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1.
Eur J Immunol ; : e2350756, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38778505

RESUMEN

Decreased monocytic HLA-DR expression is the most studied biomarker of immune competency in critically ill and autoimmune disease patients. However, the underlying regulatory mechanisms remain largely unknown. One probable HLA-DR dysregulation is through microRNAs. The aim of this study was to investigate the effects of specific microRNAs on HLA-DR expression in human monocytic cells. Four up- and four down-HLA-DR-regulating microRNAs were identified, with hsa-miR-let-7f-2-3p showing the most significant upregulation and hsa-miR-567 and hsa-miR-3972 downregulation. Anti-inflammatory glucocorticoid medication Dexamethasone-decreased HLA-DR was significantly restored by hsa-miR-let-7f-2-3p and hsa-miR-5693. Contrarily, proinflammatory cytokines IFN-γ and TNF-α-increased HLA-DR were significantly reversed by hsa-miR-567. Clinically, paired plasma samples from patients before and one day after cardiac surgery revealed up-regulated expression of hsa-miR-5693, hsa-miR-567, and hsa-miR-3972, following the major surgical trauma. In silico approaches were applied for functional microRNA-mRNA interaction prediction and candidate target genes were confirmed by qPCR analysis. In conclusion, novel monocytic HLA-DR microRNA modulators were identified and validated in vitro. Moreover, both the interaction between the microRNAs and anti- and proinflammatory molecules and the up-regulated microRNAs identified in cardiac surgery highlight the potential clinical relevance of our findings.

2.
Eur J Immunol ; 52(9): 1452-1463, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35612261

RESUMEN

HLA-DR isotype is a MHC-II cell-surface receptor found on APCs and plays a key role in initiating immune responses. In severely immunocompromised patients with conditions like sepsis, the number of HLA-DR molecules expressed on leukocytes is considered to correlate with infectious complications and patients' probability of survival. The underlying regulatory mechanisms of HLA-DR expression remain largely unknown. One probable path to regulation is through microRNAs (miRNAs), which have been implicated as regulatory elements of both innate and adaptive immune system development and function. In our study, flow cytometry-based high-throughput miRNA screening was performed in a stable HLA-DR-expressing human melanoma cell line, MelJuSo, for either up- or downregulating miRNAs of the surface HLA-DR expression. By the end of the screening, the top ten upregulators and top five downregulators were identified, and both the HLA-DR protein and mRNA regulations were further verified and validated. In-silico approaches were applied for functional miRNA-mRNA interaction prediction. The potential underlying gene regulations of different miRNAs were proposed. Our results promote the study of miRNA-mediated HLA-DR regulation under both physiological and pathological conditions, and may pave the way for potential clinical applications.


Asunto(s)
MicroARNs , Citometría de Flujo , Antígenos HLA-DR/genética , Antígenos HLA-DR/metabolismo , Humanos , MicroARNs/genética , Interferencia de ARN , ARN Mensajero/genética
3.
J Neurosci Res ; 101(9): 1504-1518, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37313595

RESUMEN

To optimize performance during vital tasks, animals are capable of tuning rhythmic neural signals that drive repetitive behaviors, such as motor reflexes under constant sensory stimuli. In the oculomotor system, animals track the moving image during slow phases while repetitively resetting the eye position from the eccentricity during quick phases. During optokinetic response (OKR), larval zebrafish occasionally show a delayed quick phase; thus, the eyes remain tonically deviated from the center. In this study, we scrutinized OKR in larval zebrafish under a broad range of stimulus velocities to determine the parametric property of the quick-phase delay. A prolonged stimulation revealed that the slow-phase (SP) duration-the interval between two quick phases-was tuned increasingly over time toward a homeostatic range, regardless of stimulus velocity. Attributed to this rhythm control, larval zebrafish exhibited a tonic eye deviation following slow phases, which was especially pronounced when tracking a fast stimulus over an extended time period. In addition to the SP duration, the fixation duration between spontaneous saccades in darkness also revealed a similar adaptive property after the prolonged optokinetic stimulation. Our results provide a quantitative description of the adaptation of rhythmic eye movements in developing animals and pave the way for potential animal models for eye movement disorders.


