnetic resonance imaging (MRI) after meniscectomy have been reported as evidence of postmeniscectomy osteonecrosis, but this pathology is unclear. We conducted a study to follow-up cases with bone marrow signal changes on MRI after meniscectomy and investigate the pathology of underlying lesions. Of 136 patients with no presurgical evidence of osteonecrosis, 29 had juxta-articular bone marrow signal changes on MRI after arthroscopic meniscectomy and subsequently underwent conservative therapy. In 6 of these 29 patients, clinical symptoms and radiographic changes began deteriorating. Based on the Koshino classification, 4 of the 6 patients had Stage-2 knee osteonecrosis and 2 had Stage-3. Arthroscopic and pathologic examinations were performed. Arthroscopic findings were fibrillation (all 6 cases), fissuring (4), ulceration (2), and eburnation (2). Histologic analysis confirmed subchondral bone fractures in all 6 cases, but osteonecrotic lesions were detected only in 2 cases with obvious radiologic deterioration. Postmeniscectomy osteonecrosis might result from subchondral bone fractures. Fracture healing is worse in patients with comorbidities than in those without it; comorbidities might be a risk factor for osteonecrosis.
Warnick, Lorin D.; Gröhn, Yrjö T.; Hoelzer, Karin; Root, Timothy P.; Siler, Julie D.; McGuire, Suzanne M.; Wright, Emily M.; Zansky, Shelley M.; Wiedmann, Martin
Abstract The objective of this study was to identify patient symptoms and case outcomes that were more likely to occur as a result of Salmonella infections caused by bovine-associated subtypes (isolates that matched contemporary bovine isolates from New York by serovar and pulsed-field gel electrophoresis pattern), as compared to salmonellosis caused by non-bovine-associated subtypes. Data were collected in 34 counties of New York that comprise the Foodborne Diseases Active Surveillance Network (FoodNet) catchment area of the Centers for Disease Control and Prevention Emerging Infections Program. Patients with specimen collection dates between March 1, 2008 and March 1, 2010 were included. Symptoms and outcomes of 40 cases infected with bovine-associated Salmonella subtypes were compared to those of 379 control-cases infected with Salmonella isolates that were not bovine-associated. Cases were significantly more likely to have invasive salmonellosis (odds ratio, 3.8; p-value=0.02), after adjusting for age group, gender, and race. In addition, there was a marginal association between case status and the presence of blood in the stool (p-value=0.1) while ill. These findings might have implications for patient management, as a history of consuming undercooked foods of bovine origin or having direct contact with cattle in the few days prior to illness could be useful for suggesting a more proactive diagnostic approach as well as close monitoring for the need to implement more aggressive therapy. PMID:22870888
Cummings, Kevin J; Warnick, Lorin D; Gröhn, Yrjö T; Hoelzer, Karin; Root, Timothy P; Siler, Julie D; McGuire, Suzanne M; Wright, Emily M; Zansky, Shelley M; Wiedmann, Martin
The objective of this study was to identify patient symptoms and case outcomes that were more likely to occur as a result of Salmonella infections caused by bovine-associated subtypes (isolates that matched contemporary bovine isolates from New York by serovar and pulsed-field gel electrophoresis pattern), as compared to salmonellosis caused by non-bovine-associated subtypes. Data were collected in 34 counties of New York that comprise the Foodborne Diseases Active Surveillance Network (FoodNet) catchment area of the Centers for Disease Control and Prevention Emerging Infections Program. Patients with specimen collection dates between March 1, 2008 and March 1, 2010 were included. Symptoms and outcomes of 40 cases infected with bovine-associated Salmonella subtypes were compared to those of 379 control-cases infected with Salmonella isolates that were not bovine-associated. Cases were significantly more likely to have invasive salmonellosis (odds ratio, 3.8; p-value=0.02), after adjusting for age group, gender, and race. In addition, there was a marginal association between case status and the presence of blood in the stool (p-value=0.1) while ill. These findings might have implications for patient management, as a history of consuming undercooked foods of bovine origin or having direct contact with cattle in the few days prior to illness could be useful for suggesting a more proactive diagnostic approach as well as close monitoring for the need to implement more aggressive therapy.
St Gallen molecular subtypes in primary breast cancer and matched lymph node metastases - aspects on distribution and prognosis for patients with luminal A tumours: results from a prospective randomised trial
Background The St Gallen surrogate molecular subtype definitions classify the oestrogen (ER) positive breast cancer into the luminal A and luminal B subtypes according to proliferation rate and/or expression of human epidermal growth factor receptor 2 (HER2) with differences in prognosis and chemo-responsiveness. Primary tumours and lymph node metastases might represent different malignant clones, but in the clinical setting only the biomarker profile of the primary tumour is used for selection of adjuvant systemic treatment. The present study aimed to classify primary breast tumours and matched lymph node metastases into luminal A, luminal B, HER2-positive and triple-negative subtypes and compare the distributions. Methods Eighty-five patients with available tumour tissue from both locations were classified. The distribution of molecular subtypes in primary tumours and corresponding lymph node metastases were compared, and related to 5-year distant disease-free survival (DDFS). Results The St Gallen molecular subtypes were discordant between primary tumours and matched lymph node metastases in 11% of the patients (p = 0.06). The luminal A subtype in the primary tumour shifted to a subtype with a worse prognostic profile in the lymph node metastases in 7 of 45 cases (16%) whereas no shift in the opposite direction was observed (0/38) (p = 0.02). All subtypes had an increased hazard for developing distant metastasis during the first 5 years after diagnosis in both primary breast tumours and matched lymph node metastases, compared with the luminal A subtype. Conclusion The classification according to the St Gallen molecular subtypes in primary tumours and matched lymph node metastases, implicates a shift to a more aggressive subtype in synchronous lymph node metastases compared to the primary breast tumour. The selection of systemic adjuvant therapy might benefit from taking the molecular subtypes in the metastatic node into account. PMID:24274821
Serna, Eva; Morales, José Manuel; Mata, Manuel; Gonzalez-Darder, José; San Miguel, Teresa; Gil-Benso, Rosario; Lopez-Gines, Concha; Cerda-Nicolas, Miguel; Monleon, Daniel
Around 20% of meningiomas histologically benign may be clinically aggressive and recur. This strongly affects management of meningioma patients. There is a need to evaluate the potential aggressiveness of an individual meningioma. Additional criteria for better classification of meningiomas will improve clinical decisions as well as patient follow up strategy after surgery. The aim of this study was to determine the relationship between gene expression profiles and new metabolic subgroups of benign meningioma with potential clinical relevance. Forty benign and fourteen atypical meningioma tissue samples were included in the study. We obtained metabolic profiles by NMR and recurrence after surgery information for all of them. We measured gene expression by oligonucleotide microarray measurements on 19 of them. To our knowledge, this is the first time that distinct gene expression profiles are reported for benign meningioma molecular subgroups with clinical correlation. Our results show that metabolic aggressiveness in otherwise histological benign meningioma proceeds mostly through alterations in the expression of genes involved in the regulation of transcription, mainly the LMO3 gene. Genes involved in tumor metabolism, like IGF1R, are also differentially expressed in those meningioma subgroups with higher rates of membrane turnover, higher energy demand and increased resistance to apoptosis. These new subgroups of benign meningiomas exhibit different rates of recurrence. This work shows that benign meningioma with metabolic aggressiveness constitute a subgroup of potentially recurrent tumors in which alterations in genes regulating critical features of aggressiveness, like increased angiogenesis or cell invasion, are still no predominant. The determination of these gene expression biosignatures may allow the early detection of clinically aggressive tumors.
Wang, Molin; Spiegelman, Donna; Kuchiba, Aya; Lochhead, Paul; Kim, Sehee; Chan, Andrew T; Poole, Elizabeth M; Tamimi, Rulla; Tworoger, Shelley S; Giovannucci, Edward; Rosner, Bernard; Ogino, Shuji
A fundamental goal of epidemiologic research is to investigate the relationship between exposures and disease risk. Cases of the disease are often considered a single outcome and assumed to share a common etiology. However, evidence indicates that many human diseases arise and evolve through a range of heterogeneous molecular pathologic processes, influenced by diverse exposures. Pathogenic heterogeneity has been considered in various neoplasms such as colorectal, lung, prostate, and breast cancers, leukemia and lymphoma, and non-neoplastic diseases, including obesity, type II diabetes, glaucoma, stroke, cardiovascular disease, autism, and autoimmune disease. In this article, we discuss analytic options for studying disease subtype heterogeneity, emphasizing methods for evaluating whether the association of a potential risk factor with disease varies by disease subtype. Methods are described for scenarios where disease subtypes are categorical and ordinal and for cohort studies, matched and unmatched case-control studies, and case-case study designs. For illustration, we apply the methods to a molecular pathological epidemiology study of alcohol intake and colon cancer risk by tumor LINE-1 methylation subtypes. User-friendly software to implement the methods is publicly available.
O'Brien, Beth A.; Wolf, Maryanne; Lovett, Maureen W.
Long-standing issues with the conceptualization, identification and subtyping of developmental dyslexia persist. This study takes an alternative approach to examine the heterogeneity of developmental dyslexia using taxometric classification techniques. These methods were used with a large sample of 671 children ages 6-8 who were diagnosed with…
Fowler, Katherine A.; Westen, Drew
Domestic violence is a serious problem with far-reaching consequences. This study applies a new methodology to derive subtypes of male perpetrators of intimate partner violence. As part of a larger National Institute of Mental Health (NIMH)-funded study, a national sample of randomly selected psychologists and psychiatrists describe 188 adult male…
Rourke, Byron P.; Fuerst, Darren E.
Evidence bearing on the relationships between profiles of neuropsychological assets and deficits, subtypes of learning disabilities, and patterns and degrees of psychosocial functioning is reviewed. Conclusions related to the neurodevelopmental bases of psychosocial functioning in children with nonverbal learning disabilities are emphasized. (SLD)
Esteban, Cristóbal; Arostegui, Inmaculada; Aburto, Myriam; Moraza, Javier; Quintana, José M.; García-Loizaga, Amaia; Basualdo, Luis V.; Aramburu, Amaia; Aizpiri, Susana; Uranga, Ane; Capelastegui, Alberto
Background Although subtypes of chronic obstructive pulmonary disease are recognized, it is unknown what happens to these subtypes over time. Our objectives were to assess the stability of cluster-based subtypes in patients with stable disease and explore changes in clusters over 1 year. Methods Multiple correspondence and cluster analysis were used to evaluate data collected from 543 stable patients included consecutively from 5 respiratory outpatient clinics. Results Four subtypes were identified. Three of them, A, B, and C, had marked respiratory profiles with a continuum in severity of several variables, while the fourth, subtype D, had a more systemic profile with intermediate respiratory disease severity. Subtype A was associated with less dyspnea, better health-related quality of life and lower Charlson comorbidity scores, and subtype C with the most severe dyspnea, and poorer pulmonary function and quality of life, while subtype B was between subtypes A and C. Subtype D had higher rates of hospitalization the previous year, and comorbidities. After 1 year, all clusters remained stable. Generally, patients continued in the same subtype but 28% migrated to another cluster. Together with movement across clusters, patients showed changes in certain characteristics (especially exercise capacity, some variables of pulmonary function and physical activity) and changes in outcomes (quality of life, hospitalization and mortality) depending on the new cluster they belonged to. Conclusions Chronic obstructive pulmonary disease clusters remained stable over 1 year. Most patients stayed in their initial subtype cluster, but some moved to another subtype and accordingly had different outcomes. PMID:27611911
Kleiner, David E; Makhlouf, Hala R
Nonalcoholic fatty liver disease (NAFLD) is the liver disease associated with obesity, diabetes, and the metabolic syndrome. Although steatosis is a key histologic feature, liver biopsies of patients with NAFLD can show a wide range of findings. Nonalcoholic steatohepatitis (NASH) is a progressive subtype of NAFLD first defined by analogy to alcoholic hepatitis. Young children may have an alternate pattern of progressive NAFLD characterized by a zone 1 distribution of steatosis, inflammation, and fibrosis. Several grading and staging systems exist, but all require adequate biopsies. Although NASH generally shows fibrosis progression over time, some patients show regression of disease.
Gundim, Lígia F.; de Araújo, Camila P.; Blanca, William T.; Guimarães, Ednaldo C.; Medeiros, Alessandra A.
Breast tumors are the most common tumors in dogs and the study of disease prognostic factors is important for establishing the appropriate treatment protocols. The purpose of this study was to clinically stage mammary tumors of bitches and correlate the stages with histological type and grade. The tumors of 63 dogs were clinically staged based on the findings of tumor sizing, lymph node evaluation, and radiographic examination. After surgical excision, the tumors were classified histologically and graded. The relationship between the tumor grade, stage, and histological type was evaluated using a binomial test. Stage I tumors were the most numerous (31.75%), followed by tumors at stages II, III, IV, and V. Animals with histological grade I carcinomas presented stage I, II, or III tumors more frequently and stage IV and V tumors less frequently. The number of animals with simple carcinomas that were at stage I of the disease was greater than that at stage V. Carcinomas in the mixed tumors were less aggressive; however, the small number of animals in stage V of the disease made any statistical association impossible. The complex carcinomas presented with the invasion of the lymph nodes and less cellular differentiation in a larger number of animals than did simple carcinomas. Histological grading proved to be the best parameter for the prognostic evaluation of the breast carcinomas. PMID:27733787
Muntan, C D; Sundine, M J; Rink, R D; Acland, R D
The inframammary fold is a defining element in the shape and structure of the female breast. It should be preserved whenever possible in ablative procedures and recreated accurately when the breast is reconstructed after mastectomy. To date, no accurate anatomic description of this essential structure exists. Previous studies have suggested that the fold is produced by a supporting ligament running from the dermis in the fold region to a variety of locations on the rib cage. This clinic's experience with mastectomy, augmentation mammaplasty, and breast reconstruction does not support the existence of a ligamentous structure. To define the structure of the inframammary fold, 10 female and 2 male cadavers were studied. The anterior chest wall was removed en bloc and frozen in orthostatic position. Parasagittal sections were made of the inframammary fold with the chest wall intact. After decalcification of the ribs and routine histologic preparation, thin sections were stained with Gomori's trichrome. On light microscopic examination, no demonstrable ligamentous structure of dense regular connective tissue could be identified in the fold region in any of the 12 specimens. Superficial and deep fascial layers were uniformly observed anterior to the pectoralis major and serratus anterior muscles. The superficial fascia was connected to the dermis in the fold region in a variety of configurations. In some cases, the deep fascia fused with the superficial fascia and dermis at the fold level. In other cases, bundles of collagen fibers arising from the superficial fascial layer were found to insert into the dermis at the inframammary fold, slightly inferior to it, or both. These bundles were observed consistently in sections from the sternum to the middle axillary line. They were distinct from Cooper's suspensory ligaments, which are seen more superiorly in the glandular tissue.
Newberry, Michelle; Williams, Nikki; Caulfield, Laura
Research into the relationship between alcohol and aggression has previously focused on men. However, in recent years there has been an increase in binge drinking and violent crime among women, behaviours which have been labelled 'ladette' culture in the UK. The current study advances the literature in this area by investigating the relationship between alcohol consumption and aggressive behaviour of females in licensed premises, including the type of aggression and motivations for aggressive incidents. Ninety-three female university students completed the Student Alcohol Questionnaire (SAQ; Engs, 2002), the Aggression Questionnaire (Buss & Perry, 1992) and a questionnaire developed to measure self-reported aggressive incidents. Females who had been involved in an aggressive incident reported spending more time on average in licensed premises per week and higher levels of aggression as well as consuming significantly more alcohol on the day of the incident than females who had not been involved in an aggressive incident. Contrary to expectations, however, those who had been involved in an aggressive incident did not report drinking more beer (a male-orientated drink) than those who had not. Verbally aggressive incidents were reported more than physically aggressive incidents, and aggression was commonly motivated by an emotional reaction or to address a grievance. The finding that average alcohol consumption per week was significantly associated with female aggression in licensed premises highlights the importance of developing interventions to reduce alcohol consumption among young females.
Mifune, Nobuhiro; Simunovic, Dora; Yamagishi, Toshio
Using a recently created preemptive strike game (PSG) with 176 participants, we investigated if the motivations of spite and/or fear promotes aggression that requires a small cost to the aggressor and imposes a larger cost on the opponent, and confirmed the earlier finding that fear does but spite does not promote intergroup aggression when the groups are characterized as minimal groups; additionally, the rate of intergroup aggression did not vary according to the group membership of the opponent. The PSG represents a situation in which both the motivations of spite and of fear can logically drive players to choose an option of aggression against an opponent. Participants decide whether or not to attack another participant, who also has the same capability. The decision is made in real time, using a computer. We discuss theoretical implications of our findings on the evolutionary foundations of intragroup cooperation and intergroup aggression. The evolutionary model of intergroup aggression, or the parochial altruism model, posits that intragroup cooperation and intergroup aggression have co-evolved, and thus it predicts both intragroup cooperation and intergroup aggression to emerge even in a minimal group devoid of a history of intergroup relationships. The finding that only intragroup cooperation but not intergroup aggression emerged in the minimal group experiments strongly suggests that intergroup aggression involves a psychological mechanism that is independent from that of intragroup cooperation. We further discuss the implications of these findings on real-world politics and military strategy. PMID:28174553
Monoamine Oxidase A (MAOA) and Catechol-O-Methyltransferase (COMT) Gene Polymorphisms Interact with Maternal Parenting in Association with Adolescent Reactive Aggression but not Proactive Aggression: Evidence of Differential Susceptibility.
Zhang, Wenxin; Cao, Cong; Wang, Meiping; Ji, Linqin; Cao, Yanmiao
To date, whether and how gene-environment (G × E) interactions operate differently across distinct subtypes of aggression remains untested. More recently, in contrast with the diathesis-stress hypothesis, an alternative hypothesis of differential susceptibility proposes that individuals could be differentially susceptible to environments depending on their genotypes in a "for better and for worse" manner. The current study examined interactions between monoamine oxidase A (MAOA) T941G and catechol-O-methyltransferase (COMT) Val158Met polymorphisms with maternal parenting on two types of aggression: reactive and proactive. Moreover, whether these potential G × E interactions would be consistent with the diathesis-stress versus the differential susceptibility hypothesis was tested. Within the sample of 1399 Chinese Han adolescents (47.2 % girls, M age = 12.32 years, SD = 0.50), MAOA and COMT genes both interacted with positive parenting in their associations with reactive but not proactive aggression. Adolescents with T alleles/TT homozygotes of MAOA gene or Met alleles of COMT gene exhibited more reactive aggression when exposed to low positive parenting, but less reactive aggression when exposed to high positive parenting. These findings provide the first evidence for distinct G × E interaction effects on reactive versus proactive aggression and lend further support for the differential susceptibility hypothesis.
Kothari, Sonal; Phan, John H; Young, Andrew N; Wang, May D
Computer-aided histological image classification systems are important for making objective and timely cancer diagnostic decisions. These systems use combinations of image features that quantify a variety of image properties. Because researchers tend to validate their diagnostic systems on specific cancer endpoints, it is difficult to predict which image features will perform well given a new cancer endpoint. In this paper, we define a comprehensive set of common image features (consisting of 12 distinct feature subsets) that quantify a variety of image properties. We use a data-mining approach to determine which feature subsets and image properties emerge as part of an "optimal" diagnostic model when applied to specific cancer endpoints. Our goal is to assess the performance of such comprehensive image feature sets for application to a wide variety of diagnostic problems. We perform this study on 12 endpoints including 6 renal tumor subtype endpoints and 6 renal cancer grade endpoints. Keywords-histology, image mining, computer-aided diagnosis.
Potapenko, Ivan O; Lüders, Torben; Russnes, Hege G; Helland, Åslaug; Sørlie, Therese; Kristensen, Vessela N; Nord, Silje; Lingjærde, Ole C; Børresen-Dale, Anne-Lise; Haakensen, Vilde D
Alterations in glycan structures are early signs of malignancy and have recently been proposed to be in part a driving force behind malignant transformation. Here, we explore whether differences in expression of genes related to the process of glycosylation exist between breast carcinoma subtypes - and look for their association to clinical parameters. Five expression datasets of 454 invasive breast carcinomas, 31 ductal carcinomas in situ (DCIS), and 79 non-malignant breast tissue samples were analysed. Results were validated in 1960 breast carcinomas. 419 genes encoding glycosylation-related proteins were selected. The DCIS samples appeared expression-wise similar to carcinomas, showing altered gene expression related to glycosaminoglycans (GAGs) and N-glycans when compared to non-malignant samples. In-situ lesions with different aggressiveness potentials demonstrated changes in glycosaminoglycan sulfation and adhesion proteins. Subtype-specific expression patterns revealed down-regulation of genes encoding glycan-binding proteins in the luminal A and B subtypes. Clustering basal-like samples using a consensus list of genes differentially expressed across discovery datasets produced two clusters with significantly differing prognosis in the validation dataset. Finally, our analyses suggest that glycolipids may play an important role in carcinogenesis of breast tumors - as demonstrated by association of B3GNT5 and UGCG genes to patient survival. In conclusion, most glycan-specific changes occur early in the carcinogenic process. We have identified glycan-related alterations specific to breast cancer subtypes including a prognostic signature for two basal-like subgroups. Future research in this area may potentially lead to markers for better prognostication and treatment stratification of breast cancer patients.
Cormanique, Thayse Fachin; de Almeida, Lirane Elize Defante Ferreto; Rech, Cynthia Alba; Rech, Daniel; Herrera, Ana Cristina da Silva do Amaral; Panis, Carolina
Objective To investigate the clinicopathological findings of women diagnosed with breast cancer and study the impact of chronic psychological stress on the pathological characteristics of these tumors. Methods We investigated a cohort composed of women diagnosed with breast cancer and divided into two groups. One group was categorized as presenting with chronic psychological stress (by using the Self-Reporting Questionnaire − SRQ-20). Another group of women with breast cancer, but with no previous history of chronic psychological stress, comprised the Control Group. Clinical and pathological data were assessed. Results Women presenting with a history of chronic distress were significantly overweight when compared to the Control Group. Furthermore, it was observed that these stressed women also had a significant percentage of aggressive breast cancer subtype, the HER2 amplified tumor, which could be putatively associated with the loss of immunosurveillance. Conclusion Our findings suggested an interaction among chronic psychological stress, overweight, and the development of more aggressive breast tumors. PMID:26466057
Tozawa, H; Brännström, M; Petrucco, O; Walker, S; Chambers, H; Pascoe, V; Norman, R J
The distribution of leukocyte subtypes in the sheep ovary following laser drilling of the ovarian capsule was examined to understand a possible mechanism by which this treatment promotes ovulation in polycystic ovarian syndrome. Ovaries were removed from sheep at different time-points following laparoscopic laser drilling and immunohistochemical detection of leukocyte subtypes, using specific monoclonal antibodies; standard histological staining was performed. Migration of leukocytes into the laser-drilled site was observed as early as 6 h after laser drilling and the total number of leukocytes in the site was found to increase up to the 12th day after surgery. In the earlier period, polymorphonuclear leukocytes were the dominant leukocyte subtypes, while macrophages and lymphocytes were the major cellular components on the 12th day and later. These results show that the tissue changes in the ovary following laser drilling are consistent with a local inflammatory reaction. The prolonged appearance of numerous macrophages following the acute inflammatory phase could lead to the secretion of cytokines and other substances suggested to be important in promoting ovulation. These data indicate that part of the effectiveness of the laser drilling in polycystic ovarian syndrome may be attributable to the secretory products of these leukocytes.
Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita
Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness. DOI: http://dx.doi.org/10.7554/eLife.07643.001 PMID:26216041
Giancola, Peter R
The primary goal of this investigation was to determine whether executive functioning (EF) would moderate the alcohol-aggression relation. Participants were 310 (152 men and 158 women) healthy social drinkers between 21 and 35 years of age. EF as well as non-EF skills were measured with 13 validated neuropsychological tests. Following the consumption of either an alcoholic or a placebo beverage, participants were tested on a modified version of the Taylor Aggression Paradigm (S. Taylor, 1967), in which mild electric shocks were received from, and administered to, a fictitious opponent. Aggressive behavior was operationalized as the shock intensities administered to the fictitious opponent. EF was negatively related to aggressive behavior for men, regardless of beverage group, even when controlling for non-EF skills. Furthermore, alcohol increased aggression only for men with lower EF scores. Finally, the mere belief that alcohol was consumed suppressed aggression for women but not for men.
