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1.
Braz. j. biol ; 83: e240842, 2023. tab
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1339375

RESUMO

Abstract This research aimed to investigate various mosquitocidal activities of Chenopodium botrys whole- plant n-hexane extract against Culex quinquefasciatus. The extract showed remarkable larvicidal, pupicidal, adulticidal, oviposition deterrent and adult emergence inhibitory activities against Cx. quinquefasciatus. During the larvicidal and pupicidal activities, the 24-hour lethal concentration (LC50) of extract against 2nd instar larvae, 4th instar larvae and pupae were 324.6, 495.6 and 950.8 ppm, respectively. During the CDC (Centers for Disease Control and Prevention) bottle bioassay for adulticidal activity, the median knockdown times (KDT50) at 1.25% concentration was 123.4 minutes. During the filter paper impregnation bioassay for adulticidal activity, the KDT50 value at 0.138 mg/cm2 concentration was 48.6 minutes. The extract was fractionated into 14 fractions through silica gel column chromatography which were then combined into six fractions on the basis of similar retention factor (Rf) value. These fractions were screened for adulticidal activity by applying CDC bottle bioassay. The fraction obtained through 60:40 to 50:50% n-hexanes-chloroform mobile phase with 0.5 Rf value showed 100% adulticidal activity at 0.2% concentration. During oviposition deterrent activity, the highest concentration (1000 ppm) showed 71.3 ± 4.4% effective repellence and 0.6 ± 0.1 oviposition activity index. During adult emergence inhibition activity, the median emergence inhibition (EI50) value was 312.3 ppm. From the outcome of the present investigation, it is concluded that the n-hexane extract of C. botrys whole- plant possesses strong larvicidal, pupicidal, adulticidal, oviposition deterrent and adult emergence inhibitory activities against Cx. quinquefasciatus.


Resumo Esta pesquisa teve como objetivo investigar várias atividades mosquitocidas do extrato n-hexano de planta inteira de Chenopodium botrys contra Culex quinquefasciatus. O extrato mostrou atividades larvicida, pupicida, adulticida, dissuasora de oviposição e inibidora da emergência de adultos contra a Cx. quinquefasciatus. Durante as atividades larvicida e pupicida, a concentração letal de 24 horas (CL50) do extrato contra larvas de 2º estádio, larvas de 4º estádio e pupa foi de 324,6, 495,6 e 950,8 ppm, respectivamente. Durante o bioensaio com frasco do CDC (Centros para Controle e Prevenção de Doenças) para adulticida, o tempo médio de desativação (KDT50) na concentração de 1,25% foi de 123,4 minutos. Durante o bioensaio de impregnação com papel de filtro para a atividade adulticida do extrato, o valor KDT50 na concentração de 0,138 mg / cm2 foi de 48,6 minutos. O extrato foi fracionado em 14 frações através de cromatografia em coluna de gel de sílica que foram então combinadas em seis frações com base em um valor de fator de retenção (Rf) semelhante. Essas frações foram selecionadas quanto à atividade adulticida por meio da aplicação do bioensaio com garrafa do CDC. A fração obtida através da fase móvel de n-hexanos-clorofórmio 60:40% a 50:50% com valor de 0,5 Rf apresentou atividade adulticida de 100% na concentração de 0,2%. Durante a atividade de dissuasão da oviposição, a maior concentração de extrato (1000 ppm) apresentou repelência efetiva de 71,3 ± 4,4% e índice de atividade de oviposição de 0,6 ± 0,1. Durante a atividade de inibição da emergência de adultos, o valor médio de inibição da emergência (EI50) foi de 312,3 ppm. A partir do resultado da presente investigação, conclui-se que o extrato de n-hexano da planta inteira de C. botrys possui fortes atividades larvicida, pupicida, adulticida, dissuasora da oviposição e inibidora da emergência de adultos contra a Cx. quinquefasciatus.