Asunto(s)
Nistagmo Optoquinético , Pez Cebra , Animales , Pez Cebra/fisiología , Larva , Reflejo/fisiología , Adaptación Fisiológica
4.
Epidemiology ; 33(4): 551-554, 2022 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35439772

RESUMEN

We expand upon a simulation study that compared three promising methods for estimating weights for assessing the average treatment effect on the treated for binary treatments: generalized boosted models, covariate-balancing propensity scores, and entropy balance. The original study showed that generalized boosted models can outperform covariate-balancing propensity scores, and entropy balance when there are likely to be nonlinear associations in both the treatment assignment and outcome models and when the other two models are fine-tuned to obtain balance only on first-order moments. We explore the potential benefit of using higher-order moments in the balancing conditions for covariate-balancing propensity scores and entropy balance. Our findings showcase that these two models should, by default, include higher-order moments and focusing only on first moments can result in substantial bias in estimated treatment effect estimates from both models that could be avoided using higher moments.


Asunto(s)
Causalidad , Sesgo , Simulación por Computador , Humanos , Puntaje de Propensión
5.
Am J Obstet Gynecol ; 224(6): 597.e1-597.e14, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33309562

RESUMEN

BACKGROUND: Contraceptive method choice is often strongly influenced by the experiences and opinions of one's social network. Although social media, including Twitter, increasingly influences reproductive-age individuals, discussion of contraception in this setting has yet to be characterized. Natural language processing, a type of machine learning in which computers analyze natural language data, enables this analysis. OBJECTIVE: This study aimed to illuminate temporal trends in attitudes toward long- and short-acting reversible contraceptive methods in tweets between 2006 and 2019 and establish social media platforms as alternate data sources for large-scale sentiment analysis on contraception. STUDY DESIGN: We studied English-language tweets mentioning reversible prescription contraceptive methods between March 2006 (founding of Twitter) and December 2019. Tweets mentioning contraception were extracted using search terms, including generic or brand names, colloquial names, and abbreviations. We characterized and performed sentiment analysis on tweets. We used Mann-Kendall nonparametric tests to assess temporal trends in the overall number and the number of positive, negative, and neutral tweets referring to each method. The code to reproduce this analysis is available at https://github.com/hms-dbmi/contraceptionOnTwitter. RESULTS: We extracted 838,739 tweets mentioning at least 1 contraceptive method. The annual number of contraception-related tweets increased considerably over the study period. The intrauterine device was the most commonly referenced method (45.9%). Long-acting methods were mentioned more often than short-acting ones (58% vs 42%), and the annual proportion of long-acting reversible contraception-related tweets increased over time. In sentiment analysis of tweets mentioning a single contraceptive method (n=665,064), the greatest proportion of all tweets was negative (65,339 of 160,713 tweets with at least 95% confident sentiment, or 40.66%). Tweets mentioning long-acting methods were nearly twice as likely to be positive compared with tweets mentioning short-acting methods (19.65% vs 10.21%; P<.002). CONCLUSION: Recognizing the influence of social networks on contraceptive decision making, social media platforms may be useful in the collection and dissemination of information about contraception.


Asunto(s)
Actitud Frente a la Salud , Anticoncepción/psicología , Anticoncepción/tendencias , Opinión Pública , Medios de Comunicación Sociales , Toma de Decisiones , Femenino , Humanos , Masculino , Procesamiento de Lenguaje Natural
6.
Proc Natl Acad Sci U S A ; 114(35): 9457-9462, 2017 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-28808023