Guo, Xucheng; Egan, Vincent; Zhang, Jianxin
The misperception of aggressive cues is considered a risk factor for inducing adolescent aggression. Poor coping with life stress is also considered a major influence on aggression. The current study examined the relationship between subjective sense of control and adolescent aggression, considering influences upon the perception of these aggressive cues. In Study 1, 60 participants took part in a 2 (sense of control: high sense of control vs. low sense of control) × 2 (aggressive cue: aggressive vs. neutral) between-subjects contextual experiment. The result found that a lower sense of control led to an increase in adolescents' aggression; only in the low-sense-of-control condition did exposure to aggressive cues boost aggression. In Study 2, the catalytic effect of aggressive cues was further explored by an experiment in which 40 adolescents were randomly assigned to a low- or high-sense-of-control condition to test the importance of aggressive cues. The results suggest that adolescents in the low-sense-of-control condition show a higher salience for aggressive cues.
Cui, Lixian; Colasante, Tyler; Malti, Tina; Ribeaud, Denis; Eisner, Manuel P
We examined the roles of sensation seeking, risk taking, and moral reasoning in the development of reactive and proactive aggression. Data were drawn from a multiethnic, longitudinal study of children from Switzerland (N = 1571; 52 % male; assessed annually over 6 years; 7-years-old at Time 1). At all 6 time points, teachers reported children's reactive and proactive aggression via questionnaire. Children's sensation seeking (at Time 1) and risk taking (at Time 2) were assessed with two interactive computer tasks and their moral reasoning was assessed at Time 2 in response to four hypothetical vignettes depicting moral transgressions. Parallel process Latent Class Growth Analysis (PP-LCGA) identified six dual trajectories of reactive and proactive aggression. Children with either childhood-limited or adolescent-onset aggression showed high sensation seeking. Children with persistent, high levels of both reactive and proactive aggression across time showed high levels of sensation seeking and risk taking, as well as low levels of moral reasoning. Children with only high risk taking were more likely to display moderate levels of aggression across time. These findings highlight the shared and differential roles of sensation seeking, risk taking, and moral reasoning in the dual development of reactive and proactive aggression from mid-childhood to early adolescence. We discuss implications for common and tailored strategies to combat these aggression subtypes.
Kaur, Gurvinder; Kane, Ari J; Sughrue, Michael E; Madden, Michelle; Oh, Michael C; Sun, Matthew Z; Safaee, Michael; El-Sayed, Ivan; Aghi, Manish; McDermott, Michael W; Berger, Mitchel S; Parsa, Andrew T
Esthesioneuroblastoma (EN) is a rare sinonasal tumor with varied aggressiveness and potential for intracranial invasion. EN is staged anatomically with radiographic evaluation using the Kadish staging system (stages A, B, and C) and histologically by using Hyam's criteria (grades 1-4). Here we show that despite radiographic evidence of aggressive features, the prognosis of patients with Kadish stage C EN is best predicted by tumor histology using Hyam's criteria. We retrospectively analyzed patients with EN with Kadish stage C who were evaluated and treated at our institution between 1995 and 2009. Clinical information was collected using patient medical records, imaging, and review of pathological specimens. Twenty patients with Kadish stage C EN were identified with mean age of 51 years (31-70 years) with a median follow-up of 41.4 months (1.3-175 months). Upon pathological review, 44.4% of patients had low-grade (1/2) and 55.6% had high-grade (3/4) histology. About 37.5% of patients with low-grade EN had undergone gross total resection (GTR) and the remaining 62.5% had GTR and adjuvant radiation, whereas 50% of patients with high-grade ER had undergone GTR, 20% had undergone GTR and adjuvant radiation, and 30% had been treated with a subtotal resection (STR) and adjuvant radiation. The 5-year and 10-year survival in patients with low-grade EN was 86% in comparison to 56% and 28% with high-grade EN, respectively. In patients with low-grade EN, the 2-year progression free survival (PFS) was 86% and the 5-year PFS was 65% in comparison to 73% and 49% in patients with high-grade EN, respectively. The patient's tumor histology (Hyam's criteria) appeared to be the best way of predicting the prognosis and for selecting patients for adjuvant radiotherapy.
Introduction Mammographic density is a strong risk factor for breast cancer overall, but few studies have examined the association between mammographic density and specific subtypes of breast cancer, especially aggressive basal-like breast cancers. Because basal-like breast cancers are less frequently screen-detected, it is important to understand how mammographic density relates to risk of basal-like breast cancer. Methods We estimated associations between mammographic density and breast cancer risk according to breast cancer subtype. Cases and controls were participants in the Carolina Breast Cancer Study (CBCS) who also had mammograms recorded in the Carolina Mammography Registry (CMR). A total of 491 cases had mammograms within five years prior to and one year after diagnosis and 528 controls had screening or diagnostic mammograms close to the dates of selection into CBCS. Mammographic density was reported to the CMR using Breast Imaging Reporting and Data System categories. The expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 1 and 2 (HER1 and HER2), and cytokeratin 5/6 (CK5/6) were assessed by immunohistochemistry and dichotomized as positive or negative, with ER+ and/or PR+, and HER2- tumors classified as luminal A and ER-, PR-, HER2-, HER1+ and/or CK5/6+ tumors classified as basal-like breast cancer. Triple negative tumors were defined as negative for ER, PR and HER2. Of the 491 cases 175 were missing information on subtypes; the remaining cases included 181 luminal A, 17 luminal B, 48 basal-like, 29 ER-/PR-/HER2+, and 41 unclassified subtypes. Odds ratios comparing each subtype to all controls and case-case odds ratios comparing mammographic density distributions in basal-like to luminal A breast cancers were estimated using logistic regression. Results Mammographic density was associated with increased risk of both luminal A and basal-like breast cancers, although estimates were imprecise. The
Sathyan, Pratheesh; Zinn, Pascal O.; Marisetty, Anantha L.; Liu, Bin; Kamal, Mohamed Mostafa; Singh, Sanjay K.; Bady, Pierre; Lu, Li; Wani, Khalida M.; Veo, Bethany L.; Gumin, Joy; Kassem, Dina Hamada; Robinson, Frederick; Weng, Connie; Baladandayuthapani, Veerabhadran; Suki, Dima; Colman, Howard; Bhat, Krishna P.; Sulman, Erik P.; Aldape, Ken; Colen, Rivka R.; Verhaak, Roel G.W.; Lu, Zhimin; Fuller, Gregory N.; Huang, Suyun; Lang, Frederick F.; Sawaya, Raymond; Hegi, Monika
Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here, we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis. Using the MiR-21–Sox2 regulatory axis, approximately half of all GBM tumors present in the Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with Class B tumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of MiR-21–Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The MiR-21–Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Therefore, this mechanism-based classification suggests the presence of two distinct populations of GBM patients with distinguishable phenotypic characteristics and clinical outcomes. SIGNIFICANCE STATEMENT Molecular profiling-based classification of glioblastoma (GBM) into four subtypes has substantially increased our understanding of the biology of the disease and has pointed to the heterogeneous nature of GBM. However, this classification is not
Reynes, E; Lorant, J
The purpose of the present study was to ascertain whether children beginning martial arts training were more aggressive than their peers. 150 8-yr.-old children were administered the Buss-Perry Aggression Questionnaire. Analysis showed that children beginning martial arts training did not score more aggressive than their peers but scored higher on the Anger scale. This difference, however, appeared only in children practicing judo.
Zhao, Ming; Teng, Xiaodong; Ru, Guoqing; Zhao, Zhongsheng; Hu, Qinqin; Han, Likai; He, Xianglei
Tubulocystic renal cell carcinoma (TCRCC) is a rare, recently characterized RCC subtype with distinctive clinicopathologic and genetic characterizations as well as typical behaviors in an indolent fashion. However, sporadic case reports in the literature have indicated that TCRCC with sarcomatoid differentiation or poorly differentiated (PD) foci could behave aggressively. Herein, we reported two cases of TCRCC with PD foci indentified from our consultative service. Both patients were male and aged 66 y and 47 y, respectively. The first patient experienced radical nephrectomy while the other was treated by partial nephrectomy. Macroscopically, both tumors were described as partly cystic and solid with the greatest diameter measuring of 12-cm and 4.5-cm, respectively. Histologically, both lesions had classic areas of TCRCC occupying most part of the tumor with small papillary RCC component. In case one, PD foci were scatteredly distributed and mixed with TCRCC and papillary RCC components, while in the other case the PD foci were adjacent to the areas of TCRCC. In both tumors, the PD foci were composed of irregular, often angulated, small tubules lined by atypical eosinophilic cells and surrounded by desmoplastic stroma, resembling collecting duct carcinoma. Immunohistochemistry, in both tumors, both TCRCC component and PD foci showed the similar immunoprofiles, i.e., labeling strongly and diffusely with PAX8, AMACR and Vimentin, and focally with CK34βE12 but not with renal cell carcinoma marker or P63. In case one, the tumor invaded extensively into the adjacent renal parenchyma and focally into both renal sinusal and perirenal adipose tissues. The patient had metastasis in the pelvic cavity at the time of diagnosis and succumbed to the disease without further treatment 3 months later. The other case was organ confined but with focal positive renal parenchymal margin. The patient subsequently underwent radical nephrectomy and was in a good status without evidence
Craig, Ian W; Halton, Kelly E
A consideration of the evolutionary, physiological and anthropological aspects of aggression suggests that individual differences in such behaviour will have important genetic as well as environmental underpinning. Surveys of the likely pathways controlling the physiological and neuronal processes involved highlight, as obvious targets to investigate, genes implicated in sexual differentiation, anxiety, stress response and the serotonin neurotransmitter pathway. To date, however, association studies on single candidates have provided little evidence for any such loci with a major effect size. This may be because genes do not operate independently, but function against a background in which other genetic and environmental factors are crucial. Indeed, a series of recent studies, particularly concentrating on the serotonin and norepinephrine metabolising enzyme, monoamine oxidase A, has emphasised the necessity of examining gene by environmental interactions if the contributions of individual loci are to be understood. These findings will have major significance for the interpretation and analysis of data from detailed whole genome association studies. Functional imaging studies of genetic variants affecting serotonin pathways have also provided valuable insights into potential links between genes, brain and aggressive behaviour.
Lichtman, S M
Persons 65 years of age and older are the fastest growing segment of the United States population. Over the next 30 years they will comprise approximately 20% of the population. There will be a parallel rise in the number of patients with non-Hodgkin's lymphoma. Age has long been known to be an adverse prognostic factor. Clinical trials of older patients are complicated by the effect of comorbid illness, particularly its effect on overall survival. CHOP (cyclophosphamide, Adriamycin, vincristine, prednisone) remains the standard therapy for all patients with aggressive non-Hodgkin's lymphoma. There are a number of regimens which may be beneficial for older patients with significant comorbidity and poor performance status. The randomized trials in the elderly has reaffirmed CHOP and emphasize the need for adequate dosing, maintaining schedule and anthracyclines. Relapsed patients have a poor prognosis but selected fit older patients may benefit from aggressive reinduction regimens and possibly bone marrow transplantation. Future research should include defining the role of comorbidity, measurement of organ dysfunction and assessment of performance status with geriatric functional scales. New drug treatments should also be explored.
Harden, K. Paige; Patterson, Megan W.; Briley, Daniel A.; Engelhardt, Laura E.; Kretsch, Natalie; Mann, Frank D.; Tackett, Jennifer L.; Tucker-Drob, Elliot M.
Background Antisocial behavior (ASB) can be meaningfully divided into non-aggressive rule-breaking versus aggressive dimensions, which differ in developmental course and etiology. Previous research has found that genetic influences on rule-breaking, but not aggression, increase from late childhood to mid-adolescence. This study tested the extent to which this developmental increase in genetic influence was associated with pubertal development compared to chronological age. Method Child and adolescent twins (n = 1,031), ranging in age from 8 to 20 years (M age = 13.5 years), were recruited from public schools as part of the Texas Twin Project. Participants reported on their pubertal development using the Pubertal Development Scale and on their involvement in ASB on an abbreviated version of the Child Behavior Checklist. Measurement invariance of ASB subtypes across age groups (≤12 years versus >12 years old) was tested using confirmatory factor analyses. Quantitative genetic modeling was used to test whether the genetic and environmental influences on aggression and rule-breaking were moderated by age, pubertal status, or both. Results Quantitative genetic modeling indicated that genetic influences specific to rule-breaking increased as a function of pubertal development controlling for age (a gene × puberty interaction), but did not vary as a function of age controlling for pubertal status. There were no developmental differences in the genetic etiology of aggression. Family-level environmental influences common to aggression and rule-breaking decreased with age, further contributing to the differentiation between these sub-types of ASB from childhood to adolescence. Conclusions Future research should discriminate between alternative possible mechanisms underlying gene × puberty interactions on rule-breaking forms of antisocial behavior, including possible effects of pubertal hormones on gene expression. PMID:25902931
Kadota, Paul Ostrom; Hajjiri, Zahraa; Finn, Patricia W.; Perkins, David L.
Among kidney transplant recipients, the treatment of choice for acute T cell-mediated rejection (TCMR) with pulse steroids or antibody protocols has variable outcomes. Some rejection episodes are resistant to an initial steroid pulse, but respond to subsequent antibody protocols. The biological mechanisms causing the different therapeutic responses are not currently understood. Histological examination of the renal allograft is considered the gold standard in the diagnosis of acute rejection. The Banff Classification System was established to standardize the histopathological diagnosis and to direct therapy. Although widely used, it shows variability among pathologists and lacks criteria to guide precision individualized therapy. The analysis of the transcriptome in allograft biopsies, which we analyzed in this study, provides a strategy to develop molecular diagnoses that would have increased diagnostic precision and assist the development of individualized treatment. Our hypothesis is that the histological classification of TCMR contains multiple subtypes of rejection. Using R language algorithms to determine statistical significance, multidimensional scaling, and hierarchical, we analyzed differential gene expression based on microarray data from biopsies classified as TCMR. Next, we identified KEGG functions, protein–protein interaction networks, gene regulatory networks, and predicted therapeutic targets using the integrated database ConsesnsusPathDB (CPDB). Based on our analysis, two distinct clusters of biopsies termed TCMR01 and TCMR02 were identified. Despite having the same Banff classification, we identified 1933 differentially expressed genes between the two clusters. These genes were further divided into three major groups: a core group contained within both the TCMR01 and TCMR02 subtypes, as well as genes unique to TCMR01 or TCMR02. The subtypes of TCMR utilized different biological pathways, different regulatory networks and were predicted to
Cardwell, Michael Steven
Transmission of aggressive behaviors to children through modeling by adults has long been a commonly held psychological concept; however, with the advent of technological innovations during the last 30 years, video media-television, movies, video games, and the Internet-has become the primary model for transmitting aggressiveness to children. This review explores the acquisition of aggressive behaviors by children through modeling behaviors in violent video media. The impact of aggressive behaviors on the child, the family, and society is addressed. Suggestive action plans to curb this societal ill are presented.
Weckerly, Floyd W.; Ricca, Mark A.
Female caribou (Rangifer tarandus) are highly gregarious, yet there has been little study of the behavioral mechanisms that foster coexistence. Quantifying patterns of aggression between male and female, particularly in the only cervid taxa where both sexes grow antlers, should provide insight into these mechanisms. We asked if patterns of aggression by male and female caribou followed the pattern typically noted in other polygynous cervids, in which males display higher frequencies and intensity of aggression. From June to August in 2011 and 2012, we measured the frequency and intensity of aggression across a range of group sizes through focal animal sampling of 170 caribou (64 males and 106 females) on Adak Island in the Aleutian Archipelago, Alaska. Males in same-sex and mixed-sex groups and females in mixed-sex groups had higher frequencies of aggression than females in same-sex groups. Group size did not influence frequency of aggression. Males displayed more intense aggression than females. Frequent aggression in mixed-sex groups probably reflects lower tolerance of males for animals in close proximity. Female caribou were less aggressive and more gregarious than males, as in other polygynous cervid species.
LeBlanc, Manon Mireille; Barling, Julian; Turner, Nick
Using conservation of resources theory, we examined the relationship between intimate partner aggression enacted against heterosexual women and 3 types of work-related outcomes for these women: withdrawal while at work (i.e., cognitive distraction, work neglect), withdrawal from work (i.e., partial absenteeism, intentions to quit), and performance. In Study 1, we compared withdrawal both at and from work across 3 clinically categorized groups of women (n = 50), showing that experiencing physical aggression is related to higher work neglect. We replicated and extended these findings in Study 2 using a community sample of employed women (n = 249) by considering the incremental variance explained by both physical aggression and psychological aggression on these same outcomes. Results showed that physical aggression predicted higher levels of withdrawal both at and from work, with psychological aggression predicting additional variance in partial absenteeism over and above the effects of physical aggression. Study 3 extended the model to include academic performance as an outcome in a sample of female college students (n = 122) in dating relationships. Controlling for the women's conscientiousness, psychological aggression predicted lower academic performance after accounting for the effects of physical aggression. We discuss theoretical and practical implications of these results, as well as directions for future research.
The present study enriches our knowledge on the relationship between security personnel and situational cues that may provoke aggression, such as arms and uniforms. The study examined 259 security personnel who completed an aggression questionnaire (AGQ). The study aimed (a) to compare the tendency toward aggression of security personnel who carry or do not carry arms and/or wear a uniform and (b) to compare the tendency toward aggression of men and women security personnel who carry or do not carry arms and/or wear a uniform. The findings indicated no main effect for aggression cueing classification. However, uniformed men had higher scores of physical aggression than women, and women scored significantly higher on anger than men when not carrying any aggressive cues. The findings also revealed that in general, men security personnel reported much higher physical aggression than women, while women showed slightly higher means of verbal aggression than men. The findings are discussed in light of the gender theory and research.
Kim, Hyoun K.; Laurent, Heidemarie K.; Capaldi, Deborah M.; Feingold, Alan
The present study examined the longitudinal course of men’s physical and psychological aggression toward a partner across 10 years, using a community sample of young couples (N = 194) from at-risk backgrounds. Findings indicated that men’s aggression decreased over time and that women’s antisocial behavior and depressive symptoms predicted changes in men’s aggression. This suggests the importance of studying social processes within the dyad to have a better understanding of men’s aggression toward a partner. PMID:19122790
In this review, the author theoretically and empirically examined motives and interpersonal functions of aggression. A factor-analysis of Averill's questionnaire items on anger revealed that motives involved in aggressive responses were clustered into two groups: the hostile and the instrumental. It was also clarified that an individual is likely to engage in aggression particularly when some hostile motives are evoked. Concerning the interpersonal functions, the author proposed that aggression might serve four principal goals. (1) Aggression can be generated as an avoidance response to an aversive stimulus, such as frustration, annoyance, or pain, and so on. It depends on the severity of the stimulus. It was however emphasized that aggression is also mediated by social cognition, such as an attribution of intent to a harm-doer. (2) Aggression can be used as a means of coercing the other person into doing something. An individual is likely to use such a power strategy if he/she is lacking in self-confidence or a perspective for influencing the target person by more peaceful strategies. (3) Aggression can be interpreted as a punishment when it is directed toward a transgressor. In this case, aggression is motivated by restoration of a social justice, and thus its intensity is determined by the perceived moral responsibility of the transgressor. Further, it was indicated that aggression is intensified if it is justified as a sanctional conduct against the immoral. (4) Aggression can be also evoked when an individual's social identity is threatened. It was suggested that impression management motives are involved in aggression by an unexpected finding that the presence of audience or the identifiability rather facilitated retaliative aggression. The aggression-inhibition effect of apology was also explained in terms of impression management. In conclusion, it was presented that aggression is a behavioral strategy as an attempt to resolve interpersonal conflicts
Loveland, Jasmine L; Fernald, Russell D
Despite continued study on the neurobiological bases of aggressive and sexual behaviors, it is still not well understood how the brain integrates social information with physiological and neural states to produce context-specific behavioral outcomes. In fishes, manipulation of endogenous levels of arginine vasotocin (AVT) through peripheral and intracerebroventricular pharmacological injections results in significant changes in social behaviors, including aggressive and reproduction-related behaviors. In addition, many features of AVT neurons have been shown to correlate with social status and associated behavioral phenotypes. In this study, we used the immediate early gene egr-1 as a marker for neuronal activity and quantified the number of AVT neurons that were positive for egr-1 mRNA by in situ hybridization in Astatotilapia burtoni males that were exposed to either a social context that would elicit aggression or to one that would elicit courtship. In these social settings, focal males readily displayed context- appropriate bouts of aggression (towards the opponent) or bouts of courting (towards females). We found that males that fought had higher levels of egr-1 expression in the preoptic area compared to courting males. A greater proportion of AVT cells was positive for egr-1 after a fight than after a bout of courting. We mapped mRNA distribution of AVT V1a receptor subtypes v1a1 and v1a2 in the brain and identified overlapping areas of expression in nuclei in the ventral telencephalon, hypothalamus and thalamus as key areas for AVT signaling in males.
Van den Bergh, Filip; Spronk, Marjolein; Ferreira, Leila; Bloemarts, Emilie; Groenink, Lucianne; Olivier, Berend; Oosting, Ronald
Impulsivity is an important symptom of many psychiatric disorders, and can be divided into two subtypes: response inhibition deficits and delay aversion. In the present study, we investigated the relationship between delay aversion and response inhibition, both to each other and to locomotion, extinction of conditioned responses, sexual behaviour, and aggressive behaviour. To that end, we quantified the behaviour of 24 rats in several tests. To measure response inhibition, rats were trained in a stop-signal task. In this operant task, rats were rewarded food if they inhibited execution of a response after presentation of an audible stop-signal. Delay aversion was measured in an operant task in which rats made a choice between a small, immediately available reward and a large reward available after a delay. The results showed that delay aversion and response inhibition were independent. Responses during extinction and various measures of aggressive behaviour were positively correlated to delay aversion. The speed of go-trials in the stop-task was correlated to non-aggressive behaviour. We conclude that the role of response inhibition in various behaviours is small, but delay aversion in particular contributes to several other behaviours, such as aggressive behaviour and extinction.
Hopp, Lydia; Lembcke, Kathrin; Binder, Hans; Wirth, Henry
We present an analytic framework based on Self-Organizing Map (SOM) machine learning to study large scale patient data sets. The potency of the approach is demonstrated in a case study using gene expression data of more than 200 mature aggressive B-cell lymphoma patients. The method portrays each sample with individual resolution, characterizes the subtypes, disentangles the expression patterns into distinct modules, extracts their functional context using enrichment techniques and enables investigation of the similarity relations between the samples. The method also allows to detect and to correct outliers caused by contaminations. Based on our analysis, we propose a refined classification of B-cell Lymphoma into four molecular subtypes which are characterized by differential functional and clinical characteristics.
Choi, Woonyoung; Porten, Sima; Kim, Seungchan; Willis, Daniel; Plimack, Elizabeth R.; Hoffman-Censits, Jean; Roth, Beat; Cheng, Tiewei; Tran, Mai; Lee, I-Ling; Melquist, Jonathan; Bondaruk, Jolanta; Majewski, Tadeusz; Zhang, Shizhen; Pretzsch, Shanna; Baggerly, Keith; Siefker-Radtke, Arlene; Czerniak, Bogdan; Dinney, Colin P.N.; McConkey, David J.
