32 research outputs found
Effects of transcranial static magnetic field stimulation over the left dorsolateral prefrontal cortex on random number generation
OBJECTIVE:
Focal application of transcranial static magnetic field stimulation (tSMS) is a neuromodulation technique, with predominantly inhibitory effects when applied to the motor, somatosensory or visual cortex. Whether this approach can also transiently interact with dorsolateral prefrontal cortex (DLPFC) function remains unclear. The suppression of habitual or competitive responses is one of the core executive functions linked to DLPFC function. This study aimed to assess the impact of tSMS on the prefrontal contributions to inhibitory control and response selection by means of a RNG task.
METHODS:
We applied 20 min of tSMS over the left DLPFC of healthy subjects, using a real/sham cross-over design, during performance of a RNG task. We used an index of randomness calculated with the measures of entropy and correlation to assess the impact of stimulation on DLPFC function.
RESULTS:
The randomness index of the sequences generated during the tSMS intervention was significantly higher compared to those produced in the sham condition.
CONCLUSIONS:
Our results indicate that application of tSMS transiently modulates specific functional brain networks in DLPFC, which indicate a potential use of tSMS for treatment of neuropsychiatric disorders.
SIGNIFICANCE:
This study provides evidence for the capacity of tSMS for modulating DLPFC function
Case-Control Analysis of the Impact of Anemia on Quality of Life in Patients with Cancer: A Qca Study Analysis
The impact of anemia on the quality of life (QoL) in cancer patients has been studied previously; however, the cut-off point used to define anemia differed among studies, thus providing inconsistent results. Therefore, we analysed the clinical impact of anemia on QoL using the same cut-off point for hemoglobin level to define anemia as that used in ESMO clinical practice guidelines. This post-hoc analysis aimed to determine the impact of anemia on QoL in cancer patients through the European Organization for Research and Treatment of Cancer Quality of life questionnaire version 3.0 (EORTC QLQ-C30) and Euro QoL 5-dimension 3-level (EQ-5D-3L) questionnaire. We found that cancer patients with anemia had significantly worse QoL in clinical terms. In addition, anemic patients had more pronounced symptoms than those in non-anemic patients.
Anemia is a common condition in cancer patients and is associated with a wide variety of symptoms that impair quality of life (QoL). However, exactly how anemia affects QoL in cancer patients is unclear because of the inconsistencies in its definition in previous reports. We aimed to examine the clinical impact of anemia on the QoL of cancer patients using specific questionnaires. We performed a post-hoc analysis of a multicenter, prospective, case-control study. We included patients with cancer with (cases) or without (controls) anemia. Participants completed the European Organization for Research and Treatment of Cancer Quality of Life questionnaire version 3.0 (EORTC QLQ-C30) and Euro QoL 5-dimension 3-level (EQ-5D-3L) questionnaire. Statistically significant and clinically relevant differences in the global health status were examined. From 2015 to 2018, 365 patients were included (90 cases and 275 controls). We found minimally important differences in global health status according to the EORTC QLQ-C30 questionnaire (case vs. controls: 45.6 vs. 58%, respectively; mean difference: -12.4, p < 0.001). Regarding symptoms, cancer patients with anemia had more pronounced symptoms in six out of nine scales in comparison with those without anemia. In conclusion, cancer patients with anemia had a worse QoL both clinically and statistically
DNA copy number profiling reveals extensive genomic loss in hereditary BRCA1 and BRCA2 ovarian carcinomas
Background: Few studies have attempted to characterise genomic changes occurring in hereditary epithelial ovarian carcinomas
(EOCs) and inconsistent results have been obtained. Given the relevance of DNA copy number alterations in ovarian oncogenesis
and growing clinical implications of the BRCA-gene status, we aimed to characterise the genomic profiles of hereditary and
sporadic ovarian tumours.
Methods: High-resolution array Comparative Genomic Hybridisation profiling of 53 familial (21 BRCA1, 6 BRCA2 and 26 non-
BRCA1/2) and 15 sporadic tumours in combination with supervised and unsupervised analysis was used to define common and/or
specific copy number features.
Results: Unsupervised hierarchical clustering did not stratify tumours according to their familial or sporadic condition or to their
BRCA1/2 mutation status. Common recurrent changes, spanning genes potentially fundamental for ovarian carcinogenesis,
regardless of BRCA mutations, and several candidate subtype-specific events were defined. Despite similarities, greater
contribution of losses was revealed to be a hallmark of BRCA1 and BRCA2 tumours.
Conclusion: Somatic alterations occurring in the development of familial EOCs do not differ substantially from the ones occurring
in sporadic carcinomas. However, some specific features like extensive genomic loss observed in BRCA1/2 tumours may be of
clinical relevance helping to identify BRCA-related patients likely to respond to PARP inhibitorsThis study was funded by the Fondo de Investigacio´n
Sanitaria (FIS), Instituto de Salud Carlos III (grants CP07/00113
and PS09/01094
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A phase I dose escalation and expansion trial of the next-generation oral SERD camizestrant in women with ER-positive, HER2-negative advanced breast cancer: SERENA-1 monotherapy results.
BACKGROUND: SERENA-1 (NCT03616587) is a phase I, multi-part, open-label study of camizestrant in pre- and post-menopausal women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Parts A and B aim to determine the safety and tolerability of camizestrant monotherapy and define doses for clinical evaluation. PATIENTS AND METHODS: Women aged ≥18 years with metastatic or recurrent ER+, HER2- breast cancer, refractory (or intolerant) to therapy, were assigned 25 mg up to 450 mg once daily (QD; escalation) or 75, 150, or 300 mg QD (expansion). Safety and tolerability, antitumor efficacy, pharmacokinetics, and impact on mutations in the estrogen receptor gene (ESR1m) circulating tumor (ct)DNA levels were assessed. RESULTS: By 9 March 2021, 108 patients received camizestrant monotherapy at 25-450 mg doses. Of these, 93 (86.1%) experienced treatment-related adverse events (TRAEs), 82.4% of which were grade 1 or 2. The most common TRAEs were visual effects (56%), (sinus) bradycardia (44%), fatigue (26%), and nausea (15%). There were no TRAEs grade 3 or higher, or treatment-related serious adverse events at doses ≤150 mg. Median tmax was achieved ∼2-4 h post-dose at all doses investigated, with an estimated half-life of 20-23 h. Efficacy was observed at all doses investigated, including in patients with prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and/or fulvestrant treatment, with and without baseline ESR1 mutations, and with visceral disease, including liver metastases. CONCLUSIONS: Camizestrant is a next-generation oral selective ER antagonist and degrader (SERD) and pure ER antagonist with a tolerable safety profile. The pharmacokinetics profile supports once-daily dosing, with evidence of pharmacodynamic and clinical efficacy in heavily pre-treated patients, regardless of ESR1m. This study established 75-, 150-, and 300-mg QD doses for phase II testing (SERENA-2, NCT04214288 and SERENA-3, NCT04588298)