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1.
Eur Arch Otorhinolaryngol ; 280(2): 661-669, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35834014

RESUMO

PURPOSE: Studies have assessed the trauma and change in hearing function from the use of otological drills on the ossicular chain, but not the effects of partial laser ablation of the incus. A study of the effectiveness of a novel middle-ear microphone for a cochlear implant, which required an incus recess for the microphone balltip, provided an opportunity to compare methods and inform a feasibility study of the microphone with patients. METHODS: We used laser Doppler vibrometry with an insert earphone and probe microphone in 23 ears from 14 fresh-frozen cadavers to measure the equivalent noise level at the tympanic membrane that would have led to the same stapes velocity as the creation of the incus recess. RESULTS: Drilling on the incus with a diamond burr created peak noise levels equivalent to 125.1-155.0 dB SPL at the tympanic membrane, whilst using the laser generated equivalent noise levels barely above the baseline level. The change in middle ear transfer function following drilling showed greater variability at high frequencies, but the change was not statistically significant in the three frequency bands tested. CONCLUSIONS: Whilst drilling resulted in substantially higher equivalent noise, we considered that the recess created by laser ablation was more likely to lead to movement of the microphone balltip, and therefore decrease performance or result in malfunction over time. For patients with greatly reduced residual hearing, the greater consistency from drilling the incus recess may outweigh the potential benefits of hearing preservation with laser ablation.


Assuntos
Terapia a Laser , Prótese Ossicular , Humanos , Bigorna/cirurgia , Orelha Média/cirurgia , Ossículos da Orelha , Estribo
2.
Adv Exp Med Biol ; 1356: 117-140, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35146620

RESUMO

Ultrasound-guided regional anaesthesia (UGRA) involves the targeted deposition of local anaesthesia to inhibit the function of peripheral nerves. Ultrasound allows the visualisation of nerves and the surrounding structures, to guide needle insertion to a perineural or fascial plane end point for injection. However, it is challenging to develop the necessary skills to acquire and interpret optimal ultrasound images. Sound anatomical knowledge is required and human image analysis is fallible, limited by heuristic behaviours and fatigue, while its subjectivity leads to varied interpretation even amongst experts. Therefore, to maximise the potential benefit of ultrasound guidance, innovation in sono-anatomical identification is required.Artificial intelligence (AI) is rapidly infiltrating many aspects of everyday life. Advances related to medicine have been slower, in part because of the regulatory approval process needing to thoroughly evaluate the risk-benefit ratio of new devices. One area of AI to show significant promise is computer vision (a branch of AI dealing with how computers interpret the visual world), which is particularly relevant to medical image interpretation. AI includes the subfields of machine learning and deep learning, techniques used to interpret or label images. Deep learning systems may hold potential to support ultrasound image interpretation in UGRA but must be trained and validated on data prior to clinical use.Review of the current UGRA literature compares the success and generalisability of deep learning and non-deep learning approaches to image segmentation and explains how computers are able to track structures such as nerves through image frames. We conclude this review with a case study from industry (ScanNav Anatomy Peripheral Nerve Block; Intelligent Ultrasound Limited). This includes a more detailed discussion of the AI approach involved in this system and reviews current evidence of the system performance.The authors discuss how this technology may be best used to assist anaesthetists and what effects this may have on the future of learning and practice of UGRA. Finally, we discuss possible avenues for AI within UGRA and the associated implications.


Assuntos
Anestesia por Condução , Inteligência Artificial , Humanos , Nervos Periféricos , Ultrassonografia , Ultrassonografia de Intervenção
3.
Audiol Neurootol ; 24(1): 20-24, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30870837

RESUMO

Important research by Rosowski et al. [Twenty-Seventh Meeting of the Association for Research in Otolaryngology, 2004, p. 275] has led to a standard practice by the American Society for Testing Materials [West Conshohocken: ASTM International; 2014] to assess normal function of temporal bones used in the development of novel middle ear actuators and sensors. Rosowki et al. [Audiol Neurotol. 2007; 12(4): 265-76] have since suggested that the original criteria are too restrictive and have proposed modified criteria. We show that both the original and modified criteria are inappropriate for assessing individual temporal bones. Moreover, we suggest that both the original and modified Rosowski criteria should be applied with caution when assessing whether mean data from a study are within physiological norms because the multiple comparisons resulting from verification at each frequency will lead to very liberal rejection. The standard practice, however, has led to the collection of more extensive and consistent data. We suggest that it is now opportune to use these data to further modify the Rosowski criteria.