Summary Muscle-invasive bladder cancers (MIBCs) are biologically heterogeneous and have widely variable clinical outcomes and responses to conventional chemotherapy. We discovered 3 molecular subtypes of MIBC that resembled established molecular subtypes of breast cancer. Basal MIBCs shared biomarkers with basal breast cancers and were characterized by p63 activation, squamous differentiation, and more aggressive disease at presentation. Luminal MIBCs contained features of active PPARγ and estrogen receptor (ER) transcription and were enriched with activating FGFR3 mutations and potentially FGFR inhibitor sensitivity. p53-like MIBCs were consistently resistant to neoadjuvant MVAC chemotherapy, and all chemoresistant tumors adopted a p53-like phenotype after therapy. Our observations have important implications for prognostication, the future clinical development of targeted agents, and disease management with conventional chemotherapy. PMID:24525232
Choi, Woonyoung; Porten, Sima; Kim, Seungchan; Willis, Daniel; Plimack, Elizabeth R; Hoffman-Censits, Jean; Roth, Beat; Cheng, Tiewei; Tran, Mai; Lee, I-Ling; Melquist, Jonathan; Bondaruk, Jolanta; Majewski, Tadeusz; Zhang, Shizhen; Pretzsch, Shanna; Baggerly, Keith; Siefker-Radtke, Arlene; Czerniak, Bogdan; Dinney, Colin P N; McConkey, David J
Muscle-invasive bladder cancers (MIBCs) are biologically heterogeneous and have widely variable clinical outcomes and responses to conventional chemotherapy. We discovered three molecular subtypes of MIBC that resembled established molecular subtypes of breast cancer. Basal MIBCs shared biomarkers with basal breast cancers and were characterized by p63 activation, squamous differentiation, and more aggressive disease at presentation. Luminal MIBCs contained features of active PPARγ and estrogen receptor transcription and were enriched with activating FGFR3 mutations and potential FGFR inhibitor sensitivity. p53-like MIBCs were consistently resistant to neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy, and all chemoresistant tumors adopted a p53-like phenotype after therapy. Our observations have important implications for prognostication, the future clinical development of targeted agents, and disease management with conventional chemotherapy.
Coyne, Sarah M
Most researchers on media and aggression have examined the behavioral effects of viewing physical aggression in the media. Conversely, in the current study, I examined longitudinal associations between viewing relational aggression on TV and subsequent aggressive behavior. Participants included 467 adolescents who completed a number of different questionnaires involving media and aggression at 3 different time points. Results revealed that viewing relational aggression on TV was longitudinally associated with future relational aggression. However, early levels of relational aggression did not predict future exposure to televised relational aggression. Conversely, there was a bidirectional relationship between TV violence and physical aggression over time. No longitudinal evidence was found for a general effect of viewing TV, as all significant media effects were specific to the type of aggression viewed. These results support the general aggression model and suggest that viewing relational aggression in the media can have a long-term effect on aggressive behavior during adolescence.
Matsushita, Yuki; Fujita, Shuichi; Kawasaki, Goro; Hirota, Yoshinosuke; Rokutanda, Satoshi; Yamashita, Kentaro; Yanamoto, Souichi; Ikeda, Tohru; Umeda, Masahiro
Granular cell ameloblastoma is classified as a histological subtype of solid/multicystic ameloblastoma. Usual granular cell ameloblastoma is histologically characterized by granular changes of stellate-like cells located in the inner portion of the epithelial follicles. Here we report a case of another type of granular cell ameloblastoma, showing predominant anastomosing double-stranded trabeculae of granular cells. This type of granular cell ameloblastoma is extremely rare, and the World Health Organization classification does not contain the entity. We tentatively termed it 'anastomosing granular cell ameloblastoma' in this report. The present case suggests the importance of differential diagnosis because the histology of 'anastomosing granular cell ameloblastoma' resembles that of salivary gland oncocytoma rather than that of usual granular cell ameloblastoma. The trabeculae observed in our case continued to the peripheral cells of a small amount of epithelial sheets of plexiform ameloblastoma, and the tumor cells were positive for CK19, which is regarded as an immunohistochemical marker of odontogenic epithelium. Similar to usual granular cell ameloblastoma, the tumor cells had CD68-positive granules. For precise diagnosis of this condition, immunohistochemistry using CK19 and CD68, as well as detailed histological observation, are recommended.
Basiri, Abbas; Movahhed, Saeed; Parvin, Mahmood; Salimi, Maziar
Purpose To assess the prevalence of intratubular germ cell neoplasia (ITGCN) in patients with concurrent testis tumor and its correlation with histologic features and serum tumor markers. Materials and Methods From 2003 to 2015, 179 patients underwent radical orchiectomy due to testicular mass. Tissue specimens were evaluated by an expert uro-pathologist using immunohistochemistry (IHC) staining, in addition to light microscopy, to identify presence of ITGCN. Patients' demographic characteristics, histologic subtypes, pathologic stage of tumor and serum tumor markers were gathered and analyzed. Results Eighty-five out of 179 patients (47.5%) had concomitant ITGCN according to IHC staining. There was not statistically significant difference in histologic type, histologic components, cryptorchidism, and lymphovascular invasion between the 2 groups (p=0.151, p=0.11, p=0.233, p=0.413, and p=0.14, respectively). The prevalence of ITGCN was significantly higher in patients with stage T2 and T3 of tumor than those with stage T1. Elevated serum alpha feto protein level is much common in patients with ITGCN (p<0.001). Conclusions The prevalence of concurrent ITGCN in our region is lower than previous data from western countries. ITGCN is more common in higher tumor stages and is accompanied with elevated serum alpha feto protein levels before surgery. Presence of ITGCN in adjacent tissue may suggest a negative cancer behavior. PMID:27195317
O'Brien, Beth A; Wolf, Maryanne; Lovett, Maureen W
Long-standing issues with the conceptualization, identification and subtyping of developmental dyslexia persist. This study takes an alternative approach to examine the heterogeneity of developmental dyslexia using taxometric classification techniques. These methods were used with a large sample of 671 children ages 6-8 who were diagnosed with severe reading disorders. Latent characteristics of the sample are assessed in regard to posited subtypes with phonological deficits and naming speed deficits, thus extending prior work by addressing whether these deficits embody separate classes of individuals. Findings support separate taxa of dyslexia with and without phonological deficits. Different latent structure for naming speed deficits was found depending on the definitional criterion used to define dyslexia. Non-phonologically based forms of dyslexia showed particular difficulty with naming speed and reading fluency.
Sperling, Michael R; Rosenow, Felix; Faught, Edward; Hebert, David; Doty, Pamela; Isojärvi, Jouko
The purpose of this post hoc exploratory analysis was to determine the effects of the antiepileptic drug, lacosamide, on focal (partial-onset) seizure subtypes. Patient data from the three lacosamide pivotal trials were grouped and pooled by focal seizure subtype at Baseline: simple partial seizures (SPS), complex partial seizures (CPS), and secondarily generalized partial seizures (SGPS). Both efficacy outcomes (median percent change from Baseline to Maintenance Phase in seizure frequency per 28 days and the proportion of patients experiencing at least a 50% reduction in seizures) were evaluated by lacosamide dose (200, 400, or 600 mg/day) compared to placebo for each seizure subtype. An additional analysis was performed to determine whether a shift from more severe focal seizure subtypes to less severe occurred upon treatment with lacosamide. In patients with CPS or SGPS at Baseline, lacosamide 400 mg/day (maximum recommended daily dose) and 600 mg/day reduced the frequency of CPS and SGPS compared to placebo. Likewise, a proportion of patients with CPS and SGPS at Baseline experienced at least a 50% reduction in the frequency of CPS and SGPS (≥50% responder rate) in the lacosamide 400 and 600 mg/day groups compared with placebo. For both outcomes, numerically greatest responses were observed in the lacosamide 600 mg/day group among patients with SGPS at Baseline. In patients with SPS at Baseline, no difference between placebo and lacosamide was observed for either efficacy outcome. An additional exploratory analysis suggests that in patients with SPS at Baseline, CPS and SGPS may have been shifted to less severe SPS upon treatment with lacosamide. The results of these exploratory analyses revealed reductions in CPS and SGPS frequency with adjunctive lacosamide. Reduction in CPS and SGPS may confound assessment of SPS since the CPS or SGPS may possibly change to SPS by effective treatment.
Khan, Abdul Waheed; Nasim, Zeeshan; Zahir, Fazli; Ali, Shahid; Ali, Abid; Iqbal, Aqib; Munir, Iqbal
Diagnostically untypeable subtypes contribute a considerable percent of hepatitis C virus (HCV) subtypes in Pakistan. In the present study, chronically infected HCV patients with known viremia were subjected to HCV genotyping. Among the total retrieved samples, 92.7% (64/69) were found typeable while 7.24% (5/69) were diagnostically untypeable. In conclusion, the presence of large number of untypeable HCV subtypes emphasizes the need of an updated type-specific genotyping assay and consideration of primers for proportionally rare subtypes to minimize the number of untypeable HCV subtypes.
Bustamante, Ana V.; Sanso, Andrea M.; Parma, Alberto E.; Lucchesi, Paula M. A.
Shiga toxin-producing Escherichia coli (STEC) causes serious human illness such as hemolytic uremic syndrome (HUS). Argentina has the world’s highest rate of this syndrome, which is the leading cause of acute renal failure among children. E. coli O157:H7 is the most common cause of HUS, but a substantial and growing proportion of this illness is caused by infection due to non-O157 strains. Multiple-locus variable-number tandem repeat analysis (MLVA) has become an established technique to subtype STEC. This review will address the use of routine STEC subtyping by MLVA in order to type this group of isolates and to get insight into the genetic diversity of native STEC. With regard to these objectives we modified and adapted two MLVA protocols, one exclusive for O157 and the other, a generic E. coli assay. A total of 202 STEC isolates, from different sources and corresponding to 20 serotypes, have been MLVA genotyped in our laboratory. In our experience, MLVA constitutes a very sensitive tool and enables us to perform an efficient STEC subtyping. The diversity found in many serotypes may be useful for future epidemiological studies of STEC clonality, applied to O157 as well as to non-O157 isolates. PMID:22919698
With 338 fifth-grade students as subjects, this study found the variations in the relation between school bullying and social preference as a function of gender and types of aggressive behavior utilized. Aggressive boys were likely to be rejected by peers, whereas aggressive girls were both rejected and accepted by peers. Children nominated…
Grumm, Mandy; Hein, Sascha; Fingerle, Michael
Aggressive behavior between children in schools is a topic that receives much interest as violence and aggressive behavior cause many maladaptive social outcomes in the school setting. In the current study the Implicit Association Test (IAT) was adapted as a measure of children's implicit aggression, by assessing the association of the self…
Coyne, Sarah M; Nelson, David A; Graham-Kevan, Nicola; Tew, Emily; Meng, K Nathan; Olsen, Joseph A
Various studies have found that viewing physical or relational aggression in the media can impact subsequent engagement in aggressive behavior. However, this has rarely been examined in the context of relationships. Accordingly, the aim of this study was to examine the connection between viewing various types of aggression in the media and perpetration of aggression against a romantic partner. A total of 369 young adults completed a variety of questionnaires asking for their perpetration of various forms of relationship aggression. Participants' exposure to both physical and relational aggression in the media was also assessed. As a whole, we found a relationship between viewing aggression in the media and perpetration of aggression; however, this depended on the sex of the participant and the type of aggression measured. Specifically, exposure to physical violence in the media was related to engagement in physical aggression against their partner only for men. However, exposure to relational aggression in the media was related to romantic relational aggression for both men and women.
Crick, Nicki R.; Ostrov, Jamie M.; Werner, Nicole E.
Although great strides have recently been made in our understanding of relational aggression and its consequences, one significant limitation has been the lack of prospective studies. The present research addressed this issue by identifying and assessing groups of relationally aggressive, physically aggressive, relationally plus physically…
Bowker, Julie C.; Ostrov, Jamie M.; Raja, Radhi
This study explored the associations between relational and overt aggression and social status, and tested whether the peer correlates of aggression vary as a function of best friends' aggression during early adolescence in urban India. One hundred and ninety-four young adolescents from primarily middle-to-upper-class families in Surat, India…
Adams, Ryan E.; Bukowski, William M.; Bagwell, Catherine
The effect of friendship reciprocation and friend aggression on the stability of aggression across a 6-month period following the transition to secondary school was studied in a sample of 298 Grade 6 children from a predominately white, middle-class, Midwestern American community. The stability of aggression was generally high but it varied as a…
Anderson, Craig A.; Morrow, Melissa
Extended and tested Deutsch's theory of competition effects. Predicted that people view competitive situations as inherently more aggressive than cooperative ones. Predicted that leading people to think of an aggressive situation in competitive terms would increase aggressive behavior. Increase of kill ratio occurred in absence of changes in…
During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics. PMID:27599892
Huband, Nick; Ferriter, Michael; Nathan, Rajan; Jones, Hannah
Background Aggression is a major public health issue and is integral to several mental health disorders. Antiepileptic drugs may reduce aggression by acting on the central nervous system to reduce neuronal hyper-excitability associated with aggression. Objectives To evaluate the efficacy of antiepileptic drugs in reducing aggression and associated impulsivity. Search methods We searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, metaRegister of Controlled Trials (mRCT) and ClinicalTrials.gov to April 2009. We also searched Cochrane Schizophrenia Group’s register of trials on aggression, National Research Record and handsearched for studies. Selection criteria Prospective, placebo-controlled trials of antiepileptic drugs taken regularly by individuals with recurrent aggression to reduce the frequency or intensity of aggressive outbursts. Data collection and analysis Three authors independently selected studies and two authors independently extracted data. We calculated standardised mean differences (SMDs), with odds ratios (ORs) for dichotomous data. Main results Fourteen studies with data from 672 participants met the inclusion criteria. Five different antiepileptic drugs were examined. Sodium valproate/divalproex was superior to placebo for outpatient men with recurrent impulsive aggression, for impulsively aggressive adults with cluster B personality disorders, and for youths with conduct disorder, but not for children and adolescents with pervasive developmental disorder. Carbamazepine was superior to placebo in reducing acts of self-directed aggression in women with borderline personality disorder, but not in children with conduct disorder. Oxcarbazepine was superior to placebo for verbal aggression and aggression against objects in adult outpatients. Phenytoin was superior to placebo on the frequency of aggressive acts in male prisoners and in outpatient men including those with personality disorder, but not on the frequency of ‘behavioral incidents’ in
Veroude, Kim; Zhang-James, Yanli; Fernàndez-Castillo, Noèlia; Bakker, Mireille J; Cormand, Bru; Faraone, Stephen V
The Research Domain Criteria (RDoC) address three types of aggression: frustrative non-reward, defensive aggression and offensive/proactive aggression. This review sought to present the evidence for genetic underpinnings of aggression and to determine to what degree prior studies have examined phenotypes that fit into the RDoC framework. Although the constructs of defensive and offensive aggression have been widely used in the animal genetics literature, the human literature is mostly agnostic with regard to all the RDoC constructs. We know from twin studies that about half the variance in behavior may be explained by genetic risk factors. This is true for both dimensional, trait-like, measures of aggression and categorical definitions of psychopathology. The non-shared environment seems to have a moderate influence with the effects of shared environment being unclear. Human molecular genetic studies of aggression are in an early stage. The most promising candidates are in the dopaminergic and serotonergic systems along with hormonal regulators. Genome-wide association studies have not yet achieved genome-wide significance, but current samples are too small to detect variants having the small effects one would expect for a complex disorder. The strongest molecular evidence for a genetic basis for aggression comes from animal models comparing aggressive and non-aggressive strains or documenting the effects of gene knockouts. Although we have learned much from these prior studies, future studies should improve the measurement of aggression by using a systematic method of measurement such as that proposed by the RDoC initiative.
Nam, Sanggeun; Park, Seho; Park, Hyung Seok; Kim, Sanghwa; Kim, Jee Ye; Kim, Seung Il
Abstract Currently, there is limited information on the clinical characteristics of breast cancer patients with insulin resistance. Hence, the purpose of this study was to investigate the association between insulin resistance and clinicopathological factors in newly diagnosed breast cancer patients without diabetes. We assessed 760 patients with breast cancer treated between 2012 and 2014. We compared the clinicopathological characteristics between patients with and without insulin resistance using univariate and multivariate analyses, including after stratification by menopausal status. Insulin resistance was defined according to the homeostatic model assessment of insulin resistance. Of 760 patients, 26.4% had insulin resistance. Age, menopausal status, body mass index, tumor size, histologic grade, Ki-67 expression, and breast cancer subtype significantly differed according to the presence of insulin resistance. Multivariate analysis revealed that postmenopausal status and obesity were significantly associated with insulin resistance. In postmenopausal women, older age, obesity, larger tumor size, advanced stage, and high proliferative luminal B subtype were significantly associated with insulin resistance. In contrast, in premenopausal patients, only obesity was related to insulin resistance. Multivariate analysis indicated that insulin resistance was independently correlated with obesity, larger tumor size, and the luminal B/human epidermal growth factor receptor-2-negative subtype in postmenopausal but not premenopausal patients. Insulin resistance was significantly associated with larger tumors and proliferative luminal B subtype breast cancer in postmenopausal women only. These findings suggest that insulin resistance could mechanistically induce tumor progression and might be a good prognostic factor, and that it could represent a therapeutic target in postmenopausal patients with breast cancer. PMID:26945364
Livasy, Chad A; Perou, Charles M; Karaca, Gamze; Cowan, David W; Maia, Diane; Jackson, Susan; Tse, Chiu-Kit; Nyante, Sarah; Millikan, Robert C
Microarray profiling of invasive breast carcinomas has identified subtypes including luminal A, luminal B, HER2-overexpressing, and basal-like. The poor-prognosis, basal-like tumors have been immunohistochemically characterized as estrogen receptor (ER)-negative, HER2/neu-negative, and cytokeratin 5/6-positive and/or epidermal growth factor receptor (EGFR)-positive. The aim of this study was to determine the prevalence of basal-like ductal carcinoma in situ in a population-based series of cases using immunohistochemical surrogates. A total of 245 pure ductal carcinoma in situ cases from a population-based, case-control study were evaluated for histologic characteristics and immunostained for ER, HER2/neu, EGFR, cytokeratin 5/6, p53, and Ki-67. The subtypes were defined as: luminal A (ER+, HER2-), luminal B (ER+, HER2+), HER2 positive (ER-, HER2+), and basal-like (ER-, HER2-, EGFR+, and/or cytokeratin 5/6+). The prevalence of breast cancer subtypes was basal-like (n = 19 [8%]); luminal A, n = 149 (61%); luminal B, n = 23 (9%); and HER2+/ER-, n = 38 (16%). Sixteen tumors (6%) were unclassified (negative for all 4 defining markers). The basal-like subtype was associated with unfavorable prognostic variables including high-grade nuclei (P < .0001), p53 overexpression (P < .0001), and elevated Ki-67 index (P < .0001). These studies demonstrate the presence of a basal-like in situ carcinoma, a potential precursor lesion to invasive basal-like carcinoma.
Nam, Sanggeun; Park, Seho; Park, Hyung Seok; Kim, Sanghwa; Kim, Jee Ye; Kim, Seung Il
Currently, there is limited information on the clinical characteristics of breast cancer patients with insulin resistance. Hence, the purpose of this study was to investigate the association between insulin resistance and clinicopathological factors in newly diagnosed breast cancer patients without diabetes. We assessed 760 patients with breast cancer treated between 2012 and 2014. We compared the clinicopathological characteristics between patients with and without insulin resistance using univariate and multivariate analyses, including after stratification by menopausal status. Insulin resistance was defined according to the homeostatic model assessment of insulin resistance. Of 760 patients, 26.4% had insulin resistance. Age, menopausal status, body mass index, tumor size, histologic grade, Ki-67 expression, and breast cancer subtype significantly differed according to the presence of insulin resistance. Multivariate analysis revealed that postmenopausal status and obesity were significantly associated with insulin resistance. In postmenopausal women, older age, obesity, larger tumor size, advanced stage, and high proliferative luminal B subtype were significantly associated with insulin resistance. In contrast, in premenopausal patients, only obesity was related to insulin resistance. Multivariate analysis indicated that insulin resistance was independently correlated with obesity, larger tumor size, and the luminal B/human epidermal growth factor receptor-2-negative subtype in postmenopausal but not premenopausal patients. Insulin resistance was significantly associated with larger tumors and proliferative luminal B subtype breast cancer in postmenopausal women only. These findings suggest that insulin resistance could mechanistically induce tumor progression and might be a good prognostic factor, and that it could represent a therapeutic target in postmenopausal patients with breast cancer.
Prewitt, Judith M. S.
The invention of the microscope disclosed a whole new world, that of the hitherto invisibly small. Histologic evidence as revealed by the microscope has become a cornerstone of medical diagnosis, and efforts are now being made to lay foundations so that the medical visual information processing burden can be alleviated significantly by cost-effective automation. This paper lays image processing foundations by presenting a graph-theoretic and syntactic model for the analysis of histologic patterns, and presents results to date.
Levrini, Gabriele; Pattacini, Pierpaolo
Desmoplastic fibroma (DF) is a benign, rare fibroblastic intraosseous neoplasm histologically resembling a desmoid soft tissue tumor. Although classified as benign, DF frequently exhibits an aggressive behavior, has a moderate-to-high recurrence rate, and often causes pathological fractures and extensive bone destruction. This case report presents an incidentally detected DF of the tibia, which was diagnosed using a minimally invasive approach. A 36-year-old African female patient was referred to the Department of Diagnostic Imaging of Arcispedale Santa Maria Nuova-IRCCS (Reggio Emilia, Italy), to be examined by a computed tomography scan on an outpatient basis, after an x-ray examination of the tibia, which was performed after an injury to exclude the presence of a fracture, revealed a hyperlucency of unknown origin. The aim of this study was to discuss the clinical, histological, immunohistochemical and radiographic characteristics of this rare neoplasm, with a focus on image-guided bone biopsy. PMID:27882239
de Boer, H H Hans; Van der Merwe, A E Lida
Paleopathology is the study of trauma and disease as may be observed in ancient (human) remains. In contrast to its central role in current medical practice, microscopy plays a rather modest role in paleopathology. This is at least partially due to the differences between fresh and decomposed (i.e., skeletonized or "dry bone") tissue samples. This review discusses these differences and describes how they affect the histological analysis of paleopathological specimens. First, we provide a summary of some general challenges related to the histological analysis of palaeopathological specimens. Second, the reader is introduced in bone tissue histology and bone tissue dynamics. The remainder of the paper is dedicated to the diagnostic value of dry bone histology. Its value and limitations are illustrated by comparing several well-studied paleopathological cases with similar contemporary, clinical cases. This review illustrates that due to post-mortem loss of soft tissue, a limited number of disorders display pathognomonic features during histological analysis of skeletonized human remains. In the remainder of cases, histology may help to narrow down the differential diagnosis or is diagnostically unspecific. A comprehensive, multidisciplinary diagnostic approach therefore remains essential. Clin. Anat. 29:831-843, 2016. © 2016 Wiley Periodicals, Inc.
Kool, Marcel; Koster, Jan; Bunt, Jens; Hasselt, Nancy E.; Lakeman, Arjan; van Sluis, Peter; Troost, Dirk; Meeteren, Netteke Schouten-van; Caron, Huib N.; Cloos, Jacqueline; Mršić, Alan; Ylstra, Bauke; Grajkowska, Wieslawa; Hartmann, Wolfgang; Pietsch, Torsten; Ellison, David; Clifford, Steven C.; Versteeg, Rogier
Background Medulloblastoma is the most common malignant brain tumor in children. Despite recent improvements in cure rates, prediction of disease outcome remains a major challenge and survivors suffer from serious therapy-related side-effects. Recent data showed that patients with WNT-activated tumors have a favorable prognosis, suggesting that these patients could be treated less intensively, thereby reducing the side-effects. This illustrates the potential benefits of a robust classification of medulloblastoma patients and a detailed knowledge of associated biological mechanisms. Methods and Findings To get a better insight into the molecular biology of medulloblastoma we established mRNA expression profiles of 62 medulloblastomas and analyzed 52 of them also by comparative genomic hybridization (CGH) arrays. Five molecular subtypes were identified, characterized by WNT signaling (A; 9 cases), SHH signaling (B; 15 cases), expression of neuronal differentiation genes (C and D; 16 and 11 cases, respectively) or photoreceptor genes (D and E; both 11 cases). Mutations in β-catenin were identified in all 9 type A tumors, but not in any other tumor. PTCH1 mutations were exclusively identified in type B tumors. CGH analysis identified several fully or partly subtype-specific chromosomal aberrations. Monosomy of chromosome 6 occurred only in type A tumors, loss of 9q mostly occurred in type B tumors, whereas chromosome 17 aberrations, most common in medulloblastoma, were strongly associated with type C or D tumors. Loss of the inactivated X-chromosome was highly specific for female cases of type C, D and E tumors. Gene expression levels faithfully reflected the chromosomal copy number changes. Clinicopathological features significantly different between the 5 subtypes included metastatic disease and age at diagnosis and histology. Metastatic disease at diagnosis was significantly associated with subtypes C and D and most strongly with subtype E. Patients below 3 yrs of
Krahé, Barbara; Möller, Ingrid; Huesmann, L Rowell; Kirwil, Lucyna; Felber, Juliane; Berger, Anja
This study examined the links between desensitization to violent media stimuli and habitual media violence exposure as a predictor and aggressive cognitions and behavior as outcome variables. Two weeks after completing measures of habitual media violence exposure, trait aggression, trait arousability, and normative beliefs about aggression, undergraduates (N = 303) saw a violent film clip and a sad or a funny comparison clip. Skin conductance level (SCL) was measured continuously, and ratings of anxious and pleasant arousal were obtained after each clip. Following the clips, participants completed a lexical decision task to measure accessibility of aggressive cognitions and a competitive reaction time task to measure aggressive behavior. Habitual media violence exposure correlated negatively with SCL during violent clips and positively with pleasant arousal, response times for aggressive words, and trait aggression, but it was unrelated to anxious arousal and aggressive responding during the reaction time task. In path analyses controlling for trait aggression, normative beliefs, and trait arousability, habitual media violence exposure predicted faster accessibility of aggressive cognitions, partly mediated by higher pleasant arousal. Unprovoked aggression during the reaction time task was predicted by lower anxious arousal. Neither habitual media violence usage nor anxious or pleasant arousal predicted provoked aggression during the laboratory task, and SCL was unrelated to aggressive cognitions and behavior. No relations were found between habitual media violence viewing and arousal in response to the sad and funny film clips, and arousal in response to the sad and funny clips did not predict aggressive cognitions or aggressive behavior on the laboratory task. This suggests that the observed desensitization effects are specific to violent content.
