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1.
Adv Mater ; 33(39): e2103000, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34397123

RESUMO

The competing and non-equilibrium phase transitions, involving dynamic tunability of cooperative electronic and magnetic states in strongly correlated materials, show great promise in quantum sensing and information technology. To date, the stabilization of transient states is still in the preliminary stage, particularly with respect to molecular electronic solids. Here, a dynamic and cooperative phase in potassium-7,7,8,8-tetracyanoquinodimethane (K-TCNQ) with the control of pulsed electromagnetic excitation is demonstrated. Simultaneous dynamic and coherent lattice perturbation with 8 ns pulsed laser (532 nm, 15 MW cm-2 , 10 Hz) in such a molecular electronic crystal initiates a stable long-lived (over 400 days) conducting paramagnetic state (≈42 Ωcm), showing the charge-spin bistability over a broad temperature range from 2 to 360 K. Comprehensive noise spectroscopy, in situ high-pressure measurements, electron spin resonance (ESR), theoretical model, and scanning tunneling microscopy/spectroscopy (STM/STS) studies provide further evidence that such a transition is cooperative, requiring a dedicated charge-spin-lattice decoupling to activate and subsequently stabilize nonequilibrium phase. The cooperativity triggered by ultrahigh-strain-rate (above 106 s- 1 ) pulsed excitation offers a collective control toward the generation and stabilization of strongly correlated electronic and magnetic orders in molecular electronic solids and offers unique electro-magnetic phases with technological promises.

2.
Asian Pac J Cancer Prev ; 22(7): 1997-2004, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34319019

RESUMO

BACKGROUND: This study investigates the socio-demographic factors associated with smoking status in five Southeast Asian countries: Malaysia, Thailand, Indonesia, Vietnam, and Philippines. METHODS: This cross-sectional study utilizes data of adults ≥15 years who completed the Global Adult Tobacco Surveys. Ordered probit analysis is used to account for the smoking statuses of non-smokers, occasional smokers, and daily smokers. RESULTS: Malaysian and Vietnamese households with more family members face lower smoking likelihoods than otherwise. Urbanites in Philippines and rural residents in Thailand and Indonesia are more likely to smoke on occasional and daily basis than others. Males are consistently more likely to smoke occasionally or daily and less likely to be non-smokers than females across all countries. Younger middle-age (retiree) individuals aged 30-35 (≥60) years in Malaysia and Thailand exhibit higher (lower) likelihoods to smoke occasionally or daily than their younger cohorts aged 15-29 years. Individuals aged 30 years and above in Indonesia, Vietnam, and Philippines display higher daily smoking propensities than others. Higher education levels dampens smoking likelihoods and increases non-smoking propensities in all countries. Non-government or self-employed workers in all countries are more likely to smoke occasionally or daily than unemployed persons. Being married is associated with higher non-smoking likelihoods in Thailand although this association is not evident in Malaysia. CONCLUSION: These findings suggest that a portfolio of targeted interventions is necessary to meet the needs of specific subpopulations within the various countries.
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3.
J Orthop Case Rep ; 11(4): 65-69, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34327169

RESUMO

Introduction: The cementless Oxford partial knee arthroplasty is associated with low perioperative complications and good long-term survival rates. However, perioperative fractures remain a serious morbidity for patients. Case Report: This case report describes an early post-operative tibial periprosthetic fracture through the keel slot, which we believe may be contributed by the deep implant keel design and the presence of a narrow metaphysis in the Asian knee. The patient subsequently underwent a revision total knee replacement and fixation of the periprosthetic fracture. Conclusion: This paper discusses the ways to identify patients at high risk of developing periprosthetic fractures and to minimize such occurrences, including adopting a modified tibial preparation, doing precise saw cuts, and considering a cemented tibial implant.