Assuntos
Orelha Média/fisiologia , Prótese Ossicular , Osso Temporal/fisiologia , Humanos
4.
Proc Natl Acad Sci U S A ; 113(35): 9792-7, 2016 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-27531961

RESUMO

Contact-dependent growth inhibition (CDI) is a widespread mechanism of bacterial competition. CDI(+) bacteria deliver the toxic C-terminal region of contact-dependent inhibition A proteins (CdiA-CT) into neighboring target bacteria and produce CDI immunity proteins (CdiI) to protect against self-inhibition. The CdiA-CT(EC536) deployed by uropathogenic Escherichia coli 536 (EC536) is a bacterial toxin 28 (Ntox28) domain that only exhibits ribonuclease activity when bound to the cysteine biosynthetic enzyme O-acetylserine sulfhydrylase A (CysK). Here, we present crystal structures of the CysK/CdiA-CT(EC536) binary complex and the neutralized ternary complex of CysK/CdiA-CT/CdiI(EC536) CdiA-CT(EC536) inserts its C-terminal Gly-Tyr-Gly-Ile peptide tail into the active-site cleft of CysK to anchor the interaction. Remarkably, E. coli serine O-acetyltransferase uses a similar Gly-Asp-Gly-Ile motif to form the "cysteine synthase" complex with CysK. The cysteine synthase complex is found throughout bacteria, protozoa, and plants, indicating that CdiA-CT(EC536) exploits a highly conserved protein-protein interaction to promote its toxicity. CysK significantly increases CdiA-CT(EC536) thermostability and is required for toxin interaction with tRNA substrates. These observations suggest that CysK stabilizes the toxin fold, thereby organizing the nuclease active site for substrate recognition and catalysis. By contrast, Ntox28 domains from Gram-positive bacteria lack C-terminal Gly-Tyr-Gly-Ile motifs, suggesting that they do not interact with CysK. We show that the Ntox28 domain from Ruminococcus lactaris is significantly more thermostable than CdiA-CT(EC536), and its intrinsic tRNA-binding properties support CysK-independent nuclease activity. The striking differences between related Ntox28 domains suggest that CDI toxins may be under evolutionary pressure to maintain low global stability.


Assuntos
Toxinas Bacterianas/química , Inibição de Contato/genética , Cisteína Sintase/química , Proteínas de Escherichia coli/química , Escherichia coli Uropatogênica/química , Sequência de Aminoácidos , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Sítios de Ligação , Clonagem Molecular , Cristalografia por Raios X , Cisteína Sintase/genética , Cisteína Sintase/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Modelos Moleculares , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Estabilidade Proteica , Estrutura Secundária de Proteína , RNA de Transferência/química , RNA de Transferência/genética , RNA de Transferência/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Ruminococcus/química , Ruminococcus/metabolismo , Especificidade por Substrato , Escherichia coli Uropatogênica/genética , Escherichia coli Uropatogênica/metabolismo
5.
Proc Natl Acad Sci U S A ; 109(52): 21480-5, 2012 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-23236156