Krahé, Barbara; Möller, Ingrid; Huesmann, L. Rowell; Kirwil, Lucyna; Felber, Juliane; Berger, Anja
This study examined the links between desensitization to violent media stimuli and habitual media violence exposure as a predictor and aggressive cognitions and behavior as outcome variables. Two weeks after completing measures of habitual media violence exposure, trait aggression, trait arousability, and normative beliefs about aggression, undergraduates (N = 303) saw a violent film clip and a sad or a funny comparison clip. Skin conductance level (SCL) was measured continuously, and ratings of anxious and pleasant arousal were obtained after each clip. Following the clips, participants completed a lexical decision task to measure accessibility of aggressive cognitions and a competitive reaction time task to measure aggressive behavior. Habitual media violence exposure correlated negatively with SCL during violent clips and positively with pleasant arousal, response times for aggressive words, and trait aggression, but it was unrelated to anxious arousal and aggressive responding during the reaction time task. In path analyses controlling for trait aggression, normative beliefs, and trait arousability, habitual media violence exposure predicted faster accessibility of aggressive cognitions, partly mediated by higher pleasant arousal. Unprovoked aggression during the reaction time task was predicted by lower anxious arousal. Neither habitual media violence usage nor anxious or pleasant arousal predicted provoked aggression during the laboratory task, and SCL was unrelated to aggressive cognitions and behavior. No relations were found between habitual media violence viewing and arousal in response to the sad and funny film clips, and arousal in response to the sad and funny clips did not predict aggressive cognitions or aggressive behavior on the laboratory task. This suggests that the observed desensitization effects are specific to violent content. PMID:21186935
Brock, Barbara L.
Relational aggression among women presents an overlooked barrier to women's quest for advancement in the workplace. Although research on women's leadership extols their ability to collaborate and form lasting, supportive relationships, one cannot assume that all women are supportive of other women. Research reveals that relational aggression,…
Liu, Jianghong; Lewis, Gary; Evans, Lois
Aggressive behavior is the observable manifestation of aggression and is often associated with developmental transitions and a range of medical and psychiatric diagnoses across the lifespan. As healthcare professionals involved in the medical and psychosocial care of patients from birth through death, nurses frequently encounter—and may serve as—both victims and perpetrators of aggressive behavior in the workplace. While the nursing literature has continually reported research on prevention and treatment approaches, less emphasis has been given to understanding the etiology, including contextual precipitants of aggressive behavior. This paper provides a brief review of the biological, social, and environmental risk factors that purportedly give rise to aggressive behavior. Further, many researchers have focused specifically on aggressive behavior in adolescence and adulthood. Less attention has been given to understanding the etiology of such behavior in young children and older adults. This paper emphasizes the unique risk factors for aggressive behavior across the developmental spectrum, including childhood, adolescence, adulthood, and late life. Appreciation of the risk factors of aggressive behavior, and, in particular, how they relate to age-specific manifestations, can aid nurses in better design and implementation of prevention and treatment programs. PMID:22471771
Goldstein, Arnold P.; And Others
American society is violent, a fact which is well-reflected in schools. This book, designed specifically for school personnel, presents the primary techniques currently being employed by educators to prevent, manage, and replace student aggression. The volume opens with a description of the origins of aggressive behavior and offers some…
Savino, Jacqueline F.; Kostich, Melissa J.
The ruffe, Gymnocephalus cernuus, is a nonindigenous percid in the Great Lakes. Ruffe are aggressive benthivores and forage over soft substrates. Laboratory studies in pools (100 cm in diameter, 15 cm water depth) were conducted to determine whether fish density (low = 2, medium = 4, high = 6 ruffe per pool) changed foraging and aggressive behaviors with a limited food supply of chironomid larvae. All fish densities demonstrated a hierarchy based on aggressive interactions, but ruffe were most aggressive at low and high fish densities. Time spent in foraging was lowest at the low fish density. The best forager at the low fish density was the most aggressive individual, but the second most aggressive fish at the medium and high fish density was the best forager and also the one chased most frequently. A medium fish density offered the best energetic benefits to ruffe by providing the lowest ratio of time spent in aggression to that spent foraging. Based on our results, ruffe should grow best at an intermediate density. With high ruffe densities, we would also expect disparity in size as the more aggressive fish are able to garner a disproportionate amount of the resources. Alternatively, as the Great Lakes are a fairly open system, ruffe could migrate out of one area to colonize another as populations exceed optimal densities.
Highlights a longitudinal study on key factors in the metamorphosis of childhood aggression into adult crime in more than 400 males/females. Results (which began with study of 875 third graders in 1960) indicate that aggressive youngsters at age eight have much higher rates of criminal/violent behavior at age 30. (JN)
Martin, Jacqueline L.; Ross, Hildy S.
Thirty-nine families were observed extensively at home when children were 2 1/2 and 4 1/2 years of age and again 2 years later. The Social Relations Model is used to investigate children's sex differences in aggression and parents' prohibiting aggression during sibling conflict. In the first observation period, boys engaged in more severe and mild…
Haug, Lore I
Aggression toward unfamiliar dogs and people is a common problem arising most commonly from fear and territoriality. A number of factors contribute to its development, including socialization deficits, hormones, and genetic and neurophysiologic components. These factors are discussed in this article, as are management and behavior modification approaches for controlling aggression.
Holt, Wilma J.
This paper reviews three studies which illustrate the use of two different techniques of behavior modification to control aggression in preschool children in classroom situations. The first technique demonstrated the use of "time-out" as a mild punishment procedure. The teacher changed events following aggression by briefly removing the child from…
Watson, Malcolm W.; Fischer, Kurt W.; Andreas, Jasmina Burdzovic; Smith, Kevin W.
In this article, Malcolm Watson, Kurt Fischer, Jasmina Burdzovic Andreas, and Kevin Smith describe and compare two approaches to assessing risk factors that lead to aggression in children. The first, the severe risks approach, focuses on how risk factors form a pathway that leads to aggressive behavior. Within this approach, an inhibited…
Dahlen, Eric R.; Czar, Katherine A.; Prather, Emily; Dyess, Christy
For this study we explored relational aggression and victimization in a college sample (N = 307), examining potential gender and race differences, correlates, and the link between relational aggression and common emotional and behavioral problems, independent of relational victimization. Gender and race differences were observed on relational…
Jones, Marc V; Bray, Steven R; Olivier, Stephen
The present study examined the relationship between aggression and game location in rugby league. We videotaped a random sample of 21 professional rugby league games played in the 2000 Super League season. Trained observers recorded the frequency of aggressive behaviours. Consistent with previous research, which used territoriality theories as a basis for prediction, we hypothesized that the home team would behave more aggressively than the away team. The results showed no significant difference in the frequency of aggressive behaviours exhibited by the home and away teams. However, the away teams engaged in substantially more aggressive behaviours in games they lost compared with games they won. No significant differences in the pattern of aggressive behaviours for home and away teams emerged as a function of game time (i.e. first or second half) or game situation (i.e. when teams were winning, losing or drawing). The findings suggest that while home and away teams do not display different levels of aggression, the cost of behaving aggressively (in terms of game outcome) may be greater for the away team.
Wehby, Joseph H.
This review describes four major hypotheses related to aggressive behavior and reviews current means for assessment. Hypotheses suggest that aggressive behavior is the result of a social skills deficit, positive or negative reinforcement, environmental deficits, or deficits in the cognitive processing of social stimuli. Changes in assessment…
Wang, Chunjing; Funk, Cory C; Eddy, James A; Price, Nathan D
Astrocytoma is the most common glioma, accounting for half of all primary brain and spinal cord tumors. Late detection and the aggressive nature of high-grade astrocytomas contribute to high mortality rates. Though many studies identify candidate biomarkers using high-throughput transcriptomic profiling to stratify grades and subtypes, few have resulted in clinically actionable results. This shortcoming can be attributed, in part, to pronounced lab effects that reduce signature robustness and varied individual gene expression among patients with the same tumor. We addressed these issues by uniformly preprocessing publicly available transcriptomic data, comprising 306 tumor samples from three astrocytoma grades (Grade 2, 3, and 4) and 30 non-tumor samples (normal brain as control tissues). Utilizing Differential Rank Conservation (DIRAC), a network-based classification approach, we examined the global and individual patterns of network regulation across tumor grades. Additionally, we applied gene-based approaches to identify genes whose expression changed consistently with increasing tumor grade and evaluated their robustness across multiple studies using statistical sampling. Applying DIRAC, we observed a global trend of greater network dysregulation with increasing tumor aggressiveness. Individual networks displaying greater differences in regulation between adjacent grades play well-known roles in calcium/PKC, EGF, and transcription signaling. Interestingly, many of the 90 individual genes found to monotonically increase or decrease with astrocytoma grade are implicated in cancer-affected processes such as calcium signaling, mitochondrial metabolism, and apoptosis. The fact that specific genes monotonically increase or decrease with increasing astrocytoma grade may reflect shared oncogenic mechanisms among phenotypically similar tumors. This work presents statistically significant results that enable better characterization of different human astrocytoma grades
Kravtsov, M N; Manukovskiĭ, V A; Zharinov, G M; Kandyba, D V; Tsibirov, A A; Savello, A V; Svistov, D V
Today vertebral hemangioma is not completely understood entity, neither its pathogenesis nor optimal treatment is determined. Nowadays in majority of clinics in this country ineffective radiotherapy remains the first-line treatment. We analyzed results of treatment of 205 patients (286 lesions) with aggressive hemangiomas operated in Department of Neurosurgery of Military Medical Academy and Department of Nuclear Medicine of of Russian Scientific Center of Radiological and Surgical Technologies (Saint-Petersburg, Russia) since 1999 till 2009. Percutaneus vertebroplasty was performed in 167 lesions, radiotherapy was applied in 119 aggressive hemangiomas. Vertebroplasty is more effective for treatment of aggressive hemangiomas in comparison with radiotherapy. Signs of hemangiomas aggression, indications for surgery, and tactics of management were determined. Use of percutaneous vertebroplasty for treatment of aggressive hemangiomas resulted in fast recovery of the patients. This procedure is minimally invasive, it reduces hospital stay and duration of recovery.
Vida, Péter; Halász, József; Gádoros, Júlia
Aggressive/attacking and helpful/emphatic/prosocial behaviors are extremely important in human relationships. Both high levels of aggression and deficits of prosociality play important role in the development and conservation of mental disorders. We review the measurement options and clinical importance of aggressive and prosocial behavior. The typical developmental pathways and the genetic and environmental background of these behaviors are presented. The clinical tools used in the measurement of aggression and prosociality are summarized in the present paper, with specific attention on questionnaires applied in Hungarian practice. The connections between diagnostic categories (conduct disorder, oppositional-defiant disorder, attention deficit and hyperactive disorder, autism spectrum disorders) and the two behaviors are evaluated. In the end, we present those additional research projects that explore the cognitive-emotional background of aggressive or prosocial behavior with clinical relevance either in the diagnosis or in the treatment of child psychiatric diseases.
Falchi, Lorenzo; Keating, Michael J.; Marom, Edith M.; Truong, Mylene T.; Schlette, Ellen J.; Sargent, Rachel L.; Trinh, Long; Wang, Xuemei; Smith, Susan C.; Jain, Nitin; Estrov, Zeev; O’Brien, Susan; Wierda, William G.; Lerner, Susan
Richter syndrome (RS) is associated with poor outcome. The prognosis of patients with histologically aggressive chronic lymphocytic leukemia (CLL), or HAC, has not been studied. We aimed to correlate 2-deoxy-2-[18F]fluoroglucose/positron emission tomography (FDG/PET) data, histological diagnosis, clinical characteristics, and survival in patients with CLL. A total of 332 patients with CLL were histologically classified as: 95 RS, 117 HAC, and 120 histologically indolent CLL (HIC). HAC and RS patients had higher maximum standardized uptake value (SUVmax), more frequent constitutional symptoms, poorer performance status (PS), lower hemoglobin and platelets, and higher lactate dehydrogenase and β-2-microglobulin. An SUVmax ≥10 strongly correlated with mortality (overall survival [OS], 56.7 vs 6.9 months in patients with SUVmax <10 vs ≥10). Survival of patients with RS and HAC was similar among patients with SUVmax <10 or ≥10. SUVmax ≥10, PS ≥2, bulky disease, and age ≥65 were independently associated with shorter OS. In patients undergoing both fine-needle aspiration and biopsy, the former proved diagnostically inadequate in 23%, 29%, and 53% of HIC, HAC, and RS, respectively. FDG/PET is a useful diagnostic tool in patients with CLL and suspected transformation. Patients with HAC show different characteristics and worse prognosis compared with those with HIC. Patients with different CLL phases, but similar SUVmax have similar outcome. Tissue biopsy should be preferred for diagnosing RS. PMID:24615780
Falchi, Lorenzo; Keating, Michael J; Marom, Edith M; Truong, Mylene T; Schlette, Ellen J; Sargent, Rachel L; Trinh, Long; Wang, Xuemei; Smith, Susan C; Jain, Nitin; Estrov, Zeev; O'Brien, Susan; Wierda, William G; Lerner, Susan; Ferrajoli, Alessandra
Richter syndrome (RS) is associated with poor outcome. The prognosis of patients with histologically aggressive chronic lymphocytic leukemia (CLL), or HAC, has not been studied. We aimed to correlate 2-deoxy-2-[(18)F]fluoroglucose/positron emission tomography (FDG/PET) data, histological diagnosis, clinical characteristics, and survival in patients with CLL. A total of 332 patients with CLL were histologically classified as: 95 RS, 117 HAC, and 120 histologically indolent CLL (HIC). HAC and RS patients had higher maximum standardized uptake value (SUVmax), more frequent constitutional symptoms, poorer performance status (PS), lower hemoglobin and platelets, and higher lactate dehydrogenase and β-2-microglobulin. An SUVmax ≥10 strongly correlated with mortality (overall survival [OS], 56.7 vs 6.9 months in patients with SUVmax <10 vs ≥10). Survival of patients with RS and HAC was similar among patients with SUVmax <10 or ≥10. SUVmax ≥10, PS ≥2, bulky disease, and age ≥65 were independently associated with shorter OS. In patients undergoing both fine-needle aspiration and biopsy, the former proved diagnostically inadequate in 23%, 29%, and 53% of HIC, HAC, and RS, respectively. FDG/PET is a useful diagnostic tool in patients with CLL and suspected transformation. Patients with HAC show different characteristics and worse prognosis compared with those with HIC. Patients with different CLL phases, but similar SUVmax have similar outcome. Tissue biopsy should be preferred for diagnosing RS.
Sabattini, S; Bettini, G
Feline cutaneous mast cell tumors (MCTs) have been histologically classified as mastocytic (well differentiated or pleomorphic) and atypical/poorly granulated. Their biologic behavior ranges from benign to malignant, but prognostic factors are not well defined. Histologic classification, number of tumors, mitotic index, cytoplasmic granularity, and infiltration by eosinophils or lymphocytes were evaluated retrospectively in 25 feline cutaneous MCTs. Immunohistochemistry was applied to assess KIT (CD117) pattern and immunoreactivity score, telomerase expression (human telomerase reverse transcriptase), and proliferation index (MIB-1/Ki67 index). Case outcome was obtained via telephone interviews. The tumors comprised 15 mastocytic well-differentiated, 7 mastocytic pleomorphic, and 3 atypical/poorly granulated MCTs. Immunohistochemically, CD117 was expressed in 13 of 25 tumors (52%), and telomerase reverse transcriptase was expressed in 15 of 22 (68%), with no correlation to histologic classification. Mitotic index, KIT immunoreactivity score, and Ki67 index were significantly higher in mastocytic pleomorphic MCTs than in the other 2 categories. Five cats (20%) died of tumor-related causes. Multiplicity of lesions, pleomorphic phenotype, KIT immunoreactivity score, and mitotic and Ki67-indices correlated with an unfavorable outcome. Mitotic index was the strongest predictive variable. These results suggest that histologic classification, CD117/KIT immunohistochemistry, and proliferation indices may help to identify potentially aggressive cases of feline cutaneous MCT. Aberrant KIT protein localization and telomerase immunoreactivity warrant further exploration as potential prognostic markers.
Michaut, Magali; Chin, Suet-Feung; Majewski, Ian; Severson, Tesa M.; Bismeijer, Tycho; de Koning, Leanne; Peeters, Justine K.; Schouten, Philip C.; Rueda, Oscar M.; Bosma, Astrid J.; Tarrant, Finbarr; Fan, Yue; He, Beilei; Xue, Zheng; Mittempergher, Lorenza; Kluin, Roelof J.C.; Heijmans, Jeroen; Snel, Mireille; Pereira, Bernard; Schlicker, Andreas; Provenzano, Elena; Ali, Hamid Raza; Gaber, Alexander; O’Hurley, Gillian; Lehn, Sophie; Muris, Jettie J.F.; Wesseling, Jelle; Kay, Elaine; Sammut, Stephen John; Bardwell, Helen A.; Barbet, Aurélie S.; Bard, Floriane; Lecerf, Caroline; O’Connor, Darran P.; Vis, Daniël J.; Benes, Cyril H.; McDermott, Ultan; Garnett, Mathew J.; Simon, Iris M.; Jirström, Karin; Dubois, Thierry; Linn, Sabine C.; Gallagher, William M.; Wessels, Lodewyk F.A.; Caldas, Carlos; Bernards, Rene
Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies. PMID:26729235
Li, Jian-Bin; Nie, Yan-Gang; Boardley, Ian D; Dou, Kai; Situ, Qiao-Min
I(3) theory assumes that aggressive behavior is dependent on three orthogonal processes (i.e., Instigator, Impellance, and Inhibition). Previous studies showed that Impellance (trait aggressiveness, retaliation tendencies) better predicted aggression when Instigator was strong and Inhibition was weak. In the current study, we predicted that another Impellance (i.e., normative beliefs about aggression) might predict aggression when Instigator was absent and Inhibition was high (i.e., the perfect calm proposition). In two experiments, participants first completed the normative beliefs about aggression questionnaire. Two weeks later, participants' self-control resources were manipulated either using the Stroop task (study 1, N = 148) or through an "e-crossing" task (study 2, N = 180). Afterwards, with or without being provoked, participants played a game with an ostensible partner where they had a chance to aggress against them. Study 1 found that normative beliefs about aggression negatively and significantly predicted aggressive behavior only when provocation was absent and self-control resources were not depleted. In Study 2, normative beliefs about aggression negatively predicted aggressive behavior at marginal significance level only in the "no-provocation and no-depletion" condition. In conclusion, the current study provides partial support for the perfect calm proposition and I(3) theory.
Preliminary results from clinical trials in a subtype of lymphoma show that for a number of patients whose disease was not cured by other treatments, the drug ibrutinib can provide significant anti-cancer responses with modest side effects.
Strang, Emily; Peterson, Zoë D
Researching the correlates of men's sexually aggressive behavior (i.e., verbal coercion and rape) is critical to both understanding and preventing sexual aggression. This study examined 120 men who completed an anonymous online questionnaire. The study aimed to determine the relative importance of two potential correlates of men's self-reported use of sexual aggression: (a) perceptions that male peers use and support sexual aggression and (b) perceptions of punishment likelihood associated with sexual aggression. Results revealed that perceptions of male friends' acceptance of sexual aggression were strongly associated with individual men's reports of using verbal coercion and rape. Perceptions of punishment likelihood were negatively correlated with verbal coercion but not with rape through intoxication and force. Implications for sexual aggression prevention are discussed.
Thomas, Duane E.; Bierman, Karen L.; Powers, CJ
Research suggests that early classroom experiences influence the socialization of aggression. Tracking changes in the aggressive behavior of 4179 children from kindergarten to second-grade (ages 5–8) this study examined the impact of two important features of the classroom context–aggregate peer aggression and climates characterized by supportive teacher-student interactions. The aggregate aggression scores of children assigned to first-grade classrooms predicted the level of classroom aggression (assessed by teacher ratings) and quality of classroom climate (assessed by observers) that emerged by the end of grade 1. HLM analyses revealed that first-grade classroom aggression and quality of classroom climate made independent contributions to changes in student aggression, as students moved from kindergarten to second grade. Implications for policy and practice are discussed. PMID:21434887
Thomas, Duane E; Bierman, Karen L; Powers, C J
Research suggests that early classroom experiences influence the socialization of aggression. Tracking changes in the aggressive behavior of 4,179 children from kindergarten to second-grade (ages 5-8), this study examined the impact of 2 important features of the classroom context--aggregate peer aggression and climates characterized by supportive teacher-student interactions. The aggregate aggression scores of children assigned to first-grade classrooms predicted the level of classroom aggression (assessed by teacher ratings) and quality of classroom climate (assessed by observers) that emerged by the end of Grade 1. Hierarchical linear model analyses revealed that first-grade classroom aggression and quality of classroom climate made independent contributions to changes in student aggression, as students moved from kindergarten to second grade. Implications for policy and practice are discussed.
Chang, Chu-Hsiang Daisy; Lyons, Brent J
Types of perpetrators of workplace aggression can vary considerably, and recent research has demonstrated that aggression from different perpetrator categories has different implications for victims. We extended research on multifoci aggression and explored affective and cognitive pathways linking verbal aggression from four perpetrator types--supervisors, coworkers, customers, and significant others--and employee morale and turnover intention. Data from a sample of 446 working adults indicated that both emotional strain and employees' corresponding judgments of their social exchange relationships with these perpetrators served as the mechanisms for the association between aggression from supervisors, coworkers, and customers and morale and turnover intention. Coworker aggression had a direct association with turnover intention and significant other aggression was related to turnover intention only through emotional strain. The theoretical and practical implications of these findings are discussed.
Renwick, Laoise; Stewart, Duncan; Richardson, Michelle; Lavelle, Mary; James, Karen; Hardy, Claire; Price, Owen; Bowers, Len
Aggression and violence are widespread in UK Mental Health Trusts, and are accompanied by negative psychological and physiological consequences for both staff and other patients. Patients who are younger, male, and have a history of substance use and psychosis diagnoses are more likely to display aggression; however, patient factors are not solely responsible for violence, and there are complex circumstances that lead to aggression. Indeed, patient-staff interactions lead to a sizeable portion of aggression and violence on inpatient units, thus they cannot be viewed without considering other forms of conflict and containment that occur before, during, and after the aggressive incident. For this reason, we examined sequences of aggressive incidents in conjunction with other conflict and containment methods used to explore whether there were particular profiles to aggressive incidents. In the present study, 522 adult psychiatric inpatients from 84 acute wards were recruited, and there were 1422 incidents of aggression (verbal, physical against objects, and physical). Cluster analysis revealed that aggressive incident sequences could be classified into four separate groups: solo aggression, aggression-rule breaking, aggression-medication, and aggression-containment. Contrary to our expectations, we did not find physical aggression dominant in the aggression-containment cluster, and while verbal aggression occurred primarily in solo aggression, physical aggression also occurred here. This indicates that the management of aggression is variable, and although some patient factors are linked with different clusters, these do not entirely explain the variation.
