1,354,265 research outputs found
Yes-associated protein and immunosuppressive microenvironment in pancreatic cancer development: A new strategy to improve immunotherapy efficacy?
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ASSOCIAZIONE TRA STATO MUTAZIONALE DI KRAS E PATTERN DI ESPRESSIONE GENETICA NEL CARCINOMA DEL PANCREAS
No full textIntroduzione: Mutazioni attivanti del gene KRAS svolgono un ruolo fondamentale nella carcinogenesi pancreatica. Tuttavia recenti studi hanno dimostrato come la mutazione di KRAS non sia presente in tutti i casi di adenocarcinoma del pancreas, mettendone in discussione l’ubiquità in questa patologia. In questo studio, abbiamo valutato la presenza di differenze a livello molecolare tra adenocarcinomi del pancreas con mutazione di KRAS e senza mutazione; abbiamo valutato inoltre il ruolo prognostico delle diverse mutazioni di KRAS in pazienti affetti da adenocarcinoma pancreatico.
Pazienti e metodi: Abbiamo analizzato l’espressione di un panel di 29 geni in 42 carcinomi pancreatici KRAS wild type (WT) confrontandoli con 42 carcinomi KRAS mutati (MT). Inoltre, abbiamo valutato gli effetti della mutazione di KRAS e dei livelli di espressione genica sulla sopravvivenza dei pazienti.
Risultati: L’analisi di espressione genica ha mostrato che MUC6 (p=0.009), VEGFR-2 (p=0.020), VEGFB (p=0.026) e HGF (p= 0,011) risultavano significativamente più espressi e SMAD4 meno soppresso (p=0.003) nei carcinomi KRAS wild type. Al contrario, SHH (p=0.012) and IHH (p=0.031) sono risultati maggiormente espressi nei tumori KRAS mutati. Non sono state evidenziate differenze significative in termini di sopravvivenza tra pazienti con carcinomi KRAS wild type e mutati o tra le diverse mutazioni di KRAS.
Conclusioni: Lo stato mutazionale di KRAS sembra identificare due sottotipi di adenocarcinoma del pancreas con prognosi simile ma con caratteristiche molecolari distinte e verosimilmente con diversi bersagli molecolari
When the brain turns on with sexual desire: fMRI findings, issues, and future directions
No full textIntroduction More than 2 decades of neuroimaging research has sought to uncover the neurologic basis of sexual desire. However, the lack of a clear conceptual distinction between sexual desire and sexual arousal or even a broadly accepted definition of sexual desire has led to confusion in the literature regarding brain areas uniquely associated with sexual desire. Objectives (1) To critically review the neuroimaging literature that seeks to identify brain areas and networks involved in sexual desire; (2) to identify and discuss those brain areas and potential networks that are most promising for providing insights to sexual desire; and (3) to offer recommendations for future studies. Methods Existing meta-analyses were used as a starting point to identify relevant neuroimaging studies on sexual desire, arousal, and love. This base was then expanded via Google Scholar and forward citation tracking of already identified studies. Results Brain areas that are commonly associated with sexual desire and arousal include the amygdala, hypothalamus, dorsal and ventral striatum, anterior cingulate, insula, and prefrontal and orbitofrontal cortex. However, because the same basic paradigm has been used to study sexual desire and arousal, unambiguous conclusions regarding areas uniquely involved in sexual desire cannot be drawn. Moreover, the lack of connectivity analyses and a failure to acknowledge negative BOLD (blood-oxygen level dependent) significantly limit conclusions on the neural basis of sexual desire. Conclusion Five recommendations are made. First, stimulus types (ie, erotic vs sexually explicit) should be selected by the meaningful theoretical conceptualization of the constructs of interest. Second, participants should be provided with definitions of sexual desire, mental sexual arousal, and perceived genital sexual arousal, so they can choose which terms best describe their experience. Third, event-related designs should be used with caution when investigating sexual desire. Fourth, time series analyses should be used to identify both positive and negative BOLD. Fifth, connectivity analyses should be performed to identify brain networks
Sexual Desire in Women: Paradoxical and Non-Linear Associations with Depression and Anxiety
No full textABSTRACT
Introduction
Previous studies aimed at defining the relationship between high levels of negative mood and sexual desire have shown that, in addition to people describing an expected decrease in sexual desire, some people report an unexpected increase in sexual desire when depressed or anxious (referred to as a “paradoxical effect”, Bancroft et al., 2003). However, these past findings are based on self-inferred causal attributions and retrospective, one-time measurements. Moreover, tests of these associations at the low extreme of negative mood have not been previously conducted.