RESUMO

Contact-dependent growth inhibition (CDI) systems encode polymorphic toxin/immunity proteins that mediate competition between neighboring bacterial cells. We present crystal structures of CDI toxin/immunity complexes from Escherichia coli EC869 and Burkholderia pseudomallei 1026b. Despite sharing little sequence identity, the toxin domains are structurally similar and have homology to endonucleases. The EC869 toxin is a Zn(2+)-dependent DNase capable of completely degrading the genomes of target cells, whereas the Bp1026b toxin cleaves the aminoacyl acceptor stems of tRNA molecules. Each immunity protein binds and inactivates its cognate toxin in a unique manner. The EC869 toxin/immunity complex is stabilized through an unusual ß-augmentation interaction. In contrast, the Bp1026b immunity protein exploits shape and charge complementarity to occlude the toxin active site. These structures represent the initial glimpse into the CDI toxin/immunity network, illustrating how sequence-diverse toxins adopt convergent folds yet retain distinct binding interactions with cognate immunity proteins. Moreover, we present visual demonstration of CDI toxin delivery into a target cell.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/toxicidade , Toxinas Bacterianas/química , Toxinas Bacterianas/toxicidade , Inibição de Contato/efeitos dos fármacos , Imunidade/efeitos dos fármacos , Proteínas de Bactérias/imunologia , Toxinas Bacterianas/imunologia , Burkholderia pseudomallei/genética , Burkholderia pseudomallei/imunologia , Burkholderia pseudomallei/metabolismo , Cristalografia por Raios X , DNA/metabolismo , Endonucleases/metabolismo , Escherichia coli/genética , Escherichia coli/imunologia , Escherichia coli/metabolismo , Modelos Moleculares , Família Multigênica/genética , Estrutura Secundária de Proteína
6.
Inorg Chem ; 53(12): 5931-40, 2014 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-24901029

RESUMO

Mycobacterium heme utilization degrader (MhuD) is a heme-degrading protein from Mycobacterium tuberculosis responsible for extracting the essential nutrient iron from host-derived heme. MhuD has been previously shown to produce unique organic products compared to those of canonical heme oxygenases (HOs) as well as those of the IsdG/I heme-degrading enzymes from Staphylococcus aureus. Here, we report the X-ray crystal structure of cyanide-inhibited MhuD (MhuD-heme-CN) as well as detailed (1)H nuclear magnetic resonance (NMR), UV/vis absorption, and magnetic circular dichroism (MCD) spectroscopic characterization of this species. There is no evidence for an ordered network of water molecules on the distal side of the heme substrate in the X-ray crystal structure, as was previously reported for canonical HOs. The degree of heme ruffling in the crystal structure of MhuD is greater than that observed for HO and less than that observed for IsdI. As a consequence, the Fe 3dxz-, 3dyz-, and 3dxy-based MOs are very close in energy, and the room-temperature (1)H NMR spectrum of MhuD-heme-CN is consistent with population of both a (2)Eg electronic state with a (dxy)(2)(dxz,dyz)(3) electron configuration, similar to the ground state of canonical HOs, and a (2)B2g state with a (dxz,dyz)(4)(dxy)(1) electron configuration, similar to the ground state of cyanide-inhibited IsdI. Variable temperature, variable field MCD saturation magnetization data establishes that MhuD-heme-CN has a (2)B2g electronic ground state with a low-lying (2)Eg excited state. Our crystallographic and spectroscopic data suggest that there are both structural and electronic contributions to the α-meso regioselectivity of MhuD-catalyzed heme cleavage. The structural distortion of the heme substrate observed in the X-ray crystal structure of MhuD-heme-CN is likely to favor cleavage at the α- and γ-meso carbons, whereas the spin density distribution may favor selective oxygenation of the α-meso carbon.


Assuntos
Cianetos/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Heme/metabolismo , Mycobacterium tuberculosis/enzimologia , Cristalografia por Raios X , Cianetos/química , Heme/química , Heme Oxigenase (Desciclizante)/química , Humanos , Modelos Moleculares , Mycobacterium tuberculosis/química , Mycobacterium tuberculosis/metabolismo , Conformação Proteica , Tuberculose/microbiologia
7.
Proc Natl Acad Sci U S A ; 108(12): 5051-6, 2011 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-21383189