Brugman, Suzanne; Lobbestael, Jill; Arntz, Arnoud; Cima, Maaike; Schuhmann, Teresa; Dambacher, Franziska; Sack, Alexander T
The aim of this study was to identify implicit cognitive predictors of aggressive behavior. Specifically, the predictive value of an attentional bias for aggressive stimuli and automatic association of the self and aggression was examined for reactive and proactive aggressive behavior in a non-clinical sample (N = 90). An Emotional Stroop Task was used to measure an attentional bias. With an idiographic Single-Target Implicit Association Test, automatic associations were assessed between words referring to the self (e.g., the participants' name) and words referring to aggression (e.g., fighting). The Taylor Aggression Paradigm (TAP) was used to measure reactive and proactive aggressive behavior. Furthermore, self-reported aggressiveness was assessed with the Reactive Proactive Aggression Questionnaire (RPQ). Results showed that heightened attentional interference for aggressive words significantly predicted more reactive aggression, while lower attentional bias towards aggressive words predicted higher levels of proactive aggression. A stronger self-aggression association resulted in more proactive aggression, but not reactive aggression. Self-reports on aggression did not additionally predict behavioral aggression. This implies that the cognitive tests employed in our study have the potential to discriminate between reactive and proactive aggression. Aggr. Behav. 9999:XX-XX, 2014. © 2014 Wiley Periodicals, Inc.
Brugman, Suzanne; Lobbestael, Jill; Arntz, Arnoud; Cima, Maaike; Schuhmann, Teresa; Dambacher, Franziska; Sack, Alexander T
The aim of this study was to identify implicit cognitive predictors of aggressive behavior. Specifically, the predictive value of an attentional bias for aggressive stimuli and automatic association of the self and aggression was examined for reactive and proactive aggressive behavior in a non-clinical sample (N = 90). An Emotional Stroop Task was used to measure an attentional bias. With an idiographic Single-Target Implicit Association Test, automatic associations were assessed between words referring to the self (e.g., the participants' name) and words referring to aggression (e.g., fighting). The Taylor Aggression Paradigm (TAP) was used to measure reactive and proactive aggressive behavior. Furthermore, self-reported aggressiveness was assessed with the Reactive Proactive Aggression Questionnaire (RPQ). Results showed that heightened attentional interference for aggressive words significantly predicted more reactive aggression, while lower attentional bias towards aggressive words predicted higher levels of proactive aggression. A stronger self-aggression association resulted in more proactive aggression, but not reactive aggression. Self-reports on aggression did not additionally predict behavioral aggression. This implies that the cognitive tests employed in our study have the potential to discriminate between reactive and proactive aggression. Aggr. Behav. 41:51-64 2015. © 2014 Wiley Periodicals, Inc.
LeBeau, Aaron M; Duriseti, Sai; Murphy, Stephanie T; Pepin, Francois; Hann, Byron; Gray, Joe W; VanBrocklin, Henry F; Craik, Charles S
Components of the plasminogen activation system, which are overexpressed in aggressive breast cancer subtypes, offer appealing targets for development of new diagnostics and therapeutics. By comparing gene expression data in patient populations and cultured cell lines, we identified elevated levels of the urokinase plasminogen activation receptor (uPAR, PLAUR) in highly aggressive breast cancer subtypes and cell lines. Recombinant human anti-uPAR antagonistic antibodies exhibited potent binding in vitro to the surface of cancer cells expressing uPAR. In vivo these antibodies detected uPAR expression in triple negative breast cancer (TNBC) tumor xenografts using near infrared imaging and (111)In single-photon emission computed tomography. Antibody-based uPAR imaging probes accurately detected small disseminated lesions in a tumor metastasis model, complementing the current clinical imaging standard (18)F-fluorodeoxyglucose at detecting non-glucose-avid metastatic lesions. A monotherapy study using the antagonistic antibodies resulted in a significant decrease in tumor growth in a TNBC xenograft model. In addition, a radioimmunotherapy study, using the anti-uPAR antibodies conjugated to the therapeutic radioisotope (177)Lu, found that they were effective at reducing tumor burden in vivo. Taken together, our results offer a preclinical proof of concept for uPAR targeting as a strategy for breast cancer diagnosis and therapy using this novel human antibody technology.
Yan, E G; Paris, J J; Ahluwalia, J; Lane, A T; Bruckner, A L
The Herlitz subtype of junctional epidermolysis bullosa (JEB-H) is a lethal genetic disorder characterized by recurrent and persistent erosions of the epithelial surfaces that heal with exuberant granulation tissue. In addition, respiratory distress, refractory anemia and failure to thrive are often seen. Mortality in the first year of life approaches 90%. JEB-H is caused by mutations in the genes that encode the protein laminin 5, a structural molecule involved in the adhesion of epidermis to dermis. There is currently no cure for JEB-H. Medical interventions treat complications but do not ultimately limit mortality. Ethical principles contend that offering comfort and company to the patient and family, not aggressive therapies, should comprise the mainstay of care for affected infants.
Wang, Zhe; Li, Wen-jie
Purpose To study the epidemic characteristics, transmission sources and routes of various subtypes of human immunodeficiency virus type 1 (HIV-1) and sequence variations in Henan, central China. To provide theoretical foundation for Acquired Immune Deficiency Syndrome (AIDS) prevention strategy in this region where the primary HIV transmission route was through former paid blood donation. Materials and Methods HIV-1 gene env and gag were amplified by nested polymerase chain reaction (PCR) from uncultured peripheral blood mononuclear cells (PBMCs) obtained from 1,287 HIV-1 confirmed samples in Henan. Results Among 1,287 samples, 5 HIV-1 strains were found including subtypes B' (95.9%), C (0.47%) and recombinant subtypes CRF 07_BC (1.09%), CRF 08_BC (1.79%) and CRF 01_AE (0.78%). Phylogenetic tree analysis found that 1,234 Henan subtype B' were closely related to those commonly found in Thailand, and were distantly related to other international subtypes. The dominant strain in former blood plasma donors (FPDs) was subtype B', and the dominant strains in sexual transmission were subtype B' and BC. Among HIV patients who were most likely infected through routes other than paid blood donation, the percentage of non-B' subtypes was much higher than those of FPD. Conclusion These findings suggest that the prevailing strain of HIV-1 in Henan is subtype B', similar to the B' subtype found in Thailand. In addition, for the first time we found subtypes C and recombinant subtypes CRF07_BC, CRF08_BC and CRF01_AE in this region. Indicating that the subtype feature of HIV-1 became more complicated than before in central China. PMID:19881967
Knox, Michele; Carey, Michael; Kim, Wun Jung
Examined differences in aggressive behavior among predominantly white adolescent inpatients with and without depression. Survey data indicated that depression and gender interacted significantly. Depressed females demonstrated more physical aggression than nondepressed females, and depressed males demonstrated less aggression than nondepressed…
Ghaziuddin, M; Quinlan, P; Ghaziuddin, N
Catatonia is a life-threatening disorder characterized by motor abnormalities, mutism, and disturbances of behaviour, which is increasingly being diagnosed in persons with autism. In this report, we describe the presentation and course of catatonia in an adolescent with autism who responded to electroconvulsive therapy (ECT). The illness started with depressive symptoms, but the predominant feature was one of extreme obsessive slowing and immobility. We propose that catatonia should be ruled out as a cause of regression sometimes seen in adolescents with autism, and that catatonia of autism may index a distinct subtype with a particularly poor outcome.
Gu, Xiaoyan; He, Yihua; Li, Zhian; Han, Jiancheng; Chen, Jian; Nixon, J V Ian
This retrospective study attempted to establish the prevalence of multiple-valve involvement in Marfan syndrome and to compare echocardiographic with histopathologic findings in Marfan patients undergoing valvular or aortic surgery. We reviewed echocardiograms of 73 Marfan patients who underwent cardiovascular surgery from January 2004 through October 2009. Tissue histology was available for comparison in 29 patients. Among the 73 patients, 66 underwent aortic valve replacement or the Bentall procedure. Histologic findings were available in 29 patients, all of whom had myxomatous degeneration. Of 63 patients with moderate or severe aortic regurgitation as determined by echocardiography, 4 had thickened aortic valves. The echocardiographic findings in 18 patients with mitral involvement included mitral prolapse in 15. Of 11 patients with moderate or severe mitral regurgitation as determined by echocardiography, 4 underwent mitral valve repair and 7 mitral valve replacement. Histologic findings among mitral valve replacement patients showed thickened valve tissue and myxomatous degeneration. Tricuspid involvement was seen echocardiographically in 8 patients, all of whom had tricuspid prolapse. Two patients had severe tricuspid regurgitation, and both underwent repair. Both mitral and tricuspid involvement were seen echocardiographically in 7 patients. Among the 73 patients undergoing cardiac surgery for Marfan syndrome, 66 had moderate or severe aortic regurgitation, although their valves manifested few histologic changes. Eighteen patients had mitral involvement (moderate or severe mitral regurgitation, prolapse, or both), and 8 had tricuspid involvement. Mitral valves were most frequently found to have histologic changes, but the tricuspid valve was invariably involved.
Rosell, Daniel R; Siever, Larry J
Aggression and violence represent a significant public health concern and a clinical challenge for the mental healthcare provider. A great deal has been revealed regarding the neurobiology of violence and aggression, and an integration of this body of knowledge will ultimately serve to advance clinical diagnostics and therapeutic interventions. We will review here the latest findings regarding the neurobiology of aggression and violence. First, we will introduce the construct of aggression, with a focus on issues related to its heterogeneity, as well as the importance of refining the aggression phenotype in order to reduce pathophysiologic variability. Next we will examine the neuroanatomy of aggression and violence, focusing on regional volumes, functional studies, and interregional connectivity. Significant emphasis will be on the amygdala, as well as amygdala-frontal circuitry. Then we will turn our attention to the neurochemistry and molecular genetics of aggression and violence, examining the extensive findings on the serotonergic system, as well as the growing literature on the dopaminergic and vasopressinergic systems. We will also address the contribution of steroid hormones, namely, cortisol and testosterone. Finally, we will summarize these findings with a focus on reconciling inconsistencies and potential clinical implications; and, then we will suggest areas of focus for future directions in the field.
Petruccelli, Filippo; Diotaiuti, Pierluigi; Verrastro, Valeria; Petruccelli, Irene; Federico, Roberta; Martinotti, Giovanni; Fossati, Andrea; Di Giannantonio, Massimo; Janiri, Luigi
Introduction. Emotionally dependent subjects may engage in controlling, restrictive, and aggressive behaviours, which limit their partner's autonomy. The underlying causes of such behaviours are not solely based on levels of aggression, but act as a mean of maintaining the subject's own sense of self-worth, identity, and general functioning. Objective. The aim of the paper is to explore the correlation between affective dependency and reactive/proactive aggression and to evaluate individual differences as predisposing factors for aggressive behaviour and emotional dependency. Methods. The Spouse-Specific Dependency Scale (SSDS) and the Reactive Proactive Questionnaire (RPQ) were administered to a sample of 3375 subjects. Results. In the whole sample, a positive correlation between emotional dependency and proactive aggression was identified. Differences with regard to sex, age group, and geographical distribution were evidenced for the scores of the different scales. Conclusion. A fundamental distinction between reactive and proactive aggression was observed, anchoring proactive aggression more strictly to emotional dependency. Sociocultural and demographical variables, together with the previous structuring of attachment styles, help to determine the scope, frequency, and intensity of the demands made to the partner, as well as to feed the fears of loss, abandonment, or betrayal. PMID:25054147
Cornaggia, Cesare Maria; Beghi, Massimiliano; Pavone, Fabrizio; Barale, Francesco
Although fairly frequent in psychiatric in-patient, episodes of aggression/violence are mainly limited to verbal aggression, but the level of general health is significantly lower in nurses who report 'frequent' exposure to violent incidents, and there is disagreement between patients and staff concerning predictors of these episodes. We searched the Pubmed, Embase and PsychInfo databases for English, Italian, French or German language papers published between 1 January 1990 and 31 March 2010 using the key words "aggress*" (aggression or aggressive) "violen*" (violence or violent) and "in-patient" or "psychiatric wards", and the inclusion criterion of an adult population (excluding all studies of selected samples such as a specific psychiatric diagnosis other than psychosis, adolescents or the elderly, men/women only, personality disorders and mental retardation). The variables that were most frequently associated with aggression or violence in the 66 identified studies of unselected psychiatric populations were the existence of previous episodes, the presence of impulsiveness/hostility, a longer period of hospitalisation, non-voluntary admission, and aggressor and victim of the same gender; weaker evidence indicated alcohol/drug misuse, a diagnosis of psychosis, a younger age and the risk of suicide. Alcohol/drug misuse, hostility, paranoid thoughts and acute psychosis were the factors most frequently involved in 12 studies of psychotic patients. Harmony among staff (a good working climate) seems to be more useful in preventing aggression than some of the other strategies used in psychiatric wards, such as the presence of male nurses.
Petrash, A.; Bylund, D.
The authors have defined alpha-2 adrenergic receptor subtypes in human and rat tissues using prazosin as a subtype selective drug. Prazosin has a lower affinity (250 nM) at alpha-2A receptor and a higher affinity (5 nM) at alpha-2B receptors. In order to determine if other adrenergic drugs are selective for one or the other subtypes, the authors performed (/sup 3/H)yohimbine inhibition experiments with various adrenergic drugs in tissues containing alpha-2A, alpha-2B or both subtypes. Oxymetazoline, WB4101 and yohimbine were found to be 80-, 20- and 10-fold more potent at alpha-2A receptors than at alpha-2B receptors. Phentolamine, adazoxan, (+)- and (-)-mianserin, clonidine, (+)-butaclamol, (-)- and (+)-norepinephrine, epinephrine, dopamine and thioridazine were found to have equal affinities for the two subtypes. These results further validate the subdivision of alpha-2 adrenergic receptors into alpha-2A and alpha-2B subtypes.
JACKSON, ROBERT R.; CROSS, FIONA R.
We use the term ‘aggressive mimic’ for predators that communicate with their prey by making signals to indirectly manipulate prey behaviour. For understanding why the aggressive mimic’s signals work, it is important to appreciate that these signals interface with the prey’s perceptual system, and that the aggressive mimic can be envisaged as playing mind games with its prey. Examples of aggressive mimicry vary from instances in which specifying a model is straight forward to instances where a concise characterisation of the model is difficult. However, the less straightforward examples of aggressive mimicry may be the more interesting examples in the context of animal cognition. In particular, there are spiders that prey on other spiders by entering their prey’s web and making signals. Web invasion brings about especially intimate contact with their prey’s perceptual system because the prey spider’s web is an important component of the prey spider’s sensory apparatus. For the web-invading spider, often there is also a large element of risk when practising aggressive mimicry because the intended prey is also a potential predator. This element of risk, combined with exceptionally intimate interfacing with prey perceptual systems, may have favoured the web-invading aggressive mimic’s strategy becoming strikingly cognitive in character. Yet a high level of flexibility may be widespread among aggressive mimics in general and, on the whole, we propose that research on aggressive mimicry holds exceptional potential for advancing our understanding of animal cognition. PMID:23976823
Batrinos, Menelaos L
Atavistic residues of aggressive behavior prevailing in animal life, determined by testosterone, remain attenuated in man and suppressed through familial and social inhibitions. However, it still manifests itself in various intensities and forms from; thoughts, anger, verbal aggressiveness, competition, dominance behavior, to physical violence. Testosterone plays a significant role in the arousal of these behavioral manifestations in the brain centers involved in aggression and on the development of the muscular system that enables their realization. There is evidence that testosterone levels are higher in individuals with aggressive behavior, such as prisoners who have committed violent crimes. Several field studies have also shown that testosterone levels increase during the aggressive phases of sports games. In more sensitive laboratory paradigms, it has been observed that participant's testosterone rises in the winners of; competitions, dominance trials or in confrontations with factitious opponents. Aggressive behavior arises in the brain through interplay between subcortical structures in the amygdala and the hypothalamus in which emotions are born and the prefrontal cognitive centers where emotions are perceived and controlled. The action of testosterone on the brain begins in the embryonic stage. Earlier in development at the DNA level, the number of CAG repeats in the androgen receptor gene seems to play a role in the expression of aggressive behavior. Neuroimaging techniques in adult males have shown that testosterone activates the amygdala enhancing its emotional activity and its resistance to prefrontal restraining control. This effect is opposed by the action of cortisol which facilitates prefrontal area cognitive control on impulsive tendencies aroused in the subcortical structures. The degree of impulsivity is regulated by serotonin inhibiting receptors, and with the intervention of this neurotransmitter the major agents of the neuroendocrine
Licaj, Idlir; Jacobsen, Bjarne Koster; Selmer, Randi Marie; Maskarinec, Gertraud; Weiderpass, Elisabete; Gram, Inger Torhild
Background: We prospectively investigated the association between different measures of smoking exposure and the risk of serous, mucinous, and endometrioid ovarian cancers (OC) in a cohort of more than 300 000 Norwegian women. Methods: We followed 300 398 women aged 19–67 years at enrolment until 31 December 2013 for OC incidence through linkage to national registries. We used Cox proportional hazards models with attained age as the underlying time scale to estimate multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for relevant confounders. Results: During more than 5.9 million person-years and a median follow-up time of 19 years, 2336 primary invasive (1647, 71%) and borderline (689, 29%) OC were identified (53% serous, 19% mucinous). Compared with never smokers, current smokers who had smoked for ⩾10 years had a higher risk of mucinous OC (HR10–19 years vs never=1.73, 95% CI 1.24–2.42; HR⩾20 vs never=2.26, 95% CI 1.77–2.89, Ptrend <0.001). When stratified by invasiveness, current smokers had a higher risk of invasive mucinous OC (HR=1.78, 95% CI 1.20–2.64) and borderline mucinous OC (HR=2.26 95% CI, 1.71–2.97) (Pheterogeneity=0.34) than never smokers. Smoking was not associated with serous or endometrioid OC. Conclusions: Using a very large cohort of women, the current analysis provides an important replication for a similar risk of invasive and borderline mucinous OC related to smoking. PMID:27959888
Velazquez, Elsa F; Chaux, Alcides; Cubilla, Antonio L
Penile squamous cell carcinomas (SCCs) and their corresponding precancerous lesions can be classified in 2 major groups: human papillomavirus (HPV) related and HPV unrelated. In the former (warty and basaloid SCC), there is a predominance of undifferentiated basaloid cells. In the latter (eg, usual, papillary, and verrucous SCC), the predominant cell is larger with abundant eosinophilic cytoplasm. Based on these morphologic features, a new term, "penile intraepithelial neoplasia" (PeIN), was proposed. PeIN was further subclassified into differentiated and undifferentiated, with the latter being subdivided into basaloid, warty, and warty-basaloid subtypes. Macroscopically, PeIN subtypes are indistinguishable. Microscopically, differentiated PeIN is characterized by acanthosis, parakeratosis, enlarged keratinocytes with abundant "pink" cytoplasm (abnormal maturation), and hyperchromatic cells in the basal layer. In basaloid PeIN the epithelium is replaced by a monotonous population of uniform, small, round, and basophilic cells. Warty PeIN is characterized by a spiky surface, prominent atypical parakeratosis, and pleomorphic koilocytosis. Warty-basaloid PeIN show features of both warty and basaloid PeIN. There is a significant association of subtypes of PeIN with specific variants of invasive SCCs. This is a simple and reproducible nomenclature for penile precancerous lesions based on cell type and differentiation. It takes into account the similarities between vulvar and penile pathology and the hypothesis of a bimodal pathway of penile cancer progression.
Fisher, Caroline A; Sewell, Katherine; Brown, Anahita; Churchyard, Andrew
Aggression is commonly reported in individuals with Huntington's disease (HD). While correlating factors for aggression are often speculated about, features that are associated with, and contribute to, aggression in this population have not been clearly determined. This systematic review investigates rates of aggression and treatment options for aggression in HD. A number of key findings were revealed. Studies reporting on rates of aggression revealed that its prevalence is high, falling between 22 and 66 percent in the majority of studies. Aggression may be more common in males with HD, and is also found in higher rates in individuals who experience frequent falls, have obsessive-compulsive symptoms and suicidal ideation. There is little research investigating antecedents for aggression in HD. A wide variety of psychotropic medications have been reported in the literature to treat individuals with HD and aggressive behaviour. However, due to methodological limitations, no treatment recommendations can be made, based on the current literature. Two non-medication therapies have been investigated, behaviour support and sensory modulation intervention. However, again, due to methodological limitations with these studies, further research is needed before they can be recommended as frontline interventions. This review highlights the need for further methodologically rigorous studies investigating the treatment of aggression in HD.
Miller, Cameron A; Parrott, Dominic J; Giancola, Peter R
This study investigated the mediating effect of trait aggressivity on the relation between agreeableness and alcohol-related aggression in a laboratory setting. Participants were 116 healthy male social drinkers between 21 and 30 years of age. Agreeableness and trait aggressivity were measured using the Big Five Inventory and the Buss-Perry Aggression Questionnaire, respectively. Following the consumption of an alcohol or no-alcohol control beverage, participants completed a modified version of the Taylor Aggression Paradigm, in which electric shocks were received from and administered to a fictitious opponent during a competitive task. Aggression was operationalized as the proportion of the most extreme shocks delivered to the fictitious opponent under conditions of low and high provocation. Results indicated that lower levels of agreeableness were associated with higher levels of trait aggressivity. In turn, higher levels of trait aggressivity predicted extreme aggression in intoxicated, but not sober, participants under low, but not high, provocation. Findings highlight the importance of examining determinants of intoxicated aggression within a broader theoretical framework of personality.
Caicedo, Juan C; Vanegas, Jorge A; Páez, Fabian; González, Fabio A
This work proposes a histology image indexing strategy based on multimodal representations obtained from the combination of visual features and associated semantic annotations. Both data modalities are complementary information sources for an image retrieval system, since visual features lack explicit semantic information and semantic terms do not usually describe the visual appearance of images. The paper proposes a novel strategy to build a fused image representation using matrix factorization algorithms and data reconstruction principles to generate a set of multimodal features. The methodology can seamlessly recover the multimodal representation of images without semantic annotations, allowing us to index new images using visual features only, and also accepting single example images as queries. Experimental evaluations on three different histology image data sets show that our strategy is a simple, yet effective approach to building multimodal representations for histology image search, and outperforms the response of the popular late fusion approach to combine information.
