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1.
J Am Vet Med Assoc ; 262(7): 924-927, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38608663

RESUMO

OBJECTIVE: To evaluate the effect of abdominal thrusts as a synergistic procedure to IV apomorphine administration on the occurrence and rate of onset of successful induction of emesis in dogs. ANIMALS: 31 client-owned dogs. METHODS: Dogs in which induction of emesis via IV apomorphine was prescribed by the attending clinician were prospectively randomized to either receive abdominal thrusts performed by a nurse or clinician or to have no physical interventions performed following IV apomorphine administration. Data collected included signalment, weight, reason for emesis, time from suspected ingestion to presentation, time from the dog's last meal to presentation, dose of apomorphine administered in milligrams, and time from apomorphine administration to emesis. RESULTS: Emesis induction was successful in 14 of 14 (100%) of the dogs in the abdominal thrust group and 13 of 17 (76.5%) in the control group (P = .02). In dogs with successful emesis, median time to emesis was 90.5 seconds (range, 36 to 348 seconds) in the abdominal thrust group and 106 seconds (range, 37 to 360 seconds) in the control group (P = .29). CLINICAL RELEVANCE: Abdominal thrusts were associated with an increased frequency of successful emesis in dogs following IV apomorphine, but did not shorten the rate of onset of emesis in dogs that vomited. Application of abdominal thrusts may be beneficial in dogs in which emesis is indicated and that do not have a clear contraindication.


Assuntos
Apomorfina , Doenças do Cão , Vômito , Animais , Cães , Vômito/veterinária , Apomorfina/administração & dosagem , Apomorfina/uso terapêutico , Doenças do Cão/tratamento farmacológico , Feminino , Masculino , Eméticos/uso terapêutico , Eméticos/administração & dosagem
2.
BMC Med Educ ; 23(1): 917, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38053154

RESUMO

BACKGROUND: The aim of the present study was to determine the impact of an innovative interprofessional educational activity on healthcare professional students' learning. The educational activity targeted student knowledge of opioid use disorder (OUD) and perceptions of working with an interprofessional team while caring for patients with OUD. METHODS: Students from nursing, pharmacy, physician assistant, dentistry, social work, and medicine programs were recruited to participate in the interprofessional educational activity. The educational experience included seven asynchronous modules and a virtual synchronous escape room. Prior to the educational programming, participants completed a pre-survey that assessed their knowledge and attitudes towards working on an interprofessional team and perceptions of patients with OUD. The asynchronous modules were required in order to participate in the escape room and each module contained its own pre/post quiz to assess student knowledge. RESULTS: A total of 402 students participated in the course. Prior to participating in the course, students disagreed that they had extensive educational experience with SUD (2.45 ± 0.79). The students displayed significant improvement in the knowledge based areas after completing the seven asynchronous modules. The largest significant area of knowledge-based improvement was seen in treatment of OUD where on the pre-quiz 65.54 ± 20.21% were answered correctly compared to 95.97 ± 9.61% on the post-quiz. Participation in the escape room significantly changed the students' perceptions of working in interprofessional teams while managing patients with OUD. Of the eleven perception variables assessed, seven showed a significant increase in the post-survey. Following the escape room, participants also strongly agreed that they now would refer patients to colleagues in other disciplines. CONCLUSIONS: An interprofessional educational experience including both an asynchronous course and virtual synchronous escape room can increase participant knowledge around OUD and may improve student perceptions of working with an interprofessional team and caring for patients with OUD.


Assuntos
Transtornos Relacionados ao Uso de Opioides , Estudantes de Farmácia , Humanos , Currículo , Pessoal de Saúde , Atitude do Pessoal de Saúde , Relações Interprofissionais
3.
Biology (Basel) ; 12(12)2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38132288

