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1.
J Intellect Disabil ; 26(4): 1033-1056, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34844460

RESUMO

People with intellectual and developmental disabilities sometimes engage in challenging behaviours. When behaviours escalate to the point where they pose imminent risk to the safety of people and environments, a crisis occurs that jeopardises community living and participation. In these situations, timely access to crisis stabilisation services is required. We conducted a systematic review of the literature to synthesise evidence on effective crisis stabilisation service models for challenging behaviours. A total of 46 publications met the inclusion criteria. The literature describes a spectrum of crisis stabilisation services of varying intensities including: outreach, outpatient, inpatient, respite, and capacity building through education and training. However, there is limited guidance on how to best structure service models. This review highlights the need for comprehensive and person-centred programme evaluations.


Assuntos
Deficiência Intelectual , Humanos
2.
J Exp Biol ; 224(7)2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34424975

RESUMO

Mastication and drinking are rhythmic and cyclic oral behaviors that require interactions between the tongue, jaw and a food or liquid bolus, respectively. During mastication, the tongue transports and positions the bolus for breakdown between the teeth. During drinking, the tongue aids in ingestion and then transports the bolus to the oropharynx. The objective of this study was to compare jaw and tongue kinematics during chewing and drinking in pigs. We hypothesized there would be differences in jaw gape cycle dynamics and tongue protraction-retraction between behaviors. Mastication cycles had an extended slow-close phase, reflecting tooth-food-tooth contact, whereas drinking cycles had an extended slow-open phase, corresponding to tongue protrusion into the liquid. Compared with chewing, drinking jaw movements were of lower magnitude for all degrees of freedom examined (jaw protraction, yaw and pitch), and were bilaterally symmetrical with virtually no yaw. The magnitude of tongue protraction-retraction (Txt), relative to a mandibular coordinate system, was greater during mastication than during drinking, but there were minimal differences in the timing of maximum and minimum Txt relative to the jaw gape cycle between behaviors. However, during drinking, the tongue tip is often located outside the oral cavity for the entire cycle, leading to differences between behaviors in the timing of anterior marker maximum Txt. This demonstrates that there is variation in tongue-jaw coordination between behaviors. These results show that jaw and tongue movements vary significantly between mastication and drinking, which hints at differences in the central control of these behaviors.


Assuntos
Arcada Osseodentária , Mastigação , Animais , Fenômenos Biomecânicos , Ingestão de Líquidos , Movimento , Suínos , Língua
3.
J Exp Biol ; 224(7)2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33674496

RESUMO

Mastication and drinking are rhythmic and cyclic oral behaviors that require interactions between the tongue, jaw and a food or liquid bolus, respectively. During mastication, the tongue transports and positions the bolus for breakdown between the teeth. During drinking, the tongue aids in ingestion and then transports the bolus to the oropharynx. The objective of this study was to compare jaw and tongue kinematics during chewing and drinking in pigs. We hypothesized there would be differences in jaw gape cycle dynamics and tongue protraction-retraction between behaviors. Mastication cycles had an extended slow-close phase, reflecting tooth-food-tooth contact, whereas drinking cycles had an extended slow-open phase, corresponding to tongue protrusion into the liquid. Compared with chewing, drinking jaw movements were of lower magnitude for all degrees of freedom examined (jaw protraction, yaw and pitch), and were bilaterally symmetrical with virtually no yaw. The magnitude of tongue protraction-retraction (Txt), relative to a mandibular coordinate system, was greater during mastication than during drinking, but there were minimal differences in the timing of maximum and minimum Txt relative to the jaw gape cycle between behaviors. However, during drinking, the tongue tip is often located outside the oral cavity for the entire cycle, leading to differences between behaviors in the timing of anterior marker maximum Txt. This demonstrates that there is variation in tongue-jaw coordination between behaviors. These results show that jaw and tongue movements vary significantly between mastication and drinking, which hints at differences in the central control of these behaviors.