Ress, Anna Lena; Aigelsreiter, Ariane; Schauer, Silvia; Wagner, Karin; Langsenlehner, Tanja; Resel, Margit; Gerger, Armin; Ling, Hui; Ivan, Cristina; Calin, George Adrian; Hoefler, Gerald; Rinner, Beate; Pichler, Martin
Spinophilin, a putative tumor suppressor gene, has been shown to be involved in the pathogenesis of certain types of cancer, but its role has never been systematically explored in breast cancer. In this study, we determined for the first time the expression pattern of spinophilin in human breast cancer molecular subtypes (n = 489) and correlated it with survival (n = 921). We stably reduced spinophilin expression in breast cancer cells and measured effects on cellular growth, apoptosis, anchorage-independent growth, migration, invasion and self-renewal capacity in vitro and metastases formation in vivo. Microarray profiling was used to determine the most abundantly expressed genes in spinophilin-silenced breast cancer cells. Spinophilin expression was significantly lower in basal-like breast cancer (p<0.001) and an independent poor prognostic factor in breast cancer patients (hazard ratio = 1.93, 95% confidence interval: 1.24-3.03; p = 0.004) A reduction of spinophilin levels increased cellular growth in breast cancer cells (p<0.05), without influencing activation of apoptosis. Anchorage-independent growth, migration and self-renewal capacity in vitro and metastatic potential in vivo were also significantly increased in spinophilin-silenced cells (p<0.05). Finally, we identified several differentially expressed genes in spinophilin-silenced cells. According to our data, low levels of spinophilin are associated with aggressive behavior of breast cancer. PMID:25857299
Kota, Suresh K.; Kulhara, Parmanand
SUMMARY Using a cross-sectional phenomenological approach, 40 schizophrenic patients satisfying Research Diagnostic Criteria were divided into positive, negative and mixed subtypes. On variables like age, duration of illness, and premorbid adjustment significant differences emerged between positive and negative subtypes. No significant differences were found when positive and negative subtypes were compared on variables like intelligence, memory, history of treatment with neuroleptics and electroconvulsive therapy and past and family history of schizophrenia. The results are compared with other studies. PMID:21927337
Pseudolabor is not a recognized conversion disorder subtype. The diagnosis of conversion disorder is suspected when a patient presents with symptoms under voluntary control that mimic a neurologic or medical condition. The term pseudolabor was first used in 1994 to describe a patient who presented at 27 weeks' gestation with monitored contraction activity and no palpable uterine contractions. A second case is presented herein. Both patients were initially managed as though they had preterm labor or uterine irritability with minimal cervical changes. The diagnosis was suspected only after each patient failed to respond to aggressive tocolysis. On external tocodynamometry, contractions were abrupt in onset and abrupt in descent. Only after palpating abdominal contractions and not uterine contractions did the attending physicians make the correct diagnosis. The development of pseudolabor in a patient with previously diagnosed pseudoseizures suggests that the condition was conversion disorder. The prevalence of pseudolabor is unknown and may be underestimated: electronic fetal monitoring has minimized the need to palpate uterine contractions in the laboring patient. The diagnosis of pseudolabor as a subtype of conversion disorder should be considered in any patient who presents with recurrent preterm uterine contractions, no (or minimal) cervical changes, and an atypical contraction pattern. PMID:15254598
Kida, Kumiko; Ishikawa, Takashi; Yamada, Akimitsu; Shimada, Kazuhiro; Narui, Kazutaka; Sugae, Sadatoshi; Shimizu, Daisuke; Tanabe, Mikiko; Sasaki, Takeshi; Ichikawa, Yasushi; Endo, Itaru
Aldehyde dehydrogenase 1 (ALDH1) has been identified as a breast cancer stem cell marker, but its value as a predictor of prognosis and chemoresistance is controversial. This study investigated the effect of ALDH1 on prognosis and chemoresponse by breast cancer subtype. We immunohistochemically analyzed 653 invasive breast cancer specimens and evaluated correlations among clinicopathological factors, survival status, response to neoadjuvant chemotherapy, and ALDH1 expression. Of 653 specimens, 139 (21.3 %) expressed ALDH1 in tumor cells. ALDH1 expression was correlated significantly with larger tumor size, node metastasis, higher nuclear grade, and with HER2(+) and progesterone/estrogen receptor (HR)(-) subtypes. ALDH1 expression was significantly observed in HER2 type and triple-negative breast cancer (TNBC). Patients with ALDH1(+) cancers had significantly shorter disease-free survival (P < 0001) and overall survival (P = 0.044). ALDH1 expression significantly affected prognosis of luminal types, but not TNBC and HER2-enriched types. For the 234 patients treated with neoadjuvant chemotherapy, pathological complete response (pCR) rate was significantly lower in ALDH1(+) cases (13.5 vs. 30.3 %, P = 0.003). pCR and ALDH1 expression were significantly correlated in TNBC patients (P = 0.003). ALDH1(+) breast cancers tended to be aggressive, with poor prognoses. Although ALDH1(+) TNBC showed higher chemoresistance, ALDH1 had significant impact on prognosis in the luminal type but not in TNBC.
Mendez, Mario F.
Patients with Alzheimer’s disease (AD), the most prevalent neurodegenerative dementia, are usually elderly; however, ~4–5% develop early-onset AD (EOAD) with onset before age 65. Most EOAD is sporadic, but about 5% of patients with EOAD have an autosomal dominant mutation such as Presenilin 1, Presenilin 2, or alterations in the Amyloid Precursor Protein gene. Although most Alzheimer’s research has concentrated on older, late-onset AD (LOAD), there is much recent interest and research in EOAD. These recent studies indicate that EOAD is a heterogeneous disorder with significant differences from LOAD. From 22–64% of EOAD patients have a predominant nonamnestic syndrome presenting with deficits in language, visuospatial abilities, praxis, or other non-memory cognition. These nonamnestic patients may differ in several ways from the usual memory or amnestic patients. Patients with nonamnestic EOAD compared to typical amnestic AD have a more aggressive course, lack the apolipoprotein E ε4 (APOE ε4) susceptibility gene for AD, and have a focus and early involvement of non-hippocampal areas of brain, particularly parietal neocortex. These differences in the EOAD subtypes indicate differences in the underlying amyloid cascade, the prevailing pathophysiological theory for the development of AD. Together the results of recent studies suggest that nonamnestic subtypes of EOAD constitute a Type 2 AD distinct from the usual, typical disorder. In sum, the study of EOAD can reveal much about the clinical heterogeneity, predisposing factors, and neurobiology of this disease. PMID:23178565
Röll, Judith; Koglin, Ute; Petermann, Franz
Accumulating evidence suggests that emotion dysregulation is associated with psychopathology. This paper provides a review of recent longitudinal studies that investigate the relationship between emotion regulation and aggressive behavior in childhood age. While there is substantial evidence for assuming a close relation of emotion regulation and aggressive behavior, moderating and mediating factors like gender and peer rejection have been established. Furthermore, results suggest emotion dysregulation as an important risk factor of aggressive behavior. Several directions for future research are pointed out to further validate and refine the reviewed relationships.
Chow, E. W. C.; Husted, J.; Weksberg, R.; Bassett, A. S.
Objective To determine whether postmaturity (gestation > 41 weeks), small for gestational age (SGA), and other pregnancy and birth complications that may elevate risk for neurodevelopmental disorders, are associated with elevated risk for schizophrenia in 22q11 Deletion Syndrome (22qDS), a genetic subtype of schizophrenia. Method Antepartum and intrapartum features were examined in 20 adults with 22qDS-schizophrenia and three comparison groups: newborn encephalopathy (n = 164) and healthy newborn controls (n = 400) from Badawi et al.’s (Br Med J 1998, 317: 1549) study, and 16 non-psychotic 22qDS adults (22qDS-NP). Results Postmaturity (OR 13.0, 95% CI 3.95, 42.77; P < 0.001) and SGA (OR 3.59, 95% CI 1.23, 10.5; P = 0.03) were more prevalent in 22qDS-SZ than controls. Postmaturity was non-significantly more prevalent in 22qDS-SZ than in newborn encephalopathy (P = 0.06) or 22qDS-NP (P = 0.2). SGA showed similar rates in the two 22qDS groups and newborn encephalopathy, but was more prevalent in 22qDS-NP than controls (P = 0.05). Conclusion The results suggest that postmaturity may be associated with expression of schizophrenia in a 22qDS subtype of schizophrenia. SGA may be a non-specific marker of neurodevelopmental disturbance. PMID:12956826
Aho, Olli-Matti; Finnilä, Mikko; Thevenot, Jerome; Saarakkala, Simo; Lehenkari, Petri
Objective Osteoarthritis (OA) has often regarded as a disease of articular cartilage only. New evidence has shifted the paradigm towards a system biology approach, where also the surrounding tissue, especially bone is studied more vigorously. However, the histological features of subchondral bone are only poorly characterized in current histological grading scales of OA. The aim of this study is to specifically characterize histological changes occurring in subchondral bone at different stages of OA and propose a simple grading system for them. Design 20 patients undergoing total knee replacement surgery were randomly selected for the study and series of osteochondral samples were harvested from the tibial plateaus for histological analysis. Cartilage degeneration was assessed using the standardized OARSI grading system, while a novel four-stage grading system was developed to illustrate the changes in subchondral bone. Subchondral bone histology was further quantitatively analyzed by measuring the thickness of uncalcified and calcified cartilage as well as subchondral bone plate. Furthermore, internal structure of calcified cartilage-bone interface was characterized utilizing local binary patterns (LBP) based method. Results The histological appearance of subchondral bone changed drastically in correlation with the OARSI grading of cartilage degeneration. As the cartilage layer thickness decreases the subchondral plate thickness and disorientation, as measured with LBP, increases. Calcified cartilage thickness was highest in samples with moderate OA. Conclusion The proposed grading system for subchondral bone has significant relationship with the corresponding OARSI grading for cartilage. Our results suggest that subchondral bone remodeling is a fundamental factor already in early stages of cartilage degeneration. PMID:28319157
Breast cancer is a complex and heterogeneous disease that affects about one out of every eight women. In the last decade, several advancements have been made that have increased our understanding of breast cancer and have allowed us to more accurately diagnose and treat this disease in a more targeted manner. For example, gene expression profiling enabled the classification of breast cancers into four main subtypes - basal-like, HER2+ (human epidermal growth factor receptor 2-positive), luminal A and luminal B - and this classification is used to direct the use of targeted therapies such as tamoxifen or trastuzumab. The luminal subtypes are generally characterized as being estrogen receptor-positive and targetable with anti-hormone therapies. However, whereas luminal A cancers have a good prognosis, luminal B cancers are associated with early relapse following endocrine therapy and a prognosis that is similar to that of the aggressive basal subtype. It is thus imperative that luminal B cancers be better characterized so that therapeutic targets and biomarkers for this disease type can be realized. In the previous issue of Breast Cancer Research, Katchman and colleagues address this need by demonstrating that quiescin sulfydryl oxidase 1 (QSOX1), a secreted enzyme involved in post-translational modifications, is associated with poor prognosis in patients with luminal B breast cancer. The authors further determined that this protein promotes breast cancer proliferation and invasion. Collectively, these studies suggest that QSOX1 is a predictive biomarker for luminal cancers and that it may be a useful target for elusive luminal B disease. PMID:23680167
Johnson, B A; Cloninger, C R; Roache, J D; Bordnick, P S; Ruiz, P
Subtyping alcoholics may provide a more accurate guide as to the course and character of the disease. Classifications of different ages of onset of problem drinking have so far resulted in categorical inconsistencies. In the past, hospital-based alcoholics have over-represented those most severely ill, and comprehensive evaluations of psychopathology for discriminating between alcoholic subtypes have been infrequent. In a heterogeneous treatment-seeking, outpatient, alcoholic population, we tested the hypothesis that age of onset represents a continuum of disease, and that greater severity of psychopathology is associated with lower ages of onset. Using a standard questionnaire, 253 male and female treatment-seeking alcoholics were stratified according to specific ages of onset: a) < 20 years; b) 20-25 years, and c) > 25 years. These age of onset groups were compared on alcohol severity and craving, family history, childhood behavior, personality, hostility, overt aggression, mood, and social functioning. Symptom severity and age of onset were negatively correlated, and the 20-25-year onset group usually had intermediate scores. The < 20 year onset group was characterized by greater severity of alcohol-related problems, family history, childhood behavioral problems, craving, hostility, antisocial traits, mood disturbance, and poor social functioning. Alcoholics with an earlier age of onset have relatively greater psychopathology than those of later onset. While the preponderance of psychopathology among those in the < 20-year onset group could be conceptualized as a clinical "subtype," such a characterization would not define an entirely homogeneous category. Yet, this clinical characterization would be clinically important if specific age of onset levels were found to be differentially sensitive to pharmacological and/or psychological treatments.
Habekova, Monika; Takacova, M; Lysy, J; Mokras, M; Camacho, R; Truska, P; Stanekova, D
Slovakia belongs to the group of European countries with a low prevalence of HIV infection. The major proportion of HIV-positive cases in Slovakia is still represented by MSM, followed by heterosexuals infected through unprotected sexual intercourse. This study was conducted to update the description of HIV subtypes circulating in Slovakia. HIV-1 partial pol gene sequences from 143 individuals were prospectively collected from 2004 to 2008 and analyzed. Phylogenetic analysis based on HIV-1 partial pol gene sequences revealed the highest prevalence of HIV-1 B subtype (93.0 %), predominantly associated with the MSM group. Ten (7.0%) individuals were infected with HIV-1 non-B subtypes. The pure subtypes were more frequent (7; 4.9%) than CRFs (3; 2.1%) and their occurrence was as follows: subtype C (3; 2, 1%), subtype A (2; 1.4%), subtype F (2; 1.4%), CRF_01AE (1; 0.7%), CRF_02AG (1; 0.7%), and CRF08_BC (1; 0.7%). Data show slightly increasing HIV-1 subtype diversity, with HIV-1 subtype B still having the highest prevalence in the Slovak-infected population.
Smith, Craig E; Fischer, Kurt W; Watson, Malcolm W
Over three decades of research have established a positive connection between fantasizing about aggression and enacting aggression. Such findings have provided strong evidence against the catharsis view of aggressive fantasy. However, little attention has been paid to the potentially nuanced nature of the link between fantasy aggression and actual aggression. In the present article, we examined the influence of four variables in the aggressive fantasy-aggressive behavior link: gender, exposure to violence, fantasy absorption, and level of fantasy about harm befalling loved ones and the self (dysphoric fantasy). Using data from a diverse, community-based sample of 7-14-year olds and their mothers, we replicated the general finding that aggressive fantasy is positively associated with real-world aggressive behavior. However, we also found that the interaction of aggressive fantasy and exposure to violence related significantly to aggression, as did the relation between aggressive fantasy and dysphoric fantasy. When exposure to violence was low, even high levels of aggressive fantasizing did not predict aggressive behavior, and, when aggressive fantasizing was low, even high levels of exposure to violence did not predict aggressive behavior. Similarly, when dysphoric fantasy was high, the connection between fantasy aggression and real aggression was markedly attenuated. The implications of these findings for intervention efforts and future research are considered.
Salmen, Fued Samir; Oliveira, Marina Reis; Navarro, Cláudia Maria; Dedivitis, Rogério Aparecido; Pereira Filho, Valfrido Antonio; Gabrielli, Mario Francisco Real
Osteoblastomas are benign bone tumors, which are unusual in the craniofacial skeleton, being most often observed in the axial skeleton and long bones. The most common site in the maxillofacial region is the mandible and the involvement of the maxilla and paranasal sinuses is extremely rare. Although it is a benign lesion, the aggressive variant raises concerns due to its huge local destructive potential and tendency to relapse. In this clinical case, an aggressive osteoblastoma is described in a 7-year-old patient. The lesion was large and fully involved the left maxilla, including the maxillary sinus and the nasal cavity. Recurrent volume increase was observed 2 months following enucleation of the lesion and en bloc resection of the maxillary segment was performed. Histological and immunohistochemical evaluation associated with clinical and imaging findings allowed to define the tumor as an aggressive variant of osteoblastoma and not osteosarcoma, despite the aggressive behavior. The patient recovered well and no relapses were observed after 12 months following maxillary resection.
Teten, Andra L; Miller, Lisa A; Bailey, Sara D; Dunn, Nancy Jo; Kent, Thomas A
Our long term interest is to develop a developmental model of impulsive aggression based on a confluence of social, psychological and biological features. This approach incorporates neurobiological research, which has identified language processing deficits as a unique characteristic of impulsive aggressors and extends it to include emotional deficits. As an initial test of this hypothesis, we examined whether empathy and alexithymia were associated with impulsive aggression. Regressions were performed to explore the associations among impaired empathy, alexithymia, impulsive aggression, verbal and physical general aggression. Among impulsive aggressive veterans (n=38) recruited from a VA trauma clinic, alexithymia predicted impulsive aggression and empathic deficits predicted verbal aggression. Neither emotional awareness deficit predicted general physical aggression in this middle-aged sample. Results suggested that empathic deficits were associated with general verbal aggression, but alexithymia was uniquely associated with impulsive aggression. Consideration of alexithymia in impulsive aggression has implications for its etiology, prevention and treatment.
Vaishya, Raju; Agarwal, Amit Kumar; Vijay, Vipul
Giant cell tumor of the bone (GCTB) presents as a lytic lesion of epiphyseometaphyseal regions of the long bones usually during the second to the fourth decade with female predilection. Histologically, they are formed of neoplastic mononuclear cells with a higher receptor activator of nuclear factor kappa-B ligand (RANKL) expression responsible for the aggressive osteolytic nature of the tumour. RANKL helps in the formation and functioning of osteoclasts. A newer molecule, Denosumab, is a monoclonal antibody directed against RANKL and thus prevents the formation and function of osteoclasts. Management of refractory, multicentric, recurrent, or metastatic GCTB remains challenging as achieving a tumor-free margin surgically is not always possible. Denosumab may play a crucial role, especially in the management of such difficult lesions. We present three cases of locally aggressive GCTB (involving proximal humerus, sacrum, and proximal femur) that were treated and responded very well to Denosumab therapy.
Vaishya, Raju; Vijay, Vipul
Giant cell tumor of the bone (GCTB) presents as a lytic lesion of epiphyseometaphyseal regions of the long bones usually during the second to the fourth decade with female predilection. Histologically, they are formed of neoplastic mononuclear cells with a higher receptor activator of nuclear factor kappa-B ligand (RANKL) expression responsible for the aggressive osteolytic nature of the tumour. RANKL helps in the formation and functioning of osteoclasts. A newer molecule, Denosumab, is a monoclonal antibody directed against RANKL and thus prevents the formation and function of osteoclasts. Management of refractory, multicentric, recurrent, or metastatic GCTB remains challenging as achieving a tumor-free margin surgically is not always possible. Denosumab may play a crucial role, especially in the management of such difficult lesions. We present three cases of locally aggressive GCTB (involving proximal humerus, sacrum, and proximal femur) that were treated and responded very well to Denosumab therapy. PMID:26251767
Schulman, F Y; Johnson, T O; Facemire, P R; Fanburg-Smith, J C
Feline peripheral nerve sheath tumors are uncommonly reported, and their clinical behavior has not been well documented. Fifty-nine peripheral nerve sheath tumors were collected from 53 cats. All of the tumors involved skin, subcutis, skeletal muscle, and/or mucous membranes. Histologically, the tumors were composed of compact to loosely arranged streams and fascicles of spindled cells with eosinophilic, often wavy cytoplasmic processes; small to occasionally moderate amounts of collagenous to myxoid matrix; and nuclear palisading. Immunohistochemically, all tumors were positive for vimentin and S-100 protein, 44 of 59 were positive for glial fibrillary acidic protein (GFAP), and all were negative for muscle specific actin. The tumors fell into 3 histologic categories: 34 benign tumors with Antoni A areas that were S-100 protein and GFAP positive, 9 benign tumors that lacked Antoni A areas and were S-100 protein positive and GFAP negative, and 16 tumors with features of malignancy. Seventy-five percent of these cases involved the head, neck, or limbs. Recurrent tumors were submitted or tumors were reported to have recurred in 9 cases. Tumor recurrence was reported for all 3 of the histologic subtypes. None was documented as having metastasized.
Gianelli, Umberto; Bossi, Anna; Cortinovis, Ivan; Sabattini, Elena; Tripodo, Claudio; Boveri, Emanuela; Moro, Alessia; Valli, Riccardo; Ponzoni, Maurilio; M Florena, Ada; F Orcioni, Giulio; Ascani, Stefano; Bonoldi, Emanuela; Iurlo, Alessandra; Gugliotta, Luigi; Franco, Vito
This study, performed on behalf of the Italian Registry of Thrombocythaemias (Registro Italiano Trombocitemie), aimed to test the inter-observer reproducibility of the histological parameters proposed by the WHO classification for the diagnosis of the Philadelphia chromosome-negative myeloproliferative neoplasms. A series of 103 bone marrow biopsy samples of Philadelphia chromosome-negative myeloproliferative neoplasms consecutively collected in 2004 were classified according to the WHO criteria as follows: essential thrombocythaemia (n=34), primary myelofibrosis (n=44) and polycythaemia vera (n=25). Two independent groups of pathologists reviewed the bone marrow biopsies. The first group was asked to reach a collegial 'consensus' diagnosis. The second group reviewed individually all the cases to recognize the main morphological parameters indicated by the WHO classification and report their results in a database. They were subsequently instructed to individually build a 'personal' diagnosis of myeloproliferative neoplasms subtype just assembling the parameters collected in the database. Our results indicate that high levels of agreement (≥70%) have been reached for about all of the morphological features. Moreover, among the 18 evaluated histological features, 11 resulted statistically more useful for the differential diagnosis among the different Philadelphia chromosome-negative myeloproliferative neoplasms. Finally, we found a high percentage of agreement (76%) between the 'personal' and 'consensus' diagnosis (Cohen's kappa statistic >0.40). In conclusion, our results support the use of the histological criteria proposed by the WHO classification for the Philadelphia chromosome-negative myeloproliferative neoplasms to ensure a more precise and early diagnosis for these patients.
Kahramancetin, Nesibe; Tihan, Tarik
Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic neoplasm that commonly affects children and young adults, and presents with seizures. PXA is typically supratentorial with a predilection to the temporal lobe, and often involves the cortex and the meninges. PXAs have a favorable prognosis with a 10-year survival probability of >70%, and are WHO grade II neoplasms. Recent observations and studies demonstrate that PXAs are clinically, histologically and genetically distinct. Some PXAs recur and exhibit aggressive clinical behavior. In such cases, certain histological and clinical factors could account for the aggressive behavior. However, the histological features that predict adverse outcome are poorly defined. In the current WHO classification of CNS tumors, there is no option for a high-grade PXA, even if the tumor had numerous recurrences and poor outcome. In this review, we focus on aggressive clinical behavior and anaplasia in PXA, and discuss how our current experience suggests modifications in the current WHO classification. We also review recent discoveries on the molecular characteristics of PXA that could help us better understand their biological behavior.
Summarizes the major research findings on the relationship between television violence and aggressive behavior; concludes that, while there is no definitive proof that such a relationship exists, the evidence points strongly in that direction. (GT)
Science News, 1978
Recent studies done by federal researchers indicate that human aggression may be affected by a critical balance of two or three key brain chemical neurotransmitters. Results of this study with human beings are included in this article. (MA)
Breast cancers that are discovered in the period between regular screening mammograms—known as interval cancers—are more likely to have features associated with aggressive behavior and a poor prognosis than cancers found via screening mammograms.
Trestman, Robert L
Forensic psychiatric units are high-risk environments for aggressive behavior. Many elements are necessary for the successful reduction or elimination of aggression in the process of creating a safe treatment environment. Many specific interventions have been attempted over the years with various degrees of, usually limited, success. Tolisano et al. present an integrated behavioral approach with solid theoretical underpinnings and opportunities to support significant safety improvements for select patients, albeit with several caveats.
Wolk, David A.; Price, Julie C.; Saxton, Judy A.; Snitz, Beth E.; James, Jeffrey A.; Lopez, Oscar L.; Aizenstein, Howard J.; Cohen, Ann D.; Weissfeld, Lisa A.; Mathis, Chester A.; Klunk, William E.; DeKosky, Steven T.
