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1.
Stroke ; 55(5): 1428-1437, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38648283

RESUMO

BACKGROUND: Intracranial aneurysms (IAs) remain a challenging neurological diagnosis associated with significant morbidity and mortality. There is a plethora of microsurgical and endovascular techniques for the treatment of both ruptured and unruptured aneurysms. There is no definitive consensus as to the best treatment option for this cerebrovascular pathology. The Aneurysm, Arteriovenous Malformation, and Chronic Subdural Hematoma Roundtable Discussion With Industry and Stroke Experts discussed best practices and the most promising approaches to improve the management of brain aneurysms. METHODS: A group of experts from academia, industry, and federal regulators convened to discuss updated clinical trials, scientific research on preclinical system models, management options, screening and monitoring, and promising novel device technologies, aiming to improve the outcomes of patients with IA. RESULTS: Aneurysm, Arteriovenous Malformation, and Chronic Subdural Hematoma Roundtable Discussion With Industry and Stroke Experts suggested the incorporation of artificial intelligence to capture sequential aneurysm growth, identify predictors of rupture, and predict the risk of rupture to guide treatment options. The consensus strongly recommended nationwide systemic data collection of unruptured IA radiographic images for the analysis and development of machine learning algorithms for rupture risk. The consensus supported centers of excellence for preclinical multicenter trials in areas such as genetics, cellular composition, and radiogenomics. Optical coherence tomography and magnetic resonance imaging contrast-enhanced 3T vessel wall imaging are promising technologies; however, more data are needed to define their role in IA management. Ruptured aneurysms are best managed at large volume centers, which should include comprehensive patient management with expertise in microsurgery, endovascular surgery, neurology, and neurocritical care. CONCLUSIONS: Clinical and preclinical studies and scientific research on IA should engage high-volume centers and be conducted in multicenter collaborative efforts. The future of IA diagnosis and monitoring could be enhanced by the incorporation of artificial intelligence and national radiographic and biologic registries. A collaborative effort between academic centers, government regulators, and the device industry is paramount for the adequate management of IA and the advancement of the field.

2.
J Robot Surg ; 18(1): 103, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427102

RESUMO

Robot-assisted partial nephrectomy (RAPN) has rapidly evolved as the standard of care for appropriately selected renal tumours, offering key patient benefits over radical nephrectomy or open surgical approaches. Accordingly, RAPN is a key competency that urology trainees wishing to treat kidney cancer must master. Training in robotic surgery is subject to numerous challenges, and simulation has been established as valuable step in the robotic learning curve. However, simulation models are often both expensive and suboptimal in fidelity. This means that the number of practice repetitions for a trainee may limited by cost restraints, and that trainees may struggle to reconcile the skills obtained in the simulation laboratory with real-world practice in the operating room. We have developed a high-fidelity, low-cost, customizable model for RAPN simulation based on porcine tissue. The model has been utilised in teaching courses at our institution, confirming both feasibility of use and high user acceptability. We share the design of our model in this proof-of-concept report.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Animais , Suínos , Procedimentos Cirúrgicos Robóticos/métodos , Nefrectomia/educação , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Carcinoma de Células Renais/cirurgia , Resultado do Tratamento
3.
BMJ Open ; 14(2): e079106, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38346886

RESUMO

OBJECTIVES: To assess the prevalence and drivers of distress, a composite of burnout, decreased meaning in work, severe fatigue, poor work-life integration and quality of life, and suicidal ideation, among nurses and physicians during the COVID-19 pandemic. DESIGN: Cross-sectional design to evaluate distress levels of nurses and physicians during the COVID-19 pandemic between June and August 2021. SETTING: Cardiovascular and oncology care settings at a Canadian quaternary hospital network. PARTICIPANTS: 261 nurses and 167 physicians working in cardiovascular or oncology care. Response rate was 29% (428 of 1480). OUTCOME MEASURES: Survey tool to measure clinician distress using the Well-Being Index (WBI) and additional questions about workplace-related and COVID-19 pandemic-related factors. RESULTS: Among 428 respondents, nurses (82%, 214 of 261) and physicians (62%, 104 of 167) reported high distress on the WBI survey. Higher WBI scores (≥2) in nurses were associated with perceived inadequate staffing (174 (86%) vs 28 (64%), p=0.003), unfair treatment, (105 (52%) vs 11 (25%), p=0.005), and pandemic-related impact at work (162 (80%) vs 22 (50%), p<0.001) and in their personal life (135 (67%) vs 11 (25%), p<0.001), interfering with job performance. Higher WBI scores (≥3) in physicians were associated with perceived inadequate staffing (81 (79%) vs 32 (52%), p=0.001), unfair treatment (44 (43%) vs 13 (21%), p=0.02), professional dissatisfaction (29 (28%) vs 5 (8%), p=0.008), and pandemic-related impact at work (84 (82%) vs 35 (56%), p=0.001) and in their personal life (56 (54%) vs 24 (39%), p=0.014), interfering with job performance. CONCLUSION: High distress was common among nurses and physicians working in cardiovascular and oncology care settings during the pandemic and linked to factors within and beyond the workplace. These results underscore the complex and contextual aspects of clinician distress, and the need to develop targeted approaches to effectively address this problem.