4.
Sci Rep ; 11(1): 7838, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33837249

RESUMO

A major complication with spinal cord injury (SCI) is the development of spasticity, a clinical symptom of hyperexcitability within the spinal H-reflex pathway. We have previously demonstrated a common structural motif of dendritic spine dysgenesis associated with hyperexcitability disorders after injury or disease insults to the CNS. Here, we used an adeno-associated viral (AAV)-mediated Cre-Lox system to knockout Rac1 protein expression in motor neurons after SCI. Three weeks after AAV9-Cre delivery into the soleus/gastrocnemius of Rac1-"floxed" adult mice to retrogradely infect spinal alpha-motor neurons, we observed significant restoration of RDD and reduced H-reflex excitability in SCI animals. Additionally, viral-mediated Rac1 knockdown reduced presence of dendritic spine dysgenesis on motor neurons. In control SCI animals without Rac1 knockout, we continued to observe abnormal dendritic spine morphology associated with hyperexcitability disorder, including an increase in mature, mushroom dendritic spines, and an increase in overall spine length and spine head size. Taken together, our results demonstrate that viral-mediated disruption of Rac1 expression in ventral horn motor neurons can mitigate dendritic spine morphological correlates of neuronal hyperexcitability, and reverse hyperreflexia associated with spasticity after SCI. Finally, our findings provide evidence of a putative mechanistic relationship between motor neuron dendritic spine dysgenesis and SCI-induced spasticity.

5.
Exp Neurol ; 340: 113669, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33647273

RESUMO

Persons living with incomplete spinal cord injuries (SCI) often struggle to regain independent walking due to deficits in walking mechanics. They often dedicate many weeks of gait training before benefits to emerge, with additional training needed for benefits to persist. Recent studies in humans with SCI found that daily bouts of breathing low oxygen (acute intermittent hypoxia, AIH) prior to locomotor training elicited persistent (weeks) improvement in overground walking speed and endurance. AIH-induced improvements in overground walking may result from changes in control strategies that also enhance intralimb coordination; however, this possibility remains untested. Here, we examined the extent to which daily AIH combined with walking practice (AIH + WALK) improved overground walking performance and intralimb motor coordination in persons with chronic, incomplete SCI. METHODS: We recruited 11 persons with chronic (> 1 year), incomplete SCI to participate in a randomized, double-blind, balanced, crossover study. Participants first received either daily (5 consecutive days) AIH (15, 90-s episodes of 10.0% O2 with 60s intervals at 20.9% O2) or SHAM (15, 90s episodes at 20.9% O2 with 60s intervals at 20.9% O2) followed by 30-min of overground walking practice. They received the second treatment after a minimum 2-week washout period. We quantified overground walking performance, in terms of speed and endurance, using the 10-Meter Walk Test (10MWT) and 6-Minute Walk Test (6MWT), respectively. We quantified intralimb motor coordination using kinematic variability measures of foot trajectory (i.e., endpoint variability, EV) and of inter-joint coupling between the hip and knee, as well as between the knee and ankle joints (i.e., angular coefficient of correspondence, ACC). We compared the changes in walking performance relative to baseline (BL) between daily AIH + WALK and daily SHAM+WALK on treatment day 5 (T5), 1-week follow-up (F1), and 2-weeks follow-up (F2). We also compared these changes between participants who used bilateral walking aids (N = 5) and those who did not. To assess the effects of daily AIH + WALK on intralimb coordination, we compared potential treatment-induced changes in EV and ACC relative to BL at F1 and F2. RESULTS: Participants improved overground walking performance (speed and endurance) after daily AIH + WALK, but not SHAM+WALK. Following daily AIH + WALK, participants decreased their 10MWT time at T5 by 28% (95% CI 0.2-10.1 s, p = 0.04), F1 by 28% (95% CI 1.1-13.5 s, p = 0.01), and F2 by 27% (95% CI 1.4-13.9 s, p = 0.01) relative to BL. The greatest decreases in the 10MWT occurred in participants who used bilateral walking aids (p < 0.05). We also found daily AIH + WALK resulted in an increase in 6MWT distance at T5 by 22% (95% CI 13.3-72.6 m, p = 0.001), F1 by 21% (95% CI 13.1-72.5 m, p = 0.001), and F2 by 16% (95% CI 2.9-62.2 m, p = 0.02). However, measures of EV and ACC during self-selected walking conditions did not change following daily AIH + WALK (all p-values >0.50). CONCLUSIONS: Consistent with prior studies, daily AIH + WALK triggered improvements in walking speed and endurance that persisted for weeks after treatment. Greatest improvements in speed occurred in participants who used bilateral walking aids. No change in EV and ACC may suggest that intralimb motor coordination was not a significant gait training priority during daily AIH + WALK.