Objective We utilized the amyloid imaging ligand Pittsburgh Compound-B (PiB) to determine the presence of AD pathology in different MCI subtypes and to relate elevated PiB binding to other markers of early AD and longitudinal outcome. Methods Twenty-six patients with MCI – 13 single domain amnestic-MCI (sd a-MCI), 6 multiple domain amnestic-MCI (md a-MCI), and 7 non-amnestic MCI (na-MCI) – underwent PiB imaging. Twenty-three had clinical follow-up [21.2 ± 16.0 (SD) months] subsequent to their PiB scan. Results Using cutoffs established from a control cohort, 14 (54%) had elevated levels of PiB retention and were considered “amyloid-positive.” All subtypes were associated with a significant proportion of amyloid-positive patients (6/13 sd a-MCI, 5/6 md a-MCI, 3/7 na-MCI). There were no obvious differences in the distribution of PiB retention in the na-MCI group despite their atypical early AD phenotype. Predictors of conversion to clinical AD in a-MCI, including poorer episodic memory, increased age, and medial temporal atrophy, were found in the amyloid-positive relative to amyloid-negative a-MCI patients. Longitudinal follow-up revealed 5/13 amyloid-positive patients, but 0/10 amyloid-negative patients, converted to clinical AD. Further, 3/10 amyloid-negative patients “reverted to normal” on follow-up. Interpretation These data support the notion that amyloid-positive patients are likely to have early AD and that the use of amyloid imaging may have an important role in determining which patients are likely to benefit from disease-specific therapies. In addition, our data is consistent with longitudinal studies suggesting that a significant percentage of all MCI subtypes will develop clinical AD. PMID:19475670
Gribbins, Kevin M
Until recently, the histology and ultrastructural events of spermatogenesis in reptiles were relatively unknown. Most of the available morphological information focuses on specific stages of spermatogenesis, spermiogenesis, and/or of the mature spermatozoa. No study to date has provided complete ultrastructural information on the early events of spermatogenesis, proliferation and meiosis in class Reptilia. Furthermore, no comprehensive data set exists that describes the ultrastructure of the entire ontogenic progression of germ cells through the phases of reptilian spermatogenesis (mitosis, meiosis and spermiogenesis). The purpose of this review is to provide an ultrastructural and histological atlas of spermatogenesis in reptiles. The morphological details provided here are the first of their kind and can hopefully provide histological information on spermatogenesis that can be compared to that already known for anamniotes (fish and amphibians), birds and mammals. The data supplied in this review will provide a basic model that can be utilized for the study of sperm development in other reptiles. The use of such an atlas will hopefully stimulate more interest in collecting histological and ultrastructural data sets on spermatogenesis that may play important roles in future nontraditional phylogenetic analyses and histopathological studies in reptiles.
Price, Charles J.; Reed, Josephine E.
This document approaches the subject of Histology by way of simple independent unicellular organisms through the lower levels of cell organization and specialization to a detailed study of the highly complex tissues of vertebrate animals. Emphasis is placed on structure, but function is explained in some detail. The relationships between tissues…
Richardson, Lorna; Graham, Liz; Moss, Julie; Burton, Nick; Roochun, Yogmatee; Armit, Chris; Baldock, Richard A
The eMouseAtlas project has undertaken to generate a new resource providing access to high-resolution colour images of the slides used in the renowned textbook 'The Atlas of Mouse Development' by Matthew H. Kaufman. The original histology slides were digitized, and the associated anatomy annotations captured for display in the new resource. These annotations were assigned to objects in the standard reference anatomy ontology, allowing the eHistology resource to be linked to other data resources including the Edinburgh Mouse Atlas Gene-Expression database (EMAGE) an the Mouse Genome Informatics (MGI) gene-expression database (GXD). The provision of the eHistology Atlas resource was assisted greatly by the expertise of the eMouseAtlas project in delivering large image datasets within a web environment, using IIP3D technology. This technology also permits future extensions to the resource through the addition of further layers of data and annotations to the resource. Database URL: www.emouseatlas.org/emap/eHistology/index.php.
Dixon, Vanessa; Kouznetsov, Alexei; Tambasco, Mauro
Pathologists examine histology sections to make diagnostic and prognostic assessments regarding cancer based on deviations in cellular and/or glandular structures. However, these assessments are subjective and exhibit some degree of observer variability. Recent studies have shown that fractal dimension (a quantitative measure of structural complexity) has proven useful for characterizing structural deviations and exhibits great potential for automated cancer diagnosis and prognosis. Computing fractal dimension relies on accurate image segmentation to capture the architectural complexity of the histology specimen. For this purpose, previous studies have used techniques such as intensity histogram analysis and edge detection algorithms. However, care must be taken when segmenting pathologically relevant structures since improper edge detection can result in an inaccurate estimation of fractal dimension. In this study, we established a reliable method for segmenting edges from grayscale images. We used a Koch snowflake, an object of known fractal dimension, to investigate the accuracy of various edge detection algorithms and selected the most appropriate algorithm to extract the outline structures. Next, we created validation objects ranging in fractal dimension from 1.3 to 1.9 imitating the size, structural complexity, and spatial pixel intensity distribution of stained histology section images. We applied increasing intensity thresholds to the validation objects to extract the outline structures and observe the effects on the corresponding segmentation and fractal dimension. The intensity threshold yielding the maximum fractal dimension provided the most accurate fractal dimension and segmentation, indicating that this quantitative method could be used in an automated classification system for histology specimens.
Trainor, Brian C.; Rowland, Michael R.; Nelson, Randy J.
Estrogens have important effects on male and female social behavior. Despite growing knowledge of the anatomy and behavioral effects of the two predominant estrogen receptor subtypes in mammals (ERα and ERβ), relatively little is known about how these receptors respond to salient environmental stimuli. Many seasonally breeding species respond to changing photoperiods that predict seasonal changes in resource availability. We characterized the effects of photoperiod on aggressive behavior in two species of Peromyscus that exhibit gonadal regression in short days. P. polionotus (old field mice) were more aggressive than P. maniculatus (deer mice) and both species were more aggressive in short days. We used immunocytochemistry and real-time polymerase chain reaction to characterize the effects of photoperiod on ERα and ERβ expression. In both species ERα-immunoreactive staining in the posterior bed nucleus of the stria terminalis (BNST) was increased in short vs. long days. Both species had reduced ERβ-immunoreactive expression in the posterior BNST in short days. In the medial amygdala ERβ immunoreactivity was increased in long days for both species. Using real-time polymerase chain reaction on punch samples that included the BNST, we observed that ERα mRNA was increased and ERβ mRNA was decreased in short days. These data suggest that the effects of photoperiod on ERα and ERβ expression may thus have important behavioral consequences. PMID:17614949
Stockley, Paula; Campbell, Anne
This paper introduces a Theme Issue combining interdisciplinary perspectives in the study of female competition and aggression. Despite a history of being largely overlooked, evidence is now accumulating for the widespread evolutionary significance of female competition. Here, we provide a synthesis of contributions to this Theme Issue on humans and other vertebrates, and highlight directions for future research. Females compete for resources needed to survive and reproduce, and for preferred mates. Although female aggression takes diverse forms, under most circumstances relatively low-risk competitive strategies are favoured, most probably due to constraints of offspring production and care. In social species, dominance relationships and threats of punishment can resolve social conflict without resort to direct aggression, and coalitions or alliances may reduce risk of retaliation. Consistent with these trends, indirect aggression is a low cost but effective form of competition among young women. Costs are also minimized by flexibility in expression of competitive traits, with aggressive behaviour and competitive signalling tailored to social and ecological conditions. Future research on female competition and the proximate mediators of female aggression will be greatly enhanced by opportunities for interdisciplinary exchange, as evidenced by contributions to this Theme Issue. PMID:24167303
Tulogdi, Aron; Biro, Laszlo; Barsvari, Beata; Stankovic, Mona; Haller, Jozsef; Toth, Mate
Our recent studies showed that brain areas that are activated in a model of escalated aggression overlap with those that promote predatory aggression in cats. This finding raised the interesting possibility that the brain mechanisms that control certain types of abnormal aggression include those involved in predation. However, the mechanisms of predatory aggression are poorly known in rats, a species that is in many respects different from cats. To get more insights into such mechanisms, here we studied the brain activation patterns associated with spontaneous muricide in rats. Subjects not exposed to mice, and those which did not show muricide were used as controls. We found that muricide increased the activation of the central and basolateral amygdala, and lateral hypothalamus as compared to both controls; in addition, a ventral shift in periaqueductal gray activation was observed. Interestingly, these are the brain regions from where predatory aggression can be elicited, or enhanced by electrical stimulation in cats. The analysis of more than 10 other brain regions showed that brain areas that inhibited (or were neutral to) cat predatory aggression were not affected by muricide. Brain activation patterns partly overlapped with those seen earlier in the cockroach hunting model of rat predatory aggression, and were highly similar with those observed in the glucocorticoid dysfunction model of escalated aggression. These findings show that the brain mechanisms underlying predation are evolutionarily conservative, and indirectly support our earlier assumption regarding the involvement of predation-related brain mechanisms in certain forms of escalated social aggression in rats.
Lobbestael, Jill; Cousijn, Janna; Brugman, Suzanne; Wiers, Reinout W
This study assessed the association between indirectly measured behavioural approach- and avoidance-related tendencies on the one hand, and reactive versus proactive aggression on the other hand. Reactive aggression (i.e. the impulsive, anger-driven aggression expressed in response to threatening stimuli) was differentiated from proactive aggression (i.e. the more controlled aggression motivated towards obtaining specific goals). A mixed sample of 118 patients and healthy controls filled out a self-report measure to assess their degree of reactive and proactive aggression, and then performed an Approach Avoidance Task in which they were asked to pull or push a joystick in response to a format-feature of a series of pictures, irrespective of their contents. The pictorial stimuli used in this task included attack-related scenes and angry faces, along with neutral, positive and negative control stimuli. The results were controlled for the level of personality disorder pathology, gender, and age. The findings indicated that reactive but not proactive aggression was related to the relative behavioural tendency to approach attack-related scenes, along with positive stimuli. These findings reflect the hyper-reactivity of the approach-related reward system in reactive aggression, and further our knowledge into the distinct correlates and precursors of reactive and proactive aggression.
Fulwiler, Carl; Eckstine, Joy; Kalsy, Sapna
Although alcohol consumption is involved in most acts of violence, most people do not become violent when they drink. Individuals also respond differently to alcohol on laboratory measures of aggression. The objective of this study was to determine whether individual differences in the effects of alcohol on a laboratory measure of aggression are related to specific personality traits and/or serotonin function, as measured by prolactin response to pharmacochallenge. Psychometric scales for impulsiveness, aggression, and anger, as well as a probe for suspiciousness, were administered to 10 healthy male social drinkers. Trait serotonin function was determined by citalopram challenge. The effect of alcohol on the Point Subtraction Aggression Paradigm was determined by comparing aggression scores with and without 1 g/kg alcohol. Impulsivity scores were significantly correlated with the change in aggressive responding after alcohol. Aggression, anger, and suspiciousness scores were not. Prolactin response did not predict the effect of alcohol on aggressive responding. The results suggest that trait impulsiveness may mediate the effects of alcohol on aggression in normal males.
Kather, Jakob Nikolas; Weis, Cleo-Aron; Marx, Alexander; Schuster, Alexander K.; Schad, Lothar R.; Zöllner, Frank Gerrit
Background Accurate evaluation of immunostained histological images is required for reproducible research in many different areas and forms the basis of many clinical decisions. The quality and efficiency of histopathological evaluation is limited by the information content of a histological image, which is primarily encoded as perceivable contrast differences between objects in the image. However, the colors of chromogen and counterstain used for histological samples are not always optimally distinguishable, even under optimal conditions. Methods and Results In this study, we present a method to extract the bivariate color map inherent in a given histological image and to retrospectively optimize this color map. We use a novel, unsupervised approach based on color deconvolution and principal component analysis to show that the commonly used blue and brown color hues in Hematoxylin—3,3’-Diaminobenzidine (DAB) images are poorly suited for human observers. We then demonstrate that it is possible to construct improved color maps according to objective criteria and that these color maps can be used to digitally re-stain histological images. Validation To validate whether this procedure improves distinguishability of objects and background in histological images, we re-stain phantom images and N = 596 large histological images of immunostained samples of human solid tumors. We show that perceptual contrast is improved by a factor of 2.56 in phantom images and up to a factor of 2.17 in sets of histological tumor images. Context Thus, we provide an objective and reliable approach to measure object distinguishability in a given histological image and to maximize visual information available to a human observer. This method could easily be incorporated in digital pathology image viewing systems to improve accuracy and efficiency in research and diagnostics. PMID:26717571
Magerova, Hana; Vyhnalek, Martin; Laczo, Jan; Andel, Ross; Rektorova, Irena; Kadlecova, Alexandra; Bojar, Martin; Hort, Jakub
Odor identification impairment is a feature of several neurodegenerative disorders. Although neurodegenerative changes in the frontotemporal lobar degeneration (FTLD) subtypes involve areas important for olfactory processing, data on olfactory function in these patients are limited. An 18-item, multiple-choice odor identification test developed at our memory clinic, the Motol Hospital smell test, was administered to 9 patients with behavioral variant frontotemporal dementia, 13 patients with the language variants, primary nonfluent aphasia (n = 7) and semantic dementia (n = 6), and 8 patients with progressive supranuclear palsy. Compared to the control group (n = 15), all FTLD subgroups showed significant impairment of odor identification (P < .05). The differences between the FTLD subgroups were not significant. No correlation between odor identification and neuropsychological tests results was found. Our data suggest that odor identification impairment is a symptom common to FTLD syndromes, and it seems to be based on olfactory structure damage rather than cognitive decline.
Guinney, Justin; Dienstmann, Rodrigo; Wang, Xin; de Reyniès, Aurélien; Schlicker, Andreas; Soneson, Charlotte; Marisa, Laetitia; Roepman, Paul; Nyamundanda, Gift; Angelino, Paolo; Bot, Brian M.; Morris, Jeffrey S.; Simon, Iris M.; Gerster, Sarah; Fessler, Evelyn; de Sousa e Melo, Felipe; Missiaglia, Edoardo; Ramay, Hena; Barras, David; Homicsko, Krisztian; Maru, Dipen; Manyam, Ganiraju C.; Broom, Bradley; Boige, Valerie; Perez-Villamil, Beatriz; Laderas, Ted; Salazar, Ramon; Gray, Joe W.; Hanahan, Douglas; Tabernero, Josep; Bernards, Rene; Friend, Stephen H.; Laurent-Puig, Pierre; Medema, Jan Paul; Sadanandam, Anguraj; Wessels, Lodewyk; Delorenzi, Mauro; Kopetz, Scott; Vermeulen, Louis; Tejpar, Sabine
Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression–based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMS) with distinguishing features: CMS1 (MSI Immune, 14%), hypermutated, microsatellite unstable, strong immune activation; CMS2 (Canonical, 37%), epithelial, chromosomally unstable, marked WNT and MYC signaling activation; CMS3 (Metabolic, 13%), epithelial, evident metabolic dysregulation; and CMS4 (Mesenchymal, 23%), prominent transforming growth factor β activation, stromal invasion, and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intra-tumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC – with clear biological interpretability – and the basis for future clinical stratification and subtype–based targeted interventions. PMID:26457759
Daoust, P-Y; van de Bildt, M; van Riel, D; van Amerongen, G; Bestebroer, T; Vanderstichel, R; Fouchier, R A M; Kuiken, T
Many subtypes of low-pathogenicity avian influenza (LPAI) virus circulate in wild bird reservoirs, but their prevalence may vary among species. We aimed to compare by real-time reverse-transcriptase polymerase chain reaction, virus isolation, histology, and immunohistochemistry the distribution and pathogenicity of 2 such subtypes of markedly different origins in Mallard ducks (Anas platyrhynchos): H2N3 isolated from a Mallard duck and H13N6 isolated from a Ring-billed Gull (Larus delawarensis). Following intratracheal and intraesophageal inoculation, neither virus caused detectable clinical signs, although H2N3 virus infection was associated with a significantly decreased body weight gain during the period of virus shedding. Both viruses replicated in the lungs and air sacs until approximately day 3 after inoculation and were associated with a locally extensive interstitial, exudative, and proliferative pneumonia. Subtype H2N3, but not subtype H13N6, went on to infect the epithelia of the intestinal mucosa and cloacal bursa, where it replicated without causing lesions until approximately day 5 after inoculation. Larger quantities of subtype H2N3 virus were detected in cloacal swabs than in pharyngeal swabs. The possible clinical significance of LPAI virus-associated pulmonary lesions and intestinal tract infection in ducks deserves further evaluation.
Lochman, John E.
Secondary prevention programs for aggressive children should be based on research about processes which mediate children's expression of aggressive behavior. The relative importance of perceived competence, self-esteem, and social problem solving processes was investigated in 20 aggressive and 18 non-aggressive fourth and fifth grade boys. Teacher…
The dopaminergic system regulates aggression in humans and other mammals. To investigate if birds with genetic propensity for high and low aggressiveness may exhibit distinctly different aggressive mediation via dopamine (DA) D1 and D2 receptor pathways, two high aggressive (DXL and LGPS) and one lo...
Risser, Scott D.
To investigate the relationship between relational aggression and school performance, this study examined the relative and combined associations among relational aggression, overt aggression, and victimization and children's academic performance. Additionally this study examined the relative associations among relational and overt aggression and…
Schwab Reese, Laura M.; Harland, Karisa; Smithart, Kelsey
Abstract Intimate partner aggression is a leading cause of injury among women of child-bearing age. Research suggests that pregnancy and the postpartum period are times of increased vulnerability to aggression. Since rural women are at an increased risk of intimate partner aggression, research is needed to examine the role of pregnancy and the presence of children on intimate partner aggression among this vulnerable population. The purpose of this study is to examine the association between young children and intimate partner aggression victimization and perpetration among a rural sample. This analysis utilized data from biologic females of child-bearing age from the Keokuk County Rural Health Study, a cohort study of over 1,000 rural families conducted from 1994 to 2011. Crude and adjusted logistic regression was used to determine the relationship between having a young child and experiencing four forms of intimate partner aggression: verbal aggression perpetration, verbal aggression victimization, physical aggression perpetration, and physical aggression victimization. Having young children was significantly associated with increased odds of perpetrating verbal aggression but not victimization of verbal aggression or perpetration and victimization of physical aggression. This significant relationship persisted after adjustment for education, employment, or location of residence but not age or marital status. The increased odds of perpetrating verbal aggression among mothers in a rural area highlight the need for interventions designed for rural parents. One method of reducing intimate partner aggression may be to incorporate intimate partner aggression prevention activities into existing child abuse intervention activities. PMID:27626037
Sutton, Sara E.; Cowen, Emory L.; Crean, Hugh F.; Wyman, Peter A.; Work, William C.
Examined correlates of aggression in highly stressed urban children in second and third grade and again in third through fifth grade. Found that difficult temperament and lack of parental warmth related to aggression in early grades; learning problems and poor social skills related to aggression at both times. Early aggression predicted later…
Spieker, Susan J.; Campbell, Susan B.; Vandergrift, Nathan; Pierce, Kim M.; Cauffman, Elizabeth; Susman, Elizabeth J.; Roisman, Glenn I.
This study examined gender differences in the level and developmental course of relational aggression in middle childhood, as well as early predictors and outcomes of relational aggression, after controlling for concurrent physical aggression. Relational (RAgg) and Physical aggression (PAgg) scores for 558 boys and 545 girls at the ages of eight…
Volk, Heather E.; Todorov, Alexandre A.; Hay, David A.; Todd, Richard D.
The results of the assessment of the accuracy of simple rules based on symptom count for assigning youths to attention deficit hyperactivity disorder subtypes show that having six or more total symptoms and fewer than three hyperactive-impulsive symptoms is an accurate predictor for the latent class sever inattentive subtype.
Tsai, Luke Y.
This paper reviews whether Rett syndrome is a subtype of pervasive developmental disorders (PDD). The paper analyzes internal and external diagnostic validity and discusses whether Rett syndrome is a neurological disorder or a mental disorder. The paper concludes that data support the idea of classifying Rett syndrome as a subtype of PDD.…
Manis, Franklin R.; And Others
Studied 51 dyslexic children, 51 age-matched normal readers, and 27 younger normal readers to explore whether there are different subtypes of developmental dyslexia, and whether developmental dyslexia represents delay or deviance. Found evidence to support two subtypes: surface and phonological dyslexia. (DR)
Pharmacologic treatments for irritable bowel syndrome (IBS) and medical management of symptoms are increasingly based on IBS subtype, so it is important to accurately differentiate patients. Few studies have classified subtypes of pediatric IBS, and conclusions have been challenged by methodologic l...
Margalit, Malka; And Others
Four subtypes of family climate were identified through analysis of the Sense of Coherence Scale, Family Environment Scale, and Global Measure of Satisfaction from Family, using 77 mothers of disabled children in Israeli kibbutzim. The four subtypes emphasized personal growth orientation, conflict orientation, nonsupportive disorganized…
Alinaghizade, Atefe; Mirjalali, Hamed; Mohebali, Mehdi; Stensvold, Christen Rune; Rezaeian, Mostafa
Blastocystis is a common intestinal parasitic protist infecting birds and mammals. Blastocystis comprises at least 17 subtypes (ST), of which ST1-ST9 have been detected in humans. Significant correlation between certain subtypes and pathogenicity remains to be established. Nevertheless, some studies suggest a potential linkage between subtypes (inter- and intra-subtype variation) and clinical manifestations. The aim of this study was to identify intra-subtype genetic variation of subtypes of Blastocystis in stools samples submitted by diarrheic and non-diarrheic patients. A 550-bp fragment of the nuclear small subunit ribosomal rRNA gene was amplified from 58 culture-positive samples isolated from diarrheic and non-diarrheic Iranian patients. PCR products were sequenced and sequences subjected to phylogenetic analysis. Intra-and inter-subtype variation was calculated. Based on comparison with reference sequences in GenBank, ST1, ST2 and ST3 were found in 18 (31.03%), 21 (36.22%), and 19 (32.75%) of the samples, respectively. Diarrheic stools were observed in eight (44.44%), 10 (47.61%), and nine (47.36%) patients with ST1, ST2, and ST3, respectively. No statistically significant correlation was found between subtypes and diarrhea (P=1.000). Multiple sequence alignment exhibited a within-subtype similarity of 98.76%, 97.17%, and 99.78% in ST1, ST2, and ST3, respectively. Highest similarity was seen among ST3 isolates, while lowest similarity was seen among ST2 isolates. Phylogenetic analysis did not suggest any correlation between diarrhea and intra-subtype variation. Inter- and intra-subtype variation in SSU rRNA gene appears not to reflect differences in the clinical outcome of Blastocystis carriage.
Tan, Tuan Zea; Yang, He; Ye, Jieru; Low, Jeffrey; Choolani, Mahesh; Tan, David Shao Peng; Thiery, Jean-Paul; Huang, Ruby Yun-Ju
Databases pertaining to various diseases provide valuable resources on particular genes of interest but lack the molecular subtype and epithelial-mesenchymal transition status. CSIOVDB is a transcriptomic microarray database of 3,431 human ovarian cancers, including carcinoma of the ovary, fallopian tube, and peritoneum, and metastasis to the ovary. The database also comprises stroma and ovarian surface epithelium from normal ovary tissue, as well as over 400 early-stage ovarian cancers. This unique database presents the molecular subtype and epithelial-mesenchymal transition status for each ovarian cancer sample, with major ovarian cancer histologies (clear cell, endometrioid, mucinous, low-grade serous, serous) represented. Clinico-pathological parameters available include tumor grade, surgical debulking status, clinical response and age. The database has 1,868 and 1,516 samples with information pertaining to overall and disease-free survival rates, respectively. The database also provides integration with the copy number, DNA methylation and mutation data from TCGA. CSIOVDB seeks to provide a resource for biomarker and therapeutic target exploration for ovarian cancer research.
Schlitter, Anna Melissa; Segler, Angela; Steiger, Katja; Michalski, Christoph W.; Jäger, Carsten; Konukiewitz, Björn; Pfarr, Nicole; Endris, Volker; Bettstetter, Markus; Kong, Bo; Regel, Ivonne; Kleeff, Jörg; Klöppel, Günter; Esposito, Irene
Pancreatic ductal adenocarcinoma (PDAC) has generally a poor prognosis, but recent data suggest that there are molecular subtypes differing in clinical outcome. This study examines the association between histopathologic heterogeneity, genetic profile, and survival. Tumor histology from 177 resected PDAC patients with follow-up data was subclassified according to predominant growth pattern, and four key genes were analyzed. PDACs were classified as conventional (51%), combined with a predominant component (41%), variants and special carcinomas (8%). Patients with combined PDACs and a dominant cribriform component survived longer than patients with conventional or other combined PDACs. Genetic alterations in at least two out of four genes were found in 95% of the patients (KRAS 93%, TP53 79%, CDKN2A/p16 75%, SMAD4 37%). Patients with less than four mutations survived significantly longer (p = 0.04) than those with alterations in all four genes. Patients with either wildtype KRAS or CDKN2A/p16 lived significantly longer than those with alterations in these genes (p = 0.018 and p = 0.006, respectively). Our data suggest that the number of altered genes, the mutational status of KRAS and certain morphological subtypes correlate with the outcome of patients with PDAC. Future pathology reporting of PDAC should therefore include the KRAS status and a detailed morphological description. PMID:28145465
Henry, D; Guerra, N; Huesmann, R; Tolan, P; VanAcker, R; Eron, L
We report a study aimed at understanding the effects of classroom normative influences on individual aggressive behavior, using samples of 614 and 427 urban elementary school children. Participants were assessed with measures of aggressive behavior and normative beliefs about aggression. We tested hypotheses related to the effects of personal normative beliefs, descriptive classroom norms (the central tendency of classmates' aggressive behavior), injunctive classroom normative beliefs (classmates' beliefs about the acceptability of aggression), and norm salience (student and teacher sanctions against aggression) on longitudinal changes in aggressive behavior and beliefs. injunctive norms affected individual normative beliefs and aggression, but descriptive norms had no effect on either. In classrooms where students and teachers made norms against aggression salient, aggressive behavior diminished over time. Implications for classroom behavior management and further research are discussed.