RESUMEN

Conscious visual perception is proposed to arise from the selective synchronization of functionally specialized but widely distributed cortical areas. It has been suggested that different frequency bands index distinct canonical computations. Here, we probed visual perception on a fine-grained temporal scale to study the oscillatory dynamics supporting prefrontal-dependent sensory processing. We tested whether a predictive context that was embedded in a rapid visual stream modulated the perception of a subsequent near-threshold target. The rapid stream was presented either rhythmically at 10 Hz, to entrain parietooccipital alpha oscillations, or arrhythmically. We identified a 2- to 4-Hz delta signature that modulated posterior alpha activity and behavior during predictive trials. Importantly, delta-mediated top-down control diminished the behavioral effects of bottom-up alpha entrainment. Simultaneous source-reconstructed EEG and cross-frequency directionality analyses revealed that this delta activity originated from prefrontal areas and modulated posterior alpha power. Taken together, this study presents converging behavioral and electrophysiological evidence for frontal delta-mediated top-down control of posterior alpha activity, selectively facilitating visual perception.


Asunto(s)
Ritmo alfa/fisiología , Corteza Prefrontal/fisiología , Percepción Visual/fisiología , Adolescente , Mapeo Encefálico/métodos , Sincronización Cortical , Electroencefalografía , Femenino , Humanos , Masculino , Estimulación Luminosa , Corteza Visual/fisiología , Adulto Joven
7.
J Exp Biol ; 220(Pt 2): 171-173, 2017 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-27811295

RESUMEN

Spontaneous alternation behavior (SAB) describes the tendency of animals to alternate their turn direction in consecutive turns. SAB, unlike other mnestic tasks, does not require any prior training or reinforcement. Because of its close correlation with the development and function of the hippocampus in mice, it is thought to reflect a type of memory. Adult zebrafish possess a hippocampus-like structure utilizing the same neurotransmitters as in human brains, and have thus been used to study memory. In the current study, we established SAB in zebrafish larvae at 6 days post-fertilization using a custom-made forced-turn maze with a rate of 57%. Our demonstration of the presence of SAB in larval zebrafish at a very early developmental stage not only provides evidence for early cognition in this species but also suggests its future usefulness as a high-throughput model for mnestic studies.


Asunto(s)
Aprendizaje por Laberinto , Memoria , Pez Cebra/fisiología , Animales , Cognición
8.
J Physiol ; 592(1): 203-14, 2014 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-24218543

RESUMEN

The optokinetic reflex (OKR) and the angular vestibulo-ocular reflex (aVOR) complement each other to stabilize images on the retina despite self- or world motion, a joint mechanism that is critical for effective vision. It is currently hypothesized that signals from both systems integrate, in a mathematical sense, in a network of neurons operating as a velocity storage mechanism (VSM). When exposed to a rotating visual surround, subjects display the OKR, slow following eye movements frequently interrupted by fast resetting eye movements. Subsequent to light-off during optokinetic stimulation, eye movements do not stop abruptly, but decay slowly, a phenomenon referred to as the optokinetic after-response (OKAR). The OKAR is most likely generated by the VSM. In this study, we observed the OKAR in developing larval zebrafish before the horizontal aVOR emerged. Our results suggest that the VSM develops prior to and without the need for a functional aVOR. It may be critical to ocular motor control in early development as it increases the efficiency of the OKR.


Asunto(s)
Movimientos Oculares , Locomoción , Reflejo Vestibuloocular , Animales , Larva/fisiología , Estimulación Luminosa , Pez Cebra
9.
Exp Brain Res ; 232(9): 2891-8, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24820290