RESUMO

Mycobacterium tuberculosis must import iron from its host for survival, and its siderophore-dependent iron acquisition pathways are well established. Here we demonstrate a newly characterized pathway, whereby M. tuberculosis can use free heme and heme from hemoglobin as an iron source. Significantly, we identified the genomic region, Rv0202c-Rv0207c, responsible for the passage of heme iron across the mycobacterial membrane. Key players of this heme uptake system were characterized including a secreted protein and two transmembrane proteins, all three specific to mycobacteria. Furthermore, the crystal structure of the key heme carrier protein Rv0203 was found to have a unique fold. The discovery of a unique mycobacterial heme acquisition pathway opens new avenues of exploration into mycobacterial therapeutics.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Transporte/metabolismo , Heme/metabolismo , Ferro/metabolismo , Mycobacterium tuberculosis/metabolismo , Proteínas de Bactérias/genética , Transporte Biológico/fisiologia , Proteínas de Transporte/genética , Membrana Celular/genética , Membrana Celular/metabolismo , Heme/genética , Mycobacterium tuberculosis/genética , Tuberculose/tratamento farmacológico , Tuberculose/genética , Tuberculose/metabolismo
8.
JASA Express Lett ; 2(4): 042001, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-36154230

RESUMO

Theoretical studies demonstrate that controlled addition of noise can enhance the amount of information transmitted by a cochlear implant (CI). The present study is a proof-of-principle for whether stochastic facilitation can improve the ability of CI users to categorize speech sounds. Analogue vowels were presented to CI users through a single electrode with independent noise on multiple electrodes. Noise improved vowel categorization, particularly in terms of an increase in information conveyed by the first and second formant. Noise, however, did not significantly improve vowel recognition: the miscategorizations were just more consistent, giving the potential to improve with experience.


Assuntos
Implante Coclear , Implantes Cocleares , Percepção da Fala , Ruído/efeitos adversos , Fonética
9.
Otol Neurotol ; 43(10): 1162-1169, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36240742

RESUMO

OBJECTIVES: All commercially available cochlear implant (CI) systems use an external microphone and sound processor; however, external equipment carries lifestyle limitations. Although totally implantable devices using subcutaneous microphones have been developed, these are compromised by problems with soft tissue sound attenuation, feedback, and intrusive body noise. This in vivo pilot study evaluates a middle ear microphone (MEM) that aims to overcome these issues and compares hearing performance with that of an external CI microphone. DESIGN: Six adult participants with an existing CI were implanted with a temporary MEM in the contralateral ear. Signals from the MEM were routed via a percutaneous plug and cable to the CI sound processor. Testing was performed in the CI microphone and MEM conditions using a range of audiometric assessments, which were repeated across four visits. RESULTS: Performance of the MEM did not differ significantly from that of the CI on the assessments of Auditory Speech Sounds Evaluation loudness scaling at either 250 or 1000 Hz, or in the accuracy of repeating keywords presented at 70 dB. However, the MEM had significantly poorer aided sound-field thresholds, particularly at higher frequencies (≥4000 Hz), and significantly poorer performance on Arthur Boothroyd words presented at 55 dB, compared with the CI. CONCLUSION: In this pilot study, the MEM showed comparable performance to that of an external CI microphone across some audiometric assessments. However, performance with the MEM was poorer than the CI in soft-level speech (55 dB) and at higher frequencies. As such, the benefits of MEM need to be considered against the compromises in hearing performance. However, with future development, MEM is a potentially promising technology.


Assuntos
Implante Coclear , Implantes Cocleares , Percepção da Fala , Adulto , Humanos , Estudos de Viabilidade , Projetos Piloto , Orelha Média
10.
Appl Clin Inform ; 13(5): 1092-1099, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36384234

RESUMO

BACKGROUND: Symptom control among cancer patients is a Tanzanian public health priority impacted by limited access to palliative care (PC) specialists and resources. Mobile Palliative Care Link (mPCL), a mobile/web application, aims to extend specialist access via shared care with local health workers (LHWs) with the African Palliative care Outcome Scale (POS) adapted for regular, automated symptom assessment as a core feature. OBJECTIVE: The aim of the study is to assess clinicians' attitudes, beliefs, and perceptions regarding mPCL usability and utility with their patients within a government-supported, urban Tanzanian cancer hospital setting. METHODS: We used a mixed methods approach including surveys, qualitative interviews, and system usage data to assess clinicians' experience with mPCL in a field study where discharged, untreatable cancer patients were randomized to mPCL or phone-contact POS collection. RESULTS: All six specialists and 10 LHWs expressed overall satisfaction with mPCL among 49 intervention arm patients. They perceived mPCL as a way to stay connected with patients and support remote symptom control. Timely access to POS responses and medical records were identified as key benefits. Some differences in perceptions of mPCL use and utility were seen between clinician groups; however, both expressed strong interest in continuing app use, recommending it to colleagues, and extending use throughout Tanzania. Primary use was for clinical status communication and care coordination. Pain and other symptom progression were the most frequently reported reasons for provider-patient interactions accounting for 34% (n = 44) and 12% (n = 15) of reasons, respectively. Usage barriers included time required to create a new clinical record, perceived need for response to non-urgent reminders or alerts, and training. necessary for competent use. System-level implementation barriers included variable patient access to smartphones and SIM cards and unreliable Internet access. CONCLUSION: This work demonstrates broad clinician desire for digital health tools to support remote community-based PC among cancer patients, particularly pain management.