RESUMO

Cultivating Limnospira maxima, renowned for its abundant proteins and valuable pigments, faces substantial challenges rooted in the limited understanding of its optimal growth parameters, associated high costs, and constraints in the procurement of traditional nitrogen sources, particularly NaNO3. To overcome these challenges, we conducted a comprehensive 4 × 3 factorial design study. Factors considered included white, red, blue, and yellow light spectra, along with nitrogen sources NaNO3 and KNO3, as well as a nitrogen-free control, for large-scale implementation. Optimal growth, measured by Optical Density, occurred with white and yellow light combined with KNO3 as the nitrogen source. These conditions also increased dry weight and Chl-a content. Cultures with nitrogen deprivation exhibited high values for these variables, attributed to carbon accumulation in response to nitrogen scarcity. Phycocyanin, a crucial pigment for nutrition and industry, reached its highest levels in cultures exposed to white light and supplemented with KNO3, with an impressive content of 384.11 g kg-1 of dry weight. These results highlight the efficacy and cost-efficiency of using a combination of white light and KNO3 for large-scale L. maxima cultivation. This strategy offers promising opportunities to address global food security challenges and enhance the production of industrially relevant pigments.

4.
Biomaterials ; 302: 122298, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37713762

RESUMO

The success of mRNA-based vaccines during the Covid-19 pandemic has highlighted the value of this new platform for vaccine development against infectious disease. However, the CD8+ T cell response remains modest with mRNA vaccines, and these do not induce mucosal immunity, which would be needed to prevent viral spread in the healthy population. To address this drawback, we developed a dendritic cell targeting mucosal vaccination vector, the homopentameric STxB. Here, we describe the highly efficient chemical synthesis of the protein, and its in vitro folding. This straightforward preparation led to a synthetic delivery tool whose biophysical and intracellular trafficking characteristics were largely indistinguishable from recombinant STxB. The chemical approach allowed for the generation of new variants with bioorthogonal handles. Selected variants were chemically coupled to several types of antigens derived from the mucosal viruses SARS-CoV-2 and type 16 human papillomavirus. Upon intranasal administration in mice, mucosal immunity, including resident memory CD8+ T cells and IgA antibodies was induced against these antigens. Our study thereby identifies a novel synthetic antigen delivery tool for mucosal vaccination with an unmatched potential to respond to an urgent medical need.


Assuntos
Linfócitos T CD8-Positivos , Pandemias , Camundongos , Humanos , Animais , Vacinação , Vacinas Sintéticas , Antígenos , Anticorpos Antivirais
5.
Cureus ; 15(6): e40635, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37476115

RESUMO

Lipoleiomyomas are rare, fatty variants of leiomyomas (commonly referred to as fibroid), which are frequently found in the uterine corpus and cervix. Here, we present a case of a robotic inguinal hernia repair with resection of an incidental lipoleiomyoma. A 74-year-old woman presented to the office with complaints of pain and a palpable mass in the right inguinal region. Physical examination revealed tender, moderate-to-large bilateral inguinal hernias. Robotic bilateral inguinal hernia repair with mesh was performed. Intraoperatively, a mass measuring 4 × 3 cm was noted near the round ligament of the uterus. The mass was encapsulated without invading any surrounding structures. The mass was resected and sent to the histopathology department. The pathological evaluation identified a leiomyoma filled with mature adipocytes, compatible with the diagnosis of an extrauterine lipoleiomyoma. Lipoleiomyoma incidentally found in the inguinal canal is extremely rare. The medical literature regarding this incidental finding is limited. Resection of the mass was easily performed using the same robotic instruments as used for the inguinal hernia repair.

6.
Nature ; 618(7966): 708-711, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37277615

RESUMO

Dust grains absorb half of the radiation emitted by stars throughout the history of the universe, re-emitting this energy at infrared wavelengths1-3. Polycyclic aromatic hydrocarbons (PAHs) are large organic molecules that trace millimetre-size dust grains and regulate the cooling of interstellar gas within galaxies4,5. Observations of PAH features in very distant galaxies have been difficult owing to the limited sensitivity and wavelength coverage of previous infrared telescopes6,7. Here we present James Webb Space Telescope observations that detect the 3.3 µm PAH feature in a galaxy observed less than 1.5 billion years after the Big Bang. The high equivalent width of the PAH feature indicates that star formation, rather than black hole accretion, dominates infrared emission throughout the galaxy. The light from PAH molecules, hot dust and large dust grains and stars are spatially distinct from one another, leading to order-of-magnitude variations in PAH equivalent width and ratio of PAH to total infrared luminosity across the galaxy. The spatial variations we observe suggest either a physical offset between PAHs and large dust grains or wide variations in the local ultraviolet radiation field. Our observations demonstrate that differences in emission from PAH molecules and large dust grains are a complex result of localized processes within early galaxies.

