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1.
Eur J Orthop Surg Traumatol ; 34(1): 59-66, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37639004

RESUMO

PURPOSE: We analyzed the published literature on return-to-driving (RTD) recommendations following lower extremity orthopedic surgery, including knee and hip arthroplasty and ankle and foot surgery. METHODS: We conducted a PubMed MEDLINE database search for the relevant literature spanning from 1988 to 2022. Data were extracted from the selected articles independently by six investigators, and the mean, standard deviation, and range of RTD recommendations for each surgical region and procedure were calculated. RESULTS: The 34 studies included in our review evaluated brake response time, reaction time, movement time, braking force, and other parameters. Average RTD recommendations in weeks were: hip surgeries, 4.1 (± 2.7); foot surgeries, 6.67 (± 0.94); Achilles surgeries, 6.67 (± 0.25); ankle surgeries, 4 (± 2); knee surgeries, 5.42 (± 0.77); and multiple lower extremity surgeries, 3.85 (± 0.15). CONCLUSION: Our findings can assist physicians in providing informed recommendations to patients, promoting safe driving practices, and optimizing postoperative recovery. LEVEL OF EVIDENCE: Therapeutic, Level III: Retrospective comparative study.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Condução de Veículo , Procedimentos Ortopédicos , Humanos , Artroplastia de Quadril/efeitos adversos , Estudos Retrospectivos , Artroplastia do Joelho/efeitos adversos , Extremidade Inferior/cirurgia , Procedimentos Ortopédicos/efeitos adversos
2.
Epilepsy Behav ; 148: 109465, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37844441

RESUMO

PURPOSE: Benign Epilepsy with Centro-Temporal Spikes (BECTS) is a pediatric epilepsy with typically good seizure control. Although BECTS may increase patients' risk of developing neurological comorbidities, their clinical care and short-term outcomes are poorly quantified. METHODS: We retrospectively assessed adherence to National Institute for Health and Care Excellence (NICE) guidelines relating to specialist referral, electroencephalogram (EEG) conduct and annual review in the care of patients with BECTS, and measured their seizure, neurodevelopmental and learning outcomes at three years post-diagnosis. RESULTS: Across ten centers in England, we identified 124 patients (74 male) diagnosed with BECTS between 2015 and 2017. Patients had a mean age at diagnosis of 8.0 (95% CI = 7.6-8.4) years. 24/95 (25%) patients were seen by a specialist within two weeks of presentation; 59/100 (59%) received an EEG within two weeks of request; and 59/114 (52%) were reviewed annually. At three years post-diagnosis, 32/114 (28%) experienced ongoing seizures; 26/114 (23%) had reported poor school progress; 15/114 (13%) were diagnosed with a neurodevelopmental disorder (six autism spectrum disorder, six attention-deficit/hyperactivity disorder); and 10/114 (8.8%) were diagnosed with a learning difficulty (three processing deficit, three dyslexia). Center-level random effects models estimated neurodevelopmental diagnoses in 9% (95% CI: 2-16%) of patients and learning difficulty diagnoses in 7% (95% CI: 2-12%). CONCLUSIONS: In this multicenter work, we found variable adherence to NICE guidelines in the care of patients with BECTS and identified a notable level of neurological comorbidity. Patients with BECTS may benefit from enhanced cognitive and behavioral assessment and monitoring.


Assuntos
Transtorno do Espectro Autista , Epilepsia Rolândica , Humanos , Criança , Masculino , Epilepsia Rolândica/diagnóstico , Epilepsia Rolândica/epidemiologia , Epilepsia Rolândica/psicologia , Estudos Retrospectivos , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/epidemiologia , Convulsões , Eletroencefalografia
3.
J Environ Manage ; 233: 410-416, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30590270