Assuntos
Neoplasias , Cuidados Paliativos , Humanos , Cuidados Paliativos/métodos , Administração de Caso , Especialização , Neoplasias/terapia , África Subsaariana
11.
Sci Rep ; 11(1): 10197, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33986304

RESUMO

It is 50 years since Sieveking et al. published their pioneering research in Nature on the geochemical analysis of artefacts from Neolithic flint mines in southern Britain. In the decades since, geochemical techniques to source stone artefacts have flourished globally, with a renaissance in recent years from new instrumentation, data analysis, and machine learning techniques. Despite the interest over these latter approaches, there has been variation in the quality with which these methods have been applied. Using the case study of flint artefacts and geological samples from England, we present a robust and objective evaluation of three popular techniques, Random Forest, K-Nearest-Neighbour, and Support Vector Machines, and present a pipeline for their appropriate use. When evaluated correctly, the results establish high model classification performance, with Random Forest leading with an average accuracy of 85% (measured through F1 Scores), and with Support Vector Machines following closely. The methodology developed in this paper demonstrates the potential to significantly improve on previous approaches, particularly in removing bias, and providing greater means of evaluation than previously utilised.

12.
Cochlear Implants Int ; 22(1): 7-16, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32674683

RESUMO

Objectives: Globally, less than 1% of people who could benefit from a cochlear implant have one and the problem is particularly acute in lower-income countries. Here we give a narrative review of the economic and logistic feasibility of cochlear implant programmes in lower-income countries and discuss future developments that would enable better healthcare. We review the incidence and aetiology of hearing loss in low- and middle-income countries, screening for hearing loss, implantation criteria, issues concerning imaging and surgery, and the professional expertise required. We also review the cost of cochlear implantation and ongoing costs. Findings: The cost effectiveness of cochlear implants in lower-income countries is more limited by the cost of the device than the cost of surgery, but there are also large ongoing costs that will deter many potential users. Conclusions: We conclude that the main barriers to the future uptake of cochlear implants are likely to be logistical rather than technical and cochlear implant provision should be considered as part of a wider programme to improve the health of those with hearing loss.


Assuntos
Implante Coclear , Implantes Cocleares , Surdez , Perda Auditiva Neurossensorial , Análise Custo-Benefício , Surdez/cirurgia , Estudos de Viabilidade , Perda Auditiva Neurossensorial/cirurgia , Humanos
13.
J Health Care Poor Underserved ; 32(2 Suppl): 148-165, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-35574220

RESUMO

Individuals just released from prison, or returning citizens (RCs), face high mortality rates during the reentry period, with cardiovascular disease (CVD) being a leading cause. Peer mentors can support RCs' health, but they traditionally work in person, which may not always be feasible, particularly during pandemic outbreaks such as COVID-19. We used human-centered design to build a prototype of RCPeer, a web/mobile application (app) to support peer-led reentry efforts through CVD risk screening, action planning, linkage to resources addressing reintegration needs (e.g., housing, transportation), and goal-setting. We assessed feasibility, acceptability, and usability of RCPeer using mixed-methods. System Usability Scale (SUS) scores were 68 for peers and 66 for RCs, indicating good usability. Qualitative data suggests that RCPeer can support reentry tasks through RCs and peers sharing data, strengthen RC-peer relationships, and facilitate RCs meeting their goals. Future work is needed to enhance usability for RCs with limited technology experience.