7.
Cells ; 12(9)2023 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-37174690

RESUMO

Many molecular targets for cancer therapy are located in the cytosol. Therapeutic macromolecules are generally not able to spontaneously translocate across membranes to reach these cytosolic targets. Therefore a strong need exists for tools that enhance cytosolic delivery. Shiga toxin B-subunit (STxB) is used to deliver therapeutic principles to disease-relevant cells that express its receptor, the glycolipid Gb3. Based on its naturally existing membrane translocation capacity, STxB delivers antigens to the cytosol of Gb3-positive dendritic cells, leading to the induction of CD8+ T cells. Here, we have explored the possibility of further increasing the membrane translocation of STxB to enable other therapeutic applications. For this, our capacity to synthesize STxB chemically was exploited to introduce unnatural amino acids at different positions of the protein. These were then functionalized with hydrophobic entities to locally destabilize endosomal membranes. Intracellular trafficking of these functionalized STxB was measured by confocal microscopy and their cytosolic arrival with a recently developed highly robust, sensitive, and quantitative translocation assay. From different types of hydrophobic moieties that were linked to STxB, the most efficient configuration was determined. STxB translocation was increased by a factor of 2.5, paving the path for new biomedical opportunities.


Assuntos
Linfócitos T CD8-Positivos , Toxina Shiga , Citosol/metabolismo , Toxina Shiga/química , Toxina Shiga/metabolismo , Membranas Intracelulares/metabolismo , Endossomos/metabolismo
8.
NPJ Parkinsons Dis ; 9(1): 51, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37005418

RESUMO

Our assessments of effort are critically shaped by experiences of exertion. However, it is unclear how the nervous system transforms physical exertion into assessments of effort. Availability of the neuromodulator dopamine influences features of motor performance and effort-based decision-making. To test dopamine's role in the translation of effortful exertion into assessments of effort, we had participants with Parkinson's disease, in dopamine depleted (OFF dopaminergic medication) and elevated (ON dopaminergic medication) states, exert levels of physical exertion and retrospectively assess how much effort they exerted. In a dopamine-depleted state, participants exhibited increased exertion variability and over-reported their levels of exertion, compared to the dopamine-supplemented state. Increased exertion variability was associated with less accurate effort assessment and dopamine had a protective influence on this effect, reducing the extent to which exertion variability corrupted assessments of effort. Our findings provide an account of dopamine's role in the translation of features of motor performance into judgments of effort, and a potential therapeutic target for the increased sense of effort observed across a range of neurologic and psychiatric conditions.

9.
Science ; 378(6619): 560-565, 2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36264825

RESUMO

Monkeypox is a viral zoonotic disease endemic in Central and West Africa. In May 2022, dozens of non-endemic countries reported hundreds of monkeypox cases, most with no epidemiological link to Africa. We identified two lineages of monkeypox virus (MPXV) among two 2021 and seven 2022 US monkeypox cases: the major 2022 outbreak variant called B.1 and a minor contemporaneously sampled variant called A.2. Analyses of mutations among these two variants revealed an extreme preference for GA-to-AA mutations indicative of human APOBEC3 cytosine deaminase activity among Clade IIb MPXV (previously West African, Nigeria) sampled since 2017. Such mutations were not enriched within other MPXV clades. These findings suggest that APOBEC3 editing may be a recurrent and a dominant driver of MPXV evolution within the current outbreak.