RESUMO

Improvement of sludge dewaterability is greatly hindered by the presence of large amounts of interstitial water molecules trapped in the sludge as a result of strong hydrophilic characteristics. This study has investigated the influence of six different polyacrylamide (PAM) flocculants with different molecular architecture (linear, slightly and highly branched), charge density (CD) and molecular weight (MW) on the electro-kinetics and dewatering of highly stable industrial membrane bioreactor (MBR) sludge. The impact of PAM on flocculation is manifested in the supernatant turbidity, particle zeta potential, sludge capillary suction time (CST), floc size and settleability. Turbidity removal and reduction in zeta potential are used to identify the optimum polymer dose. An optimum dose of 70 mg.L-1 has been determined for linear PAM of 40% CD. However, a highly-branched PAM, with the same CD, has shown an optimum value of 30 mg.L-1. In all cases, a turbidity removal of more than 99% and CST reduction of 51-64% is attained; the linear PAMs have resulted in the highest CST reduction. Higher PAM doses have resulted in larger flocs and the maximum particle size is observed at the saturation point. The reduction in sludge volume relates with the floc size and PAM dose. For sludge conditioning and dewaterability, highly branched PAM with low MW has shown superior performance over linear high MW PAM. Enhancement of flocculation and dewatering is correlated with the surface charge neutralization and bridging mechanisms.


Assuntos
Polieletrólitos , Purificação da Água , Reatores Biológicos , Floculação , Esgotos , Água
4.
Anticancer Drugs ; 28(3): 263-270, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27861173

RESUMO

Overexpression of epidermal growth factor receptor (EGFR) plays a significant role in the development and metastasis of many solid tumors. Strategies based on anti-EGFR immunotoxins have shown promising results in several studies, but immunogenicity of antibody and toxin moieties is a limitation of this type of therapeutics. In the present study, a novel humanized anti-EGFR immunotoxin (huscFv-PE25) was developed by genetic fusing of a humanized anti-EGFR single-chain variable fragment (huscFv) with a modified Pseudomonas aeruginosa exotoxin A (PE25KDEL). The reactivity and toxicity of this immunotoxin with tumor cells were assessed by dot-blot, enzyme-linked immunosorbent assay, and MTT procedures. Results of enzyme-linked immunosorbent assay and dot-blot assay indicated that the immunotoxin recognizes and efficiently binds to EGFR-overexpressing tumor cells. MTT assay showed a specific growth-inhibitory effect of huscFv-PE25 on EGFR-overexpressing A431 cells, without any inhibitory effect on EGFR-negative cells. In conclusion, the results of this study indicated that huscFv-PE25 can recognize and exert an inhibitory effect on EGFR-overexpressing cancer cells, despite its smaller size and lower immunogenicity. This may provide a basis for the development of novel clinical therapeutic agents against EGFR-overexpressing tumor cells.


Assuntos
ADP Ribose Transferases/farmacologia , Toxinas Bacterianas/farmacologia , Receptores ErbB/imunologia , Exotoxinas/farmacologia , Imunotoxinas/química , Imunotoxinas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Fatores de Virulência/farmacologia , Células A549 , ADP Ribose Transferases/química , Animais , Toxinas Bacterianas/química , Células CHO , Linhagem Celular Tumoral , Cetuximab/farmacologia , Cricetulus , Ensaio de Imunoadsorção Enzimática , Receptores ErbB/biossíntese , Exotoxinas/química , Região Variável de Imunoglobulina/química , Região Variável de Imunoglobulina/imunologia , Imunotoxinas/imunologia , Imunotoxinas/isolamento & purificação , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/imunologia , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/imunologia , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/imunologia , Fatores de Virulência/química , Exotoxina A de Pseudomonas aeruginosa
5.
Int J Pediatr Otorhinolaryngol ; 176: 111816, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38104524

RESUMO

OBJECTIVES: To assess the influence of social media platforms, including TikTok, Instagram, and Facebook, in shaping public perceptions about tonsillectomies and to identify the nature of the content disseminated on these platforms. METHODS: A comprehensive analysis of 1482 relevant social media posts related to tonsillectomies was conducted across major platforms, including TikTok, Instagram, and Facebook. Content was categorized based on author, topic of the post, timeframe, and overall tone. The study also compared engagement metrics across platforms. RESULTS: TikTok emerged as the most engaging platform with a mean of 3272.8 likes per post. Patients drove 61.6 % of the discourse, with 63.9 % of discussions being lifestyle oriented. Educational content constituted 12.5 % of the overall discourse. Sentiments towards the procedure were almost evenly split, with 29.4 % positive and 28.5 % negative; 92 % of the negative posts were authored by patients. CONCLUSIONS: Patients were the most common social media authors, driving the conversation and a significant portion expressing negative views. Physicians, conversely, showed a low level of social media engagement. By understanding and addressing online narratives, clinicians can offer more informed patient support, debunk myths, and provide empathetic insights, ensuring positive patient experiences in the era of digital health communication.


