Right Brain: The Unraveling.

"The Unraveling" is a personal reflection from my perspective as a new fellow in Multiple Sclerosis/Neuroimmunology on the impact of multiple sclerosis on patients and their loved ones. I compare my more recent patient encounters with past experiences working with a different, also mostly female, patient population that included those affected by intimate partner violence. Female vulnerability and the spectrum of human suffering serve as common themes throughout. However, my ultimate goal is to empower readers, from trainees to faculty to patients, to overcome their unique challenges in life and help others do the same.

Chagas Immunochromatographic Rapid Test in the Serological Diagnosis of Trypanosoma cruzi Infection in Wild and Domestic Canids.

Canis lupus familiaris (domestic dog) represents a reliable sentinel for the occurrence of a well-established transmission cycle of Trypanosoma cruzi among wild mammals in the surroundings and, consequently, where the risk of human infection exists. Serological diagnosis is the chosen method to identify T. cruzi infection in dogs that, in Brazil, rarely present positive parasitological tests. The use of recombinant chimeric parasitic antigens results in a sensitive and specific serological diagnostic test in contrast to the use of crude T. cruzi antigens. Our objective was to evaluate the Chagas/Bio-Manguinhos Lateral Flow Immunochromatographic Rapid Test (Chagas-LFRT) for the diagnosis of T. cruzi infection in domestic dogs and the potential of application of this diagnostic platform to wild canid species. Two recombinant proteins (IBMP-8.1 and IBMP-8.4) that displayed the best performance in the enzyme immunoassay (ELISA) in previous studies were tested in a platform with two diagnostic bands. A panel of 281 dog serum samples was evaluated: 133 positive for T. cruzi by serological diagnosis, including 20 samples with positive blood cultures belonging to different discrete typing units (DTUs); 129 negative samples; and 19 samples from dogs infected by other trypanosomatids: Leishmania infantum, Trypanosoma rangeli, Trypanosoma caninum and Crithidia mellificae, in addition to samples infected by Anaplasma platys, Dirofilaria immitis and Erlichia sp. that were employed to evaluate eventual cross-reactions. We also evaluated the Chagas-LFRT to detect T. cruzi infection in 9 serum samples from six wild canid species. We observed that the intensity pattern of the bands was directly proportional to the serological titer observed in IFAT. The sensitivity was 94%, the specificity was 91% according to the ROC curve, and the defined cutoff was an optical density of 4.8. The agreement obtained was considered substantial by the kappa analysis (84%). From T. cruzi positive hemoculture samples, 88.9% were positive by Chagas-LFRT. The test was efficient in recognizing infections by five of the six T. cruzi DTUs. Cross-reactions were not observed in infections by L. infantum, T. rangeli, T. caninum and D. immitis; however, they were observed in sera of dogs infected by Crithidia mellificae, Anaplasma sp. and Erlichia sp. A strong reaction was observed when serum samples from wild canids were submitted to the Protein A affinity test, confirming its applicability for these species. This test will allow rapid preventive actions in areas with high risk to the emergence of Chagas disease in a safer, reliable, low-cost and immediate manner, without the need for more complex laboratory tests.

Persistent seropositivity in oophorectomy-resistant anti-NMDA receptor encephalitis.

To discuss (1) the significance of seropositivity in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and (2) clinical decision making in oophorectomy resistant disease. Patient A (a 35-year-old woman) had high CSF and serum anti-NMDA antibody titres, a complicated hospital course, little improvement with first and second-line therapies, and remained with high CSF and serum antibody titres despite unilateral oophorectomy, requiring a nearly 13-month long hospitalisation. Conversely, patient B (a 29-year-old woman) had low CSF titres, seronegative disease and quickly recovered to her baseline with first line therapies and oophorectomy. Anti-NMDAR antibodies are themselves pathological, causing signalling dysfunction and internalisation of the NMDAR. Seropositivity with anti-NMDAR antibodies likely reflects leakage from the blood-brain barrier, with high serum titres being a downstream effect of high CSF titres. Empiric bilateral oophorectomies is controversial but appropriate on a case-by-case basis in extremely treatment-resistant NMDAR encephalitis given the possibility of antigenic microteratomas, which may not be detected on imaging or even bilateral ovarian biopsies.

Individual- and City-Level Socioeconomic Factors and Tooth Loss among Elderly People: A Cross-Level Multilevel Analysis.