Assuntos
Desaminases APOBEC , Interações Hospedeiro-Patógeno , Monkeypox virus , Mpox , Edição de RNA , Humanos , Mpox/enzimologia , Mpox/virologia , Monkeypox virus/genética , Monkeypox virus/isolamento & purificação , Nigéria/epidemiologia , Estados Unidos/epidemiologia , Mutação , Evolução Molecular , Desaminases APOBEC/metabolismo , Adenosina/genética , Citidina/genética
10.
MMWR Morb Mortal Wkly Rep ; 71(28): 904-907, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35834423

RESUMO

As part of public health preparedness for infectious disease threats, CDC collaborates with other U.S. public health officials to ensure that the Laboratory Response Network (LRN) has diagnostic tools to detect Orthopoxviruses, the genus that includes Variola virus, the causative agent of smallpox. LRN is a network of state and local public health, federal, U.S. Department of Defense (DOD), veterinary, food, and environmental testing laboratories. CDC developed, and the Food and Drug Administration (FDA) granted 510(k) clearance* for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set (non-variola Orthopoxvirus [NVO] assay), a polymerase chain reaction (PCR) diagnostic test to detect NVO. On May 17, 2022, CDC was contacted by the Massachusetts Department of Public Health (DPH) regarding a suspected case of monkeypox, a disease caused by the Orthopoxvirus Monkeypox virus. Specimens were collected and tested by the Massachusetts DPH public health laboratory with LRN testing capability using the NVO assay. Nationwide, 68 LRN laboratories had capacity to test approximately 8,000 NVO tests per week during June. During May 17-June 30, LRN laboratories tested 2,009 specimens from suspected monkeypox cases. Among those, 730 (36.3%) specimens from 395 patients were positive for NVO. NVO-positive specimens from 159 persons were confirmed by CDC to be monkeypox; final characterization is pending for 236. Prompt identification of persons with infection allowed rapid response to the outbreak, including isolation and treatment of patients, administration of vaccines, and other public health action. To further facilitate access to testing and increase convenience for providers and patients by using existing provider-laboratory relationships, CDC and LRN are supporting five large commercial laboratories with a national footprint (Aegis Science, LabCorp, Mayo Clinic Laboratories, Quest Diagnostics, and Sonic Healthcare) to establish NVO testing capacity of 10,000 specimens per week per laboratory. On July 6, 2022, the first commercial laboratory began accepting specimens for NVO testing based on clinician orders.


Assuntos
Técnicas e Procedimentos Diagnósticos , Surtos de Doenças , Mpox , Surtos de Doenças/prevenção & controle , Humanos , Laboratórios , Mpox/diagnóstico , Mpox/epidemiologia , Orthopoxvirus , Estados Unidos/epidemiologia , Vírus da Varíola
11.
J Forensic Sci ; 67(4): 1715-1727, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35324005

RESUMO

A critical concern with crime scene documentation is the accuracy with which a crime scene can be reconstructed. Here, we discuss the accuracy of eight documentation methods as a function of measurement distance between reference ground targets in an outdoor scene. The relative accuracy of each documentation method was assessed with respect to a widely accepted and well-established standard method for land surveying, Total Station, from which measurements served as "ground truth" or reference data. For the majority of methods, the actual relative difference between measurements when compared to Total Station was small (less than a quarter of an inch). Measurements from FARO LiDAR agreed the most with to those of Total Station, while drone without the use of ground control points (GCPs) agreed the least. GCPs or a reference scale were also found to be important in mitigating increasing imprecision with increasing distance when measuring between two targets ~9-85 ft apart via drone and orthomosaic methods. Additionally, there were no statistical differences in the use of 2D (horizontal) or 3D (slope) measurement configurations for the Total Station. Overall, linear regression of difference plots did not reveal meaningful correlation between increasing distance measured and the error of a method when compared to Total Station. As more measurement methods become available, and the need for training and validating new tools become a necessity, these results point to the importance of establishing a ground truth or known distance range on which crime scene measurement methods can be validated.


Assuntos
Crime , Ciências Forenses , Documentação , Ciências Forenses/métodos
12.
J Vet Emerg Crit Care (San Antonio) ; 32(2): 165-167, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35224840

RESUMO

Diversity, equity, and inclusion (DEI) are crucial elements of successful veterinary emergency and critical care practices across the world. Embracing the elements of DEI creates a work environment that is safe and welcoming for all the members of the team. The American College of Veterinary Emergency and Critical Care DEI committee was formed to enhance and support efforts to increase racial diversity in veterinary emergency and critical care, as well as provide resources that will generate DEI practices across the country. This article provides an overview of the vision of the committee and some of the steps that have been taken to create a welcoming space for all represented in veterinary emergency and critical care.