RESUMEN

The afternystagmus that occurs in the dark after gaze fixation during optokinetic stimulation is directed in the opposite direction relative to the previous optokinetic stimulus. The mechanism responsible for such afternystagmus after suppression of optokinetic nystagmus (ASOKN) is unclear. Several hypotheses have been put forward to explain it, but none is conclusive. We hypothesized that ASOKN is driven by the interaction of two mechanisms: (1) motion-aftereffect (MAE)-induced eye movements and (2) retinal afterimages (RAIs) produced by fixation during the suppression of optokinetic nystagmus (OKN). We examined the correlation among ASOKN, MAE-induced eye movements, and RAIs in healthy subjects. Adapting stimuli consisted of moving random dot patterns and a fixation spot and their brightness was adjusted to induce different RAI durations. Test patterns were a stationary random dot pattern (to test for the presence of a MAE), a dim homogeneous background (to test for MAE driven eye movements), and a black background (to test for ASOKN and RAIs). MAEs were reported by 16 out of 17 subjects, but only 7 out of 17 subjects demonstrated MAE-induced eye movements. Importantly, ASOKN was only found when these seven subjects reported a RAI after suppression of OKN. Moreover, the duration of ASOKN was longer for high-brightness stimuli compared with low-brightness stimuli, just as RAIs persist longer with increasing brightness. We conclude that ASOKN results from the interaction of MAE-induced eye movements and RAIs.


Asunto(s)
Postimagen/fisiología , Oscuridad , Percepción de Movimiento/fisiología , Nistagmo Optoquinético/fisiología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reconocimiento Visual de Modelos , Estimulación Luminosa , Adulto Joven
10.
Contraception ; 129: 110300, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37802460

RESUMEN

OBJECTIVES: This study aimed to explore the contraception content topics on the highly popular social media platform TikTok to understand this influential information source patients may bring into birth control counseling visits. STUDY DESIGN: Utilizing a snapshot method, we collected the 100 most popular TikTok English-language videos for each of the eight contraception-specific search terms. We abstracted video content topics addressed and creator attributes. Two independent abstractors coded each video with high agreement, with a third coder adjudicating discrepancies. RESULTS: The final data set included 700 unique videos, with a total of 1.18 billion views, 131 million likes, 1.5 million comments, and 4.1 million shares. In these videos, the most common topics addressed were patient experience (n = 365, 52.1%) and logistics of use (n = 351, 50.1%). Health care professionals created only 19.3% of videos (n = 135), but these videos accounted for a larger portion of the total video views (41.3%). Health care professionals largely made educational videos (92.6%) compared to 22.5% of videos coded as educational videos when made by perceived non-health care professionals. A small number of prolific video creators developed the majority of videos made by health care professionals, with 91 (67.4%) made by six TikTok creators. CONCLUSIONS: TikTok contains highly accessible contraception content, which garners high viewership, especially when created by health care providers. Clinicians should be aware of TikTok's potential to influence patients prior to contraceptive counseling visits and recognize this platform as a public health instrument to disseminate contraceptive information to a key demographic. IMPLICATIONS: Few previous studies have examined the presence and popularity of contraception content topics on TikTok; little is known about the health content on this highly popular platform. Providers should be aware of the contraceptive topics on TikTok for understanding both patient perceptions and the potential for health education through this media.


Asunto(s)
Medios de Comunicación Sociales , Humanos , Anticoncepción , Anticonceptivos , Dispositivos Anticonceptivos , Concienciación
11.
Contracept Reprod Med ; 9(1): 5, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38321582

RESUMEN

BACKGROUND: Information on social media may affect peoples' contraceptive decision making. We performed an exploratory analysis of contraceptive content on Twitter (recently renamed X), a popular social media platform. METHODS: We selected a random subset of 1% of publicly available, English-language tweets related to reversible, prescription contraceptive methods posted between January 2014 and December 2019. We oversampled tweets for the contraceptive patch to ensure at least 200 tweets per method. To create the codebook, we identified common themes specific to tweet content topics, tweet sources, and tweets soliciting information or providing advice. All posts were coded by two team members, and differences were adjudicated by a third reviewer. Descriptive analyses were reported with accompanying qualitative findings. RESULTS: During the study period, 457,369 tweets about reversible contraceptive methods were published, with a random sample of 4,434 tweets used for final analysis. Tweets most frequently discussed contraceptive method decision-making (26.7%) and side effects (20.5%), particularly for long-acting reversible contraceptive methods and the depot medroxyprogesterone acetate shot. Tweets about logistics of use or adherence were common for short-acting reversible contraceptives. Tweets were frequently posted by contraceptive consumers (50.6%). A small proportion of tweets explicitly requested information (6.2%) or provided advice (4.2%). CONCLUSIONS: Clinicians should be aware that individuals are exposed to information through Twitter that may affect contraceptive perceptions and decision making, particularly regarding long-acting reversible contraceptives. Social media is a valuable source for studying contraceptive beliefs missing in traditional health research and may be used by professionals to disseminate accurate contraceptive information.