2.
Braz. j. biol ; 83: e250373, 2023. tab, graf
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1339376

RESUMO

Abstract Honey is a suitable matrix for the evaluation of environmental contaminants including organochlorine insecticides. The present study was conducted to evaluate residues of fifteen organochlorine insecticides in honey samples of unifloral and multifloral origins from Dir, Pakistan. Honey samples (5 g each) were extracted with GC grade organic solvents and then subjected to Rotary Evaporator till dryness. The extracts were then mixed with n-Hexane (5 ml) and purified through Column Chromatography. Purified extracts (1μl each) were processed through Gas Chromatograph coupled with Electron Capture Detector (GC-ECD) for identification and quantification of the insecticides. Of the 15 insecticides tested, 46.7% were detected while 53.3% were not detected in the honey samples. Heptachlor was the most prevalent insecticide with a mean level of 0.0018 mg/kg detected in 80% of the samples followed by β-HCH with a mean level of 0.0016 mg/kg detected in 71.4% of the honey samples. Honey samples from Acacia modesta Wall. were 100% positive for Heptachlor with a mean level of 0.0048 mg/kg followed by β-HCH with a mean level of 0.003 mg/kg and frequency of 83.3%. Minimum levels of the tested insecticides were detected in the unifloral honey from Ziziphus jujuba Mill. Methoxychlor, Endosulfan, Endrin and metabolites of DDT were not detected in the studied honey samples. Some of the tested insecticides are banned in Pakistan but are still detected in honey samples indicating their use in the study area. The detected levels of all insecticides were below the Maximum Residue Levels (MRLs) and safe for consumers. However, the levels detected can cause mortality in insect fauna. The use of banned insecticides is one of the main factors responsible for the declining populations of important insect pollinators including honeybees.


Resumo O mel é uma matriz adequada para a avaliação de contaminantes ambientais, incluindo inseticidas organoclorados. O presente estudo foi conduzido para avaliar resíduos de 15 inseticidas organoclorados em amostras de mel de origem unifloral e multifloral de Dir, Paquistão. Amostras de mel (5 g cada) foram extraídas com solventes orgânicos de grau GC e, em seguida, submetidas ao evaporador rotativo até a secura. Os extratos foram então misturados com n-hexano (5 ml) e purificados por cromatografia em coluna. Os extratos purificados (1μl cada) foram processados através de cromatógrafo gasoso acoplado a detector de captura de elétrons (GC-ECD) para identificação e quantificação dos inseticidas. Dos 15 inseticidas testados, 46,7% foram detectados enquanto 53,3% não foram detectados nas amostras de mel. O heptacloro foi o inseticida mais prevalente com um nível médio de 0,0018 mg / kg detectado em 80% das amostras, seguido por β-HCH com um nível médio de 0,0016 mg / kg detectado em 71,4% das amostras de mel. Amostras de mel da parede de Acacia modesta foram 100% positivos para heptacloro com um nível médio de 0,0048 mg / kg seguido por β-HCH com um nível médio de 0,003 mg / kg e frequência de 83,3%. Níveis mínimos dos inseticidas testados foram detectados no mel unifloral de Ziziphus jujuba da usina. Metoxicloro, Endosulfan, Endrin e metabólitos do DDT não foram detectados nas amostras de mel estudadas. Alguns dos inseticidas testados são proibidos no Paquistão, mas ainda são detectados em amostras de mel, indicando seu uso na área de estudo. Os níveis detectados de todos os inseticidas estavam abaixo dos Níveis Máximos de Resíduos (MRLs) e seguros para os consumidores. No entanto, os níveis detectados podem causar mortalidade na fauna de insetos. O uso de inseticidas proibidos é um dos principais fatores responsáveis pelo declínio das populações de importantes insetos polinizadores, incluindo as abelhas.