This study aimed to test the association of contextual and individual socioeconomic status with tooth loss among Brazilian elderly people aged 65-74 years. Data from 5435 elderly participants from the Brazilian National Oral Health Survey (2010) were linked to city-level data for 27 state capitals and the Federal District. Tooth loss was clinically assessed according to the number of missing natural teeth. Contextual social variables included Human Development Index income (HDI-income) and HDI-education. Individual socioeconomic measures were monthly family income and years of schooling. Covariates included sex, skin colour, number of residents per room and number of goods. Multilevel Negative Binomial regression models were used to estimate rate ratios (RR) and 95% confidence intervals between contextual and individual variables and tooth loss. Contextual and individual income and education measures were consistently associated with tooth loss. Elderly people living in cities with low HDI-income and low HDI-education were respectively 21% and 33% more likely to present tooth loss. Cross-level interaction suggested that the relationship of lower income and lower schooling with tooth loss is different across levels of city-level income and city-level education inequality, respectively. Public policies aiming to reduce the income and education gaps and preventive dental interventions are imperative to tackle tooth loss among elderly people.

Ultrastructural aspects of primary anetoderma.

Anetoderma is a rare cutaneous disorder characterized by focal loss of dermal elastic tissue due to unknown mechanisms. Primary anetoderma develops on clinical normal skin, without any preceding dermatosis and it can be associated with autoimmune conditions. Secondary anetoderma develops on the same area of a previous disorder, such as infectious, neoplastic or inflammatory diseases. A 37-year-old female patient noticed for 4 years circumscribed, normochromic, asymptomatic herniated plaques on the trunk and upper limbs. Family history was negative. Only a positive antinuclear factor (ANF) test, with titer of 1:160 and nuclear homogeneous pattern was found. Light microscopy with Weigert staining showed a lessening of elastic fibers with fragmentation; the oxytalanic fibers were also affected or absent. Transmission electron microscopy showed fragmentation and granular degeneration of elastic fibers. With greater magnification, fragments similar to those seen with optical microscopy were identified. The collagen fibers did not present any alteration. The examination of the dermis with scanning electron microscopy also identified fragmentation and significant fissures of the elastic tissue, granular degeneration was also observed. With greater magnification fragmented elastic fibers were seen.

Effectiveness of E-Learning in Oral Radiology Education: A Systematic Review.

E-learning has been used recently in dental curricula to support traditional learning methods. However, the published literature concerning e-learning in oral radiology has shown mixed conclusions. The aim of this systematic review was to provide a synthesis of the effectiveness of e-learning in oral radiology education when compared with traditional classroom learning methods. A search of the literature was conducted on the LILACS, PubMed, Science Direct, Scopus, and Web of Science databases. Trials registries were also consulted for ongoing trials, and a partial grey literature search was conducted. Controlled trials about oral radiology education that compared any e-learning method with a control group using any traditional classroom instruction method were included. E-learning effectiveness was measured using three outcomes from Kirkpatrick's model of evaluation: attitudes about e-learning, knowledge gain, and performance on clinical procedures. Data were analyzed descriptively. Qualitative appraisal was performed according to the Cochrane risk of bias tool for randomized trials and MINORS tool for non-randomized trials. Eleven studies met the inclusion criteria. Risk of bias was identified related to the selection procedures, blinding, lack of sample size calculation, and incomplete analyses. Ten studies reported that students had positive attitude when using e-learning. Results from the knowledge gain outcome were mixed. Only two studies examined performance on clinical procedures, showing contrasting results. The evidence reviewed in this study suggests that e-learning in oral radiology is at least as effective as traditional learning methods and that students have positive attitudes about e-learning.

An empirical evaluation of the translation to Brazilian Portuguese of the Loss of Control over Eating Scale (LOCES)

Abstract Background Loss of control over eating is a key feature of the most prevalent eating disorders. The Loss of Control over Eating Scale (LOCES) enables a thorough assessment of loss of control over eating. Objective This study empirically evaluated the translation of the LOCES from English to Brazilian Portuguese. Methods The scale was translated to Brazilian Portuguese and back translated to English in order to check accuracy of the translation. Two hundred and ninety-three medicine and nursing students, 60 males and 233 females, 18-55 years old, with mean body mass index (BMI) 23.2 kg/m2 (SD 4.1), recruited between August and December 2014, answered the Brazilian Portuguese LOCES. An exploratory factor analysis was performed. Results Exploratory factor analysis of the Brazilian Portuguese LOCES showed three distinct factors of the loss of control over eating (disgust/negative sensations, cognitive experiences/dissociation, and “positive” effects) as well as moderate consistency with previous reports of exploratory factor analysis of the English version. Discussion This study showed satisfactory translation of the LOCES from English to Brazilian Portuguese, which is now ready for further validation.

