Inhibition of Dihydrotestosterone Synthesis in Prostate Cancer by Combined Frontdoor and Backdoor Pathway Blockade

Androgen deprivation therapy (ADT) is palliative and prostate cancer (CaP) recurs as lethal castration-recurrent/resistant CaP (CRPC). One mechanism that provides CaP resistance to ADT is primary backdoor androgen metabolism, which uses up to four 3α-oxidoreductases to convert 5α-androstane-3α,17β-diol (DIOL) to dihydrotestosterone (DHT). The goal was to determine whether inhibition of 3α-oxidoreductase activity decreased conversion of DIOL to DHT. Protein sequence analysis showed that the four 3α-oxidoreductases have identical catalytic amino acid residues. Mass spectrometry data showed combined treatment using catalytically inactive 3α-oxidoreductase mutants and the 5α-reductase inhibitor, dutasteride, decreased DHT levels in CaP cells better than dutasteride alone. Combined blockade of frontdoor and backdoor pathways of DHT synthesis provides a therapeutic strategy to inhibit CRPC development and growth

A timeline of cognitive functioning in glioma patients who undergo awake brain tumor surgery

BACKGROUND: The purpose of awake brain tumor surgery is to maximize the resection of the tumor and to minimize the risk of neurological and cognitive impairments. The aim of this study is to gain understanding of the development of possible postoperative cognitive deficits after awake brain tumor surgery in patients with suspected gliomas, by comparing preoperative, early postoperative, and late postoperative functioning. A more detailed timeline will be helpful in informing candidates for surgery about what to expect regarding their cognitive functioning. METHODS: Thirty-seven patients were included in this study. Cognitive functioning was measured by means of a broad cognitive screener preoperatively, days after surgery and months after surgery in patients who underwent awake brain tumor surgery with cognitive monitoring. The cognitive screener included tests for object naming, reading, attention span, working memory, inhibition, inhibition/switching, and visuoperception. We performed a Friedman ANOVA to analyze on group level. RESULTS: Overall, no significant differences were found between preoperative cognitive functioning, early postoperative cognitive functioning, and late postoperative cognitive functioning, except for performances on the inhibition task. Directly after surgery, patients were significantly slower on this task. However, in the following months after surgery, they returned to their preoperative level. CONCLUSION: The timeline of cognitive functioning after awake tumor surgery appeared overall stable in the early and late postoperative phase, except for inhibition, which is more difficult in the first days after awake brain tumor surgery. This more detailed timeline of cognitive functioning, in combination with future research, can possibly be contributing in informing patients and caregivers what to expect after awake brain tumor surgery

A timeline of cognitive functioning in glioma patients who undergo awake brain tumor surgery

BACKGROUND: The purpose of awake brain tumor surgery is to maximize the resection of the tumor and to minimize the risk of neurological and cognitive impairments. The aim of this study is to gain understanding of the development of possible postoperative cognitive deficits after awake brain tumor surgery in patients with suspected gliomas, by comparing preoperative, early postoperative, and late postoperative functioning. A more detailed timeline will be helpful in informing candidates for surgery about what to expect regarding their cognitive functioning. METHODS: Thirty-seven patients were included in this study. Cognitive functioning was measured by means of a broad cognitive screener preoperatively, days after surgery and months after surgery in patients who underwent awake brain tumor surgery with cognitive monitoring. The cognitive screener included tests for object naming, reading, attention span, working memory, inhibition, inhibition/switching, and visuoperception. We performed a Friedman ANOVA to analyze on group level. RESULTS: Overall, no significant differences were found between preoperative cognitive functioning, early postoperative cognitive functioning, and late postoperative cognitive functioning, except for performances on the inhibition task. Directly after surgery, patients were significantly slower on this task. However, in the following months after surgery, they returned to their preoperative level. CONCLUSION: The timeline of cognitive functioning after awake tumor surgery appeared overall stable in the early and late postoperative phase, except for inhibition, which is more difficult in the first days after awake brain tumor surgery. This more detailed timeline of cognitive functioning, in combination with future research, can possibly be contributing in informing patients and caregivers what to expect after awake brain tumor surgery

Cognitive-behavioural therapy augments the effects of deep brain stimulation in obsessive-compulsive disorder

Deep brain stimulation (DBS) is a promising new treatment for patients with treatment-refractory obsessive-compulsive disorder (OCD). However, since most DBS patients only show a partial response, the treatment still needs to be improved. In this study we hypothesized that cognitive-behavioural therapy (CBT) could optimize the post-operative management in DBS and we evaluated the efficacy of CBT as augmentation to DBS targeted at the nucleus accumbens. A total of 16 patients with treatment-refractory OCD were treated with DBS targeted at the nucleus accumbens. After stabilization of decline in OCD symptoms, a standardized 24-week CBT treatment programme was added to DBS in an open-phase trial of 8 months. Changes in obsessive-compulsive, anxiety and depressive symptoms were evaluated using the Yale-Brown Obsessive Compulsive Scale, Hamilton Anxiety Scale and Hamilton Rating Scale for Depression. Following the addition of CBT to DBS, a significant decrease in obsessive-compulsive symptoms was observed, but not in anxiety and depressive symptoms. In a subsequent double-blind phase, in which stimulation was discontinued, OCD symptoms returned to baseline (relapse) and anxiety and depressive symptoms worsened (rebound) compared with baseline. The results of this explorative study suggest that a combined treatment of accumbens DBS and CBT may be optimal for improving obsessive-compulsive symptoms in treatment-refractory OCD. However, a subsequent randomized controlled trial is necessary to draw firm conclusions. It seems that DBS results in affective changes that may be required to enable response prevention in CBT. This may indicate that DBS and CBT act as two complementary treatment

Antibacterial silk fibroin/nanohydroxyapatite hydrogels with silver and gold nanoparticles for bone regeneration

The rapid emergence of antibiotic resistance is becoming an imminent problem in bone tissue engineering, and therefore biomaterials must be modified to promote the tissue integration before bacterial adhesion. In this work, silk fibroin/nanohydroxyapatite hydrogel was modified with in situ synthesized silver and gold nanoparticles (AgNPs and AuNPs), taking advantage of the tyrosine amino acid. The presence of AgNPs and AuNPs in the hydrogels was characterized by UV spectrophotometer, transmission electron microscopy and thermogravimetric analysis. In vitro antimicrobial studies revealed that hydrogels with AgNPs and AuNPs exhibited significant inhibition ability against both gram-positive and gram-negative bacteria. Cytocompatibility studies carried out using osteoblastic cells revealed that up to 0.5 wt% of AgNPs, and for all concentrations of AuNPs, the hydrogels can be effectively used as antimicrobial materials, without compromising cell behavior. On the basis of the aforementioned observations, these hydrogels are very attractive for bone tissue engineering131231239sem informaçãosem informaçã