12.
J Neurosci ; 32(50): 18079-86, 2012 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-23238723

RESUMEN

Infantile nystagmus syndrome (INS), formerly known as congenital nystagmus, is an ocular motor disorder in humans characterized by spontaneous eye oscillations (SOs) and, in several cases, reversed optokinetic response (OKR). Its etiology and pathomechanism is largely unknown, but misrouting of the optic nerve has been observed in some patients. Likewise, optic nerve misrouting, a reversed OKR and SOs with INS-like waveforms are observed in zebrafish belladonna (bel) mutants. We aimed to investigate whether and how misrouting of the optic nerve correlates with the ocular motor behaviors in bel larvae. OKR and SOs were quantified and subsequently the optic nerve fibers were stained with fluorescent lipophilic dyes. Eye velocity during OKR was reduced in larvae with few misprojecting optic nerve fibers and reversed in larvae with a substantial fraction of misprojecting fibers. All larvae with reversed OKR also displayed SOs. A stronger reversed OKR correlated with more frequent SOs. Since we did not find a correlation between additional retinal defects and ocular motor behavior, we suggest that axon misrouting is in fact origin of INS in the zebrafish animal model. Depending on the ratio between misprojecting ipsilateral and correctly projecting contralateral fibers, the negative feedback loop normally regulating OKR can turn into a positive loop, resulting in an increase in retinal slip. Our data not only give new insights into the etiology of INS but may also be of interest for studies on how the brain deals with and adapts to conflicting inputs.


Asunto(s)
Nistagmo Congénito/patología , Nervio Óptico/patología , Animales , Modelos Animales de Enfermedad , Proteínas con Homeodominio LIM/genética , Larva , Mutación , Proteínas del Tejido Nervioso/genética , Fenotipo , Estimulación Luminosa , Factores de Transcripción/genética , Pez Cebra , Proteínas de Pez Cebra/genética
13.
Sci Rep ; 13(1): 15217, 2023 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-37709941

RESUMEN

Neutrophils can release neutrophil extracellular traps (NETs) containing DNA fibres and antimicrobial peptides to immobilize invading pathogens. NET formation (NETosis) plays a vital role in inflammation and immune responses. In this study we investigated the impact of surgical trauma on NETosis of neutrophils. Nine patients undergoing "Transcatheter/percutaneous aortic valve implantation" (TAVI/PAVI, mild surgical trauma), and ten undergoing "Aortocoronary bypass" (ACB, severe surgical trauma) were included in our pilot study. Peripheral blood was collected before, end of, and after surgery (24 h and 48 h). Neutrophilic granulocytes were isolated and stimulated in vitro with Phorbol-12-myristate-13-acetate (PMA). NETosis rate was examined by microscopy. In addition, HLA-DR surface expression on circulating monocytes was analysed by flow-cytometry as a prognostic marker of the immune status. Both surgical procedures led to significant down regulation of monocytic HLA-DR surface expression, albeit more pronounced in ACB patients, and there was a similar trend in NETosis regulation over the surgical 24H course. Upon PMA stimulation, no significant difference in NETosis was observed over time in TAVI/PAVI group; however, a decreasing NETosis trend with a significant drop upon ACB surgery was evident. The reduced PMA-induced NETosis in ACB group suggests that the inducibility of neutrophils to form NETs following severe surgical trauma may be compromised. Moreover, the decreased monocytic HLA-DR expression suggests a post-operative immunosuppressed status in all patients, with a bigger impact by ACB, which might be attributed to the extracorporeal circulation or tissue damage occurring during surgery.