Three-dimensional morphometric analysis of microglial changes in a mouse model of virus encephalitis: age and environmental influences.

Many RNA virus CNS infections cause neurological disease. Because Piry virus has a limited human pathogenicity and exercise reduces activation of microglia in aged mice, possible influences of environment and aging on microglial morphology and behavior in mice sublethal encephalitis were investigated. Female albino Swiss mice were raised either in standard (S) or in enriched (EE) cages from age 2 to 6 months (young - Y), or from 2 to 16 months (aged - A). After behavioral tests, mice nostrils were instilled with Piry-virus-infected or with normal brain homogenates. Brain sections were immunolabeled for virus antigens or microglia at 8 days post-infection (dpi), when behavioral changes became apparent, and at 20 and 40 dpi, after additional behavioral testing. Young infected mice from standard (SYPy) and enriched (EYPy) groups showed similar transient impairment in burrowing activity and olfactory discrimination, whereas aged infected mice from both environments (EAPy, SAPy) showed permanent reduction in both tasks. The beneficial effects of an enriched environment were smaller in aged than in young mice. Six-hundred and forty microglial cells, 80 from each group were reconstructed. An unbiased, stereological sampling approach and multivariate statistical analysis were used to search for microglial morphological families. This procedure allowed distinguishing between microglial morphology of infected and control subjects. More severe virus-associated microglial changes were observed in young than in aged mice, and EYPy seem to recover microglial homeostatic morphology earlier than SYPy . Because Piry-virus encephalitis outcomes were more severe in aged mice, it is suggested that the reduced inflammatory response in those individuals may aggravate encephalitis outcomes.

Monitor intracardíaco implantável (AngelMed Guardian) para detectação de isquemia miocárdica / Implantable intracardiac monitor (AngelMed Guardian) for the detection of myocardial ischemia

A maioria das mortes por infarto agudo do miocárdio (IAM) ocorre nas primeiras horas da manifestação da oclusão coronariana; portanto, em geral, acontece fora do ambiente hospitalar. O tempo decorrido entre o início da oclusão coronariana até o tratamento ser realizado é diretamente proporcional à morbidade e mortalidade cardiovascular. O prognóstico dos pacientes depende da rapidez em chegar a um hospital e quão rápido o hospital possa diagnosticar o IAM e realizar reperfusão coronariana. Estudos indicam que o tempo médio decorrido entre o início da apresentação de sintomas de IAM e a chegada do paciente ao hospital permanece entre 2 e 3 horas; no entanto, sabe-se que um terço dos IAMs é assintomático e, nesses casos, o diagnóstico é realizado posteriormente por achados clínicos através de exames complementares. Para tanto, o diagnóstico precoce é essencial para melhorar os resultados terapêuticos. Um dispositivo que monitore o coração, continuamente, via uma conexão intracardíaca, pode ser benéfico para indivíduos com doença arterial coronária (DAC) e alto risco cardiovascular, por alertá-los em tempo real quando alterações eletrocardiográficas agudas no segmento ST são detectadas (indicando oclusão coronariana aguda). Estudos nos EUA e no Brasil demonstraram que indivíduos que receberam o monitor intracardíaco implantável (MICI) apresentaram tempo médio de resposta, entre o início de um evento coronariano oclusivo e a chegada ao hospital, de 19,5 minutos, mostrando redução substancial no tempo habitual de resposta de 2-3 horas. Outros estudos demonstraram a segurança, a viabilidade e o potencial benefício de se utilizar um dispositivo de monitoramento intracardíaco para alertar o paciente de eventos coronarianos, mesmo que eles eventos sejam assintomáticos. Dessa forma, um sistema com capacidade de alertar em tempo real poderia antecipar a terapia de reperfusão e potencialmente prevenir, em vez de interromper, IAM em pacientes com DAC...

Citations of Brazilian physical therapy journals in national publications.