3.
Braz J Biol ; 83: e246904, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34706025

RESUMO

Hyperhydricity is a serious physiological disorder and affects In vitro propagation of many plants and as well of Salvia santolinifolia. The donor material to initiate the in vitro culture was the callus taken from the in vitro shoots produced on Murashig and Skoogs (MS) medium at 4.0 mg/l BA. This callus formed numerous hyperhydric shoots on culturing upon the medium of the same composition. The aim was to systematically evaluate the effect of cytokinins (Benzyladnine (BA) and N6-(-2-isopentenyl) adenine (2iP), culture vessels magnitude, medium solidification, source of nitrogen and calcium chloride for the alleviation of hyperhydricity. In the tissue cultures of S. santolinifolia BA and 2iP induced severe hyperhydricity, when other factors i.e. culture vessels magnitude and a suitable concentration of agar, ammonium nitrate (NH4NO3), potassium nitrate (KNO3) & calcium chloride (CaCl2.2H2O) were not optimized. After 30 days' culture, we observed 83.82% hyperhydric shoots at increased level (1.5 mg/l 2iP) and 81.59% at decreased levels (1.0 mg/l 2iP). On the other hand, hyperhydricity percentage at decreased (0.4%) and at increased (0.8%) levels of agar were 72.37% and 39.08%, respectively. MS medium modification with NH4NO3 (412 mg/l), KNO3 (475 mg/l) and CaCl2.2H2O (880 mg/l) was found the best medium to reduced hyperhydricity (23.6%).


Assuntos
Salvia , Meios de Cultura , Brotos de Planta
4.
J Neurophysiol ; 126(6): 1843-1859, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34669485

RESUMO

Spinal cord injury (SCI) commonly results in permanent loss of motor, sensory, and autonomic function. Recent clinical studies have shown that epidural spinal cord stimulation may provide a beneficial adjunct for restoring lower extremity and other neurological functions. Herein, we review the recent clinical advances of lumbosacral epidural stimulation for restoration of sensorimotor function in individuals with motor complete SCI and we discuss the putative neural pathways involved in this promising neurorehabilitative approach. We focus on three main sections: review recent clinical results for locomotor restoration in complete SCI; discuss the contemporary understanding of electrical neuromodulation and signal transduction pathways involved in spinal locomotor networks; and review current challenges of motor system modulation and future directions toward integrative neurorestoration. The current understanding is that initial depolarization occurs at the level of large diameter dorsal root proprioceptive afferents that when integrated with interneuronal and latent residual supraspinal translesional connections can recruit locomotor centers and augment downstream motor units. Spinal epidural stimulation can initiate excitability changes in spinal networks and supraspinal networks. Different stimulation parameters can facilitate standing or stepping, and it may also have potential for augmenting myriad other sensorimotor and autonomic functions. More comprehensive investigation of the mechanisms that mediate the transformation of dysfunctional spinal networks to higher functional states with a greater focus on integrated systems-based control system may reveal the key mechanisms underlying neurological augmentation and motor restoration after severe paralysis.

6.
Eur J Nutr ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34716465

RESUMO

PURPOSE: Extracellular RNAs are unstable and rapidly degraded unless protected. Bovine-milk extracellular vesicles (EVs) confer protection to dietary miRNAs, although it remains unclear whether this importantly improves their chances of reaching host target cells to exert biological effects. METHODS: Caco-2, HT-29, Hep-G2 and FHs-74 cell lines were exposed to natural/labelled milk EVs to evaluate cellular uptake. Five frequently reported human milk miRNAs (miR-146b-5p, miR-148a-3p, miR-30a-5p, miR-26a-5p, and miR-22-3p) were loaded into EVs. The intracellular concentration of each miRNA in cells was determined. In addition, an animal study giving an oral dose of loaded EVs in C57BL6/ mice were performed. Gene expression regulation was assessed by microarray analysis. RESULTS: Digestive stability analysis showed high overall degradation of exogenous miRNAs, although EV-protected miRNAs better resisted gastrointestinal digestion compared to free miRNAs (tenfold higher levels). Importantly, orally delivered EV-loaded miRNAs reached host organs, including brain, in mice. However, no biological effect has been identified. CONCLUSION: Milk EVs protect miRNAs from degradation and facilitate cellular uptake. miRNA concentration in EVs from bovine milk might be insufficient to produce gene modulation. Nevertheless, sizable amounts of exogenous miRNAs may be loaded into EVs, and orally delivered EV-loaded miRNAs can reach tissues in vivo, increasing the possibility of exerting biological effects. Further investigation is justified as this could have an impact in the field of nutrition and health (i.e., infant formulas elaboration).