Assuntos
COVID-19 , Doenças Cardiovasculares , Aplicativos Móveis , Telemedicina , COVID-19/epidemiologia , Humanos , Pandemias
14.
JMIR Cancer ; 7(1): e24062, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33755022

RESUMO

BACKGROUND: Improving access to end-of-life symptom control interventions among cancer patients is a public health priority in Tanzania, and innovative community-based solutions are needed. Mobile health technology holds promise; however, existing resources are limited, and outpatient access to palliative care specialists is poor. A mobile platform that extends palliative care specialist access via shared care with community-based local health workers (LHWs) and provides remote support for pain and other symptom management can address this care gap. OBJECTIVE: The aim of this study is to design and develop mobile-Palliative Care Link (mPCL), a web and mobile app to support outpatient symptom assessment and care coordination and control, with a focus on pain. METHODS: A human-centered iterative design framework was used to develop the mPCL prototype for use by Tanzanian palliative care specialists (physicians and nurses trained in palliative care), poor-prognosis cancer patients and their lay caregivers (patients and caregivers), and LHWs. Central to mPCL is the validated African Palliative Care Outcome Scale (POS), which was adapted for automated, twice-weekly collection of quality of life-focused patient and caregiver responses and timely review, reaction, and tracking by specialists and LHWs. Prototype usability testing sessions were conducted in person with 21 key informants representing target end users. Sessions consisted of direct observations and qualitative and quantitative feedback on app ease of use and recommendations for improvement. Results were applied to optimize the prototype for subsequent real-world testing. Early pilot testing was conducted by deploying the app among 10 patients and caregivers, randomized to mPCL use versus phone-contact POS collection, and then gathering specialist and study team feedback to further optimize the prototype for a broader randomized field study to examine the app's effectiveness in symptom control among cancer patients. RESULTS: mPCL functionalities include the ability to create and update a synoptic clinical record, regular real-time symptom assessment, patient or caregiver and care team communication and care coordination, symptom-focused educational resources, and ready access to emergency phone contact with a care team member. Results from the usability and pilot testing demonstrated that all users were able to successfully navigate the app, and feedback suggests that mPCL has clinical utility. User-informed recommendations included further improvement in app navigation, simplification of patient and caregiver components and language, and delineation of user roles. CONCLUSIONS: We designed, built, and tested a usable, functional mobile app prototype that supports outpatient palliative care for Tanzanian patients with cancer. mPCL is expressly designed to facilitate coordinated care via customized interfaces supporting core users-patients or caregivers, LHWs, and members of the palliative care team-and their respective roles. Future work is needed to demonstrate the effectiveness and sustainability of mPCL to remotely support the symptom control needs of Tanzanian cancer patients, particularly in harder-to-reach areas.

15.
JCO Glob Oncol ; 7: 1306-1315, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34406856

RESUMO

PURPOSE: Late-stage cancer patient symptom control is a national priority in Tanzania. Mobile health promises to improve the reach of a limited pool of palliative care specialists through interprofessional, community-based care coordination. This work assessed the effectiveness of a smartphone- or Web-based app, mPalliative Care Link (mPCL), to extend specialist access via shared data and communication with local health workers. Central to mPCL is the African Palliative care Outcome Scale (POS), adapted for automated mobile symptom assessment and response. METHODS: Adult patients with incurable cancer were randomly assigned at hospital discharge to mPCL versus phone-contact POS collection. Sociodemographic, clinical, and POS data were obtained at baseline. Twice-weekly POS responses were collected and managed via mPCL or phone contact with clinician study personnel for up to 4 months, on the basis of study arm assignment. Patient end-of-study care satisfaction was assessed via phone survey. RESULTS: Forty-nine patients per arm participated. Comparison of baseline characteristics showed an insignificant trend toward more women (P = .07) and higher discharge morphine use (P = .09) in the mPCL group compared with phone-contact and significant between-group differences in cancer types (P = .003). Proportions of deaths were near equal between groups (mPCL: 27%; phone-contact: 29%). Overall symptom severity was significantly lower in the phone-contact group (P < .0001), and symptom severity decreased over time in both groups (P = .0001); however, between-group change in overall symptoms over time did not vary significantly (P = .34). Care satisfaction was generally high in both groups. CONCLUSION: Higher symptom severity scores in the mPCL arm likely reflect between-group sociodemographic and clinical differences and clinical support of phone-contact arm participants. Similar rates of care satisfaction in both groups suggest that mPCL may support symptom-focused care coordination in a more efficient and scalable manner than phone contact. A broader study of mPCL's cost efficiency and utility in Tanzania is needed.


