Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours

Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions

Specific, sensitive and rapid detection of human plasmodium knowlesi infection by loop-mediated isothermal amplification (LAMP) in blood samples

<p>Abstract</p> <p>Background</p> <p>The emergence of <it>Plasmodium knowlesi </it>in humans, which is in many cases misdiagnosed by microscopy as <it>Plasmodium malariae </it>due to the morphological similarity has contributed to the needs of detection and differentiation of malaria parasites. At present, nested PCR targeted on <it>Plasmodium </it>ssrRNA genes has been described as the most sensitive and specific method for Plasmodium detection. However, this method is costly and requires trained personnel for its implementation. Loop-mediated isothermal amplification (LAMP), a novel nucleic acid amplification method was developed for the clinical detection of <it>P. knowlesi</it>. The sensitivity and specificity of LAMP was evaluated in comparison to the results obtained via microscopic examination and nested PCR.</p> <p>Methods</p> <p>LAMP assay was developed based on <it>P. knowlesi </it>genetic material targeting the apical membrane antigen-1 (AMA-1) gene. The method uses six primers that recognize eight regions of the target DNA and it amplifies DNA within an hour under isothermal conditions (65°C) in a water-bath.</p> <p>Results</p> <p>LAMP is highly sensitive with the detection limit as low as ten copies for AMA-1. LAMP detected malaria parasites in all confirm cases (n = 13) of <it>P. knowlesi </it>infection (sensitivity, 100%) and none of the negative samples (specificity, 100%) within an hour. LAMP demonstrated higher sensitivity compared to nested PCR by successfully detecting a sample with very low parasitaemia (< 0.01%).</p> <p>Conclusion</p> <p>With continuous efforts in the optimization of this assay, LAMP may provide a simple and reliable test for detecting <it>P. knowlesi </it>malaria parasites in areas where malaria is prevalent.</p

Eficácia do exercício físico na fadiga dos pacientes com câncer durante o tratamento ativo: revisão sistemática e meta-análise

El objetivo del estudio fue determinar la efectividad del ejercicio físico en la fatiga de pacientes con cáncer durante el tratamiento activo. Las bases de datos de PubMed Central, EMBASE y OVID fueron consultadas hasta abril de 2014 para identificar ensayos clínicos aleatorizados, que evaluaran el efecto del ejercicio en la fatiga de pacientes con cáncer sometidos a tratamiento activo. Once estudios (n = 1.407) fueron incluidos. La quimioterapia fue el tratamiento más común (n = 1.028). Los estudios tuvieron bajo riesgo de sesgo y alta calidad metodológica. Las estimaciones de efecto mostraron que el ejercicio físico mejoró significativamente la fatiga (SMD = -3,0; IC95%: -5,21; -0,80), p < 0,0001. Se encontraron efectos similares para el entrenamiento de resistencia (SMD = -4,5; IC95%: -7,24; -1,82), p = 0,001. Se encontraron mejoras significativas en pacientes con cáncer de mama y de próstata (p < 0,05). El ejercicio es una intervención segura y eficaz en el control de la fatiga en pacientes sometidos a tratamiento activoThis study aimed to determine the effectiveness of physical exercise in decreasing fatigue in cancer patients during active treatment. The PubMed Central, EMBASE, and OVID databases were consulted up to April 2014 to identify randomized clinical trials that evaluated the effect of exercise on fatigue in cancer patients undergoing active treatment. Eleven studies (n = 1,407) were included. Chemotherapy was the most common form of treatment (n = 1,028). The studies showed a low risk of bias and high methodological quality. Effect estimates showed that physical exercise significantly improved fatigue (SMD = -3.0; 95%CI: -5.21; -0.80), p < 0.0001. Similar effects were found for resistance training (SMD = -4.5; 95%CI: -7.24; -1.82), p = 0.001. Significant improvements were found in breast and prostate cancer patients (p < 0.05). Exercise is a safe and effective intervention in the management fatigue in cancer patients undergoing active treatmentO objetivo foi determinar a efetividade do exercício físico sobre a fadiga em pacientes com câncer durante o tratamento ativo. As bases de dados PubMed Central, EMBASE e OVID foram consultadas até abril de 2014 para identificar ensaios clínicos randomizados que avaliaram o efeito do exercício sobre a fadiga em pacientes com câncer em tratamento ativo. Onze estudos (n = 1.407) foram incluídos. A quimioterapia foi o tratamento mais comum (n = 1.028). Os estudos tiveram baixo risco de viés e alta qualidade metodológica. As estimativas de efeito mostraram que o exercício melhorou significativamente a fadiga (DMP = -3,0; IC95%: -5,21; -0,80), p < 0,0001. Efeitos semelhantes sobre o treinamento de resistência (DMP = -4,5; IC95%: -7,24; -1,82), p = 0,001 foram encontrados. O exercício físico é uma intervenção segura e eficaz contra a fadiga em pacientes submetidos ao tratamento ativoEl presente trabajo forma parte del Proyecto Práctica del autoexamen de seno y los conocimientos, factores de riesgo y estilos de vida relacionados con el cáncer de mama en mujeres jóvenes de la Universidad Santo Tomás de Bogotá: un análisis transversal (9ª Convocatoria FODEIN- Código del proyecto 4110060001 - 008)