Objective
The aim of the present study was to replicate and expand previous findings regarding paradoxical effects of negative mood on sexual desire (Bancroft et al., 2003; Lykins, Janssen & Graham, 2006), by analyzing the associations between negative mood and sexual desire across the entire range of depression and anxiety symptoms. Moreover, to address previous limitations, we sought to test for replication using methods that are unaffected by recall bias, and that don't require participants to infer causal associations between their mood and sexual desire.
Methods
A sample of n=213 university-aged women completed daily questionnaires for two full menstrual cycles (M = 58 daily reports per participant). Measurement included changes in sexual desire, as well as psychological changes (anxiety and depression) and other symptoms associated with the menstrual cycle. Multilevel modeling with random intercepts and slopes, were used to test for individual differences in linear and non-linear associations between mood symptoms and changes in sexual desire. Cluster analyses were used to identify different patterns of change in sexual desire associated with different levels of mood.
Results
Previous findings were successfully replicated. Specifically, high levels of depression were associated with increased sexual desire in 12% of the sample (paradoxical association), and high levels of anxiety were associated with increased sexual desire in 20% of the sample (paradoxical association). Thus, in addition to women who showed either no significant changes or a decrease in sexual desire when depressed or anxious, results confirmed the presence of paradoxical associations between high levels of negative mood and sexual desire (see shaded area on Fig.1). Interestingly, these between-group paradoxical effects were also present at low levels of negative mood. That is, at low levels of negative mood some women reported increased sexual desire while others reported decreased sexual desire. Moreover, for both depression and anxiety, analyses revealed three clusters of women presenting different patterns of change in sexual desire across different levels of mood symptoms. Specifically, results demonstrated the presence of within-person paradoxical associations, whereby, there are some women for whom both low and high levels of negative mood are associated with the same change (an increase or a decrease) in sexual desire. These groups are labeled "Positive Paradoxical" and "Negative Paradoxical" in Fig.1.
Conclusions
Results from the present study underline the importance of considering individual variability when studying sexual desire. Multiple mechanisms, based on personality traits, learning, autonomic activity, or situational factors, might moderate the relationship between mood and sexual desire. A new integrative theoretical framework is proposed to interpret these results (see Figure 2).
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Sexual Desire in Women: Paradoxical and Nonlinear Associations with Anxiety and Depressed Mood
No full textThe aim of the present study was to expand previous findings regarding paradoxical effects of negative mood on sexual desire. This was done by considering the full range of depressed mood and anxiety symptoms and using methods that are unaffected by recall bias and that don’t require participants to infer causal associations between their mood and sexual desire. A convenience sample of 213 university students completed daily questionnaires for approximately two months. Multilevel random-effects models were used to estimate average effects for the entire sample and to test for variability across participants in the associations between negative mood and sexual desire, controlling also for potential influences of the menstrual cycle. Previous findings showing that some women report decreased sexual desire and others increased sexual desire when depressed or anxious were confirmed. More importantly, for both depressed mood and anxiety, results demonstrated the presence of within-person paradoxical associations, whereby there were some women for whom both low and high levels of negative mood were associated with the same change (an increase or a decrease) in sexual desire. Related to these diverse response patterns, paradoxical associations between negative mood and sexual desire were also present at low levels of negative mood. The discussion underlines the importance of considering individual variability and multifactorial nonlinear models when studying sexual desire
Oral contraceptive use and prevalence of vulvodynia: Are genital-specific side effects of OC use early signs of risk?