Assuntos
Mídias Sociais , Tonsilectomia , Voz , Humanos , Comunicação , Saúde Digital
6.
World Neurosurg ; 185: e209-e242, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38741326

RESUMO

OBJECTIVE: Spinal pathologies are prevalent in Nigeria, though epidemiological data remains sparse. This systematic review used pooled patient-level data from across the country to generate a standardized epidemiological reference. METHODS: Four research databases and gray literature sources were searched. Risk of bias assessment was conducted using Risk of Bias in Non-Randomised Studies - of Interventions and Cochrane's risk of bias tool. We descriptively analyzed all article metrics and statistically analyzed relevant data variables via paired t-test and χ2 independence tests (α = 0.05). RESULTS: One hundred twenty-seven articles, comprising a patient cohort of 8425 patients, were analyzed. Most were retrospective cohort studies (46.5%) and case reports/series (31.5%), with an overall moderate-high risk of bias. Most studies were published in the last 20 years. Most patients were male (∼2.5 males per female), with an average age of 43.2 years (±16.4). Clinical diagnoses spanned the breadth of spinal neurosurgery. Approximately 45.0% of patients had complete spinal impairment. Pain (41.7%) was the most reported presenting feature. X-ray (45.1%) was the most common investigation used. Intervertebral disc herniation (18.9%) was the most prevalent imaging finding on MRI. Most patients were managed nonoperatively (57.8%), with a favorable outcome in 27.4% of patients. Posttreatment complications included pressure sores, infection, and motor deficits. CONCLUSIONS: This systematic review and pooled analysis provide an epidemiological overview of spinal neurosurgery in Nigeria over the last 60 years and serves as a useful reference to direct future global research in this arena.


Assuntos
Doenças da Coluna Vertebral , Humanos , Nigéria/epidemiologia , Doenças da Coluna Vertebral/cirurgia , Doenças da Coluna Vertebral/epidemiologia , Procedimentos Neurocirúrgicos , Masculino , Feminino , Adulto , Neurocirurgia
7.
World Neurosurg ; 185: e243-e263, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38741327

RESUMO

OBJECTIVE: Vascular neurosurgery has developed significantly in Nigeria, but its burden and challenges remain unclear. This study systematically reviewed vascular neurosurgical literature from Nigeria. METHODS: Four research databases and gray literature sources were searched from 1962-2021. ROBINS-I tool was used to assess risk of bias. Descriptive, narrative, and statistical analyses were conducted on all variables. Where appropriate, paired t-tests and Chi-squared independence tests were used (α = 0.05). RESULTS: 56 articles were included and 3203 patients pooled for analysis. Risk of bias was moderate-high. Most articles were published over the last 20 years with retrospective cohort studies and case reports being the most common study designs. The cohort had a relatively even gender split and an average age of 49 years (±22). Cerebrovascular accidents accounted for over 85% of diagnoses, with most etiologies being traumatic. Headache and motor deficit were the most prevalent clinical features. X-ray and carotid angiography were the most commonly reported imaging modalities, closely followed by computed tomography (CT) and CT angiography. The top two radiological diagnoses were ischemic cerebrovascular disease and intracerebral hematoma. Aneurysmal clipping and hematoma evacuation were the most commonly reported treatment modalities. Outcome at last follow-up was favorable in 48%. The mortality rate was 6%. Post-treatment complications included chest infection and rebleeding. CONCLUSIONS: This study illustrates the epidemiological burden of neurovascular pathology (based on the available data in published literature) in Nigeria, and raises awareness amongst service providers and researchers of the attendant challenges and epochal trends seen within vascular neurosurgery in Nigeria.


Assuntos
Transtornos Cerebrovasculares , Nigéria/epidemiologia , Humanos , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/cirurgia , Procedimentos Neurocirúrgicos , Pessoa de Meia-Idade , Masculino
8.
World Neurosurg ; 185: e99-e142, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38741332