Assuntos
Esgotamento Profissional , COVID-19 , Médicos , Humanos , COVID-19/epidemiologia , Pandemias , Melhoria de Qualidade , Prevalência , Estudos Transversais , Qualidade de Vida , Canadá/epidemiologia , Esgotamento Profissional/epidemiologia , Hospitais , Inquéritos e Questionários , Satisfação no Emprego
4.
BMC Health Serv Res ; 24(1): 246, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38408946

RESUMO

OBJECTIVE: Clinician distress is a multidimensional condition that includes burnout, decreased meaning in work, severe fatigue, poor work-life integration, reduced quality of life, and suicidal ideation. It has negative impacts on patients, providers, and healthcare systems. In this three-phase qualitative investigation, we identified workplace-related factors that drive clinician distress and co-designed actionable interventions with inter-professional cardiovascular clinicians to decrease their distress and improve well-being within a Canadian quaternary hospital network. METHODS: Between October 2021 and May 2022, we invited nurses, allied health professionals, and physicians to participate in a three-phase qualitative investigation. Phases 1 and 2 included individual interviews and focus groups to identify workplace-related factors contributing to distress. Phase 3 involved co-design workshops that engaged inter-professional clinicians to develop interventions addressing drivers of distress identified. Qualitative information was analyzed using descriptive thematic analysis. RESULTS: Fifty-one clinicians (24 nurses, 10 allied health professionals, and 17 physicians) participated. Insights from Phases 1 and 2 identified five key thematic drivers of distress: inadequate support within inter-professional teams, decreased joy in work, unsustainable workloads, limited opportunities for learning and professional growth, and a lack of transparent leadership communication. Phase 3 co-design workshops yielded four actionable interventions to mitigate clinician distress in the workplace: re-designing daily safety huddles, formalizing a nursing coaching and mentorship program, creating a value-added program e-newsletter, and implementing an employee experience platform. CONCLUSION: This study increases our understanding on workplace-related factors that contribute to clinician distress, as shared by inter-professional clinicians specializing in cardiovascular care. Healthcare organizations can develop effective interventions to mitigate clinician distress by actively engaging healthcare workers in identifying workplace drivers of distress and collaboratively designing tailored, practical interventions that directly address these challenges.


Assuntos
Esgotamento Profissional , Médicos , Humanos , Qualidade de Vida , Canadá , Local de Trabalho , Pessoal Técnico de Saúde , Esgotamento Profissional/prevenção & controle
5.
Eur Ann Otorhinolaryngol Head Neck Dis ; 141(1): 27-31, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38036312

RESUMO

OBJECTIVE: To define the indications for each imaging modality in the screening, characterization, extension and follow-up of salivary gland tumors. MATERIAL AND METHODS: The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group who drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group, according to the formal consensus method. RESULTS: If a swelling of a salivary gland is palpable for 3 weeks, an ultrasound scan is recommended to confirm a tumoral lesion and rule out differential diagnoses. For a salivary gland tumor, MRI is recommended with diffusion-weighted and dynamic contrast-enhanced techniques. In the case of histologically proven malignancy or a highly suspicious lesion, a CT scan of the neck and chest is recommended to assess the tumor, lymph nodes and metastases. FDG-PET is not currently recommended in routine clinical practice for initial diagnosis, assessment of extension, evaluation of response to treatment, staging of recurrence, or follow-up of salivary gland tumors. CONCLUSION: Assessing salivary tumors is based on MRI. Extension assessment is based on neck and chest CT.


