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Also, thrombin directly links the coagulation system to the immune system by activating interleukin-1α. Such effects of thrombin can result in both short-term brain injury and long-term functional deficits, making extravascular thrombin an understudied therapeutic target for stroke. This review examines the role of thrombin and PARs in brain injury following hemorrhagic and ischemic stroke and the potential treatment strategies which are complicated by their role in both hemostasis and brain.
European drug regulations aim for a patient-centered approach, including involving patients in the pharmacovigilance (PV) systems. However many patient organizations have little experience on how they can participate in PV activities.
The aim of this study was to understand patient organizations' perceptions of PV, the barriers they face when implementing PV activities, and their interaction with other stakeholders and suggest methods for the stimulation of patient organizations as promoters of PV.
A sequential qualitative method study was conducted and integrated with the quantitative study performed by Matos, Weits, and van Hunsel to complete a mixed method study.
The qualitative phase expands the understanding of the quantitative results from a previous study by broadening the knowledge on external barriers and internal barriers that patient organizations face when implementing PV activities. The strategies to stimulate patient-organization participation are the creation of more awareness campaignseness and participation of their members in drug safety, but still face internal and external barriers that can hamper their involvement.
The activation of microglia in various brain pathologies is accompanied by an increase in the expression of peripheral benzodiazepine receptor/18kDa translocator protein (PBR/TSPO). However, whether activated microglia have a neuroprotective or neurotoxic effect on neurons in the brain is yet to be determined. In this study, we investigated the ability of the novel PBR/TSPO ligand FEPPA to detect activated microglia in an animal model of primary neurotoxic microglia activation.
[
F] FEPPA positron emission tomography (PET) imaging was performed before and after intraperitoneal administration of lipopolysaccharide (LPS) (LPS group) or saline (control group) in a unilateral 6-hydroxydopamine (6-OHDA) lesion rat model of Parkinson's disease. Images were compared between these groups. After imaging, the brains were collected, and the activated microglia at the disease sites were analyzed by the expression of inflammatory cytokines and immunohistochemistry staining. These results were then comparatively exami a novel PET detection system that can monitor neurodegenerative diseases.
PET signal enhancement by PBR/TSPO at the site of brain injury correlated with the activation of microglia and production of inflammatory cytokines. Furthermore, because FEPPA enables the detection of neurotoxic microglia on PET images, we successfully constructed a novel PET detection system that can monitor neurodegenerative diseases.
The capsid protein (VP1) of the foot-and-mouth (FMD) AKT-III strain was expressed on the surface of the T7 phage capsid (AKT-T7 strain) and the potential of AKT-T7 strain as an FMD vaccine was evaluated.
The AKT-T7 strain was successfully constructed and was not cytotoxic to BHK-21, MDBK, or sheep kidney cells. The AKT-T7 strain was well phagocytosed by mouse macrophages. Immunization of BALB/c mice revealed that animals were quickly induced and produced high levels of FMDV antibodies. Monitoring data indicated that FMDV antibody levels could be maintained at higher levels for longer periods of time. The AKT-T7 strain induced high levels of IFN-γ levels in mice with little effect on IL-4.
The AKT-T7 induced the mice to produce FMDV antibodies, which has the advantage of phage and FMDV, and is a potential candidate for an FMD vaccine.
The AKT-T7 induced the mice to produce FMDV antibodies, which has the advantage of phage and FMDV, and is a potential candidate for an FMD vaccine.Recent dual-task studies observed worse performance in task-pair switches than in task-pair repetitions and interpreted these task-pair switch costs as evidence that the identity of the two individual tasks performed within a dual task is jointly represented in a single mental representation, termed "task-pair set." In the present study, we conducted two experiments to examine (a) whether task-pair switch costs are due to switching cues or/and task pairs and (b) at which time task-pair sets are activated during dual-task processing. In Experiment 1, we used two cues per task-pair and found typical dual-task interference, indicating that performance in the individual tasks performed within the dual task deteriorates as a function of increased temporal task overlap. Moreover, we observed cue switch costs, possibly reflecting perceptual cue priming. Importantly, there were also task-pair switch costs that occur even when controlling for cue switching. This suggests that task-pair switching per se produces a performance cost that cannot be reduced to costs of cue switching. In Experiment 2, we employed a go/no-go-like manipulation and observed task-pair switch costs after no-go trials where subjects prepared for a task-pair, but did not perform it. This indicates that task-pair sets are activated before performing a dual task. Together, the findings of the present study provide further evidence for a multicomponent hierarchical representation consisting of a task-pair set organized at a hierarchically higher level than the task sets of the individual tasks performed within a dual task.
Radioactive seed localization (RSL) and the Savi Scout
radar (SSR) are newer alternatives to wire-guided localization (WL) for nonpalpable breast lesions.