RESUMO

OBJECTIVE: Neurotrauma is a significant cause of morbidity and mortality in Nigeria. We conducted this systematic review to generate nationally generalizable reference data for the country. METHODS: Four research databases and gray literature sources were electronically searched. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies of Interventions and Cochrane's risk of bias tools. Descriptive analysis, narrative synthesis, and statistical analysis (via paired t-tests and χ2 independence tests) were performed on relevant article metrics (α = 0.05). RESULTS: We identified a cohort of 45,763 patients from 254 articles. The overall risk of bias was moderate to high. Most articles employed retrospective cohort study designs (37.4%) and were published during the last 2 decades (81.89%). The cohort's average age was 32.5 years (standard deviation, 20.2) with a gender split of ∼3 males per female. Almost 90% of subjects were diagnosed with traumatic brain injury, with road traffic accidents (68.6%) being the greatest cause. Altered consciousness (48.4%) was the most commonly reported clinical feature. Computed tomography (53.5%) was the most commonly used imaging modality, with skull (25.7%) and vertebral fracture (14.1%) being the most common radiological findings for traumatic brain injury and traumatic spinal injury, respectively. Two-thirds of patients were treated nonoperatively. Outcomes were favorable in 63.7% of traumatic brain injury patients, but in only 20.9% of traumatic spinal injury patients. Pressure sores, infection, and motor deficits were the most commonly reported complications in the latter. CONCLUSIONS: This systematic review and pooled analysis demonstrate the significant burden of neurotrauma across Nigeria.


Assuntos
Lesões Encefálicas Traumáticas , Humanos , Nigéria/epidemiologia , Lesões Encefálicas Traumáticas/epidemiologia , Lesões Encefálicas Traumáticas/terapia , Feminino , Masculino , Adulto , Acidentes de Trânsito/estatística & dados numéricos , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/terapia
9.
World Neurosurg ; 185: e75-e85, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38741331

RESUMO

BACKGROUND: Although women have made remarkable strides in several medical specialties in Sub-Saharan Africa, their presence and contribution to the development of neurosurgery remain limited. We sought to study the gender differences within Nigerian neurosurgery, identify challenges resulting from these differences, and recommend how African female neurosurgeons can maximize their effects in neurosurgery. METHODS: A structured online survey captured data on neurosurgical infrastructural capacity, workforce, and training from neurosurgical consultants and residents in neurosurgical centers in Nigeria. All the collected data were coded and analyzed. RESULTS: Altogether, 82 neurosurgical consultants and 67 neurosurgical residents from 50 primary medical institutions in Nigeria completed the online survey. Only 8 of the respondents (5.4%) were women, comprising 3 consultants, 2 senior residents, and 3 junior residents. Although 40.2% of the respondents did not believe that being female affected the decision of whether to specialize in neurosurgery, 46.3% believed that being female was a disadvantage. Most did not believe that being female affected admission (57.8%), completion of a neurosurgery residency (58.5%), or life working as a neurosurgeon after graduation (63.4%). The most common challenges women face while navigating through neurosurgery training and practice are erosion of family and social life, lack of female mentors, and lack of a work-life balance. CONCLUSIONS: There is a deficit of both female consultants and trainees among Nigerian neurosurgeons. Identifying female medical students with a strong interest in neurosurgery and providing early mentorship might increase the number of female neurosurgeons.


Assuntos
Internato e Residência , Neurocirurgiões , Neurocirurgia , Médicas , Humanos , Nigéria , Feminino , Estudos Transversais , Médicas/estatística & dados numéricos , Neurocirurgia/educação , Masculino , Inquéritos e Questionários , Adulto , Escolha da Profissão , Equilíbrio Trabalho-Vida , Mentores
10.
World Neurosurg ; 185: e16-e29, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38741324

RESUMO

OBJECTIVE: There has been a modest but progressive increase in the neurosurgical workforce, training, and service delivery in Nigeria in the last 2 decades. However, these resources are unevenly distributed. This study aimed to quantitatively assess the availability and distribution of neurosurgical resources in Nigeria while projecting the needed workforce capacity up to 2050. METHODS: An online survey of Nigerian neurosurgeons and residents assessed the country's neurosurgical infrastructure, workforce, and resources. The results were analyzed descriptively, and geospatial analysis was used to map their distribution. A projection model was fitted to predict workforce targets for 2022-2050. RESULTS: Out of 86 neurosurgery-capable health facilities, 65.1% were public hospitals, with only 17.4% accredited for residency training. Dedicated hospital beds and operating rooms for neurosurgery make up only 4.0% and 15.4% of the total, respectively. The population disease burden is estimated at 50.2 per 100,000, while the operative coverage was 153.2 cases per neurosurgeon. There are currently 132 neurosurgeons and 114 neurosurgery residents for a population of 218 million (ratio 1:1.65 million). There is an annual growth rate of 8.3%, resulting in a projected deficit of 1113 neurosurgeons by 2030 and 1104 by 2050. Timely access to neurosurgical care ranges from 21.6% to 86.7% of the population within different timeframes. CONCLUSIONS: Collaborative interventions are needed to address gaps in Nigeria's neurosurgical capacity. Investments in training, infrastructure, and funding are necessary for sustainable development and optimized outcomes.


