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Ventricle stimulation as a potential gold-standard control stimulation site for transcranial focused ultrasound stimulation
Get PDF© 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).No abstract availablehttps://www.brainstimjrnl.com/article/S1935-861X(24)00198-0/fulltex
The cellular and extracellular proteomic signature of human dopaminergic neurons carrying the LRRK2 G2019S mutation
Get PDF© 2024 Knab, Guaitoli, Jarboui, von
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which does not comply with these termsBACKGROUND: Extracellular vesicles are easily accessible in various biofluids and allow the assessment of disease-related changes in the proteome. This has made them a promising target for biomarker studies, especially in the field of neurodegeneration where access to diseased tissue is very limited. Genetic variants in the LRRK2 gene have been linked to both familial and sporadic forms of Parkinson's disease. With LRRK2 inhibitors entering clinical trials, there is an unmet need for biomarkers that reflect LRRK2-specific pathology and target engagement. METHODS: In this study, we used induced pluripotent stem cells derived from a patient with Parkinson's disease carrying the LRRK2 G2019S mutation and an isogenic gene-corrected control to generate human dopaminergic neurons. We isolated extracellular vesicles and neuronal cell lysates and characterized their proteomic signature using data-independent acquisition proteomics. Then, we performed differential expression analysis to identify dysregulated proteins in the mutated line. We used Metascape and gene ontology enrichment analysis on the dysregulated proteomes to identify changes in associated functional networks. RESULTS: We identified 595 significantly differentially regulated proteins in extracellular vesicles and 3,205 in cell lysates. We visualized functionally relevant protein-protein interaction networks and identified key regulators within the dysregulated proteomes. Using gene ontology, we found a close association with biological processes relevant to neurodegeneration and Parkinson's disease. Finally, we focused on proteins that were dysregulated in both the extracellular and cellular proteomes. We provide a list of ten biomarker candidates that are functionally relevant to neurodegeneration and linked to LRRK2-associated pathology, for example, the sonic hedgehog signaling molecule, a protein that has tightly been linked to LRRK2-related disruption of cilia function. CONCLUSION: In conclusion, we characterized the cellular and extracellular proteome of dopaminergic neurons carrying the LRRK2 G2019S mutation and proposed an experimentally based list of biomarker candidates for future studies.https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1502246/ful
Safety and efficacy of adjunctive intra-arterial antithrombotic therapy during endovascular thrombectomy for acute ischemic stroke: A systematic review and meta-analysis
No full textAvailable to read on the publisher's website here: https://doi.org/10.1136/jnis-2023-021244.Background Half of patients who achieve successful recanalization following endovascular thrombectomy (EVT) for acute ischemic stroke experience poor functional outcome. We aim to investigate whether the use of adjunctive intra-arterial antithrombotic therapy (AAT) during EVT is safe and efficacious compared with standard therapy (ST) of EVT with or without prior intravenous thrombolysis. Methods Electronic databases were searched (PubMed/MEDLINE, Embase, Cochrane Library) from 2010 until October 2023. Data were pooled using a random-effects model and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias was assessed using ROBINS-I and ROB-2. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes were successful recanalization (modified Thrombolysis In Cerebral Infarction (TICI) 2b-3), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. Results 41 randomized and non-randomized studies met the eligibility criteria. Overall, 15 316 patients were included; 3296 patients were treated with AAT during EVT and 12 020 were treated with ST alone. Compared with ST, patients treated with AAT demonstrated higher odds of functional independence (46.5% AAT vs 42.6% ST; OR 1.22, 95% CI 1.07 to 1.40, P=0.004, I2=48%) and a lower likelihood of 90-day mortality (OR 0.71, 95% CI 0.61 to 0.83, P=48%) and a lower likelihood of 90-day mortality (OR 0.71, 95% CI 0.61 to 0.83, P2=20%). The rates of sICH (OR 1.00, 95% CI 0.82 to 1.22,P=0.97, I2=13%) and successful recanalization (OR 1.09, 95% CI 0.84 to 1.42, P=0.52, I2=76%) were not significantly different. Conclusion The use of AAT during EVT may improve functional outcomes and reduce mortality rates compared with ST alone, without an increased risk of sICH. These findings should be interpreted with caution pending the results from ongoing phase III trials to establish the efficacy and safety of AAT during EVT.Copyright © Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.https://doi.org/10.1136/jnis-2023-02124