Assuntos
Hipóxia , Desempenho Psicomotor/fisiologia , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/terapia , Caminhada/fisiologia , Adulto , Idoso , Doença Crônica , Terapia Combinada/métodos , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismos da Medula Espinal/fisiopatologia , Fatores de Tempo , Adulto Jovem
6.
Phys Ther Sport ; 49: 157-163, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33721625

RESUMO

OBJECTIVES: To examine knee flexion range-of-motion, quadriceps strength, and knee self-efficacy trajectory curves over 6 months after anterior cruciate ligament reconstruction (ACLR), stratified by patients' Month-6 sports activity level. DESIGN: Prospective longitudinal study. SETTING: Hospital outpatient physiotherapy department. PARTICIPANTS: 595 individuals after unilateral ACLR (mean age, 27 years). MAIN OUTCOME MEASURES: At 2-, 3-, and 6-months post-surgery, knee flexion range-of-motion, quadriceps strength, and self-efficacy were quantified. Flexion range-of-motion was additionally measured at 2- and 4-weeks post-surgery. Sports activity levels were assessed using the Tegner Activity Score at 6-months post ACLR. RESULTS: The various measures improved nonlinearly over time, with substantial improvements observed in the first 2-4 months post-surgery. In multivariable generalized least squares models, greater knee flexion range-of-motion, quadriceps strength, and self-efficacy over time were significantly associated with higher Month-6 Tegner levels (all P values < 0.01). Additionally, receiving a bone-patellar-tendon-bone graft or meniscal repair was associated with lower quadriceps strength trajectories (P-values<0.001) while female sex was associated with lower knee self-efficacy trajectories (P = 0.02). CONCLUSIONS: Greater knee flexion range-of-motion, quadriceps strength, and self-efficacy were associated with higher Month-6 Tegner levels. The derived trajectory curves may be useful for effective management decision making and adequate results interpretation during the rehabilitation process.


Assuntos
Reconstrução do Ligamento Cruzado Anterior/reabilitação , Joelho/fisiologia , Força Muscular , Músculo Quadríceps/fisiologia , Autoeficácia , Adulto , Lesões do Ligamento Cruzado Anterior/reabilitação , Lesões do Ligamento Cruzado Anterior/cirurgia , Feminino , Humanos , Joelho/cirurgia , Estudos Longitudinais , Masculino , Estudos Prospectivos , Amplitude de Movimento Articular , Adulto Jovem
7.
J Pharm Pract ; : 897190020987127, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33433248

RESUMO

INTRODUCTION: Medication history assessment during hospital admissions is an important element in the medication reconciliation process. It ensures continuity of care and reduces medication errors. OBJECTIVES: This study aimed to determine the incidence of unintentional discrepancies (medication errors), types of medication errors with its potential severity of patient harm and acceptance rate of pharmaceutical care interventions. METHODS: A four-month cross-sectional study was conducted in the general medical wards of a tertiary hospital. All newly admitted patients with at least one prescription medication were recruited via purposive sampling. Medication history assessments were done by clinical pharmacists within 24 hours or as soon as possible after admission. Pharmacist-acquired medication histories were then compared with in-patient medication charts to detect discrepancies. Verification of the discrepancies, interventions, and assessment of the potential severity of patient harm resulting from medication errors were collaboratively carried out with the treating doctors. RESULTS: There were 990 medication discrepancies detected among 390 patients recruited in this study. One hundred and thirty-five (13.6%) medication errors were detected in 93 (23.8%) patients (1.45 errors per patient). These were mostly contributed by medication omissions (79.3%), followed by dosing errors (9.6%). Among these errors, 88.2% were considered "significant" or "serious" but none were "life-threatening." Most (83%) of the pharmaceutical interventions were accepted by the doctors. CONCLUSION: Medication history assessment by pharmacists proved vital in detecting medication errors, mostly medication omissions. Majority of the errors intervened by pharmacists were accepted by the doctors which prevented potential significant or serious patient harm.