Assuntos
Neoplasias das Glândulas Salivares , Humanos , Consenso , Neoplasias das Glândulas Salivares/diagnóstico por imagem , Neoplasias das Glândulas Salivares/patologia , Tomografia Computadorizada por Raios X , Tomografia por Emissão de Pósitrons , Imageamento por Ressonância Magnética , Fluordesoxiglucose F18
6.
Clin Genitourin Cancer ; 22(1): e75-e85.e1, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37604745

RESUMO

INTRODUCTION: Abiraterone acetate (ABI) or docetaxel (DOC), in addition to androgen-deprivation therapy (ADT), are current treatment options for metastatic hormone-sensitive prostate cancer (mHSPC). No randomized head-to-head trial has compared these 2 mHSPC treatments, and real-world data regarding their outcomes in Asian patients are lacking. PATIENTS AND METHODS: The medical records of mHSPC patients who began upfront ABI or DOC treatment in addition to ADT at seven public oncology centers in Hong Kong between 2015 and 2021 were reviewed. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), prostate-specific antigen (PSA) response, and toxicities. Kaplan-Meier and multivariate Cox regression analyses were performed. RESULTS: A total of 574 patients were included, of whom 419 received DOC and 155 received ABI. The median follow-up duration was 22.4 (DOC group: 23.8; ABI group: 17.3) months. The ABI group demonstrated significantly better PFS than the DOC group (not reached vs. 15.1 months: hazard ratio = 0.37; 95% confidence interval = 0.28-0.50; P < .001). No significant OS difference was observed (P = .58). Failure to achieve a ≥ 90% decline in PSA level at 3 months and failure to achieve an undetectable PSA nadir were each associated with unfavorable PFS and OS. Patients who received DOC had a higher rate of febrile neutropenia, whereas those who received ABI had higher rates of grade ≥ 3 hypokalemia and elevated alanine transaminase. Treatment discontinuation due to toxicities was more common in the DOC (3.6%) than the ABI (0.6%) group. CONCLUSION: In Asian mHSPC patients, upfront ABI + ADT was associated with better PFS than DOC + ADT, with no significant OS difference. PSA kinetics may help stratify the prognosis for treatment intensification. Toxicity profiles were different, with a higher rate of toxicity-related treatment discontinuation in the DOC group.


Assuntos
Acetato de Abiraterona , Neoplasias da Próstata , Masculino , Humanos , Docetaxel/uso terapêutico , Acetato de Abiraterona/efeitos adversos , Neoplasias da Próstata/patologia , Antagonistas de Androgênios/efeitos adversos , Antígeno Prostático Específico , Hormônios , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resultado do Tratamento , Estudos Retrospectivos
7.
Artigo em Inglês | MEDLINE | ID: mdl-38052702

RESUMO

OBJECTIVE: To determine the indications and modalities for resection in the management of primary sublingual and minor salivary gland cancer, and the specific features of each primary location. MATERIAL AND METHODS: The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group who drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group, according to the formal consensus method. RESULTS: Histological evidence (submucosal biopsy) is recommended before surgical treatment of minor salivary gland carcinoma. Surgical treatment is recommended, with optimal oncologic margins, adapted to anatomical factors, histologic type and grade and functional consequences, with reconstruction if necessary. CONCLUSION: Treatment of primary minor salivary and sublingual gland cancer is surgical, with wide resection margins. The modalities of resection and reconstruction are highly dependent on tumor location, extension and histologic type.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38040591

RESUMO

OBJECTIVE: To determine the role of surgery of the primary tumor site in the management of primary major salivary gland cancer. MATERIAL AND METHODS: The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group, which drafted a non-systematic narrative review of the literature published on Medline, and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group, according to the formal consensus method. RESULTS: Treatment of salivary gland tumor is mainly surgical. The gold standard for parotid cancer is a total parotidectomy, to obtain clear margins and remove all intraparotid lymph nodes. For low-grade tumors, partial parotidectomy with wide excision of the tumor is acceptable in the case of postoperative diagnosis on definitive histology. In the event of positive margins on definitive analysis, revision surgery should be assessed for feasibility, and performed if possible. CONCLUSION: Treatment of primary major salivary gland cancer is based on surgery with clear resection margins, as far away as possible from the tumor. The type of surgery depends on tumor location, pathologic type and extension.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38030444