Assuntos
Neoplasias , Telemedicina , Assistência Terminal , Feminino , Humanos , Neoplasias/terapia , Cuidados Paliativos , Satisfação do Paciente
16.
Biochem Biophys Res Commun ; 397(3): 479-85, 2010 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-20515655

RESUMO

Childhood spinal muscular atrophy (SMA) is caused by a reduction in survival motor neuron (SMN) protein. SMN is a ubiquitously expressed house keeping protein that is involved in RNA production and processing. However, although SMN is expressed in every cell type, only the lower motor neurons of the spinal cord are degraded in SMA. It remains unclear why this is the case. Recently, SMN has been linked to the axonal transport of beta-actin mRNA from the cell body down to the growth cones. beta-Actin is transported actively in neurite granules (NGs). However, it remains unclear which known SMN-binding partners are present in these SMN-NGs. To address this we have analysed SMN-NGs in a human neuronal cell line, SH-SY5Y, using antibodies against the majority of reported SMN-binding partners, including: Gemin2, Gemin3, Gemin4, Gemin5, Gemin6, Gemin7, Sm core proteins, fibrillarin, EWS, PFNII, Unrip and ZPR1. The obtained results highlight the metamorphic nature of the SMN complex, suggesting that not all the "core" SMN-binding proteins are transported in SMN-NGs.


Assuntos
Corpos Enovelados/metabolismo , Atrofia Muscular Espinal/metabolismo , Neuritos/metabolismo , Proteínas do Complexo SMN/metabolismo , Vesículas Transportadoras/metabolismo , Pré-Escolar , Citoplasma/metabolismo , Células HeLa , Humanos , Transporte Proteico
17.
Biochem Biophys Res Commun ; 394(1): 211-6, 2010 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-20188701

RESUMO

Childhood spinal muscular atrophy (SMA) is caused by a reduction in survival motor neuron (SMN) protein. SMN is expressed in every cell type, but it is predominantly the lower motor neurones of the spinal cord that degenerate in SMA. SMN has been linked to the axonal transport of beta-actin mRNA, a breakdown in which could trigger disease onset. It is known that SMN is present in transport ribonucleoproteins (RNPs) granules that also contain Gemin2 and Gemin3. To further characterise these granules we have performed live cell imaging of GFP-tagged SMN, GFP-Gemin2, GFP-Gemin3, GFP-Gemin6 and GFP-Gemin7. In all, we have made two important observations: (1) SMN granules appear metamorphic; and (2) the SMN-Gemin complex(es) appears to localise to two distinct subsets of bodies in neurites; stationary bodies and smaller dynamic bodies. This study provides an insight into the neuronal function of the SMN complex.


Assuntos
Neuritos/metabolismo , Proteínas do Complexo SMN/metabolismo , Proteína 1 de Sobrevivência do Neurônio Motor/metabolismo , Vesículas Transportadoras/metabolismo , Linhagem Celular Tumoral , Proteínas de Fluorescência Verde/metabolismo , Humanos , Atrofias Musculares Espinais da Infância/metabolismo
18.
Biochem Biophys Res Commun ; 390(4): 1197-201, 2009 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-19879242

RESUMO

The Ewing Sarcoma (EWS) protein is a ubiquitously expressed RNA processing factor that localises predominantly to the nucleus. However, the mechanism through which EWS enters the nucleus remains unclear, with differing reports identifying three separate import signals within the EWS protein. Here we have utilized a panel of truncated EWS proteins to clarify the reported nuclear localisation signals. We describe three C-terminal domains that are important for efficient EWS nuclear localization: (1) the third RGG-motif; (2) the last 10 amino acids (known as the PY-import motif); and (3) the zinc-finger motif. Although these three domains are involved in nuclear import, they are not independently capable of driving the efficient import of a GFP-moiety. However, collectively they form a complex tripartite signal that efficiently drives GFP-import into the nucleus. This study helps clarify the EWS import signal, and the identification of the involvement of both the RGG- and zinc-finger motifs has wide reaching implications.