Assuntos
Acessibilidade aos Serviços de Saúde , Neurocirurgiões , Neurocirurgia , Nigéria , Humanos , Neurocirurgia/tendências , Neurocirurgia/educação , Acessibilidade aos Serviços de Saúde/tendências , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Neurocirurgiões/provisão & distribuição , Neurocirurgiões/tendências , Mão de Obra em Saúde/tendências , Mão de Obra em Saúde/estatística & dados numéricos , Procedimentos Neurocirúrgicos/tendências , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Recursos Humanos/estatística & dados numéricos , Recursos Humanos/tendências , Internato e Residência/tendências , Inquéritos e Questionários , Previsões
11.
World Neurosurg ; 185: e30-e43, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38741328

RESUMO

BACKGROUND: Like many low- and-middle-income countries in Africa, documented assessment of the neurosurgical workforce, equipment, infrastructure, and scope of service delivery in Nigeria is lacking. This study aimed to assess the capacity for the delivery of neurosurgical services in Nigeria. METHODS: An 83-question survey was disseminated to neurosurgeons and residents in Nigeria. We report the findings from the capacity assessment section of the survey, which used the modified neurological-PIPES (personnel, infrastructure, procedures, equipment, and supplies) (MN-PIPES) tool to evaluate the availability of neurosurgical personnel, infrastructure, procedures, equipment, and supplies. A comparative analysis was done using the domain and total MN-PIPES scores and MN-PIPES index. RESULTS: The national average MN-PIPES score and index were 176.4 and 9.8, respectively. Overall, the southwest and northwest regions had the highest scores and frequently had high subscores. The survey respondents reported that the main challenges impeding neurosurgery service delivery were a lack of adjunctive supplies (75.2%), a dearth of diagnostic and interventional equipment (72.4%), and an absence of a dedicated intensive care unit (72.4%). CONCLUSIONS: The availability of workforce, infrastructure, equipment, and supplies needed to provide optimal neurosurgical care is uneven in many institutions in Nigeria. Although major strides have been made in recent years, targeted collaborative interventions at local, national, regional, and international levels will further improve neurosurgical service delivery in Nigeria and will have positive ripple effects on the rest of the healthcare system.


Assuntos
Neurocirurgiões , Neurocirurgia , Nigéria , Humanos , Procedimentos Neurocirúrgicos , Inquéritos e Questionários
12.
World J Gastrointest Surg ; 16(6): 1835-1844, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38983343

RESUMO

BACKGROUND: Data regarding the worldwide gastrointestinal surgery rates in patients with Crohn's disease (CD) remains limited. AIM: To systematically review the global variation in the rates of surgery in CD. METHODS: A comprehensive search analysis was performed using multiple electronic databases from inception through July 1, 2020, to identify all full text, randomized controlled trials and cohort studies pertaining to gastrointestinal surgery rates in adult patients with CD. Outcomes included continent based demographic data, CD surgery rates over time, as well as the geoepidemiologic variation in CD surgery rates. Statistical analyses were conducted using R. RESULTS: Twenty-three studies spanning four continents were included. The median proportion of persons with CD who underwent gastrointestinal surgery in studies from North America, Europe, Asia, and Oceania were 30% (range: 1.7%-62.0%), 40% (range: 0.6%-74.0%), 17% (range: 16.0%-43.0%), and 38% respectively. No clear association was found regarding the proportion of patients undergoing gastrointestinal surgery over time in North America (R 2 = 0.035) and Europe (R 2 = 0.100). A moderate, negative association was seen regarding the proportion of patients undergoing gastrointestinal surgery over time (R 2 = 0.520) in Asia. CONCLUSION: There appears to be significant inter-continental variation regarding surgery rates in CD. Homogenous evidence-based guidelines accounting for the geographic differences in managing patients with CD is prudent. Moreover, as a paucity of data on surgery rates in CD exists outside the North American and European continents, future studies, particularly in less studied locales, are warranted.