7.
Transfus Med Hemother ; 48(4): 234-239, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34539317

RESUMO

Therapeutic apheresis (TA) is prescribed to patients that suffer from a severe progressive disease that is not sufficiently treated by conventional medications. A way to gain more knowledge about this treatment is usually by the local analysis of data. However, the use of large quality assessment registries enables analyses of even rare findings. Here, we report some of the recent data from the World Apheresis Association (WAA) registry. Data from >104,000 procedures were documented, and TA was performed on >15,000 patients. The main indication for TA was the collection of autologous stem cells (45% of patients) as part of therapy for therapy. Collection of stem cells from donors for allogeneic transplantation was performed in 11% of patients. Patients with indications such as neurological diseases underwent plasma exchange (28%). Extracorporeal photochemotherapy, lipid apheresis, and antibody removal were other indications. Side effects recorded in the registry have decreased significantly over the years, with approximately only 10/10,000 procedures being interrupted for medical reasons. Conclusion: Collection of data from TA procedures within a multinational and multicenter concept facilitates the improvement of treatment by enabling the analysis of and feedback on indications, procedures, effects, and side effects.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34586373

RESUMO

BACKGROUND: Fosfomycin is used increasingly in the treatment of MDR bacteria. It is eliminated by renal excretion, but data regarding dosing recommendations for patients undergoing modern means of renal replacement therapies are scarce. OBJECTIVES: Evaluation of the pharmacokinetics (PK) of fosfomycin in patients undergoing prolonged intermittent renal replacement therapy (PIRRT) to guide dosing recommendations. METHODS: Fosfomycin was given in 11 (7 female) patients with severe infections undergoing PIRRT. Plasma levels were measured at several timepoints on the first day of fosfomycin therapy, as well as 5-6 days into therapy, before and after the dialyser, to calculate its clearance. Fosfomycin was measured in the collected spent dialysate. RESULTS: The median (IQR) plasma dialyser clearance for fosfomycin was 183.4 (156.9-214.9) mL/min, eliminating a total amount of 8834 (4556-10 440) mg of fosfomycin, i.e. 73.9% (45.3%-93.5%) of the initial dose. During PIRRT, the fosfomycin half-life was 2.5 (2.2-3.4) h. Data from multiple-dose PK showed an increase in fosfomycin Cmax from 266.8 (166.3-438.1) to 926.1 (446.8-1168.0) mg/L and AUC0-14 from 2540.5 (1815.2-3644.3) to 6714 (4060.6-10612.6) mg·h/L. Dialysis intensity during the study was 1.5 L/h. T>MIC was 100% in all patients. CONCLUSIONS: Patients undergoing PIRRT experience significant fosfomycin elimination, requiring a dose of 5 g/8 h to reach adequate plasma levels. However, drug accumulation may occur, depending on dialysis frequency and intensity.

9.
Braz J Biol ; 83: e240842, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34550279

RESUMO

This research aimed to investigate various mosquitocidal activities of Chenopodium botrys whole- plant n-hexane extract against Culex quinquefasciatus. The extract showed remarkable larvicidal, pupicidal, adulticidal, oviposition deterrent and adult emergence inhibitory activities against Cx. quinquefasciatus. During the larvicidal and pupicidal activities, the 24-hour lethal concentration (LC50) of extract against 2nd instar larvae, 4th instar larvae and pupae were 324.6, 495.6 and 950.8 ppm, respectively. During the CDC (Centers for Disease Control and Prevention) bottle bioassay for adulticidal activity, the median knockdown times (KDT50) at 1.25% concentration was 123.4 minutes. During the filter paper impregnation bioassay for adulticidal activity, the KDT50 value at 0.138 mg/cm2 concentration was 48.6 minutes. The extract was fractionated into 14 fractions through silica gel column chromatography which were then combined into six fractions on the basis of similar retention factor (Rf) value. These fractions were screened for adulticidal activity by applying CDC bottle bioassay. The fraction obtained through 60:40 to 50:50% n-hexanes-chloroform mobile phase with 0.5 Rf value showed 100% adulticidal activity at 0.2% concentration. During oviposition deterrent activity, the highest concentration (1000 ppm) showed 71.3 ± 4.4% effective repellence and 0.6 ± 0.1 oviposition activity index. During adult emergence inhibition activity, the median emergence inhibition (EI50) value was 312.3 ppm. From the outcome of the present investigation, it is concluded that the n-hexane extract of C. botrys whole- plant possesses strong larvicidal, pupicidal, adulticidal, oviposition deterrent and adult emergence inhibitory activities against Cx. quinquefasciatus.