Assuntos
Neoplasias Ósseas/metabolismo , Núcleo Celular/metabolismo , Sinais de Localização Nuclear , Proteína EWS de Ligação a RNA/metabolismo , Sarcoma de Ewing/metabolismo , Dedos de Zinco , Transporte Ativo do Núcleo Celular , Citoplasma/metabolismo , Análise Mutacional de DNA , Humanos , Mutação , Sinais Direcionadores de Proteínas , Proteína EWS de Ligação a RNA/genética
19.
Biochem Biophys Res Commun ; 375(1): 33-7, 2008 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-18675250

RESUMO

Gemin4 is a ubiquitously expressed multifunctional protein that is involved in U snRNP assembly, apoptosis, nuclear/cytoplasmic transportation, transcription, and RNAi pathways. Gemin4 is one of the core components of the Gemin-complex, which also contains survival motor neuron (SMN), the seven Gemin proteins (Gemin2-8), and Unrip. Mutations in the SMN1 gene cause the autosomal recessive disorder spinal muscular atrophy (SMA). Although the functions assigned to Gemin4 predominantly occur in the nucleus, the mechanisms that mediate the nuclear import of Gemin4 remain unclear. Here, using a novel panel of Gemin4 constructs we identify a canonical nuclear import sequence (NLS) in the N-terminus of Gemin4. The Gemin4 NLS is necessary and independently sufficient to mediate nuclear import of Gemin4. This is the first functional NLS identified within the SMN-Gemin complex.


Assuntos
Sinais de Localização Nuclear/metabolismo , Ribonucleoproteínas Nucleares Pequenas/metabolismo , Transporte Ativo do Núcleo Celular , Núcleo Celular/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Citoplasma/metabolismo , Células HeLa , Humanos , Antígenos de Histocompatibilidade Menor , Mutação , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Sinais de Localização Nuclear/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Ribonucleoproteínas Nucleares Pequenas/genética , Proteínas do Complexo SMN , Proteína 1 de Sobrevivência do Neurônio Motor
20.
Trends Hear ; 22: 2331216518807535, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30378468

RESUMO

Cochlear-implant users who have experienced both analog and pulsatile sound coding strategies often have strong preferences for the sound quality of one over the other. This suggests that analog and pulsatile stimulation may provide different information or sound quality to an implant listener. It has been well documented that many implant listeners both prefer and perform better with multichannel analog than multichannel pulsatile strategies, although the reasons for these differences remain unknown. Here, we examine the perceptual differences between analog and pulsatile stimulation on a single electrode. A multidimensional scaling task, analyzed across two dimensions, suggested that pulsatile stimulation was perceived to be considerably different from analog stimulation. Two associated tasks using single-dimensional scaling showed that analog stimulation was perceived to be less Clean on average than pulsatile stimulation and that the perceptual differences were not related to pitch. In a follow-up experiment, it was determined that the perceptual differences between analog and pulsatile stimulation were not dependent on the interpulse gap present in pulsatile stimulation. Although the results suggest that there is a large perceptual difference between analog and pulsatile stimulation, further work is needed to determine the nature of these differences.


Assuntos
Percepção Auditiva , Implante Coclear/instrumentação , Implantes Cocleares , Surdez/reabilitação , Pessoas com Deficiência Auditiva/reabilitação , Estimulação Acústica , Adulto , Idoso , Surdez/diagnóstico , Surdez/fisiopatologia , Surdez/psicologia , Estimulação Elétrica , Feminino , Audição , Humanos , Percepção Sonora , Masculino , Pessoa de Meia-Idade , Pessoas com Deficiência Auditiva/psicologia , Percepção da Altura Sonora , Desenho de Prótese , Processamento de Sinais Assistido por Computador
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