BACKGROUND: Quotations in Brazilian journals are mainly obtained from national articles (articles from Brazilian journals); thus, it is essential to determine how frequently these articles reference Brazilian journals. OBJECTIVE: This study sought to verify how frequently national papers are cited in the references of three Brazilian physical therapy journals. METHOD: All references for articles published in Fisioterapia em Movimento, Fisioterapia e Pesquisa and Revista Brasileira de Fisioterapia between 2010 and 2012 were evaluated. In particular, the numbers of national articles and international articles (articles from international journals) cited in these references were determined. RESULTS: A total of 13,009 references cited by 456 articles were analyzed, and 2,924 (22.47%) of the cited works were national articles. There were no significant differences among the three examined years. A total of 36 (7.89%) articles did not cite national articles, whereas 65 (13.25%) articles cited more national articles than international articles. CONCLUSION: On average, 22.47% of the works cited by the evaluated articles were national articles. No significant differences were detected among the three analyzed years.

Intranodal papillary epithelial proliferations: a local process with a spectrum of morphologies and frequent association with papillomas in the breast.

Lymph nodes, particularly those draining in major anatomic sites like axilla, pelvis, and neck are potential sites for the occasional presence of ectopic tissue, usually representative of the organ being drained. Owing to the uncertainty surrounding the processes causing such findings, and particularly in the setting of lymph node dissection and sampling for cancer staging, intranodal epithelial inclusions, rare as they may be, might be fertile soil for overdiagnosis of metastatic disease. Intranodal papillary inclusions are particularly problematic and challenging because of their complex architecture that may easily mimic a metastasis. From the files of the Breast Consultation Service, Department of Pathology at the Vanderbilt University Medical Center in Nashville, we identified 6 cases in which histopathologic examination of axillary lymph nodes revealed intranodal papillary inclusions (papillary epithelial proliferations). One case showed atypical ductal hyperplasia, 1 showed low-grade ductal carcinoma in situ, and 1 showed usual ductal hyperplasia. The corresponding breast lesions were papillomas in 5 of 6 cases, 2 of which displayed atypical ductal hyperplasia, whereas 3 showed low-grade ductal carcinoma in situ. One case showed intermediate-grade invasive ductal carcinoma, and the associated intranodal papilloma lacked atypia. Our findings suggest that intranodal papillary proliferations are often, although not exclusively, associated with papillary and noninvasive breast neoplasms, hence highlighting the origin of these intranodal lesions as independent de novo nodal processes rather than metastatic deposits.

Citations of Brazilian physical therapy journals in national publications / Citacao de periodicos de fisioterapia brasileiros em publicacoes nacionais

Background: Quotations in Brazilian journals are mainly obtained from national articles (articles from Brazilian journals); thus, it is essential to determine how frequently these articles reference Brazilian journals. Objective: This study sought to verify how frequently national papers are cited in the references of three Brazilian physical therapy journals. Method: All references for articles published in Fisioterapia em Movimento, Fisioterapia e Pesquisa and Revista Brasileira de Fisioterapia between 2010 and 2012 were evaluated. In particular, the numbers of national articles and international articles (articles from international journals) cited in these references were determined. Results: A total of 13,009 references cited by 456 articles were analyzed, and 2,924 (22.47%) of the cited works were national articles. There were no significant differences among the three examined years. A total of 36 (7.89%) articles did not cite national articles, whereas 65 (13.25%) articles cited more national articles than international articles. Conclusion: On average, 22.47% of the works cited by the evaluated articles were national articles. No significant differences were detected among the three analyzed years. .

Contextualização: A principal fonte das citações dos periódicos brasileiros provém de artigos nacionais, sendo fundamental conhecer o quanto eles referenciam artigos de periódicos brasileiros. Objetivo: Verificar a frequência com que artigos nacionais são citados nas referências de artigos de três periódicos brasileiros de fisioterapia. Método: Avaliaram-se todas as referências dos artigos publicados nos periódicos: Fisioterapia em Movimento, Fisioterapia e Pesquisa e Revista Brasileira de Fisioterapia nos anos de 2010 a 2012, verificando a quantidade de artigos provenientes de revistas nacionais e internacionais. Resultados: Foram analisadas 13.009 referências, dispostas em 456 artigos nas três revistas. Desse total, 2.924 (22,47%) foram de periódicos nacionais. Não houve diferença significativa entre os períodos analisados. Trinta e seis (7,89%) dos artigos não citaram artigo de periódico nacional, e 65 (14,25%) citaram mais artigos nacionais que estrangeiros. Conclusão: O valor médio da porcentagem de artigos nacionais citados nos artigos estudados foi de 22,47%. Não houve diferença entre os períodos estudados. .