8.
Arthroscopy ; 37(1): 328-337, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32721544

RESUMO

PURPOSE: The aim of this meta-analysis was to compare the postoperative stability and functional outcomes of anteromedial (AM)- and transtibial (TT)-based single-bundle hamstring anterior cruciate ligament (ACL) reconstruction techniques. METHODS: A meta-analysis comparing the outcomes of single-bundle hamstring ACL reconstruction using the AM and TT techniques was performed. Prospective randomized controlled trials identified from searches of PubMed, Cochrane, and Embase were included in this review. The outcome measures analyzed included postoperative Lachman test and pivot-shift test results, side-to-side difference, International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner activity score. RESULTS: A total of 7 randomized controlled trials (654 patients) were included in this review. The AM technique, compared with the TT technique, resulted in superior postoperative stability based on the negative Lachman test rate (risk ratio [RR], 1.12; 95% confidence interval [CI], 1.01 to 1.24; P = .03; 95% prediction interval [PI], 0.32 to 3.46), negative pivot-shift test rate (RR, 1.16; 95% CI, 1.06 to 1.28; P = .002; 95% PI, 0.40 to 2.88), and side-to-side difference (weighted mean difference [WMD], -0.32 mm; 95% CI, -0.48 to -0.16; P < .0001; 95% PI, -0.55 to -0.09). Likewise, the AM technique contributed to superior postoperative functional outcomes based on the proportion of IKDC grade A findings (RR, 1.16; 95% CI, 1.02 to 1.32; P = .03; 95% PI, 0.40 to 2.83) and the Lysholm score (WMD, 0.82; 95% CI, 0.23 to 1.41; P = .007; 95% PI, -0.22 to 1.86). However, the AM and TT techniques had comparable subjective IKDC scores (WMD, 0.98; 95% CI, -0.91 to 2.88; P = .31; 95% PI, -3.18 to 5.14) and Tegner activity scores (WMD, 0.32; 95% CI, -0.23 to 0.86; P = .25; 95% PI, -3.84 to 4.48). CONCLUSIONS: The AM method of single-bundle hamstring ACL reconstruction results in superior postoperative stability and functional outcomes compared with the TT method. LEVEL OF EVIDENCE: Level I, systematic review of Level I studies.


Assuntos
Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Ligamento Cruzado Anterior/cirurgia , Músculos Isquiossurais/transplante , Articulação do Joelho/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Escore de Lysholm para Joelho
9.
J Neurosci Methods ; 348: 108972, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33157146

RESUMO

BACKGROUND: The Neurodata Without Borders data standard (NWB) unifies diverse modalities of neurophysiology data in a single format. Integrating NWB with a database unleashes its full potential to promote collaboration, standardize analyses, capitalize on historical data, and ensures data integrity by maintaining process transparency. NWB database technology is the bedrock of analytical systems used by academic leaders including the Allen Institute and the International Brain Laboratory. Here we present the benefits of incorporating NWB design principles in a big data analytics application. NEW METHOD: Data standards and databases are the foundation of big data analytics. To demonstrate the benefits of using these systems together, we implemented NWB in Jupyter notebooks using DataJoint to streamline database operations. RESULTS: We demonstrate the utility of combining the NWB with DataJoint in a Jupyter-based electronic lab journal. We convert open-field behavioral data (using X, Y coordinates) to NWB format and process it with a DataJoint pipeline. Additional notebooks demonstrate working NWB files, data sharing, combining data from diverse sources, and retrospective analyses with data query filtering techniques. COMPARISON WITH EXISTING METHODS: NWB describes how to structure and store neurophysiology data and is streamlined for research settings. In contrast to other data standards, combining NWB with DataJoint's database interface can dramatically increase data analytical capabilities. CONCLUSIONS: The joint use of NWB with DataJoint transforms traditional laboratory datasets and workflows. Our Jupyter notebooks showcase the analytical and collaborative advantages of adopting big data analytics and can be tailored to other modalities by researchers interested in evaluating NWB.


Assuntos
Disseminação de Informação , Software , Ciência de Dados , Estudos Retrospectivos , Fluxo de Trabalho
10.
Thromb Res ; 198: 86-92, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33302212