RESUMO

OBJECTIVE: To determine the frequency and modality of post-treatment monitoring of primary salivary gland cancer. MATERIAL AND METHODS: The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group who drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group, according to the formal consensus method. RESULTS: Clinical monitoring should be adapted to the risk of recurrence: initially every 3 months and progressively spaced out, becoming annual after 5 years. Post-treatment head and neck and chest imaging is recommended at 3 months. Local and regional monitoring can then be carried out yearly or twice yearly with contrast-enhanced head and neck imaging. An annual chest CT scan is recommended for high-grade tumors. For lesions at high risk of late recurrence, very prolonged annual surveillance (up to 15 years) is recommended, including screening for pulmonary metastases. CONCLUSION: Given the wide range of malignant salivary gland tumors, the modalities and frequency of post-treatment monitoring must be adapted to the expected course of the disease.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38036313

RESUMO

OBJECTIVE: To determine the indications for neck dissection in the management of parotid, submandibular or minor salivary gland cancers depending on the clinical situation: i.e., clinical lymph node involvement (cN+) or not (cN0); low or high risk of occult nodal metastasis; diagnosis of malignancy before, during or after surgery. MATERIAL AND METHODS: The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group which drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group according to the formal consensus method. RESULTS: In cN+ salivary gland cancer, ipsilateral neck dissection is recommended. In cN0 salivary gland cancer, ipsilateral neck dissection is recommended, except for tumors at low risk of occult nodal metastasis. If definitive pathology reveals a high risk of occult nodal involvement, additional neck treatment is recommended: ipsilateral neck dissection or elective nodal irradiation. CONCLUSION: The rate of occult lymph node involvement, and therefore the indication for elective neck dissection, depends primarily on the pathologic grade of the salivary gland cancer.

11.
BJU Int ; 132(5): 531-540, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37656050

RESUMO

OBJECTIVES: To evaluate the pressure range generated in the human renal collecting system during ureteroscopy (URS), in a large patient sample, and to investigate a relationship between intrarenal pressure (IRP) and outcome. PATIENTS AND METHODS: A prospective multi-institutional study was conducted, with ethics board approval; February 2022-March 2023. Recruitment was of 120 consecutive consenting adult patients undergoing semi-rigid URS and/or flexible ureterorenoscopy (FURS) for urolithiasis or diagnostic purposes. Retrograde, fluoroscopy-guided insertion of a 0.036-cm (0.014″) pressure guidewire (COMET™ II, Boston Scientific, Marlborough, MA, USA) to the renal pelvis was performed. Baseline and continuous ureteroscopic IRP was recorded, alongside relevant operative variables. A 30-day follow-up was completed. Descriptive statistics were applied to IRP traces, with mean (sd) and maximum values and variance reported. Relationships between IRP and technical variables, and IRP and clinical outcome were interrogated using the chi-square test and independent samples t-test. RESULTS: A total of 430 pressure traces were analysed from 120 patient episodes. The mean (sd) baseline IRP was 16.45 (5.99) mmHg and the intraoperative IRP varied by technique. The mean (sd) IRP during semi-rigid URS with gravity irrigation was 34.93 (11.66) mmHg. FURS resulted in variable IRP values: from a mean (sd) of 26.78 (5.84) mmHg (gravity irrigation; 12/14-F ureteric access sheath [UAS]) to 87.27 (66.85) mmHg (200 mmHg pressurised-bag irrigation; 11/13-F UAS). The highest single pressure peak was 334.2 mmHg, during retrograde pyelography. Six patients (5%) developed postoperative urosepsis; these patients had significantly higher IRPs during FURS (mean [sd] 81.7 [49.52] mmHg) than controls (38.53 [22.6] mmHg; P < 0.001). CONCLUSIONS: A dynamic IRP profile is observed during human in vivo URS, with IRP frequently exceeding expected thresholds. A relationship appears to exist between elevated IRP and postoperative urosepsis.