The Role and Limitations of 18-Fluoro-2-deoxy-d-glucose Positron Emission Tomography (FDG-PET) Scan and Computerized Tomography (CT) in Restaging Patients with Hepatic Colorectal Metastases Following Neoadjuvant Chemotherapy: Comparison with Operative and Pathological Findings

BACKGROUND: Recent data confirmed the importance of 18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in the selection of patients with colorectal hepatic metastases for surgery. Neoadjuvant chemotherapy before hepatic resection in selected cases may improve outcome. The influence of chemotherapy on the sensitivity of FDG-PET and CT in detecting liver metastases is not known. METHODS: Patients were assigned to either neoadjuvant treatment or immediate hepatic resection according to resectability, risk of recurrence, extrahepatic disease, and patient preference. Two-thirds of them underwent FDG-PET/CT before chemotherapy; all underwent preoperative contrast-enhanced CT and FDG-PET/CT. Those without extensive extrahepatic disease underwent open exploration and resection of all the metastases according to original imaging findings. Operative and pathological findings were compared to imaging results. RESULTS: Twenty-seven patients (33 lesions) underwent immediate hepatic resection (group 1), and 48 patients (122 lesions) received preoperative neoadjuvant chemotherapy (group 2). Sensitivity of FDG-PET and CT in detecting colorectal (CR) metastases was significantly higher in group 1 than in group 2 (FDG-PET: 93.3 vs 49%, P < 0.0001; CT: 87.5 vs 65.3, P = 0.038). CT had a higher sensitivity than FDG-PET in detecting CR metastases following neoadjuvant therapy (65.3 vs 49%, P < 0.0001). Sensitivity of FDG-PET, but not of CT, was lower in group 2 patients whose chemotherapy included bevacizumab compared to patients who did not receive bevacizumab (39 vs 59%, P = 0.068). CONCLUSIONS: FDG-PET/CT sensitivity is lowered by neoadjuvant chemotherapy. CT is more sensitive than FDG-PET in detecting CR metastases following neoadjuvant therapy. Surgical decision-making requires information from multiple imaging modalities and pretreatment findings. Baseline FDG-PET and CT before neoadjuvant therapy are mandatory

Harnessing Naturally Occurring Tumor Immunity: A Clinical Vaccine Trial in Prostate Cancer

International audienceBACKGROUND:Studies of patients with paraneoplastic neurologic disorders (PND) have revealed that apoptotic tumor serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. The purpose of this study was to assess the feasibility, safety, and immunogenicity of an apoptotic tumor-autologous dendritic cell (DC) vaccine.METHODS AND FINDINGS:We have modeled PND tumor immunity in a clinical trial in which apoptotic allogeneic prostate tumor cells were used to generate an apoptotic tumor-autologous dendritic cell vaccine. Twenty-four prostate cancer patients were immunized in a Phase I, randomized, single-blind, placebo-controlled study to assess the safety and immunogenicity of this vaccine. Vaccinations were safe and well tolerated. Importantly, we also found that the vaccine was immunogenic, inducing delayed type hypersensitivity (DTH) responses and CD4+ and CD8+ T cell proliferation, with no effect on FoxP3+ regulatory T cells. A statistically significant increase in T cell proliferation responses to prostate tumor cells in vitro (p = 0.002), decrease in prostate specific antigen (PSA) slope (p = 0.016), and a two-fold increase in PSA doubling time (p = 0.003) were identified when we compared data before and after vaccination.CONCLUSIONS:An apoptotic cancer cell vaccine modeled on naturally occurring tumor immune responses in PND patients provides a safe and immunogenic tumor vaccine

High-risk human papillomavirus infections in breast cancer in Syrian women and their association with Id-1 expression: a tissue microarray study