Asunto(s)
Trampas Extracelulares , Humanos , Proyectos Piloto , Neutrófilos , Regulación hacia Abajo , Granulocitos
14.
Cells ; 11(7)2022 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-35406649

RESUMEN

Nociceptin and the nociceptin receptor (NOP) have been described as targets for treatment of pain and inflammation, whereas toll-like receptors (TLRs) play key roles in inflammation and impact opioid receptors and endogenous opioids expression. In this study, interactions between the nociceptin and TLR systems were investigated. Human THP-1 cells were cultured with or without phorbol myristate acetate (PMA 5 ng/mL), agonists specific for TLR2 (lipoteichoic acid, LTA 10 µg/mL), TLR4 (lipopolysaccharide, LPS 100 ng/mL), TLR7 (imiquimod, IMQ 10 µg/mL), TLR9 (oligonucleotide (ODN) 2216 1 µM), PMA+TLR agonists, or nociceptin (0.01−100 nM). Prepronociceptin (ppNOC), NOP, and TLR mRNAs were quantified by RT-qPCR. Proteins were measured using flow cytometry. PMA upregulated ppNOC mRNA, intracellular nociceptin, and cell membrane NOP proteins (all p < 0.05). LTA and LPS prevented PMA's upregulating effects on ppNOC mRNA and nociceptin protein (both p < 0.05). IMQ and ODN 2216 attenuated PMA's effects on ppNOC mRNA. PMA, LPS, IMQ, and ODN 2216 increased NOP protein levels (all p < 0.05). PMA+TLR agonists had no effects on NOP compared to PMA controls. Nociceptin dose-dependently suppressed TLR2, TLR4, TLR7, and TLR9 proteins (all p < 0.01). Antagonistic effects observed between the nociceptin and TLR systems suggest that the nociceptin system plays an anti-inflammatory role in monocytes under inflammatory conditions.


Asunto(s)
Lipopolisacáridos , Receptor Toll-Like 2 , Humanos , Inflamación , Lipopolisacáridos/farmacología , Péptidos Opioides , ARN Mensajero/genética , Acetato de Tetradecanoilforbol , Receptor Toll-Like 4 , Receptor Toll-Like 7 , Receptor Toll-Like 9 , Receptores Toll-Like/genética , Nociceptina
15.
iScience ; 25(11): 105335, 2022 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-36325052

RESUMEN

Experience-dependent brain circuit plasticity underlies various sensorimotor learning and memory processes. Recently, a novel set-point adaptation mechanism was identified that accounts for the pronounced negative optokinetic afternystagmus (OKAN) following a sustained period of unidirectional optokinetic nystagmus (OKN) in larval zebrafish. To investigate the physiological significance of optokinetic set-point adaptation, animals in the current study were exposed to a direction-alternating optokinetic stimulation paradigm that better resembles their visual experience in nature. Our results reveal that not only was asymmetric alternating stimulation sufficient to induce the set-point adaptation and the resulting negative OKAN, but most strikingly, under symmetric alternating stimulation some animals displayed an inherent bias of the OKN gain in one direction, and that was compensated by the similar set-point adaptation. This finding, supported by mathematical modeling, suggests that set-point adaptation allows animals to cope with asymmetric optokinetic behaviors evoked by either external stimuli or innate oculomotor biases.