13.
World Neurosurg ; 185: e185-e208, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38741325

RESUMO

OBJECTIVE: Access to neuro-oncologic care in Nigeria has grown exponentially since the first reported cases in the mid-1960s. In this systematic review and pooled analysis, we characterize the growth of neurosurgical oncology in Nigeria and build a reference paper to direct efforts to expand this field. METHODS: We performed an initial literature search of several article databases and gray literature sources. We included and subsequently screened articles published between 1962 and 2021. Several variables were extracted from each study, including the affiliated hospital, the number of patients treated, patient sex, tumor pathology, the types of imaging modalities used for diagnosis, and the interventions used for each individual. Change in these variables was assessed using Chi-squared independence tests and univariate linear regression when appropriate. RESULTS: A total of 147 studies were identified, corresponding to 5,760 patients. Over 4000 cases were reported in the past 2 decades from 21 different Nigerian institutions. The types of tumors reported have increased over time, with increasingly more patients being evaluated via computed tomography (CT) and magnetic resonance imaging (MRI). There is also a prevalent use of radiotherapy, though chemotherapy remains an underreported treatment modality. CONCLUSIONS: This study highlights key trends regarding the prevalence and management of neuro-oncologic pathologies within Nigeria. Further studies are needed to continue to learn and guide the future growth of this field in Nigeria.


Assuntos
Neoplasias Encefálicas , Nigéria/epidemiologia , Humanos , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/diagnóstico por imagem , Oncologia/tendências , Neurocirurgia/tendências
14.
Biomed Microdevices ; 15(2): 255-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23160842

RESUMO

We show measurements of the human cardiac potassium ion channel Kv11.1 (hERG) in droplet bilayers incorporated directly from commercial membrane preparations of HEK293 cells. Although we do not obtain ensemble conductance kinetics and rectification observed in patch clamp measurements of hERG, ensemble currents measured in our system showed inhibition dependent on astemizole and E-4031 concentration, with IC50 values similar to those found with patch clamp. The availability of engineered HEK cells expressing a variety of ion channels, combined with the simplicity of the inhibition measurement, suggest that droplet bilayers may have considerable technological potential for determination of ion channel drug potency.


Assuntos
Avaliação Pré-Clínica de Medicamentos/instrumentação , Canais de Potássio Éter-A-Go-Go/química , Bicamadas Lipídicas/química , Potenciais da Membrana/efeitos dos fármacos , Técnicas Analíticas Microfluídicas/instrumentação , Bloqueadores dos Canais de Potássio/química , Bloqueadores dos Canais de Potássio/farmacologia , Canal de Potássio ERG1 , Desenho de Equipamento , Análise de Falha de Equipamento , Canais de Potássio Éter-A-Go-Go/efeitos dos fármacos , Ativação do Canal Iônico/efeitos dos fármacos
15.
Analyst ; 138(22): 6793-800, 2013 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-24056299

RESUMO

Membrane permeability assays play an important role in assessing drug transport activities across biological membranes. However, in conventional parallel artificial membrane permeability assays (PAMPA), the membrane model used is dissimilar to biological membranes physically and chemically. Here, we describe a microfluidic passive permeability assay using droplet interface bilayers (DIBs). In a microfluidic network, nanoliter-sized donor and acceptor aqueous droplets are alternately formed in cross-flowing oil containing phospholipids. Subsequently, selective removal of oil through hydrophobic pseudo-porous sidewalls induces the contact of the lipid monolayers, creating arrayed planar DIBs between the donor and acceptor droplets. Permeation of fluorescein from the donor to the acceptor droplets was fluorometrically measured. From the measured data and a simple diffusion model we calculated the effective permeabilities of 5.1 × 10(-6) cm s(-1), 60.0 × 10(-6) cm s(-1), and 87.6 × 10(-6) cm s(-1) with donor droplets at pH values of 7.5, 6.4 and 5.4, respectively. The intrinsic permeabilities of specific monoanionic and neutral fluorescein species were obtained similarly. We also measured the permeation of caffeine in 10 min using UV microspectroscopy, obtaining a permeability of 20.8 × 10(-6) cm s(-1). With the small solution volumes, short measurement time, and ability to measure a wide range of compounds, this device has considerable potential as a platform for high-throughput drug permeability assays.