Component mix-match for natomic total shoulder arthroplasty revision: a case report
No full textAlthough mixing and matching components is a common, safe, and well-documented practice in hip revision surgery, our extensive search indicates that it has not been previously reported for shoulder arthroplasty. This case report presents the use of mixed implants in shoulder revision surgery to reduce morbidity and address flaws in the initial implant design. We describe a case of a patient with multiple epiphyseal dysplasia who was treated for osteoarthritis in his left shoulder with an anatomic shoulder replacement in 2014. In 2018, the patient presented with deteriorating function, increasing pain, and radiological signs of glenoid component wear and loosening. A decision was made to proceed with revision shoulder arthroplasty. Given the patient's young age and intact rotator cuff function, the revision was planned as an anatomic construct. The challenge was a well-fixed, fully hydroxyapatite-coated stem and a glenoid metal-backed component with a failing polyethylene locking mechanism. After extensive discussion with the patient, a combined decision was made to retain the well-fixed humeral stem and revise the glenoid side using impaction grafting with allograft, followed by cementing an all-polyethylene glenoid from a different company. The revision surgery was performed uneventfully, resulting in pain relief and improved function beyond the levels achieved in the initial operation. Notably, the original head and the revision glenoid had a curvature radius mismatch, in contrast to the original design's absolute congruence. Recent studies suggest that such a mismatch, within limits, can recreate normal shoulder kinematics and reduce glenoid loosening. Copyright ┬® 2024, Tsolis et al.https://www.cureus.com/articles/274409-component-mix-match-for-anatomic-total-shoulder-arthroplasty-revision-a-case-report#!
Medication required : p*RN - promoting healthy attitudes and improved access to pornography in wathwood hospital
No full textAims. The key aim of this project was to update and modernise the hospital procedure on how patients access pornographic material whilst detained at Wathwood Hospital. Within the update, we aimed to promote inclusivity and acceptance of all patients' sexual identities as well as utilising the opportunity to emphasise healthy consenting sexual relationships. Patients in Forensic Mental Health settings are often inpatients for a significant amount of time, with multiple restrictions imposed on their private and family life. Current policy allows patients to purchase pornography for private use in their own room. It must be material of the same nature available in a main street outlet. In practice, material is usually purchased in DVD format from the Amazon website and subsequently screened for suitability by Security staff and finally approval by the Responsible Clinician. There have been numerous incident reports involving the trading of pornographic material. Methods. Qualitative semi-Structured group interviews (up to 5 people at a time) were conducted with patients in the mediumsecure forensic services of Wathwood Hospital. They were recruited from the fortnightly Patient Forum. Anonymised questionnaires involving Likert scales and free text response spaces were also distributed at the Patient Forum. Data gathered investigated the percentage of patients who were aware of the current procedure, if they felt it worked well and what they thought the impact of accessing pornographic material might be. Staff were invited to complete a similar anonymised questionnaire, again considering their opinions on the positive or negative impacts of pornography for patients. In addition, we gathered data on whether there was a difference on the degree of comfort/discomfort about pornography, depending on whether the material involved opposite sex or same sex couples. In total, there were 40 survey participants. Results. Some key areas for concern were found, for example, only 17% of staff and 16% of patients thought the current policy works well despite 69% of staff and 84% of patients feeling it is a patient's right to access pornography. Free text and focus group feedback established many benefits to it. It was clear that there were some areas of difficulty in the hospital policy, which would benefit from being refreshed. Conclusion. Staff and patients overall feel that access to pornography is important for many of the patients. We identified areas for improvement in how this is accessed and a need to continually be considering the need to consider meeting the holistic needs for the patients.https://www.cambridge.org/core/journals/bjpsych-open/article/medication-required-prn-promoting-healthy-attitudes-and-improved-access-to-pornography-in-wathwood-hospital/47206A503CF5C82D96F214367D1437D