Assuntos
Chenopodium , Culex , Inseticidas , Animais , Hexanos , Inseticidas/farmacologia , Larva , Extratos Vegetais/farmacologia , Folhas de Planta
10.
Braz J Biol ; 83: e250373, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34550295

RESUMO

Honey is a suitable matrix for the evaluation of environmental contaminants including organochlorine insecticides. The present study was conducted to evaluate residues of fifteen organochlorine insecticides in honey samples of unifloral and multifloral origins from Dir, Pakistan. Honey samples (5 g each) were extracted with GC grade organic solvents and then subjected to Rotary Evaporator till dryness. The extracts were then mixed with n-Hexane (5 ml) and purified through Column Chromatography. Purified extracts (1µl each) were processed through Gas Chromatograph coupled with Electron Capture Detector (GC-ECD) for identification and quantification of the insecticides. Of the 15 insecticides tested, 46.7% were detected while 53.3% were not detected in the honey samples. Heptachlor was the most prevalent insecticide with a mean level of 0.0018 mg/kg detected in 80% of the samples followed by ß-HCH with a mean level of 0.0016 mg/kg detected in 71.4% of the honey samples. Honey samples from Acacia modesta Wall. were 100% positive for Heptachlor with a mean level of 0.0048 mg/kg followed by ß-HCH with a mean level of 0.003 mg/kg and frequency of 83.3%. Minimum levels of the tested insecticides were detected in the unifloral honey from Ziziphus jujuba Mill. Methoxychlor, Endosulfan, Endrin and metabolites of DDT were not detected in the studied honey samples. Some of the tested insecticides are banned in Pakistan but are still detected in honey samples indicating their use in the study area. The detected levels of all insecticides were below the Maximum Residue Levels (MRLs) and safe for consumers. However, the levels detected can cause mortality in insect fauna. The use of banned insecticides is one of the main factors responsible for the declining populations of important insect pollinators including honeybees.


Assuntos
Mel , Inseticidas , Resíduos de Praguicidas , Animais , Abelhas , Endossulfano/análise , Biomarcadores Ambientais , Mel/análise , Inseticidas/toxicidade , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/toxicidade
11.
J Adv Model Earth Syst ; 13(6): e2020MS002356, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34434489

RESUMO

Earth system/ice-sheet coupling is an area of recent, major Earth System Model (ESM) development. This work occurs at the intersection of glaciology and climate science and is motivated by a need for robust projections of sea-level rise. The Community Ice Sheet Model version 2 (CISM2) is the newest component model of the Community Earth System Model version 2 (CESM2). This study describes the coupling and novel capabilities of the model, including: (1) an advanced energy-balance-based surface mass balance calculation in the land component with downscaling via elevation classes; (2) a closed freshwater budget from ice sheet to the ocean from surface runoff, basal melting, and ice discharge; (3) dynamic land surface types; and (4) dynamic atmospheric topography. The Earth system/ice-sheet coupling is demonstrated in a simulation with an evolving Greenland Ice Sheet (GrIS) under an idealized high CO2 scenario. The model simulates a large expansion of ablation areas (where surface ablation exceeds snow accumulation) and a large increase in surface runoff. This results in an elevated freshwater flux to the ocean, as well as thinning of the ice sheet and area retreat. These GrIS changes result in reduced Greenland surface albedo, changes in the sign and magnitude of sensible and latent heat fluxes, and modified surface roughness and overall ice sheet topography. Representation of these couplings between climate and ice sheets is key for the simulation of ice and climate interactions.