16.
Neuropharmacology ; 202: 108860, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-34736959

RESUMEN

We reported previously that the selective agonist U50,488H promoted phosphorylation of the mouse kappa opioid receptor (mKOR) in vitro at four residues in the C-terminal domain. In this study, we generated a mutant mouse line in which all the four residues were mutated to Ala (K4A) to examine the in vivo functional significance of agonist-induced KOR phosphorylation. U50,488H promoted KOR phosphorylation in brains of the wildtype (WT), but not K4A, male and female mice. Autoradiography of [3H] 69,593 binding to KOR in brain sections showed that WT and K4A mice had similar KOR distribution and expression levels in brain regions without sex differences. In K4A mice, U50,488H inhibited compound 48/80-induced scratching and attenuated novelty-induced hyperlocomotion to similar extents as in WT mice without sex differences. Interestingly, repeated pretreatment with U50,488H (80 mg/kg, s.c.) resulted in profound tolerance to the anti-scratch effects of U50,488H (5 mg/kg, s.c.) in WT mice of both sexes and female K4A mice, while in male K4A mice tolerance was attenuated. Moreover, U50,488H (2 mg/kg) induced conditioned place aversion (CPA) in WT mice of both sexes and male K4A mice, but not in female K4A mice. In contrast, U50,488H (5 mg/kg) caused CPA in male, but not female, mice, regardless of genotype. Thus, agonist-promoted KOR phosphorylation plays important roles in U50,488H-induced tolerance and CPA in a sex-dependent manner, without affecting acute U50,488H-induced anti-pruritic and hypo-locomotor effects. These results are the first to demonstrate sex differences in the effects of GPCR phosphorylation on the GPCR-mediated behaviors.


Asunto(s)
3,4-Dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclohexil)-bencenacetamida, (trans)-Isómero/farmacología , Conducta Animal/efectos de los fármacos , Receptores Opioides kappa/agonistas , Caracteres Sexuales , Animales , Encéfalo/metabolismo , Células Cultivadas , Femenino , Locomoción/efectos de los fármacos , Masculino , Ratones , Ratones Mutantes , Fosforilación/efectos de los fármacos , Receptores Opioides kappa/metabolismo , p-Metoxi-N-metilfenetilamina/antagonistas & inhibidores
17.
MedEdPublish (2016) ; 10: 139, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-38486547

RESUMEN

This article was migrated. The article was marked as recommended. With nearly half the world's population using social media, platforms like Instagram, Twitter, and Facebook have become popular sources of information gathering and sharing for the general public. In medicine, social media is increasingly used to educate patients due its wide reach and interactive nature. Early studies showed that these social media-based initiatives can even promote behavioral change by increasing public knowledge and self-efficacy. Several barriers such as time and technical skills, however, prevent healthcare workers from using social media platforms to promote public health education. The following twelve tips may help reduce these barriers and create more opportunities for patients to easily access quality medical information on social media. Creating an effective public health education platform on social media involves identifying clear goals, understanding the social context of all messaging, recruiting a motivated team, creating a style guide, vetting content for accuracy, and interacting with social media followers. These tips will help build an accurate and quality social media public health education campaign.

18.
Sci Rep ; 9(1): 19039, 2019 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-31836778

RESUMEN

Motor learning is essential to maintain accurate behavioral responses. We used a larval zebrafish model to study ocular motor learning behaviors. During a sustained period of optokinetic stimulation in 5-day-old wild-type zebrafish larvae the slow-phase eye velocity decreased over time. Then interestingly, a long-lasting and robust negative optokinetic afternystagmus (OKAN) was evoked upon light extinction. The slow-phase velocity, the quick-phase frequency, and the decay time constant of the negative OKAN were dependent on the stimulus duration and the adaptation to the preceding optokinetic stimulation. Based on these results, we propose a sensory adaptation process during continued optokinetic stimulation, which, when the stimulus is removed, leads to a negative OKAN as the result of a changed retinal slip velocity set point, and thus, a sensorimotor memory. The pronounced negative OKAN in larval zebrafish not only provides a practical solution to the hitherto unsolved problems of observing negative OKAN, but also, and most importantly, can be readily applied as a powerful model for studying sensorimotor learning and memory in vertebrates.