Dysregulation of BMI1 and microRNA-16 collaborate to enhance an anti-apoptotic potential in the side population of refractory mantle cell lymphoma.

The proto-oncogene BMI1 and its product, Bmi1, is overexpressed in various types of tumors, particularly in aggressive tumors and tumors resistant to conventional chemotherapy. BMI1/Bmi1 is also crucially involved in cancer-initiating cell maintenance, and is recurrently upregulated in mantle cell lymphoma (MCL), especially aggressive variants. Recently, side population (SP) cells were shown to exhibit tumor-initiating characteristics in various types of tumors. In this study, we show that recurrent MCL cases significantly exhibit upregulation of BMI1/Bmi1. We further demonstrate that clonogenic MCL SP shows such tumor-initiating characteristics as high tumorigenicity and self-renewal capability, and that BMI1 was upregulated in the SP from recurrent MCL cases and MCL cell lines. On screening for upstream regulators of BMI1, we found that expression of microRNA-16 (miR-16) was downregulated in MCL SP cells by regulating Bmi1 in the SPs, leading to reductions in tumor size following lymphoma xenografts. Moreover, to investigate downstream targets of BMI1 in MCL, we performed cross-linking/chromatin immunoprecipitation assay against MCL cell lines and demonstrated that Bmi1 directly regulated pro-apoptotic genes such as BCL2L11/Bim and PMAIP1/Noxa, leading to enhance anti-apoptotic potential of MCL. Finally, we found that a proteasome inhibitor bortezomib, which has been recently used for relapsed MCL, effectively induced apoptosis among MCL cells while reducing expression of Bmi1 and increasing miR-16 in MCL SP. These results suggest that upregulation of BMI1 and downregulation of miR-16 in MCL SP has a key role in the disease's progression by reducing MCL cell apoptosis. Our results provide important new insight into the pathogenesis of MCL and strongly suggest that targeting BMI1/Bmi1 might be an effective approach to treating MCL, particularly refractory and recurrent cases.

O fator de impacto influencia na ética das instruções aos autores de uma revista? / Does impact factor influence the ethics of the instructions provided to journal authors?

OBJETIVO: Verificar se o fator de impacto de um periódico é um mecanismo modificador dos quesitos éticos descritos nas instruções aos autores de revistas médicas nacionais. MÉTODOS: Foram selecionadas 48 revistas divididas em dois grupos: grupo com fator de impacto (n = 24), e grupo sem fator de impacto (n = 24). Foi comparada a quantidade de quesitos éticos entre os dois grupos baseados num protocolo de pesquisa próprio, variando de zero a seis pontos, analisando a presença de aprovação por Comitê de Ética em Pesquisa; citação de que a pesquisa segue os preceitos da Declaração de Helsinque e as normas da resolução 196/96; uso de Termo de Consentimento Livre e Esclarecido; informação sobre os conflitos de interesse dos Pesquisadores; e solicitação para que os estudos clínicos sejam cadastrados no Registro Brasileiro de Estudos Clínicos. RESULTADOS: A média da pontuação do grupo com fator de impacto foi significativamente maior que o grupo sem fator de impacto (3,12 ±1,03 vs. 2,08 ±1,64, p = 0,0121). Quando cada quesito ético foi comparado entre os grupos, houve diferença significativa apenas entre a solicitação do TCLE e o conflito de interesses (p < 0,05). CONCLUSÃO: O fator de impacto é um fator determinante na ética contida nas instruções aos autores das revistas científicas, mostrando que as revistas de maior qualidade buscam artigos com melhores desenhos e que sejam criteriosos quando do início da pesquisa.

OBJECTIVE: Verify whether a journal's impact factor is a mechanism that modifies the ethi cal requirements described in the instructions provided to authors of articles published in Brazilian medical journals. METHODS: 48 selected journals were divided into two groups: impact-factor (n = 24), and no impact-factor (n = 24). The number of ethical requirements was compared between both groups based on a specific research protocol, ranging from zero to six points, analyzing the presence of an approval by a research ethics committee; reference to the fact that the research follows the precepts of the Declaration of Helsinki and the rules of Resolution 196/96; use of an informed consent; information about the authors' conflicts of interest; and a request for registration of clinical trials in the Brazilian Clinical Trials Registry. RESULTS: The average score of the impact-factor group was significantly higher than that of the no-impact-factor group (3.12 ± 1.03 vs. 2.08 ± 1.64, p = 0.0121). When each ethical requirement was compared between the groups, there was significant difference only between the requirement of an informed consent and the disclosure of conflicts of interest (p < 0.05). CONCLUSION: The impact factor is a determinant factor on the ethics included in the instructions to authors of articles in scientific journals, showing that higher-quality journals seek better-designed articles that are conscientious at the beginning of the research.