High-risk human papillomaviruses (HPVs) could be important risk factors for breast carcinogenesis and metastasis. Based on this hypothesis, we recently studied the effect of E6/E7 onco-proteins of high-risk HPV type 16 in two non-invasive human breast cancer cell lines, BT20 and MCF7; we reported that E6/E7 converts these cell lines to invasive cells. This is accompanied by an overexpression of Id-1, which is an important regulator of breast metastasis. In this investigation, we examined the presence of high-risk HPVs (16, 18, 31, 33 and 35) and the expression of their E6 onco-protein as well as their correlation with Id-1 gene expression, using polymerase chain reaction (PCR) and tissue microarray (TMA) analysis, respectively, in a cohort of 113 Syrian breast cancer patients. We found that high-risk HPV types 16, 18, 31, 33 and 35 are present in 8.84, 9.73, 7.07, 55.75 and 37.16% of our samples, respectively, which represent invasive breast cancers. Overall, 69 (61.06%) of the 113 samples are HPV positive; among these specimens 24 tissues (34.78%) are coinfected with more than one HPV type. Furthermore, we report that the expression of the E6 onco-protein of these high-risk HPVs is correlated with Id-1 overexpression in the majority of invasive breast cancer tissue samples. Our data suggest that high-risk HPV infections are associated with human breast cancer progression in Syrian women

PTB Domain-Directed Substrate Targeting in a Tyrosine Kinase from the Unicellular Choanoflagellate Monosiga brevicollis

Choanoflagellates are considered to be the closest living unicellular relatives of metazoans. The genome of the choanoflagellate Monosiga brevicollis contains a surprisingly high number and diversity of tyrosine kinases, tyrosine phosphatases, and phosphotyrosine-binding domains. Many of the tyrosine kinases possess combinations of domains that have not been observed in any multicellular organism. The role of these protein interaction domains in M. brevicollis kinase signaling is not clear. Here, we have carried out a biochemical characterization of Monosiga HMTK1, a protein containing a putative PTB domain linked to a tyrosine kinase catalytic domain. We cloned, expressed, and purified HMTK1, and we demonstrated that it possesses tyrosine kinase activity. We used immobilized peptide arrays to define a preferred ligand for the third PTB domain of HMTK1. Peptide sequences containing this ligand sequence are phosphorylated efficiently by recombinant HMTK1, suggesting that the PTB domain of HMTK1 has a role in substrate recognition analogous to the SH2 and SH3 domains of mammalian Src family kinases. We suggest that the substrate recruitment function of the noncatalytic domains of tyrosine kinases arose before their roles in autoinhibition

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Repertoire Enhancement with Adoptively Transferred Female Lymphocytes Controls the Growth of Pre-Implanted Murine Prostate Cancer

In prostate cancer, genes encoding androgen-regulated, Y-chromosome-encoded, and tissue-specific antigens may all be overexpressed. In the adult male host, however, most high affinity T cells targeting these potential tumor rejection antigens will be removed during negative selection. In contrast, the female mature T-cell repertoire should contain abundant precursors capable of recognizing these classes of prostate cancer antigens and mediating effective anti-tumor immune responses.We find that syngeneic TRAMP-C2 prostatic adenocarcinoma cells are spontaneously rejected in female hosts. Adoptive transfer of naïve female lymphocytes to irradiated male hosts bearing pre-implanted TRAMP-C2 tumor cells slows tumor growth and mediates tumor rejection in some animals. The success of this adoptive transfer was dependent on the transfer of female CD4 T cells and independent of the presence of CD25-expressing regulatory T cells in the transferred lymphocytes. We identify in female CD4 T cells stimulated with TRAMP-C2 a dominant MHC II-restricted response to the Y-chromosome antigen DBY. Furthermore, CD8 T cell responses in female lymphocytes to the immunodominant MHC I-restricted antigen SPAS-1 are markedly increased compared to male mice. Finally, we find no exacerbation of graft-versus-host disease in either syngeneic or minor-antigen mismatched allogeneic lymphocyte adoptive transfer models by using female into male versus male into male cells.This study shows that adoptively transferred female lymphocytes, particularly CD4 T cells, can control the outgrowth of pre-implanted prostatic adenocarcinoma cells. This approach does not significantly worsen graft-versus-host responses suggesting it may be viable in the clinic. Further, enhancing the available immune repertoire with female-derived T cells may provide an excellent pool of prostate cancer reactive T cells for further augmentation by combination with either vaccination or immune regulatory blockade strategies