No full textBackground Past research suggests that oral contraceptive (OC) use increases the risk for vulvodynia/vestibulodynia, although results are often mixed or inconsistent.Aim To test whether OC use is associated with having a diagnosis of vulvodynia/vestibulodynia, whether the observed association varies across the type of OC, and whether side effects associated with OC use (ie, genital specific, negative affect, non-genital physical symptoms) are associated with having a diagnosis of vulvodynia/vestibulodynia.Methods A sample of n = 2171 adult females completed a questionnaire regarding OC use and associated side effects, and provided information on having a diagnosis of vulvodynia or vestibulodynia. Recruitment oversampled for women with genitopelvic pain, which provided n = 582 women (26.8% of overall sample) who had a diagnosis of vulvodynia or vestibulodynia. Binary logistic regressions were conducted to test for associations.Outcome Self-report of having received a diagnosis of vulvodynia or vestibulodynia.Results Results showed that all types of OCs were significantly associated with having a diagnosis, and that genital-specific side effects (vulvar/genital pain and vaginal dryness), but not affective or non-genital physical side effects, were associated with having a diagnosis of vulvodynia/vestibulodynia, with the strongest and most consistent effect being for vulvar/genital pain. Specifically, participants who reported vulvar/genital pain as a side effect of OC use were 3-5 times more likely than those without this side effect to have a diagnosis of vulvodynia/vestibulodynia. Analyses also controlled for 23 potential comorbid diagnoses with no or very little change to the associations between vulvodynia/vestibulodynia and the OC-use variables.Clinical Implications Early recognition and identification of genital-specific side effects of OC use may provide an opportunity for preventing genital pain from becoming chronic and difficult to manage.Strengths and Limitations This study uses a large sample, assesses unique associations with combined and progestin-only OCs, and for the first time addresses diverse OC-related side effects as potential risk indicators of vulvodynia. Limitations are the lack of prospective data, reliance on self-report measures, recruitment through social media outlets that may result in overestimating the effect sizes, and a lack of information on specific OCs used.Conclusions The present study provides evidence that OC use and genital-specific side effects of OC use are associated with having a diagnosis of vulvodynia/vestibulodynia and provides important information for managing potential OC-related risk for vulvodynia/vestibulodynia
Palliative treatment
No full textAlthough there has been a slow but steady decrease in incidence, gastric cancer remains the second leading cause of cancer death worldwide. Several aspects of the oncological and surgical management are still controversial and so gastric cancer represents a challenge for the surgeon. This book aims to delineate the state of the art in the surgical and oncological treatment of gastric cancer, describing the new TNM staging system, the extent of visceral resection and lymphadenectomy focusing on the different open and minimally invasive surgical techniques and discussing intraoperative chemohyperthermia and neoadjuvant and adjuvant treatment. Operative endoscopy and endoscopic ultrasonography are also discussed, as these now have an important role in both diagnostic work-up and palliative care of gastric cancer patients. Only a multidisciplinary approach involving the surgeon, gastroenterologist, and oncologist can produce the comprehensive and integrated overview that today constitutes a winning strategy for the optimization of results.What we hope we have achieved is a flexible, up-to-date, exhaustive publication, rich in illustrations and consistent with evidence-based medicin
Doses of capecitabine and oral vinorelbine are not relevant for efficacy in breast cancer patients: An analysis of dose intensity
No full textThe combination of capecitabine and vinorelbine is a valuable regimen in metastatic breast cancer treatment, even in pretreated patients.Forty-one pretreated consecutive patients were treated with capecitabine, 1000 mg/m2, twice daily, for two of three weeks, and vinorelbine, given orally at a dose of 60 mg/m2, days 1 and 8 in three-week cycles.A total of 301 courses was given, with a median of 8 courses (range, 3-13). Median dose intensity of capecitabine was 75\% of the planned dose and for vinorelbine it was 72\%. We observed 18 partial response (43.9\%), 15 stable disease (36.6\%), and 8 progressive disease (19.5\%). Median progression-free survival was 9 months (range, 1-22) and median overall survival was 27.2 months (range, 4-40). Overall response rate (complete + partial response) was not statistically different between patients who received more or less than the median dose intensity of capecitabine and vinorelbine, and there was no difference in overall survival or progression-free survival. CONCLUSIONS; Capecitabine and oral vinorelbine is an effective and well-tolerated "all-oral" regimen for advanced breast cancer patients. The use of lower doses than those currently recommended should be not detrimental in terms of efficacy
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