RESUMO

INTRODUCTION: Although chemoprophylaxis against venous thromboembolism (VTE) after Total Joint Arthroplasty (TJA) is commonly practiced, epidemiology studies have shown Asians have a much lower incidence of VTE. The authors aim to investigate if chemoprophylaxis is really necessary in the Asian population undergoing TJA. MATERIAL AND METHODS: Literature searched was conducted for randomized controlled trials or quasi-experimental studies investigating efficacy and/or safety of chemoprophylaxis for TJA without language restrictions. Network meta-analysis, comparing the incidence of 'VTE to be treated', 'VTE not to be treated', 'Minor bleeding', and 'Major bleeding' amongst the different interventions was performed using multivariate meta-regression model. RESULTS: 38 studies (11,769 patients) were included. Total incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) were 14.2% and 0.73% respectively. For outcome on efficiency, edoxaban, low-molecular-weight-heparin (LMWH), fondaparinux, and enoxaparin showed significantly lower Risk Ratio (RR) for 'VTE to be treated' compared to Control/Placebo. Although no interventions showed increased incidence of major bleeding, LMWH and fondaparinux showed higher RR for minor bleeding. Enoxaparin displayed the best efficacy and safety profile. Total incidence of symptomatic DVT in studies involving enoxaparin was 1.98% (1.07% in patients who received enoxaparin, 2.92% in Control/Placebo). Total incidence of proximal DVT was 2.93% (2.67% in patients who received enoxaparin, 3.11% in Control/Placebo). CONCLUSION: Asian population has a much lower incidence of VTE events after TJA compared to the Western population. Although Enoxaparin is still efficacious in reducing symptomatic and proximal DVT after TJA, its benefit-to-risk ratio is much lower than described in the Western literature.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Quimioprevenção , Heparina de Baixo Peso Molecular , Humanos , Metanálise em Rede , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
11.
FEMS Microbiol Lett ; 367(24)2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33264398

RESUMO

Flagellar motility plays a central role in the bacterial foodborne pathogen Campylobacter jejuni, as flagellar motility is required for reaching the intestinal epithelium and subsequent colonisation or disease. Flagellar proteins also contribute strongly to biofilm formation during transmission. Chemotaxis is the process directing flagellar motility in response to attractant and repellent stimuli, but its role in biofilm formation of C. jejuni is not well understood. Here we show that inactivation of the core chemotaxis genes cheVAWY in C. jejuni strain NCTC 11168 affects both chemotactic motility and biofilm formation. Inactivation of any of the core chemotaxis genes (cheA, cheY, cheV or cheW) impaired chemotactic motility but did not affect flagellar assembly or growth. The ∆cheY mutant swam in clockwise loops, while complementation restored normal motility. Inactivation of the core chemotaxis genes interfered with the ability to form a discrete biofilm at the air-media interface, and the ∆cheY mutant displayed reduced dispersal/shedding of bacteria into the planktonic fraction. This suggests that while the chemotaxis system is not required for biofilm formation per se, it is necessary for organized biofilm formation. Hence interference with the Campylobacter chemotaxis system at any level disrupts optimal chemotactic motility and transmission modes such as biofilm formation.


Assuntos
Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Campylobacter jejuni/genética , Fatores Quimiotáticos/genética , Quimiotaxia/genética , Inativação Gênica , Mutação
12.
Bone Jt Open ; 1(6): 222-228, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33225293

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented challenges to healthcare systems worldwide. Orthopaedic departments have adopted business continuity models and guidelines for essential and non-essential surgeries to preserve hospital resources as well as protect patients and staff. These guidelines broadly encompass reduction of ambulatory care with a move towards telemedicine, redeployment of orthopaedic surgeons/residents to the frontline battle against COVID-19, continuation of education and research through web-based means, and cancellation of non-essential elective procedures. However, if containment of COVID-19 community spread is achieved, resumption of elective orthopaedic procedures and transition plans to return to normalcy must be considered for orthopaedic departments. The COVID-19 pandemic also presents a moral dilemma to the orthopaedic surgeon considering elective procedures. What is the best treatment for our patients and how does the fear of COVID-19 influence the risk-benefit discussion during a pandemic? Surgeons must deliberate the fine balance between elective surgery for a patient's wellbeing versus risks to the operating team and utilization of precious hospital resources. Attrition of healthcare workers or Orthopaedic surgeons from restarting elective procedures prematurely or in an unsafe manner may render us ill-equipped to handle the second wave of infections. This highlights the need to develop effective screening protocols or preoperative COVID-19 testing before elective procedures in high-risk, elderly individuals with comorbidities. Alternatively, high-risk individuals should be postponed until the risk of nosocomial COVID-19 infection is minimal. In addition, given the higher mortality and perioperative morbidity of patients with COVID-19 undergoing surgery, the decision to operate must be carefully deliberated. As we ramp-up elective services and get "back to business" as orthopaedic surgeons, we have to be constantly mindful to proceed in a cautious and calibrated fashion, delivering the best care, while maintaining utmost vigilance to prevent the resurgence of COVID-19 during this critical transition period. Cite this article: Bone Joint Open 2020;1-6:222-228.