Narrowing the gap in differential attainment for psychiatry core trainees in East Midlands through mentorship scheme
No full textAims. The use of mentorship schemes may be a pragmatic approach to bridging the differential attainment gap for psychiatry trainees. There is robust evidence that mentorship improves outcomes for core trainees across several domains including exam pass rates, ARCP outcomes and clinical practice. A survey was developed to elicit core psychiatry trainees' perspective about the need for mentoring as well as their expectations. This was an initial survey done as part of a Quality Improvement project focused on mentoring scheme for psychiatry core trainees in the East Midlands region. Methods. A 16-item self-rated questionnaire was designed to elicit information relating to respondents' demographics, professional qualifications, UK experience prior to commencement of training, perception of mentorship as an unmet need as well as expected focus of potential mentoring relationship. These were administered to psychiatry core trainees in the East Midlands region. The data was collected in February 2023. Results. About a quarter of the core trainees (n = 21) participated in the survey. Majority (47.6%) of the respondents had Black or Black British ethnic origin and 11 (52.4%) were in their second year of training. Although 13 (61.9%) had a non-UK primary medical qualification, majority had some months of UK experience before commencement of training (median = 1.4 years). Twenty (95%) of the respondents identified mentoring as an unmet need and they highlighted the areas of need. Conclusion. This survey showed a high level of acceptance of the mentoring scheme among the trainees. Their expectations and suggestions helped further the design of the mentoring scheme which is currently ongoing.https://www.cambridge.org/core/journals/bjpsych-open/article/narrowing-the-gap-in-differential-attainment-for-psychiatry-core-trainees-in-east-midlands-through-mentorship-scheme/A4C6CFA67FC51BFC45ACE5AF4F423D4
Real world effectiveness of rTMS in depression and anxiety
No full textAims. Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive brain stimulation recommended by NICE for treatment of depression with minimal side-effects and a high patient acceptability. Our aim was to assess the effectiveness of rTMS in real world clinical service in alleviating symptoms of depression and anxiety. Methods. All patients receiving rTMS in our Centre for Neuromodulation Services (CNS) received 5 daily treatment sessions a week for a period of 5 weeks (25 sessions in total). All patients routinely completed PHQ-9, BDI-II and GAD-7 measures before and after the course of treatment. The scores on these measures were retrospectively analysed using paired-Sample t-test. Results. All 15 patients completed the PHQ-9 and GAD-7 scales while 10 patients completed BDI-II. Eleven patients (73%) had improved PHQ-9 scores post-treatment with average improvement of 5.5 points which was statistically significant [pairedsample t-test: t(14) = 3.019, p = 0.009]. Nine patients (90%) had improved BDI-II scores post-treatment with average reduction of 36% from baseline which was statistically significant [t (9) = 3.681, p = 0.005]. Eleven patients (73%) had improved GAD-7 scores post-treatment, with average reduction of 4 points. This reduction was also statistically significant [t(14) = 3.038, p = 0.009]. Improvement in all measures was also of a level that would be considered clinically significant for these measures. All patients tolerated the treatment well with no patients dropping out due to side effects. Conclusion. With the limitation of relatively small sample size, our initial analysis indicates that rTMS treatment offered in real world clinical service is effective in treating symptoms of depression. Although our protocol was not intended to treat anxiety, our patients had remarkable improvement in anxiety symptoms as well.https://www.cambridge.org/core/journals/bjpsych-open/article/real-world-effectiveness-of-rtms-in-depression-and-anxiety/EC0C358C498EB176D3CD1E59AE7F703
Unilateral hemichorea and hemiballismus in a woman in her late 70s