12.
BMJ Open ; 11(8): e048890, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433601

RESUMO

OBJECTIVE: To obtain insight into experiences of patients with a neuromuscular disease and chronic fatigue and their healthcare professionals regarding content and delivery of a multidisciplinary outpatient self-management group programme to improve social participation. This will inform future implementation. DESIGN: A mixed method study alongside a randomised controlled trial. SETTING: University hospital, rehabilitation centre and community health centre. PARTICIPANTS: 29 patients with a neuromuscular disease and chronic fatigue and 13 healthcare professionals participated in this mixed methods study. INTERVENTION: Multidisciplinary group programme, called Energetic, consisted of a 4 months intervention with weekly meetings and covered four modules: (1) individually tailored aerobic exercise training; (2) education about aerobic exercise; (3) self-management training in applying energy conservation strategies and (4) implementation and relapse prevention in daily life. MAIN MEASURES: Quantitative data were collected by a questionnaire measuring patients' (n=25, all completed the programme) satisfaction with the perceived results, content and delivery of the programme. Qualitative data were collected by individual and focus group interviews to gain insight in the experiences of patients (n=18), next of kin (n=2) and healthcare professionals (n=13) with facilitators and barriers to programme implementation. RESULTS: Patients were satisfied with the number and length of the sessions, the different modules and the therapists. Analysis of the interviews led to five themes: (1) the combination of modules makes a complete picture, (2) the programme is physically and mentally intensive, (3) the group setting is valuable, (4) small variations in delivery occur in different settings, (5) therapists are coaches. Suggestions for programme improvement include a combination of face to face and e-health, enhancement of therapists' skills in guiding group interventions and inclusion of more booster sessions to evaluate and maintain self-management competencies. CONCLUSIONS: The Energetic programme could be implemented in different healthcare settings and group settings, and a combination of modules proved to be a facilitator for improving self-management. TRIAL REGISTRATION NUMBER: NCT02208687.


Assuntos
Síndrome de Fadiga Crônica , Doenças Neuromusculares , Autogestão , Humanos , Doenças Neuromusculares/terapia , Participação Social , Inquéritos e Questionários
13.
BMC Neurol ; 21(1): 313, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384384

RESUMO

BACKGROUND: SELENON (SEPN1)-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive proximal muscle weakness, early onset spine rigidity and respiratory insufficiency. A muscular dystrophy caused by mutations in the LAMA2 gene (LAMA2-related muscular dystrophy, LAMA2-MD) has a similar clinical phenotype, with either a severe, early-onset due to complete Laminin subunit α2 deficiency (merosin-deficient congenital muscular dystrophy type 1A (MDC1A)), or a mild, childhood- or adult-onset due to partial Laminin subunit α2 deficiency. For both muscle diseases, no curative treatment options exist, yet promising preclinical studies are ongoing. Currently, there is a paucity on natural history data and appropriate clinical and functional outcome measures are needed to reach trial readiness. METHODS: LAST STRONG is a natural history study in Dutch-speaking patients of all ages diagnosed with SELENON-RM or LAMA2-MD, starting August 2020. Patients have four visits at our hospital over a period of 1.5 year. At all visits, they undergo standardized neurological examination, hand-held dynamometry (age ≥ 5 years), functional measurements, questionnaires (patient report and/or parent proxy; age ≥ 2 years), muscle ultrasound including diaphragm, pulmonary function tests (spirometry, maximal inspiratory and expiratory pressure, sniff nasal inspiratory pressure; age ≥ 5 years), and accelerometry for 8 days (age ≥ 2 years); at visit one and three, they undergo cardiac evaluation (electrocardiogram, echocardiography; age ≥ 2 years), spine X-ray (age ≥ 2 years), dual-energy X-ray absorptiometry (DEXA-)scan (age ≥ 2 years) and full body magnetic resonance imaging (MRI) (age ≥ 10 years). All examinations are adapted to the patient's age and functional abilities. Correlation between key parameters within and between subsequent visits will be assessed. DISCUSSION: Our study will describe the natural history of patients diagnosed with SELENON-RM or LAMA2-MD, enabling us to select relevant clinical and functional outcome measures for reaching clinical trial-readiness. Moreover, our detailed description (deep phenotyping) of the clinical features will optimize clinical management and will establish a well-characterized baseline cohort for prospective follow-up. CONCLUSION: Our natural history study is an essential step for reaching trial readiness in SELENON-RM and LAMA2-MD. TRIAL REGISTRATION: This study has been approved by medical ethical reviewing committee Region Arnhem-Nijmegen (NL64269.091.17, 2017-3911) and is registered at ClinicalTrial.gov ( NCT04478981 ).