12.
J Endourol ; 37(11): 1191-1199, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37725588

RESUMO

Objectives: To explore beliefs and practice patterns of urologists regarding intrarenal pressure (IRP) during ureteroscopy (URS). Methods: A customized questionnaire was designed in a 4-step iterative process incorporating a systematic review of the literature and critical analysis of topics/questions by six endourologists. The 19-item questionnaire interrogated perceptions, practice patterns, and key areas of uncertainty regarding ureteroscopic IRP, and was disseminated via urologic societies, networks, and social media to the international urologic community. Consultants/attendings and trainees currently practicing urology were eligible to respond. Quantitative responses were compiled and analyzed using descriptive statistics and chi-square test, with subgroup analysis by procedure volume. Results: Responses were received from 522 urologists, practicing in six continents. The individual question response rate was >97%. Most (83.9%, 437/515) respondents were practicing at a consultant/attending level. An endourology fellowship incorporating stone management had been completed by 59.2% (307/519). The vast majority of respondents (85.4%, 446/520) scored the perceived clinical significance of IRP during URS ≥7/10 on a Likert scale. Concern was uniformly reported, with no difference between respondents with and without a high annual case volume (p = 0.16). Potential adverse outcomes respondents associated with elevated ureteroscopic IRP were urosepsis (96.2%, 501/520), collecting system rupture (80.8%, 421/520), postoperative pain (67%, 349/520), bleeding (63.72%, 332/520), and long-term renal damage (26.1%, 136/520). Almost all participants (96.2%, 501/520) used measures aiming to reduce IRP during URS. Regarding the perceived maximum acceptable threshold for mean IRP during URS, 30 mm Hg (40 cm H2O) was most frequently selected [23.2% (119/463)], with most participants (78.2%, 341/463) choosing a value ≤40 mm Hg. Conclusions: This is the first large-scale analysis of urologists' perceptions of ureteroscopic IRP. It identifies high levels of concern among the global urologic community, with almost unanimous agreement that elevated IRP is associated with adverse clinical outcomes. Equipoise remains regarding appropriate IRP limits intraoperatively and the most appropriate technical strategies to ensure adherence to these.


Assuntos
Ureteroscopia , Urologia , Humanos , Ureteroscopia/métodos , Estudos Transversais , Urologistas , Rim
14.
ACS Nano ; 17(17): 17499-17515, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37579222

RESUMO

Programmable manipulation of inorganic-organic interfacial electronic properties of ligand-functionalized plasmonic nanoparticles (NPs) is the key parameter dictating their applications such as catalysis, photovoltaics, and biosensing. Here we report the localized surface plasmon resonance (LSPR) properties of gold triangular nanoprisms (Au TNPs) in solid state that are functionalized with dipolar, conjugated ligands. A library of thiocinnamate ligands with varying surface dipole moments were used to functionalize TNPs, which results in ∼150 nm reversible tunability of LSPR peak wavelength with significant peak broadening (∼230 meV). The highly adjustable chemical system of thiocinnamate ligands is capable of shifting the Au work function down to 2.4 eV versus vacuum, i.e., ∼2.9 eV lower than a clean Au (111) surface, and this work function can be modulated up to 3.3 eV, the largest value reported to date through the formation of organothiolate SAMs on Au. Interestingly, the magnitude of plasmonic responses and work function modulation is NP shape dependent. By combining first-principles calculations and experiments, we have established the mechanism of direct wave function delocalization of electrons residing near the Fermi level into hybrid electronic states that are mostly dictated by the inorganic-organic interfacial dipole moments. We determine that both interfacial dipole and hybrid electronic states, and vinyl conjugation together are the key to achieving such extraordinary changes in the optoelectronic properties of ligand-functionalized, plasmonic NPs. The present study provides a quantitative relationship describing how specifically constructed organic ligands can be used to control the interfacial properties of NPs and thus the plasmonic and electronic responses of these functional plasmonics for a wide range of plasmon-driven applications.

15.
BJU Int ; 132(4): 353-364, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37259476

RESUMO

OBJECTIVE: To perform a systematic review and network meta-analysis (NMA) to determine the advantages and disadvantages of open (OPN), laparoscopic (LPN), and robot-assisted partial nephrectomy (RAPN) with particular attention to intraoperative, immediate postoperative, as well as longer-term functional and oncological outcomes. METHODS: A systematic review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-NMA guidelines. Binary data were compared using odds ratios (ORs). Mean differences (MDs) were used for continuous variables. ORs and MDs were extracted from the articles to compare the efficacy of the various surgical approaches. Statistical validity is guaranteed when the 95% credible interval does not include 1. RESULTS: In total, there were 31 studies included in the NMA with a combined 7869 patients. Of these, 33.7% (2651/7869) underwent OPN, 20.8% (1636/7869) LPN, and 45.5% (3582/7689) RAPN. There was no difference for either LPN or RAPN as compared to OPN in ischaemia time, intraoperative complications, positive surgical margins, operative time or trifecta rate. The estimated blood loss (EBL), postoperative complications and length of stay were all significantly reduced in RAPN when compared with OPN. The outcomes of RAPN and LPN were largely similar except the significantly reduced EBL in RAPN. CONCLUSION: This systematic review and NMA suggests that RAPN is the preferable operative approach for patients undergoing surgery for lower-staged RCC.