Assuntos
Bioensaio/instrumentação , Bicamadas Lipídicas/química , Microfluídica , Bioensaio/métodos , Cafeína/química , Concentração de Íons de Hidrogênio , Permeabilidade , Água/química
16.
Environ Microbiome ; 18(1): 36, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37085932

RESUMO

BACKGROUND: Microbiomes are critical to plants, promoting growth, elevating stress tolerance, and expanding the plant's metabolic repertoire with novel defense pathways. However, generally microbiomes within plant tissues, which intimately interact with their hosts, remain poorly characterized. These endospheres have become a focus in banana (Musa spp.)-an important plant for study of microbiome-based disease protection. Banana is important to global food security, while also being critically threatened by pandemic diseases. Domestication and clonal propagation are thought to have depleted protective microbiomes, whereas wild relatives may hold promise for new microbiome-based biological controls. The goal was to compare metapangenomes enriched from 7 Musa genotypes, including wild and cultivated varieties grown in sympatry, to assess the host associations with root and leaf endosphere functional profiles. RESULTS: Density gradients successfully generated culture-free microbial enrichment, dominated by bacteria, with all together 24,325 species or strains distinguished, and 1.7 million metagenomic scaffolds harboring 559,108 predicted gene clusters. About 20% of sequence reads did not match any taxon databases and ~ 62% of gene clusters could not be annotated to function. Most taxa and gene clusters were unshared between Musa genotypes. Root and corm tissues had significantly richer endosphere communities that were significantly different from leaf communities. Agrobacterium and Rhizobium were the most abundant in all samples while Chitinophagia and Actinomycetia were more abundant in roots and Flavobacteria in leaves. At the bacterial strain level, there were > 2000 taxa unique to each of M. acuminata (AAA genotype) and M. balbisiana (B-genotype), with the latter 'wild' relatives having richer taxa and functions. Gene ontology functional enrichment showed core beneficial functions aligned with those of other plants but also many specialized prospective beneficial functions not reported previously. Some gene clusters with plant-protective functions showed signatures of phylosymbiosis, suggesting long-standing associations or heritable microbiomes in Musa. CONCLUSIONS: Metapangenomics revealed key taxa and protective functions that appeared to be driven by genotype, perhaps contributing to host resistance differences. The recovery of rich novel taxa and gene clusters provides a baseline dataset for future experiments in planta or in vivo bacterization or engineering of wild host endophytes.

17.
Front Microbiol ; 14: 1127606, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37362937

RESUMO

Introduction: Viruses generally cause disease, but some viruses may be beneficial as resident regulators of their hosts or host microbiomes. Plant-associated viruses can help plants survive by increasing stress tolerance or regulating endophytic communities. The goal of this study was to characterize endophytic virus communities in banana and plantain (Musa spp.) genotypes, including cultivated and wild species, to assess virome repertoires and detect novel viruses. Methods: DNA viral communities were characterized by shotgun sequencing of an enriched endosphere extract from leaves and roots or corm of 7 distinct Musa genotypes (M. balbisiana, Thai Black, M. textilis, M. sikkimensis, Dwarf Cavendish, Williams Hybrid, and FHIA-25 Hybrid). Results: Results showed abundant virus-like contigs up to 108,191 bp long with higher relative abundance in leaves than roots. Analyses predicted 733 phage species in 51 families, with little overlap in phage communities among plants. Phage diversity was higher in roots and in diploid wild hosts. Ackermanniviridae and Rhizobium phage were generally the most abundant taxa. A Rhizobium RR1-like phage related to a phage of an endophytic tumor-causing rhizobium was found, bearing a holin gene and a partial Shiga-like toxin gene, raising interest in its potential to regulate endophytic Rhizobiaceae. Klebsiella phages were of interest for possible protection against Fusarium wilt, and other phages were predicted with potential to regulate Erwinia, Pectobacterium, and Ralstonia-associated diseases. Although abundant phage-containing contigs were functionally annotated, revealing 1,038 predicted viral protein domains, gene repertoires showed high divergence from database sequences, suggesting novel phages in these banana cultivars. Plant DNA viruses included 56 species of Badnavirus and 26 additional non-Musa plant viruses with distributions that suggested a mixture of resident and transient plant DNA viruses in these samples. Discussion: Together, the disparate viral communities in these plants from a shared environment suggest hosts drive the composition of these virus communities. This study forms a first step in understanding the endophytic virome in this globally important food crop, which is currently threatened by fungal, bacterial, and viral diseases.