Assuntos
Distrofias Musculares , Adulto , Criança , Humanos , Laminina/genética , Imageamento por Ressonância Magnética , Distrofias Musculares/genética , Distrofias Musculares/terapia , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos
14.
Biomech Model Mechanobiol ; 20(6): 2287-2297, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34431032

RESUMO

The sensory hairs of the Venus flytrap (Dionaea muscipula Ellis) detect mechanical stimuli imparted by their prey and fire bursts of electrical signals called action potentials (APs). APs are elicited when the hairs are sufficiently stimulated and two consecutive APs can trigger closure of the trap. Earlier experiments have identified thresholds for the relevant stimulus parameters, namely the angular displacement [Formula: see text] and angular velocity [Formula: see text]. However, these experiments could not trace the deformation of the trigger hair's sensory cells, which are known to transduce the mechanical stimulus. To understand the kinematics at the cellular level, we investigate the role of two relevant mechanical phenomena: viscoelasticity and intercellular fluid transport using a multi-scale numerical model of the sensory hair. We hypothesize that the combined influence of these two phenomena and [Formula: see text] contribute to the flytrap's rate-dependent response to stimuli. In this study, we firstly perform sustained deflection tests on the hair to estimate the viscoelastic material properties of the tissue. Thereafter, through simulations of hair deflection tests at different loading rates, we were able to establish a multi-scale kinematic link between [Formula: see text] and the cell wall stretch [Formula: see text]. Furthermore, we find that the rate at which [Formula: see text] evolves during a stimulus is also proportional to [Formula: see text]. This suggests that mechanosensitive ion channels, expected to be stretch-activated and localized in the plasma membrane of the sensory cells, could be additionally sensitive to the rate at which stretch is applied.

15.
Clin Neurophysiol ; 132(10): 2404-2415, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34454267

RESUMO

OBJECTIVE: Brain-Computer Interface (BCI) spellers that make use of code-modulated Visual Evoked Potentials (cVEP) may provide a fast and more accurate alternative to existing visual BCI spellers for patients with Amyotrophic Lateral Sclerosis (ALS). However, so far the cVEP speller has only been tested on healthy participants. METHODS: We assess the brain responses, BCI performance and user experience of the cVEP speller in 20 healthy participants and 10 ALS patients. All participants performed a cued and free spelling task, and a free selection of Yes/No answers. RESULTS: 27 out of 30 participants could perform the cued spelling task with an average accuracy of 79% for ALS patients, 88% for healthy older participants and 94% for healthy young participants. All 30 participants could answer Yes/No questions freely, with an average accuracy of around 90%. CONCLUSIONS: With ALS patients typing on average 10 characters per minute, the cVEP speller presented in this paper outperforms other visual BCI spellers. SIGNIFICANCE: These results support a general usability of cVEP signals for ALS patients, which may extend far beyond the tested speller to control e.g. an alarm, automatic door, or TV within a smart home.