Assuntos
Cuidados Críticos , Local de Trabalho , Animais , Estados Unidos
13.
Front Med (Lausanne) ; 8: 724344, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604259

RESUMO

Topical antiaging products are often a first-line intervention to counter visible signs of facial photoaging, aiming for sustained cosmetic improvement. However, prolonged application of a single active topical compound was observed clinically to lead to a plateau effect in improving facial photoaging. In view of this, we set out to reduce this effect systematically using a multi-tiered approach with laboratory evidence and clinical trials. The objective of the study was to evaluate the effects of active topical ingredients applied either alone, in combination, or in a rotational manner on modulation of facial photoaging. The study methodology included in vitro, organotypic, and ex vivo skin explants; in vivo biopsy study; as well as clinical trials. We demonstrate for the first time that a pair of known antiaging ingredients applied rotationally, on human dermal fibroblasts, maximized pro-collagen I production. Indeed, rotational treatment with retinol and phytol/glycolic acid (PGA) resulted in better efficacy than application of each active ingredient alone as shown by explants and in vivo biopsy study, with penetration of active ingredients confirmed by Raman spectroscopy. Furthermore, two split-face, randomized, double-blinded clinical trials were conducted, one for 12 months to compare treated vs. untreated and the other for 6 months followed by a 2-month regression to compare treated vs. commercially marketed products. In both studies, rotational regimen showed superior results to its matching comparison as assessed by clinical grading and image analysis of crow's feet wrinkles. In conclusion, rotational regimen using retinol and PGA is effective in treating facial photoaging signs with long-lasting benefits.

14.
J Parkinsons Dis ; 11(4): 2073-2084, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511512

RESUMO

BACKGROUND: Gait slowing is a common feature of Parkinson's disease (PD). Many therapies aim to improve gait speed in persons with PD, but goals are often imprecise. How fast should each patient walk? And how do persons with PD benefit from walking faster? There is an important need to understand how walking speed affects fundamental aspects of gait-including energy cost and stability-that could guide individualized therapy decisions in persons with PD. OBJECTIVE: We investigated how changes in walking speed affected energy cost and spatiotemporal gait parameters in persons with PD. We compared these effects between dopaminergic medication states and to those observed in age-matched control participants. METHODS: Twelve persons with PD and twelve control participants performed treadmill walking trials spanning at least five different speeds (seven speeds were desired, but not all participants could walk at the fastest speeds). Persons with PD participated in two walking sessions on separate days (once while optimally medicated, once after 12-hour withdrawal from dopaminergic medication). We measured kinematic and metabolic data across all trials. RESULTS: Persons with PD significantly reduced energy cost by walking faster than their preferred speeds. This held true across medication conditions and was not observed in control participants. The patient-specific walking speeds that reduced energy cost did not significantly affect gait variability metrics (used as proxies for gait stability). CONCLUSION: The gait slowing that occurs with PD results in energetically suboptimal walking. Rehabilitation strategies that target patient-specific increases in walking speed could result in a less effortful gait.


Assuntos
Metabolismo Energético , Doença de Parkinson , Velocidade de Caminhada , Dopaminérgicos/uso terapêutico , Marcha , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Caminhada
15.
J Am Mosq Control Assoc ; 37(1): 10-19, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33857319