No full textChorea is a hyperkinetic movement disorder characterised by involuntary, brief, random and irregular contractions. Acquired chorea can present acutely or subacutely and may be asymmetrical or unilateral. A detailed history and examination are crucial to identify triggering factors and underlying cause. In this case, a woman in her late 70s presented with progressively increasing involuntary movements in her right upper and lower limbs, triggered by active movements but ceasing with rest. Her medical history included a transient ischaemic attack (TIA) 3 years prior. Examination revealed choreoathetoid movements on the right side, occasionally manifesting as ballismus, which disappeared with rest. MRI showed small areas of restricted diffusion in the left parietal lobe suggestive of a microbleed, and carotid duplex ultrasonography revealed significant stenosis in the left carotid artery. The differential diagnosis included secondary paroxysmal kinesigenic dyskinesia and limb-shaking TIA/haemodynamic factors. In this report, we discuss both these differentials and how to approach.https://casereports.bmj.com/content/17/10/e26268
A multicentre prospective evaluation of health-related quality of life and patient related outcomes in pancreatic and peripancreatic cancer: PROMCAN study
No full textBackground: The temporal evolution of HRQoL and the importance of other PROs to patients, following resection for pancreatic and peripancreatic malignancy remains unexplored. Methods: Patients undergoing pancreatic resection between 2021 and 2022 were enrolled from 2 UK HPB centres. Patients completed the EORTC QLQ-C30, QLQ-PAN26 tools and rated 56 PROs preoperatively (T1), at discharge (T2), 6-weeks (T3), 3-months (T4) and 6-months (T5) postoperatively. ANOVA followed by post-hoc analysis was used to examine patterns in HRQoL through time. Multivariable ANOVA was used to identify impact of clinical factors on HRQoL. Results: 63 patients were recruited [median age, 72 (IQR 41-85); 39/63 male]. Physical functioning declined from 70.4 (26.2) at T1 to 53.5 (20.9) at T2 (p = 0.016). Global QoL score increased significantly from 41.0 (23.0) at T2 to 60.0 (26.1) at T5 (p = 0.007), as did role functioning [21.1 (27.9) at T2 to 59.4 (32.8) at T5, p < 0.001]. Chemotherapy status and the postoperative complications did not significantly change HRQoL. General QoL and health were the only PROs rated as 'very important' (scores 7-9) by more than 80 % of participants at five time-points. Conclusion: Recuperation of HRQoL measures is seen at 6-months postoperative and was not affected by chemotherapy or postoperative complications. Notably, PROs important to patients varied over time.https://www.hpbonline.org/article/S1365-182X(24)00018-2/abstrac
Early and mid-term outcomes after aortic valve replacement using a novel tissue bioprosthesis: a systematic review
No full textObjectives: While current data show a clear trend towards the use of bioprosthetic valves during aortic valve replacement (AVR), durability of bioprosthetic valves remains the most important concern. We conducted a 1st systematic review of all available evidence that analysed early and mid-term outcomes after AVR using the Inspiris RESILIA™ bioprosthesis. Methods: A systematic literature search was performed to identify all relevant studies evaluating early and mid-term outcomes after AVR using the Inspiris RESILIA bioprosthesis and including at least 20 patients with no restriction on the publication date. Subgroup meta-analysis was performed to compare Inspiris RESILIA and PERIMOUNT Magna Ease bioprosthesis and to pool the early postoperative mortality and stroke rates. Results: A total of 416 studies were identified, of which 15 studies met the eligibility criteria. The studies included a total of 3202 patients with an average follow-up of up to 5.3 years. The average age of patients across the studies was 52.2-75.1 years. Isolated AVR was performed in 39.0-86.4% of patients. In-hospital or 30-day postoperative mortality was 0-2.8%. At the mid-term follow-up, freedom from all-cause mortality was up to 85.4%. Among studies with mid-term follow-up, trace/mild paravalvular leak was detected in 0-3.0%, while major paravalvular leak was found only in up to 2.0% of patients. No statistically significant differences in terms of mortality (P = 0.98, odds ratio 1.02, 95% confidence interval 0.36-2.83) and stroke (P = 0.98, odds ratio 1.01, 95% confidence interval 0.38-2.73) between the Inspiris RESILIA bioprosthesis and PERIMOUNT Magna Ease bioprosthesis were observed in the subgroup meta-analysis. Conclusions: Mid-term data on the safety and haemodynamic performance of the novel aortic bioprosthesis are encouraging. Further comparative studies with other bioprostheses and longer follow-up are still required to endorse durability and safety of the novel bioprosthesis.https://academic.oup.com/ejcts/article-abstract/65/2/ezae045/7603974?redirectedFrom=fulltext&login=fals