The aim of this study was to compare three localization devices when multiple devices were used for preoperative localization for breast surgery.
Between July 2017 and July 2018, 68 patients had a partial mastectomy (n=54) or breast biopsy (n=14) with preoperative image-guided localization using multiple wires or device placement for nonpalpable lesions. Operative timing, outcomes, and 30-day complications were evaluated.
Overall, 41 patients (60%) had WL, 11 patients (16%) had RSL, and 16 patients (24%) had SSR localization. Fifty-four patients (79.4%) had localization of two lesions and 13 patients (19.1%) had localization of three lesions. Twenty-three patients (33.8%) had a lesion that was bracketed. There was no difference in retained biopsy clip among the groups (average 7.4%; p=0.962). For operations performed in the hospital, there was no difference in operative time among the groups, with a median of 77.5 min (p=0.705) or total perioperative time of 508 min (p=0.210). Among operations with delayed start times, there was a longer average delay of 95.5 min in WL, compared with 42 min in SSR (p=0.004). A greater volume of tissue was excised in the WL group (29.5g WL vs. CP 43 15.9g RSL vs. 12.1g SSR; p=0.022). There was no difference in positive margin rate and 30-day complications among groups.
SSR and RSL can be used to localize multiple breast lesions, with no difference in positive margin rates or complications and less tissue excised compared with WL.
SSR and RSL can be used to localize multiple breast lesions, with no difference in positive margin rates or complications and less tissue excised compared with WL.
Traditional indications for mastectomy include multiple ipsilateral lesions and/or disease spanning ≥ 5cm. Neoadjuvant chemotherapy increases breast conservation but does not improve survival. We hypothesized that oncoplastic breast-conserving surgery (OPS) may allow for breast conservation while providing full staging and tumor profiling information to guide systemic therapy decisions, thereby permitting more judicious chemotherapy use.
This was an observational cohort of patients with invasive breast cancer with multiple lesions and/or disease spanning ≥ 5cm who underwent OPS from 2012 to 2018. Clinicopathologic features, mastectomy rate, chemotherapy use, and recurrence were evaluated.
Overall, 100 patients were identified. Average disease span was 62.8 ± 20.1mm, with an average of 2.9 lesions (range 1-13). 'No ink on tumor' was achieved at the index operation in 80 patients; 13 patients underwent completion mastectomy to achieve adequate margins. Eighty-one patients completed radiation therapy. Breaevaluating long-term oncologic and cosmetic outcomes is warranted.
This study aimed to evaluate the impact of rapid genetic testing (RGT) for BRCA1 and BRCA2 at the time of breast cancer diagnosis on treatment choices. Bilateral mastectomy for the treatment of breast cancer in women with a BRCA1 or BRCA2 mutation offers a reduction in the risk of contralateral breast cancer. It is unclear whether offering RGT at the time of breast cancer diagnosis has an impact on women's surgical decision-making.
Women with breast cancer diagnosed between June 2013 and May 2018 were recruited from four academic health sciences centers in Toronto, Canada. The participants completed a questionnaire before genetic testing, then one week and one year after disclosure of the genetic test result. Before surgery, RGT was performed. Diagnostic, pathologic, and treatment data were compared between those with and those without a BRCA mutation.
The study enrolled 1007 women who consented to RGT. The mean age of the participants was 46.3years, and the median time to result disclosure was 10days. A BRCA mutation was found in 6% of the women. The women with a BRCA mutation were significantly more likely to elect for bilateral mastectomy than the women without a BRCA mutation (p < 0.0001). Of the BRCA-positive patients, 95.7% reported that they used their genetic test result to make a surgical decision.
The women provided with RGT at the time of breast cancer diagnosis use the genetic information to make treatment decisions, and the majority of those identified with a BRCA mutation elect for a bilateral mastectomy.
The women provided with RGT at the time of breast cancer diagnosis use the genetic information to make treatment decisions, and the majority of those identified with a BRCA mutation elect for a bilateral mastectomy.
The aim of this study was to determine the difference in proportion of shoulder MRIs that influence the management plan of shoulder patients based on whether MRI was ordered by a shoulder specialist, orthopaedic surgeon or primary care provider prior to referral to a specialist.
This observational analytical study was conducted in a private practice setting. Data were obtained from 153 MRIs performed on 151 patients. Seventy-seven MRIs were ordered by a specialist shoulder surgeon and 76 by a primary care provider (general practitioner, non-operative sports medicine physician or physiotherapist).
Specialist-ordered MRIs influenced patient management significantly more often than primary care-ordered MRIs (82% vs. 22%, p < 0.001). Fifty-four percent of referral letters from primary care providers to the specialist did not have documentation of a physical examination, yet an MRI had been ordered. The most common diagnoses for primary care-ordered MRIs which did not have influence on patient management were subacromial bursitis and adhesive capsulitis.