Assuntos
Neoplasias Renais , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Neoplasias Renais/cirurgia , Neoplasias Renais/complicações , Metanálise em Rede , Resultado do Tratamento , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Nefrectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Laparoscopia/efeitos adversos , Estudos Retrospectivos
16.
Front Neurosci ; 16: 1006203, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36188476

RESUMO

Connections between altered iron homeostasis and certain neurodegenerative diseases are highlighted by numerous studies suggesting iron neurotoxicity. Iron causes aggregation in neurodegenerative disease-linked proteins as well as others and additionally facilitates oxidative damage. Iron and oxidative damage can cause cell death including by ferroptosis. As treatment for neurodegeneration, chelation therapy alone is sometimes used with modest, varying efficacy and has not in general proven to reverse or halt the damage long term. Questions often focus on optimal chelator partitioning and fine-tuning binding strength; however iron oxidation state chemistry implies a different approach. More specifically, my perspective is that applying a redox-based component to iron mobilization and handling is crucial because ferrous iron is in general a more soluble, weaker biological binder than ferric. Once cellular iron becomes oxidized to ferric, it binds tenaciously, exchanges ligands more slowly, and enhances protein aggregation, which importantly can be reversed by iron reduction. This situation escalates with age as brain reducing ability decreases, iron concentration increases, autophagic clearance decreases, and cell stress diminishes iron handling capacity. Taken together, treatment employing chelation therapy together with a strong biological reductant may effectively remove inappropriately bound cellular iron or at least inhibit accumulation. This approach would likely require high concentration ascorbate or glutathione by IV along with chelation to enhance iron mobilization and elimination, thus reducing cumulative cellular damage and perhaps restoring partial function. Potential treatment-induced oxidative damage may be attenuated by high reductant concentration, appropriate choice of chelator, and/or treatment sequence. Comprehensive study is urged.

17.
CNS Spectr ; : 1-14, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35837681

RESUMO

This article is a clinical guide which discusses the "state-of-the-art" usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion-this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy-while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward "bridging" methods that may be used to transition simply and safely from other antidepressants to MAOIs.

18.
J Vis ; 22(8): 11, 2022 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-35848903

RESUMO

The magnocellular (MC) pathway in the primate has much higher achromatic contrast sensitivity than the parvocellular (PC) pathway, and is implicated in luminance contrast detection. But MC pathway responses tend to saturate at lower achromatic contrast than do PC pathway responses. It has been proposed that the PC pathway plays a major role in discriminating suprathreshold achromatic contrast, because the MC pathway is in saturation. This has been termed the pulsed-pedestal protocol. To test this hypothesis, responses of MC and PC pathway ganglion cells have been examined under suprathreshold conditions with stimulus configurations similar to those in psychophysical tests. For MC cells, response saturation was much less for flashed or moving edges than for sinusoidal modulation, and MC cell thresholds predicted for these stimuli were similar to psychophysical discrimination (and detection) data. Results suggest the protocol is not effective in segregating MC and PC function.


Assuntos
Sensibilidades de Contraste , Vias Visuais , Animais , Neurônios , Estimulação Luminosa/métodos , Psicofísica , Vias Visuais/fisiologia
19.
PLoS One ; 17(7): e0270846, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35802674

RESUMO

The COVID-19 pandemic has changed the course of human development. In this manuscript we analyze the long-term effect of COVID-19 on poverty at the country-level across various income thresholds to 2050. We do this by introducing eight quantitative scenarios that model the future of Sustainable Development Goal 1 (SDG1) achievement using alternative assumptions about COVID-19 effects on both economic growth and inequality in the International Futures model. Relative to a scenario without the pandemic (the No COVID scenario), the COVID Base scenario increases global extreme poverty by 73.9 million in 2020 (the range across all scenarios: 43.5 to 155.0 million), 63.6 million in 2030 (range: 9.8 to 167.2 million) and 57.1 million in 2050 (range: 3.1 to 163.0 million). The COVID Base results in seven more countries not meeting the SDG1 target by 2030 that would have achieved the target in a No COVID scenario. The most pessimistic scenario results in 17 more countries not achieving SDG1 compared with a No COVID scenario. The greatest pandemic driven increases in poverty occur in South Asia and sub-Saharan Africa.


Assuntos
COVID-19 , África Subsaariana , COVID-19/epidemiologia , Humanos , Renda , Pandemias , Pobreza
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