15.
J Grad Med Educ ; 12(4): 493-497, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32879692

RESUMO

Background: Graduate medical education in Singapore recently underwent significant restructuring, leading to the accreditation of residency programs by the Accreditation Council for Graduate Medical Education-International (ACGME-I). In radiology, this involved a change in teaching and quality assurance of plain film (PF) reporting. PF reported by junior residents (postgraduate year 1-3) are subject to a 50% random audit. To date, national data on junior resident performance in PF reporting have not been published. Objective: We reviewed performance in PF reporting under the current teaching and audit framework. Methods: Retrospective review of junior resident reported PF audit data from all 3 radiology residency programs in Singapore. The number of residents audited, number of PF reported and audited, and major discrepancy rates were analyzed. Results: On average, 86 440 PF were audited annually nationwide from an estimated 184 288 junior resident-reported PF. Each program trained between 4 to 24 junior residents annually (mean 15), averaging about 44 each year nationwide. A mean of 28 813 PF were audited annually in each program (range 4355-50 880). An estimated mean of 4148 PF (range 1452-9752) were reported per junior resident per year, about 346 PF per month. The major discrepancy rate ranged from 0.04% to 1.13% (mean 0.34%). One resident required remediation in the study period. Conclusions: Structured residency training in Singapore has produced a high level of junior resident competency in PF interpretation.


Assuntos
Internato e Residência , Radiografia/normas , Radiologia/educação , Competência Clínica/normas , Educação de Pós-Graduação em Medicina/normas , Humanos , Estudos Retrospectivos , Singapura
16.
Neurosci Insights ; 15: 2633105520951164, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32864619

RESUMO

Dendritic spines are microscopic protrusions on neurons that house the postsynaptic machinery necessary for neurotransmission between neurons. As such, dendritic spine structure is intimately linked with synaptic function. In pathology, dendritic spine behavior and its contribution to disease are not firmly understood. It is well known that dendritic spines are highly dynamic in vivo. In our recent publication, we used an intravital imaging approach, which permitted us to repeatedly visualize the same neurons located in lamina II, a nociceptive processing region of the spinal cord. Using this imaging platform, we analyzed the intravital dynamics of dendritic spine structure before and after nerve injury-induced pain. This effort revealed a time-dependent relationship between the progressive increase in pain outcome, and a switch in the steady-state fluctuations of dendritic spine structure. Collectively, our in vivo study demonstrates how injury that leads to abnormal pain may also contribute to synapse-associated structural remodeling in nociceptive regions of the spinal cord dorsal horn. By combining our live-imaging approach with measures of neuronal activity, such as with the use of calcium or other voltage-sensitive dyes, we expect to gain a more complete picture of the relationship between dendritic spine structure and nociceptive physiology.

17.
Brain ; 143(8): 2421-2436, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32830219

RESUMO

Vincristine, a widely used chemotherapeutic agent, produces painful peripheral neuropathy. The underlying mechanisms are not well understood. In this study, we investigated whether voltage-gated sodium channels are involved in the development of vincristine-induced neuropathy. We established a mouse model in which repeated systemic vincristine treatment results in the development of significant mechanical allodynia. Histological examinations did not reveal major structural changes at proximal sciatic nerve branches or distal toe nerve fascicles at the vincristine dose used in this study. Immunohistochemical studies and in vivo two-photon imaging confirmed that there is no significant change in density or morphology of intra-epidermal nerve terminals throughout the course of vincristine treatment. These observations suggest that nerve degeneration is not a prerequisite of vincristine-induced mechanical allodynia in this model. We also provided the first detailed characterization of tetrodotoxin-sensitive (TTX-S) and resistant (TTX-R) sodium currents in dorsal root ganglion neurons following vincristine treatment. Accompanying the behavioural hyperalgesia phenotype, voltage-clamp recordings of small and medium dorsal root ganglion neurons from vincristine-treated animals revealed a significant upregulation of TTX-S Na+ current in medium but not small neurons. The increase in TTX-S Na+ current density is likely mediated by Nav1.6, because in the absence of Nav1.6 channels, vincristine failed to alter TTX-S Na+ current density in medium dorsal root ganglion neurons and, importantly, mechanical allodynia was significantly attenuated in conditional Nav1.6 knockout mice. Our data show that TTX-S sodium channel Nav1.6 is involved in the functional changes of dorsal root ganglion neurons following vincristine treatment and it contributes to the maintenance of vincristine-induced mechanical allodynia.