RESUMO

Mosquito-borne diseases are a major public health concern in the Caribbean. Domestic water-storage containers are preferred breeding habitats for synanthropic mosquito species, among which Aedes aegypti stands out due to its role in arbovirus transmission. To determine the microenvironmental features associated with container-dwelling mosquitoes, a house-to-house cross-sectional entomological survey was carried out in 9 Dominican provinces affected by Zika virus in 2016. All containers with the potential to store water were sampled, all immature mosquitoes were collected, and information on the type, capacity, volume of stored water, building material, presence of flowers, and house location was documented. The specimens were identified and larval indices (House index [HI], Container index [CI], Breteau index [BI], and Ae. aegypti Breeding Percentage) were applied. A total of 665 dwellings were surveyed across 30 neighborhoods. A total of 1,420 water-filled container habitats were sampled, 19.3% of which harbored immature mosquitoes of 5 species, including 4 important vectors. The dominance of Ae. aegypti was marked, as it was present in all sampled neighborhoods, inhabiting 272 containers (19.1%). Larval indices were higher than the threshold values accepted (5% for the HI and BI, and 3% for the CI) in almost all neighborhoods. The presence of Aedes spp. was associated with the serviceability of water-holding containers (χ2 = 16.56522; P < 0.001), and the difference in volume between water-holding containers was associated with the presence of Aedes spp. infection (χ2 = 4; P < 0.001), the containers up to 5 liters being the most infested. This is the first entomological research based on synanthropic mosquito breeding habitats that cover urban areas of the 3 macro-regions of the Dominican Republic.


Assuntos
Distribuição Animal , Culicidae/fisiologia , Meio Ambiente , Animais , Culicidae/crescimento & desenvolvimento , República Dominicana , Feminino , Larva/crescimento & desenvolvimento , Larva/fisiologia , Masculino , Pupa/crescimento & desenvolvimento , Pupa/fisiologia
16.
Contracept Reprod Med ; 6(1): 2, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402228

RESUMO

BACKGROUND: Despite endorsements supporting the use of intrauterine devices (IUDs) for adolescents and young adult women (AYA), they have limited knowledge about them Male partners can influence contraceptive decisions, however their perceived knowledge about IUDs is lower than their objective knowledge. We aim to establish current AYA baseline contraceptive knowledge and attitudes so providers can better target their sexual health educational interventions. METHODS: Females and males, aged 13 to 23 years old, from our suburban adolescent clinic, completed an anonymous survey that assessed their knowledge and attitudes towards methods of contraception, with an emphasis on the IUD. RESULTS: Completed surveys totaled 130 (99 females/31 males). Demographic results revealed 31.3% Black/African-American, 30.5% Latino/Hispanic, 17.6% White, 3.0% Asian, and 14.5% Other. The majority of participants (80%) were sexually active. The majority (69.5%) stated they/their partner were currently using a contraceptive method; only 2.6% used IUDs. Half of females (56.6%) and 10.1% of males had heard of IUDs. Despite this, male and female participants lacked knowledge regarding specific IUD facts. Of the participants who had used emergency contraception (EC), only 6.4% knew the copper IUD could be used for EC. CONCLUSION: Contraceptive knowledge deficits, especially regarding the IUD, continue to exist for AYA patients. Many participants stated they required EC despite "satisfaction" with their birth control method(s) and most were unaware that the copper IUD could be used as EC. These discrepancies highlight the importance of comprehensive contraceptive education for AYA patients. Enhanced and consistent contraceptive options counseling can help providers ensure that their AYA patients make well-informed decisions about family planning, thus improving their quality of life.

17.
Vet Clin North Am Small Anim Pract ; 50(6): 1237-1259, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32891440

RESUMO

Respiratory distress is commonly seen in dogs and cats presenting to the emergency room. Rapid identification of respiratory difficulty with strategic stabilization and diagnostic efforts are warranted to maximize patient outcome. This article focuses on the relevant anatomy and physiology of the respiratory system and the clinical recognition, stabilization, and initial diagnostic planning for small animal patients that present for respiratory emergencies.


Assuntos
Doenças do Gato/terapia , Doenças do Cão/terapia , Oxigenoterapia/veterinária , Insuficiência Respiratória/veterinária , Animais , Gatos , Cães , Emergências/veterinária , Insuficiência Respiratória/terapia
18.
MAbs ; 11(6): 1025-1035, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31185801