Light and electron microscopy of classical Ehlers-Danlos syndrome.

A 12-year-old boy with difficulty in wound healing and abnormal scars since early childhood was examined. Light microscopy showed loose and disperse dermal collagen with rare bundles, and fibroblasts show an irregular morphology. The fibrous sheath of hair presented a normal parallel distribution of the collagen fibers with normal spindle-shaped fibroblasts. Transmission electron microscopy also found disorganized collagen fibers, which were seen in a same field in longitudinal and cross sections. With high magnifications, an amorphous substance was seen near to loose collagen fibers, which showed variable diameters in cross sections. Scanning electron microscopy of the dermis showed disorganized collagen fibers and with higher magnification, important collagen disarrangement was observed with isolated and crossed-over fibers.

Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance.

Neoadjuvant chemotherapy (NAC) induces a pathological complete response (pCR) in ~30% of patients with breast cancer. However, many patients have residual cancer after chemotherapy, which correlates with a higher risk of metastatic recurrence and poorer outcome than those who achieve a pCR. We hypothesized that molecular profiling of tumors after NAC would identify genes associated with drug resistance. Digital transcript counting was used to profile surgically resected breast cancers after NAC. Low concentrations of dual specificity protein phosphatase 4 (DUSP4), an ERK phosphatase, correlated with high post-NAC tumor cell proliferation and with basal-like breast cancer (BLBC) status. BLBC had higher DUSP4 promoter methylation and gene expression patterns of Ras-ERK pathway activation relative to other breast cancer subtypes. DUSP4 overexpression increased chemotherapy-induced apoptosis, whereas DUSP4 depletion dampened the response to chemotherapy. Reduced DUSP4 expression in primary tumors after NAC was associated with treatment-refractory high Ki-67 scores and shorter recurrence-free survival. Finally, inhibition of mitogen-activated protein kinase kinase (MEK) synergized with docetaxel treatment in BLBC xenografts. Thus, DUSP4 downregulation activates the Ras-ERK pathway in BLBC, resulting in an attenuated response to anti-cancer chemotherapy.

Rapid improvement of osseous sarcoidosis after the treatment of pulmonary aspergillosis by itraconazole.

Osseous sarcoidosis is relatively uncommon, and treatment with corticosteroids is not always effective. Moreover, patients with an advanced stage of pulmonary sarcoidosis are sometimes infected with aspergillus in the cavities of the pulmonary lesions, and long-term use of corticosteroids should be prohibited to prevent the development of fatal invasive pulmonary aspergillosis. Here, we described a unique case of osseous sarcoidosis with pulmonary aspergillosis, showing a rapid improvement of the osseous symptoms just after the administration of the antifungal agent, itraconazole. Itraconazole is likely to become a candidate among new therapeutic agents for osseous sarcoidosis.

The role of microRNA-150 as a tumor suppressor in malignant lymphoma.

MicroRNA (miRNA; miR) is a class of small regulatory RNA molecules, the aberrant expression of which can lead to the development of cancer. We recently reported that overexpression of miR-21 and/or miR-155 leads to activation of the phosphoinositide 3-kinase (PI3K)-AKT pathway in malignant lymphomas expressing CD3(-)CD56(+) natural killer (NK) cell antigen. Through expression analysis, we show in this study that in both NK/T-cell lymphoma lines and samples of primary lymphoma, levels of miR-150 expression are significantly lower than in normal NK cells. To examine its role in lymphomagenesis, we transduced miR-150 into NK/T-cell lymphoma cells, which increased the incidence of apoptosis and reduced cell proliferation. Moreover, the miR-150 transductants appeared senescent and showed lower telomerase activity, resulting in shortened telomeric DNA. We also found that miR-150 directly downregulated expression of DKC1 and AKT2, reduced levels of phosphorylated AKT(ser473/4) and increased levels of tumor suppressors such as Bim and p53. Collectively, these results suggest that miR-150 functions as a tumor suppressor, and that its aberrant downregulation induces continuous activation of the PI3K-AKT pathway, leading to telomerase activation and immortalization of cancer cells. These findings provide new insight into the pathogenesis of malignant lymphoma.