Assuntos
Esclerose Amiotrófica Lateral/fisiopatologia , Esclerose Amiotrófica Lateral/terapia , Interfaces Cérebro-Computador , Auxiliares de Comunicação para Pessoas com Deficiência , Potenciais Evocados Visuais/fisiologia , Fixação Ocular/fisiologia , Adulto , Idoso , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Ecol Evol ; 11(14): 9489-9497, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34306637

RESUMO

The saltmarsh sparrow Ammospiza caudacuta and Nelson's sparrow A. nelsoni differ in ecological niche, mating behavior, and plumage, but they hybridize where their breeding distributions overlap. In this advanced hybrid zone, past interbreeding and current backcrossing result in substantial genomic introgression in both directions, although few hybrids are currently produced in most locations. However, because both species are nonterritorial and have only brief male-female interactions, it is difficult to determine to what extent assortative mating explains the low frequency of hybrid offspring. Since females often copulate with multiple males, a role of sperm as a postcopulatory prezygotic barrier appears plausible. Here, we show that sperm length differs between the two species in the hybrid zone, with low among-male variation consistent with strong postcopulatory sexual selection on sperm cells. We hypothesize that divergence in sperm length may constitute a reproductive barrier between species, as sperm length co-evolves with the size of specialized female sperm storage tubules. Sperm does not appear to act as a postzygotic barrier, as sperm from hybrids was unexceptional.

17.
Clin Infect Dis ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272564

RESUMO

BACKGROUND: Staphylococcus aureus bacteremia (SAB) is in 10% to 20% of cases complicated by infective endocarditis (SA-IE). Clinical prediction scores may select SAB patients at highest risk for endocarditis, improving the diagnostic process of endocarditis. We compared the accuracy of the POSITIVE, PREDICT and VIRSTA scores for classifying the likelihood of endocarditis in SAB patients. METHODS: Between August 2017 and September 2019 we enrolled consecutive adult patients with SAB in a prospective cohort study in seven hospitals in the Netherlands. Using the modified Duke Criteria for definite endocarditis as reference standard, sensitivity, specificity, negative predictive (NPV) and positive predictive values (PPV) were determined for the POSITIVE, PREDICT and VIRSTA scores. A NPV of at least 98% was considered safe for excluding endocarditis. RESULTS: Of 477 SAB patients enrolled, 33% had community-acquired SAB, 8% had a prosthetic valve and 11% a cardiac implantable electronic device. Echocardiography was performed in 87% of patients, and 42% received a TEE. 87 (18.2%) had definite endocarditis. Sensitivity was 77.6% (65.8 - 86.9), 85.1% (75.8 - 91.8) and 98.9% (95.7 - 100) for the POSITIVE (n=362), PREDICT and VIRSTA scores, respectively. NPVs were 92.5% (87.9 - 95.8), 94.5% (90.7 - 97.0), and 99.3% (94.9 - 100).) For the POSITIVE, PREDICT and VIRSTA scores, 44.5%, 50.7% and 70.9% of SAB patients, respectively were classified as high-risk for endocarditis. CONCLUSIONS: Only the VIRSTA score had a NPV of at least 98%, but at the expense of a high number of patients classified as high risk and thus requiring TEE.

20.
Br J Haematol ; 194(2): 453-462, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34109608

RESUMO

The short half-life of coagulation factor IX (FIX) for haemophilia B (HB) therapy has been prolonged through fusion with human serum albumin (HSA), which drives the neonatal Fc receptor (FcRn)-mediated recycling of the chimera. However, patients would greatly benefit from further FIX-HSA half-life extension. In the present study, we designed a FIX-HSA variant through the engineering of both fusion partners. First, we developed a novel cleavable linker combining the two FIX activation sites, which resulted in improved HSA release. Second, insertion of the FIX R338L (Padua) substitution conferred hyperactive features (sevenfold higher specific activity) as for FIX Padua alone. Furthermore, we exploited an engineered HSA (QMP), which conferred enhanced human (h)FcRn binding [dissociation constant (KD ) 0·5 nM] over wild-type FIX-HSA (KD 164·4 nM). In hFcRn transgenic mice, Padua-QMP displayed a significantly prolonged half-life (2·7 days, P < 0·0001) versus FIX-HSA (1 day). Overall, we developed a novel FIX-HSA protein with improved activity and extended half-life. These combined properties may result in a prolonged functional profile above the therapeutic threshold, and thus in a potentially widened therapeutic window able to improve HB therapy. This rational engineering of both partners may pave the way for new fusion strategies for the design of engineered biotherapeutics.

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