RESUMO

Accelerated development of monoclonal antibody (mAb) tool reagents is an essential requirement for the successful advancement of therapeutic antibodies in today's fast-paced and competitive drug development marketplace. Here, we describe a direct, flexible, and rapid nanofluidic optoelectronic single B lymphocyte antibody screening technique (NanOBlast) applied to the generation of anti-idiotypic reagent antibodies. Selectively enriched, antigen-experienced murine antibody secreting cells (ASCs) were harvested from spleen and lymph nodes. Subsequently, secreted mAbs from individually isolated, single ASCs were screened directly using a novel, integrated, high-content culture, and assay platform capable of manipulating living cells within microfluidic chip nanopens using structured light. Single-cell polymerase chain reaction-based molecular recovery on select anti-idiotypic ASCs followed by recombinant IgG expression and enzyme-linked immunosorbent assay (ELISA) characterization resulted in the recovery and identification of a diverse and high-affinity panel of anti-idiotypic reagent mAbs. Combinatorial ELISA screening identified both capture and detection mAbs, and enabled the development of a sensitive and highly specific ligand binding assay capable of quantifying free therapeutic IgG molecules directly from human patient serum, thereby facilitating important drug development decision-making. The ASC import, screening, and export discovery workflow on the chip was completed within 5 h, while the overall discovery workflow from immunization to recombinantly expressed IgG was completed in under 60 days.


Assuntos
Anticorpos Monoclonais Murinos/imunologia , Linfócitos B/imunologia , Imunoglobulina G/imunologia , Animais , Linfócitos B/citologia , Células CHO , Cricetulus , Ensaio de Imunoadsorção Enzimática , Humanos , Camundongos
19.
Neurorehabil Neural Repair ; 33(8): 602-613, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31208276

RESUMO

Background. Humans typically walk in ways that minimize energy cost. Recent work has found that healthy adults will even adopt new ways of walking when a new pattern costs less energy. This suggests potential for rehabilitation to drive changes in walking by altering the energy costs of walking patterns so that the desired pattern becomes energetically optimal (ie, costs least energy of all available patterns). Objective. We aimed to change gait symmetry in healthy adults and persons poststroke by creating environments where changing symmetry allowed the participants to save energy. Methods. Across 3 experiments, we tested healthy adults (n = 12 in experiment 1, n = 20 in experiment 2) and persons poststroke (n = 7 in experiment 3) in a novel treadmill environment that linked asymmetric stepping and gait speed-2 factors that influence energy cost-to create situations where walking with one's preferred gait symmetry (or asymmetry, in the case of the persons poststroke) was no longer the least energetically costly way to walk. Results. Across the 3 experiments, we found that most participants changed their gait when experiencing the new energy landscape. Healthy adults often adopted an asymmetric gait if it saved energy, and persons poststroke often began to step more symmetrically than they prefer to walk in daily life. Conclusions. We used a novel treadmill environment to show that people with and without stroke change clinically relevant features of walking to save energy. These findings suggest that rehabilitation approaches aimed at making symmetric walking energetically "easier" may promote gait symmetry after stroke.


Assuntos
Acidente Vascular Cerebral/fisiopatologia , Caminhada/fisiologia , Adulto , Idoso , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/fisiopatologia , Consumo de Oxigênio , Acidente Vascular Cerebral/complicações , Reabilitação do Acidente Vascular Cerebral , Adulto Jovem
20.
Sci Rep ; 9(1): 9322, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31249379

RESUMO

Learning new movements through an error-based process called motor adaptation is thought to involve multiple mechanisms which are still largely not understood. Previous studies have shown that young children adapt movement more slowly than adults, perhaps supporting the involvement of distinct neural circuits that come online at different stages of development. Recent studies in adults have shown that in addition to recalibrating a movement, motor adaptation also leads to changes in the perception of that movement. However, we do not yet understand the relationship between the processes that underlie motor and perceptual recalibration. Here we studied motor and perceptual recalibration with split-belt walking adaptation in adults and children aged 6-8 years. Consistent with previous work, we found that this group of children adapted their walking patterns more slowly than adults, though individual children ranged from slow to adult-like in their adaptation rates. Perceptual recalibration was also reduced in the same group of children compared to adults, with individual children ranging from having no recalibration to having adult-like recalibration. In sum, faster motor adaptation and the ability to recalibrate movement perception both come online within a similar age-range, raising the possibility that the same sensorimotor mechanisms underlie these processes.


Assuntos
Aprendizagem , Movimento/fisiologia , Percepção/fisiologia , Adaptação Fisiológica/fisiologia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Caracteres Sexuais , Adulto Jovem
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