18.
World Neurosurg ; 2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37931875

RESUMO

OBJECTIVE: This study investigates the scope, trends, and challenges of neurosurgical research in Nigeria since inception of the specialty in 1962. METHODS: A bibliometric review of the neurosurgical literature from Nigeria was done. Variables extracted included year and journal of publication, article topic, article type, research type, study design, article focus area, and limitations. Descriptive and quantitative analyses were performed for all variables. Trends of research publications were described in three periods - pioneering (1962-1981), recession (1982-2001), and resurgent (2002-2021). RESULTS: Of the 1023 included articles, 10.0% were published in the pioneering period, 9.2% in the recession period, and 80.8% in the resurgent period. Papers were predominantly published in World Neurosurgery (4.5%) and Nigerian Journal of Clinical Practice ( 4.0%). 79.9% of the 4618 authors were from Nigerian institutions. 86.3% of the articles covered clinical research and were mainly focused on service delivery and epidemiology (89.9%). The most prominent topics were traumatic brain injury (25.8%) and CNS malignancy (21.4%). Only 4.4% of the publications received funding, mostly from agencies in the US (31.7%). Barriers to neurosurgical research included lack of clinical databases (18.0%), increasing burden of disease (12.5%), and diagnostic challenges (12.4%). CONCLUSION: Neurosurgical research in Nigeria continues to grow due to increased training, workforce, and infrastructural improvements. Addressing the major challenges through establishment of research databases, development of evidence-based management guidelines, and increasing research training, funding and opportunities can increase research capacity in Nigeria.

19.
World Neurosurg ; 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37939879

RESUMO

OBJECTIVE: This study aims to provide a comprehensive overview of pediatric neurosurgery in Nigeria, since 1962, by assessing epidemiological data, management strategies, and case outcomes. METHODS: A systematic bibliometric review of Nigerian neurosurgical literature was reported with the PRISMA guidelines. The Risk of Bias Assessment Tool was applied to all non-randomized studies, and a descriptive analysis was performed for all variables. RESULTS: We identified 12,295 pediatric patients from 196 published studies. Most publications (72.4%) occurred in the recent two decades, of which 40.3% were observational case reports/series. The patients were predominantly male (57.2%) and aged 0-18 years, with the majority (66.1%) belonging to the 0-5 age range. Most patients (63.4%) presented between 1-12 months. The most common presenting feature was altered consciousness (7.7%), with computed tomography (38.8%) being the most frequently utilized diagnostic imaging modality. The diagnoses with the greatest prevalence (60.2%) were congenital abnormalities such as hydrocephalus and neural tube defects. 57.5% of cases received surgical therapy, with ventriculoperitoneal shunt placement being the most noticeable procedure performed (36.4%). Complications were identified in 9.5% of cases, with a 4.5% death rate. The Glasgow Outcome Score (95.7%) was the primary outcome measure utilized, with positive outcomes reported in 59.3% of cases. CONCLUSION: This review provides significant epidemiological data which emphasizes the country's enormous burden of pediatric neurosurgical cases. The findings can help guide clinical decisions as well as future research and policy development.

20.
World Neurosurg ; 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37979680

RESUMO

OBJECTIVE: Despite the well-known neurosurgical workforce deficit in Sub-Saharan Africa, there remains a low number of neurosurgical training programs in Nigeria. This study sought to re-assess the current status of specialist neurosurgical training in the country. METHODS: An electronic survey was distributed to all consultant neurosurgeons and neurosurgery residents in Nigeria. Demographic information and questions relating to the content, process, strengths, and challenges of neurosurgical training were explored as part of a broader survey assessing neurosurgical capacity. Descriptive statistics were used for analysis. RESULTS: Respondents identified 15 neurosurgical training centers in Nigeria. All 15 are accredited by the West African College of Surgeons (WACS), and 6 by the National Postgraduate Medical College of Nigeria (NPMCN). The average duration of core neurosurgical training was 5 years. Some identified strengths of Nigerian neurosurgical training included learning opportunities provided to residents, recent growth in the neurosurgical training capacity, and satisfaction with training. Challenges included a continued low number of training programs compared to the population density, lack of subspecialty training programs, and inadequate training infrastructure. CONCLUSION: Despite the high number of neurosurgery training centers in Nigeria, compared to other West African countries, the programs are still limited in number and capacity. Although this study shows apparent trainee satisfaction with the training process and contents, multiple challenges exist. Efforts at improving training capacity should focus on continuing the development and expansion of current programs, commencing subspecialty training, driving health insurance to improve funding, and increasing available infrastructure for training.

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