Assuntos
Antineoplásicos Fitogênicos/toxicidade , Hiperalgesia/induzido quimicamente , Hiperalgesia/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.6/metabolismo , Células Receptoras Sensoriais/metabolismo , Vincristina/toxicidade , Animais , Feminino , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/metabolismo , Células Receptoras Sensoriais/efeitos dos fármacos
19.
BMC Neurol ; 20(1): 273, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641012

RESUMO

BACKGROUND: Restoring community walking remains a highly valued goal for persons recovering from traumatic incomplete spinal cord injury (SCI). Recently, studies report that brief episodes of low-oxygen breathing (acute intermittent hypoxia, AIH) may serve as an effective plasticity-inducing primer that enhances the effects of walking therapy in persons with chronic (> 1 year) SCI. More persistent walking recovery may occur following repetitive (weeks) AIH treatment involving persons with more acute SCI, but this possibility remains unknown. Here we present our clinical trial protocol, designed to examine the distinct influences of repetitive AIH, with and without walking practice, on walking recovery in persons with sub-acute SCI (< 12 months) SCI. Our overarching hypothesis is that daily exposure (10 sessions, 2 weeks) to AIH will enhance walking recovery in ambulatory and non-ambulatory persons with subacute (< 12 months) SCI, presumably by harnessing endogenous mechanisms of plasticity that occur soon after injury. METHODS: To test our hypothesis, we are conducting a randomized, placebo-controlled clinical trial on 85 study participants who we stratify into two groups according to walking ability; those unable to walk (non-ambulatory group) and those able to walk (ambulatory group). The non-ambulatory group receives either daily AIH (15, 90s episodes at 10.0% O2 with 60s intervals at 20.9% O2) or daily SHAM (15, 90s episodes at 20.9% O2 with 60s intervals at 20.9% O2) intervention. The ambulatory group receives either 60-min walking practice (WALK), daily AIH + WALK, or daily SHAM+WALK intervention. Our primary outcome measures assess overground walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up & Go Test). For safety, we also measure levels of pain, spasticity, systemic hypertension, and autonomic dysreflexia. We record outcome measures at baseline, days 5 and 10, and follow-ups at 1 week, 1 month, 6 months, and 12 months post-treatment. DISCUSSION: The goal of this clinical trial is to reveal the extent to which daily AIH, alone or in combination with task-specific walking practice, safely promotes persistent recovery of walking in persons with traumatic, subacute SCI. Outcomes from this study may provide new insight into ways to enhance walking recovery in persons with SCI. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02632422 . Registered 16 December 2015.


Assuntos
Terapia por Exercício , Hipóxia , Traumatismos da Medula Espinal/fisiopatologia , Caminhada/fisiologia , Método Duplo-Cego , Humanos , Dor/etiologia , Recuperação de Função Fisiológica
20.
J Knee Surg ; 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32512594

RESUMO

Performing anterior cruciate ligament (ACL) surgery in the immediate period after injury is controversial. However, there may be instances where the opportunity cost of delayed surgery for the patient may be unacceptable. Concomitant meniscus injuries may also prevent the patient from regaining range of motion in the preoperative period. Every week that surgery is delayed may increase pain and impair mobility for this group of patients. We investigate the functional and clinical outcomes in patients with ACL surgery in the immediate 3-week period following ACL injury. A cohort study was performed to compare the outcome of early ACL (less than 3 weeks after injury) and late ACL surgery (more than 3 weeks after surgery). A total of 58 patients were followed up at fixed time points over a 2-year period. Clinical measurements (range of motion and knee laxity scores) and functional outcome scores (International Knee Documentation Committee, Lysholm's Knee and Tegner's scores) were used to document outcomes over time. The mean time to surgery from the time of injury in the early ACL surgery group was 2 weeks (standard deviation [SD] = 0.45) and the 20 weeks (SD = 9.64) in the late ACL surgery group. The absence or presence of meniscal injuries had no significant effect on the improvement over time for both groups of patients (p > 0.05). Patients in the early ACL group had faster rates of improvement for clinical measurements and functional outcome scores but had started out initially with poorer outcomes at baseline. However, both groups had comparable outcomes (p > 0.05) at the 1- and 2-year mark postsurgery. Patients in both groups had no adverse outcomes. ACL Surgery within 3 weeks of injury (2 weeks SD = 0.45) is safe and has comparable outcomes compared to patients with delayed surgery (20 weeks SD = 9.64).

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