Asunto(s)
Adaptación Ocular/fisiología , Nistagmo Optoquinético/fisiología , Pez Cebra/fisiología , Animales , Ojo/fisiopatología , Larva/fisiología , Modelos Biológicos , Estimulación Luminosa , Factores de Tiempo
19.
Front Neurol ; 9: 151, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29593643

RESUMEN

Abnormal projection of the optic nerves to the wrong cerebral hemisphere transforms the optokinetic system from its usual negative feedback loop to a positive feedback loop with characteristic ocular motor instabilities including directional reversal of the optokinetic nystagmus (OKN) and spontaneous nystagmus, which are common features of infantile nystagmus syndrome (INS). Visual input plays a critical role in INS linked to an underlying optic nerve misprojection such as that often seen in albinism. However, spontaneous nystagmus often continues in darkness, making the visual, sensory-driven etiology questionable. We propose that sensorimotor adaptation during the constant nystagmus of patients in the light could account for continuing nystagmus in the dark. The OKN is a stereotyped reflexive eye movement in response to motion in the surround and serves to stabilize the visual image on the retina, allowing high resolution vision. Robust negative optokinetic afternystagmus (negative OKAN), referring to the continuous nystagmus in the dark with opposite beating direction of the preceding OKN, has been identified in various non-foveated animals. In humans, a robust afternystagmus in the same direction as previous smooth-pursuit movements (the eye's continuous tracking and foveation of a moving target) induced by visual stimuli has been known to commonly mask negative OKAN. Some INS patients are often associated with ocular hypopigmentation, foveal hypoplasia, and compromised smooth pursuit. We identified an INS case with negative OKAN in the dark, in contrast to the positive afternystagmus in healthy subjects. We hypothesize that spontaneous nystagmus in the dark in INS patients may be attributable to sensory adaptation in the optokinetic system after a sustained period of spontaneous nystagmus with directional visual input in light.

20.
Invest Ophthalmol Vis Sci ; 58(7): 3149-3157, 2017 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-28632848

RESUMEN

Purpose: Infantile nystagmus syndrome (INS) is a disorder characterized by typical horizontal eye oscillations. Due to the uncertain etiology of INS, developing specific treatments remains difficult. Single reports demonstrated, on limited measures, alleviating effects of gabapentin and memantine. In the current study, we employed the zebrafish INS model belladonna (bel) to conduct an in-depth study of how gabapentin and memantine interventions alleviate INS signs, which may further restore visual conditions in affected subjects. Moreover, we described the influence of both medications on ocular motor functions in healthy zebrafish, evaluating possible iatrogenic effects. Methods: Ocular motor function and INS characteristics were assessed by eliciting optokinetic response, spontaneous nystagmus, and spontaneous saccades in light and in dark, in 5- to 6-day postfertilization bel larvae and heterozygous siblings. Single larvae were recorded before and after a 1-hour drug treatment (200 mM gabapentin/0.2 mM memantine). Results: Both interventions significantly reduced nystagmus intensity (gabapentin: 59.98%, memantine: 39.59%). However, while the application of gabapentin affected all tested ocular motor functions, memantine specifically reduced nystagmus amplitude and intensity, and thus left controls completely unaffected. Finally, both drug treatments resulted in specific changes in nystagmus waveform and velocity. Conclusions: Our study provides deeper insight into gabapentin and memantine treatment effect in the zebrafish INS model. Moreover, this study should establish zebrafish as a pharmacologic animal model for treating nystagmus and ocular motor disease, serving as a basis for future large-scale drug screenings.


Asunto(s)
Aminas/farmacología , Ácidos Ciclohexanocarboxílicos/farmacología , Movimientos Oculares/fisiología , Memantina/farmacología , Nistagmo Congénito/tratamiento farmacológico , Ácido gamma-Aminobutírico/farmacología , Animales , Bloqueadores de los Canales de Calcio/farmacología , Modelos Animales de Enfermedad , Antagonistas de Aminoácidos Excitadores/farmacología , Movimientos Oculares/efectos de los fármacos , Gabapentina , Nistagmo Congénito/fisiopatología , Síndrome , Pez Cebra
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