Bozdag, Serdar; Li, Aiguo; Baysan, Mehmet; Fine, Howard A
Glioblastoma multiforme (GBM) is the most common malignant brain tumor. GBM samples are classified into subtypes based on their transcriptomic and epigenetic profiles. Despite numerous studies to better characterize GBM biology, a comprehensive study to identify GBM subtype- specific master regulators, gene regulatory networks, and pathways is missing. Here, we used FastMEDUSA to compute master regulators and gene regulatory networks for each GBM subtype. We also ran Gene Set Enrichment Analysis and Ingenuity Pathway Analysis on GBM expression dataset from The Cancer Genome Atlas Project to compute GBM- and GBM subtype-specific pathways. Our analysis was able to recover some of the known master regulators and pathways in GBM as well as some putative novel regulators and pathways, which will aide in our understanding of the unique biology of GBM subtypes.
Heipertz, Richard A.; Ayemoba, Ojor; Sanders-Buell, Eric; Poltavee, Kultida; Pham, Phuc; Kijak, Gustavo H.; Lei, Esther; Bose, Meera; Howell, Shana; O'Sullivan, Anne Marie; Bates, Adam; Cervenka, Taylor; Kuroiwa, Janelle; Akintunde, Akindiran; Ibezim, Onyekachukwu; Alabi, Abraham; Okoye, Obumneke; Manak, Mark; Malia, Jennifer; Peel, Sheila; Maisaka, Mohammed; Singer, Darrell; O’Connell, Robert J.; Robb, Merlin L.; Kim, Jerome H.; Michael, Nelson L.; Njoku, Ogbonnaya; Tovanabutra, Sodsai
Abstract While abundant sequence information is available from human immunodeficiency virus type 1 (HIV-1) subtypes A, B, C and CRF01_AE for HIV-1 vaccine design, sequences from West Africa are less represented. We sought to augment our understanding of HIV-1 variants circulating in 6 Nigerian cities as a step to subsequent HIV-1 vaccine development. The G/CRF02_AG multi-region hybridization assay (MHA) was developed to differentiate subtype G, CRF02_AG and their recombinants from other subtypes based on 7 HIV-1 segments. Plasma from 224 HIV-1 infected volunteers enrolled in a cohort examining HIV-1 prevalence, risk factor, and subtype from Makurdi (30), Abuja (18), Enugu (11), Kaduna (12), Tafa (95), and Ojo/Lagos (58) was analyzed using MHA. HIV-1 genomes from 42 samples were sequenced to validate the MHA and fully explore the recombinant structure of G and CRF02_AG variants. The sensitivity and specificity of MHA varied between 73–100% and 90–100%, respectively. The subtype distribution as identified by MHA among 224 samples revealed 38% CRF02_AG, 28% G, and 26% G/CRF02_AG recombinants while 8% remained nontypeable strains. In envelope (env) gp120, 38.84% of the samples reacted to a G probe while 31.25% reacted to a CRF02 (subtype A) probe. Full genome characterization of 42 sequences revealed the complexity of Nigerian HIV-1 variants. CRF02_AG, subtype G, and their recombinants were the major circulating HIV-1 variants in 6 Nigerian cities. High proportions of samples reacted to a G probe in env gp120 confirms that subtype G infections are abundant and should be considered in strategies for global HIV-1 vaccine development. PMID:27512845
Gasser, Luciano; Malti, Tina; Gutzwiller-Helfenfinger, Eveline
The authors investigated 7- and 9-year-old children's moral understanding of retaliation as compared to unprovoked aggression with regard to their aggressive behavior status. Based on peer ratings, 48 children were selected as overtly aggressive and 91 as nonaggressive. Their moral understanding of retaliation and unprovoked aggression was…
Coyne, Sarah M.
Most researchers on media and aggression have examined the behavioral effects of viewing physical aggression in the media. Conversely, in the current study, I examined longitudinal associations between viewing "relational aggression" on TV and subsequent aggressive behavior. Participants included 467 adolescents who completed a number of…
Coyne, Sarah M.; Archer, John; Eslea, Mike
Numerous studies have shown that viewing violence in the media can influence an individual's subsequent aggression, but none have examined the effect of viewing indirect aggression. This study examines the immediate effect of viewing indirect and direct aggression on subsequent indirect aggression among 199 children ages 11 to 14 years. They were…
Calvete, E; Gamez-Guadix, M; Orue, I; Gonzalez-Diez, Z; Lopez de Arroyabe, E; Sampedro, R; Pereira, R; Zubizarreta, A; Borrajo, E
The objective of this study was to develop a questionnaire to assess child-to-parent aggression in adolescents and to document the extent of the problem. The questionnaire developed in this study, the Child-to-Parent Aggression Questionnaire (CPAQ), includes forms of physical and psychological aggression directed at both the mother and the father. It also includes open questions about the reasons for the aggressive acts. The CPAQ was completed by a sample of 2719 adolescents (age range: 13-18 years old, 51.4% girls). Confirmatory factor analysis supported a four-factor correlated structure (physical aggression against mother, physical aggression against father, psychological aggression against mother, and psychological aggression against father). Psychological and physical aggression against the mother was more frequent than against the father. However, there were no differences with regard to severe forms of aggression. Girls scored significantly higher on all indicators of psychological aggression, including severe psychological aggression. Nevertheless, except for the prevalence of physical aggression against mothers, which was higher in females, there were no significant differences in physical aggression against parents. Finally, the reasons provided by the adolescents for the aggression included both instrumental (e.g., to obtain permission to get home late and to access their computers) and reactive reasons (e.g., anger and self-defense). These findings highlight the complexity of child-to-parent aggression in adolescence.
Badesch, D B; Zamora, M; Fullerton, D; Weill, D; Tuder, R; Grover, F; Schwarz, M I
Acute rejection after lung transplantation occurs commonly and is usually characterized histologically by a perivascular mononuclear infiltrate. We report five cases of pulmonary capillaritis with a histologic appearance distinct from typical rejection, occurring in patients ranging in age from 18 to 45 years, with a variety of underlying diseases including alpha1 antitrypsin deficiency, pulmonary hypertension, cystic fibrosis, and rheumatoid arthritis. Four of the five patients had alveolar hemorrhage histologically, and two had frank hemoptysis. Time of onset ranged from 3 weeks to many months after transplantation. Three cases were fulminant, and there were two deaths. In only one case, with methicillin-resistant Staphylococcus aureus bronchitis, could infection be established. All were treated with intensification of immunosuppressive therapy. Plasmapheresis was carried out in two cases and coincided with temporary improvement, but its efficacy was questionable because of concurrent immunosuppressive therapy. Two had recurrent biopsy-proven acute rejection within 6 weeks of treatment, and one had recurrent severe pulmonary hemorrhage that abated with total lymphoid irradiation. Our experience suggests that pulmonary capillaritis in lung transplant recipients can be an acute, fatal illness with the potential for recurrence in the survivors. We speculate that it represents a form of acute vascular rejection. Early pathologic diagnosis and aggressive immunosuppressive therapy are recommended. Although a humoral component was not documented, the possible response to plasmapheresis requires continued evaluation.
Chamandar, Fateme; Jabbari, D. Susan
The purpose of this study is the content analysis of children's stories based on the components of aggression. Participants are 66 elementary school students (16 girls and 50 boys) selected from fourth and fifth grades, using the Relational and Overt Aggression Questionnaire; completed by the teachers. Draw a Story Test (Silver, 2005) is…
Lee, Eunju J.
This study examines whether the instability of self-esteem (i.e., a high intraindividual variability in self-esteem) is differentially associated with different types of aggressive behavior by using a sample of 235 preadolescent children. Self-esteem was measured four times for four consecutive days, and proactive and reactive aggressive behaviors…
Thomas, Duane E; Bierman, Karen L
Prior research suggests that exposure to elementary classrooms characterized by high levels of student aggression may contribute to the development of child aggressive behavior problems. To explore this process in more detail, this study followed a longitudinal sample of 4,907 children and examined demographic factors associated with exposure to high-aggression classrooms, including school context factors (school size, student poverty levels, and rural vs. urban location) and child ethnicity (African American, European American). The developmental impact of different temporal patterns of exposure (e.g., primacy, recency, chronicity) to high-aggression classrooms was evaluated on child aggression. Analyses revealed that African American children attending large, urban schools that served socioeconomically disadvantaged students were more likely than other students to be exposed to high-aggressive classroom contexts. Hierarchical regressions demonstrated cumulative effects for temporal exposure, whereby children with multiple years of exposure showed higher levels of aggressive behavior after 3 years than children with primacy, less recent, and less chronic exposure, controlling for initial levels of aggression. Implications are discussed for developmental research and preventive interventions.
Runions, Kevin C; Bak, Michal; Shaw, Thérèse
Aggression in online contexts has received much attention over the last decade, yet there is a need for measures identifying the proximal psychological drivers of cyber-aggressive behavior. The purpose of this study was to present data on the newly developed Cyber-Aggression Typology Questionnaire (CATQ) designed to distinguish between four distinct types of cyber-aggression on dimensions of motivational valence and self-control. A sample 314 undergraduate students participated in the study. The results confirmed the predicted four-factor structure providing evidence for distinct and independent impulsive-aversive, controlled-aversive, impulsive-appetitive, and controlled-appetitive cyber-aggression types. Further analyses with the Berlin Cyberbullying Questionnaire, Reactive Proactive Aggression Questionnaire, and the Behavior Inhibition and Activation Systems Scale provide support for convergent and divergent validity. Understanding the motivations facilitating cyber-aggressive behavior could aid researchers in the development of new prevention and intervention strategies that focus on individual differences in maladaptive proximal drivers of aggression. Aggr. Behav. 43:74-84, 2017. © 2016 Wiley Periodicals, Inc.
Maxwell, J P; Visek, A J
Aggressive players who intentionally cause injury to their opponents are common in many sports, particularly collision sports such as Rugby Union. Although some acts of aggression fall within the rules (sanctioned), others do not (unsanctioned), with the latter tending to be less acceptable than the former. This study attempts to identify characteristics of players who are more likely to employ unsanctioned methods in order to injure an opponent. Male Rugby Union players completed questionnaires assessing aggressiveness, anger, past aggression, professionalization, and athletic identity. Players were assigned to one of two groups based on self-reported past unsanctioned aggression. Results indicated that demographic variables (e.g., age, playing position, or level of play) were not predictive of group membership. Measures of aggressiveness and professionalization were significant predictors; high scores on both indicated a greater probability of reporting the use of unsanctioned aggressive force for the sole purpose of causing injury or pain. In addition, players who had been taught how to execute aggressive illegal plays without detection were also more likely to report using excessive force to injure an opponent. Results provide further support that highly professionalized players may be more likely to use methods outside the constitutive rules of Rugby Union in order to intentionally injure their opponents. Results are discussed within the context of the increasing win-at-all-cost attitude that is becoming more prevalent in sport and its implications for youth athletes.
Baron, Robert A.; Bell, Paul A.
Eighty-six undergraduate males participated in an experiment designed to investigate the impact of various types of erotic stimuli upon aggression. On the basis of previous research, it was hypothesized that exposure to mild erotic stimuli would tend to inhibit subsequent aggression, while exposure to more arousing stimuli of this type would…
Wölfer, Ralf; Hewstone, Miles
Two theories offer competing explanations of sex differences in aggressive behavior: sexual-selection theory and social-role theory. While each theory has specific strengths and limitations depending on the victim's sex, research hardly differentiates between intrasex and intersex aggression. In the present study, 11,307 students (mean age = 14.96 years; 50% girls, 50% boys) from 597 school classes provided social-network data (aggression and friendship networks) as well as physical (body mass index) and psychosocial (gender and masculinity norms) information. Aggression networks were used to disentangle intra- and intersex aggression, whereas their class-aggregated sex differences were analyzed using contextual predictors derived from sexual-selection and social-role theories. As expected, results revealed that sexual-selection theory predicted male-biased sex differences in intrasex aggression, whereas social-role theory predicted male-biased sex differences in intersex aggression. Findings suggest the value of explaining sex differences separately for intra- and intersex aggression with a dual-theory framework covering both evolutionary and normative components.
Poland, Sarah E; Monks, Claire P; Tsermentseli, Stella
Executive function (EF) has been implicated in childhood aggression. Understanding of the role of EF in aggression has been hindered, however, by the lack of research taking into account the function and form of aggression and the almost exclusive focus on cool EF. This study examined the role of cool and hot EF in teacher reported aggression, differentiating between reactive and proactive as well as physical and relational aggression. Children (N = 106) completed laboratory tasks measuring cool (inhibition, planning, working memory) and hot EF (affective decision-making, delay of gratification). Cool, but not hot, EF significantly contributed to understanding of childhood aggression. Inhibition was a central predictor of childhood aggression. Planning and working memory, in contrast, were significant independent predictors of proactive relational aggression only. Added to this, prosocial behaviour moderated the relationship between working memory and reactive relational aggression. This study therefore suggests that cool EF, particularly inhibition, is associated with childhood aggression across the different functions and forms.
Stanković, Gordana; Nikolić, Valentina; Puskas, Laslo; Filipović, Branislav; Stojsić-Dzunja, Ljubica; Krivokuća, Dragan
Cerebral (sylvian) aqueduct is a narrow channel in the mesencephalon. It lies between the tectum and the tegmentum of the mesencephalon and is surrounded by the periaqueductal gray matter. The aim of this study was to determine the shape of the aqueduct of sylvius and the structure of its walls in a series of transverse histological sections. Serial transverse sections of the mesencephalon were examined in twenty adult brains of both sexes. Six sections were stained by the hematoxylin-eosin method. The rostral part of the the aqueduct has a triangular shape with dorsal concavity caused by retrocommissural fossae. In the middle, its shape is oval to irregular, the rostral part has a T shape due to isthmic recess on the floor. Walls of the aqueduct are coated with a layer of prismatic cells. Determination of the morphological and histological features of the mesencephalic aqueduct is important for differentiation between physiological and pathological processes in this region.
Valdiserri, R.O.; Borochovitz, D.
Thyroid tissue from 90 patients with a history of therapeutic irradiation to the head and neck in childhood and adolescence was examined microscopically. In addition to the well-known observation that these individuals have an increased incidence of primary thyroid carcinoma, it was also demonstrated that they have an increased incidence of benign histologic changes. These changes represent a spectrum from nonspecific hyperplastic lesions to benign neoplasis and thyroidltis.
Priday, Lee J.; Ireland, Carol A.; Chu, Simon; Kilcoyne, Jennifer; Mulligan, Caroline
Background Risk assessment instruments have become a preferred means for predicting future aggression, claiming to predict long-term aggression risk. Aims To investigate the predictive value over 12 months and 4 years of two commonly applied instruments (Historical, Clinical and Risk Management - 20 (HCR-20) and Violence Risk Appraisal Guide (VRAG)). Method Participants were adult male psychiatric patients detained in a high secure hospital. All had a diagnosis of personality disorder. The focus was on aggression in hospital. Results The actuarial risk assessment (VRAG) was generally performing better than the structured risk assessment (HCR-20), although neither approach performed particularly well overall. Any value in their predictive potential appeared focused on the longer time period under study (4 years) and was specific to certain types of aggression. Conclusions The value of these instruments for assessing aggression in hospital among patients with personality disorder in a high secure psychiatric setting is considered. Declaration of interest J.L.I., C.A.M. and J.K. are employed by the trust where the data were collected. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703760
Mizutani, Masaomi; Nawata, Shin-ichi; Hirai, Ichiro; Murakami, Gen; Kimura, Wataru
A regional lymphatic system is composed of the first, second, third and even fourth or much more intercalated nodes along the lymptatic route from the periphery to the venous angle or the thoracic duct. The third or fourth node is usually termed the last-intercalated node or end node along the route. Similarly, one of the supraclavicular nodes is known to correspond to the end node along the thoracic duct. It is generally called 'Virchow's node', in which the famous 'Virchow's metastasis' of advanced gastric cancer occurs. The histology of this node has not been investigated, although region-specific differences in histology are evident in human lymph nodes. We found macroscopically the end node in five of 30 donated cadavers. Serial sections were prepared for these five nodes and sections stained with hematoxylin and eosin. Histological investigation revealed that, on the inferior or distal side of the end node, the thoracic duct divided into three to 10 collateral ducts and these ducts surrounded the node. The node communicated with the thoracic duct and its collaterals at multiple sites in two to three hilus-like portions, as well as along the subcapsular sinus. Thus, the end node was aligned parallel to the thoracic duct. Moreover, the superficial and deep cortex areas of the end node were fragmented to make an island-like arrangement, which may cause the short-cut intranodal shunt. Consequenly, the filtration function of most of Virchow's node seemed to be quite limited.
Pourghasem, Mohsen; Shafi, Hamid; Babazadeh, Zahra
Diabetes mellitus is the most common cause of chronic renal disorders and end-stage kidney disease in developed countries. It is the major cause of dialysis and transplantation. Failure in renal function causes wide disorders in the body. Diabetes results in wide range of alterations in the renal tissue. It is believed that early histological changes in diabetic nephropathy are detectable 2 years after diabetes is diagnosed. The glomerular alterations are the most important lesions in the diabetic nephropathy (DN). The Renal Pathology Society provides a new pathological classification for the detection of histopathology of DN. It divides diabetic nephropathy into four hierarchical glomerular lesions. Alloxan or streptozotocin induced diabetic rat is the one most widely used specie to study DN. Histological changes in the rat DN closely resemble the human disease and the most information of this review was obtained through the study of rat DN. All cell types of the kidney such as mesangial cells, podocytes and tubulointerstitial cells are liable to be affected in the event of DN. Severity of renal lesions is associated to the clinical aspect of renal outcome, but the aim of this article was only to review the histological changes of kidney in diabetes mellitus. PMID:26644877
Aggarwal, Deepti; Soin, Navmeet; Kalita, Dipti; Pant, Leela; Kudesia, Madhur; Singh, Sompal
Papillary lesions of the breast pose diagnostic challenges on aspiration cytology due to overlapping features of benign and malignant entities. Accurate cytologic diagnosis of papillary breast carcinoma cannot usually be made pre-operatively. We present the case of an adult female who underwent fine-needle aspiration (FNA) of a left breast lump. FNA smears were highly cellular showing cohesive clusters, complex papillary fragments and few singly dispersed intact cells. The tumor cells had hyperchromatic nuclei, prominent nucleoli and mild nuclear pleomorphism. A cytologic impression of papillary lesion, possibly malignant (in view of high cellularity, complex papillae and single intact cells) was rendered. The lesion proved to be a papillary carcinoma with microscopic foci of stromal invasion on histologic examination. Papillary carcinoma, an uncommon subtype of breast carcinoma, should be considered while evaluating a papillary lesion with complex branching papillae containing delicate fibrovascular cores and singly lying intact atypical cells.
Ishida, Emi; Yamada, Masanobu; Horiguchi, Kazuhiko; Taguchi, Ryo; Ozawa, Atsushi; Shibusawa, Nobuyuki; Hashimoto, Koshi; Satoh, Tetsuro; Yoshida, Sachiko; Tanaka, Yoshiki; Yokota, Machiko; Tosaka, Masahiko; Hirato, Junko; Yamada, Shozo; Yoshimoto, Yuhei; Mori, Masatomo
Tumors in multiple endocrine neoplasia type 1 (MEN1) are generally benign. Since information on the pathogenesis of MEN1 in malignant cases is limited, we conducted genetic analysis and compared the expression of menin, p27(Kip1)(p27)/CDKN1B and p18(Ink4C)(p18)/CDKN2C with levels in benign cases. We describe the case of a 56 year-old male with an atypical prolactinoma and malignant pancreatic neuroenocrine tumor. At age 50, he had undergone transsphenoidal surgery to remove a prolactinoma. However, the tumor relapsed twice. Histological analysis of the recurrent prolactinoma revealed the presence of prolactin, a high MIB-1 index (32.1 %), p53-positive cells (0.2%), and an unusual association with FSH-positive cells. A few years later, he was also found to have a non-functioning pancreatic tumor with probable metastasis to the extradullar region. The metastatic region tested positive for chromogranin and CD56, and negative for prolactin, with 1.2 % of cells p53-positive. Although genetic analyses of the MEN1, p27, and p18 genes demonstrated no mutation, numbers of menin, p27 and p18 immuno-positive cells were significantly down-regulated in the recurrent prolactinoma, but that of p18 was intact in the metastatic region. Furthermore, MEN1 and p27 mRNA levels of the recurrent prolactinoma were down-regulated, particularly the MEN1 mRNA level, compared to levels in 10 cases of benign prolactinoma, while the p18 mRNA level was similar to that of normal pituitary. The tumor in this case may be a subtype of MEN1 showing more aggressive and malignant features probably induced by low levels of menin and p27.
Tirode, Franck; Surdez, Didier; Ma, Xiaotu; Parker, Matthew; Le Deley, Marie Cécile; Bahrami, Armita; Zhang, Zhaojie; Lapouble, Eve; Grossetête-Lalami, Sandrine; Rusch, Michael; Reynaud, Stéphanie; Rio-Frio, Thomas; Hedlund, Erin; Wu, Gang; Chen, Xiang; Pierron, Gaelle; Oberlin, Odile; Zaidi, Sakina; Lemmon, Gordon; Gupta, Pankaj; Vadodaria, Bhavin; Easton, John; Gut, Marta; Ding, Li; Mardis, Elaine R.; Wilson, Richard K.; Shurtleff, Sheila; Laurence, Valérie; Michon, Jean; Marec-Bérard, Perrine; Gut, Ivo; Downing, James; Dyer, Michael; Zhang, Jinghui; Delattre, Olivier
Ewing sarcoma is a primary bone tumor initiated by EWSR1–ETS gene fusions. To identify secondary genetic lesions that contribute to tumor progression, we performed whole-genome sequencing of 112 Ewing sarcoma samples and matched germline DNA. Overall, Ewing sarcoma tumors had relatively few single-nucleotide variants, indels, structural variants and copy-number alterations. Apart from whole chromosome arm copy-number changes, the most common somatic mutations were detected in STAG2 (17%), CDKN2A (12%), TP53 (7%), EZH2, BCOR, and ZMYM3 (2.7% each). Strikingly, STAG2 mutations and CDKN2A deletions were mutually exclusive, as confirmed in Ewing sarcoma cell lines. In an expanded cohort of 299 patients with clinical data, we discovered that STAG2 and TP53 mutations are often concurrent and are associated with poor outcome. Finally, we detected subclonal STAG2 mutations in diagnostic tumors and expansion of STAG2 immuno-negative cells in relapsed tumors as compared with matched diagnostic samples. PMID:25223734
Li, Hui; Zhu, Yitan; Burnside, Elizabeth S; Huang, Erich; Drukker, Karen; Hoadley, Katherine A; Fan, Cheng; Conzen, Suzanne D; Zuley, Margarita; Net, Jose M; Sutton, Elizabeth; Whitman, Gary J; Morris, Elizabeth; Perou, Charles M; Ji, Yuan; Giger, Maryellen L
Using quantitative radiomics, we demonstrate that computer-extracted magnetic resonance (MR) image-based tumor phenotypes can be predictive of the molecular classification of invasive breast cancers. Radiomics analysis was performed on 91 MRIs of biopsy-proven invasive breast cancers from National Cancer Institute's multi-institutional TCGA/TCIA. Immunohistochemistry molecular classification was performed including estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and for 84 cases, the molecular subtype (normal-like, luminal A, luminal B, HER2-enriched, and basal-like). Computerized quantitative image analysis included: three-dimensional