Assuntos
Ingestão de Líquidos , Mastigação , Animais , Fenômenos Biomecânicos , Arcada Osseodentária , Movimento , Suínos , Língua
4.
Epilepsy Behav ; 97: 123-129, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31247523

RESUMO

BACKGROUND: Innovative uses of mobile health (mHealth) technology for real-time measurement and management of epilepsy may improve the care provided to patients. For instance, seizure detection and quantifying related problems will have an impact on quality of life and improve clinical management for people experiencing frequent and uncontrolled seizures. Engaging patients with mHealth technology is essential, but little is known about patient perspectives on their acceptability. The aim of this study was to conduct an in-depth qualitative analysis of what people with uncontrolled epilepsy think could be the potential uses of mHealth technology and to identify early potential barriers and facilitators to engagement in three European countries. METHOD: Twenty people currently experiencing epileptic seizures took part in five focus groups held across the UK, Italy, and Spain. Participants all completed written consent and a demographic questionnaire prior to the focus group commencing, and each group discussion lasted 60-120 min. A coding frame, developed from a systematic review of the previous literature, was used to structure a thematic analysis. We extracted themes and subthemes from the discussions, focusing first on possible uses of mHealth and then the barriers and facilitators to engagement. RESULTS: Participants were interested in mHealth technology as a clinical detection tool, e.g., to aid communication about seizure occurrence with their doctors. Other suggested uses included being able to predict or prevent seizures, and to improve self-management. Key facilitators to engagement were the ability to raise awareness, plan activities better, and improve safety. Key barriers were the potential for increased stigma and anxiety. Using familiar and customizable products could be important moderators of engagement. CONCLUSION: People with uncontrolled epilepsy think that there is a scope for mHealth technology to be useful in healthcare as a detection or prediction tool. The costs will be compared with the benefits when it comes to engagement, and ongoing work with patients and other stakeholders is needed to design practical resources.


Assuntos
Comunicação , Epilepsia/terapia , Aceitação pelo Paciente de Cuidados de Saúde , Relações Médico-Paciente , Autogestão , Telemedicina , Adulto , Atitude Frente a Saúde , Gerenciamento Clínico , Feminino , Grupos Focais , Teoria Fundamentada , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Participação do Paciente , Qualidade de Vida , Convulsões , Espanha , Reino Unido , Adulto Jovem
5.
J Med Internet Res ; 21(1): e11696, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30626564

RESUMO

BACKGROUND: Access to internet-enabled technology and Web-based services has grown exponentially in recent decades. This growth potentially excludes some communities and individuals with mental health difficulties, who face a heightened risk of digital exclusion. However, it is unclear what factors may contribute to digital exclusion in this population. OBJECTIVE: To explore in detail the problems of digital exclusion in mental health service users and potential facilitators to overcome them. METHODS: We conducted semistructured interviews with 20 mental health service users who were deemed digitally excluded. We recruited the participants from a large secondary mental health provider in South London, United Kingdom. We employed thematic analysis to identify themes and subthemes relating to historical and extant reasons for digital exclusion and methods of overcoming it. RESULTS: There were three major themes that appeared to maintain digital exclusion: a perceived lack of knowledge, being unable to access the necessary technology and services owing to personal circumstances, and the barriers presented by mental health difficulties. Specific facilitators for overcoming digital exclusion included intrinsic motivation and a personalized learning format that reflects the individual's unique needs and preferences. CONCLUSIONS: Multiple factors contribute to digital exclusion among mental health service users, including material deprivation and mental health difficulties. This means that efforts to overcome digital exclusion must address the multiple deprivations individuals may face in the offline world in addition to their individual mental health needs. Additional facilitators include fostering an intrinsic motivation to overcome digital exclusion and providing a personalized learning format tailored to the individual's knowledge gaps and preferred learning style.


Assuntos
Serviços de Saúde Mental/normas , Telemedicina/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa
6.
J Exp Biol ; 221(Pt 2)2018 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-29378880

RESUMO

In mammals, chewing movements can be modified, or flexible, in response to changes in food properties. Variability between and within food in the temporal characteristics of chewing movements can impact chewing frequency and rhythmicity, which in turn may affect food breakdown, energy expenditure and tooth wear. Here, we compared total chewing cycle duration and intra-cycle phase durations in pigs chewing on three foods varying in toughness and stiffness: apples (low toughness, low stiffness), carrots (high toughness, low stiffness), and almonds (high toughness, high stiffness). We also determined whether within-food variability in timing parameters is modified in response to changes in food properties. X-ray Reconstruction Of Moving Morphology (XROMM) demonstrates that the timing of jaw movements are flexible in response to changes in food properties. Within each food, pigs also exhibited flexibility in their ability to vary cycle parameters. The timing of jaw movements during processing of high-toughness foods is more variable, potentially decreasing chewing rhythmicity. In contrast, low-toughness foods result in jaw movements that are more stereotyped in their timing parameters. In addition, the duration of tooth-food-tooth contact is more variable during the processing of low-stiffness foods compared with tough or stiff foods. Increased toughness is suggested to alter the timing of the movements impacting food fracture whereas increased stiffness may require a more cautious control of jaw movements. This study emphasizes that flexibility in biological movements in response to changes in conditions may not only be observed in timing but also in the variability of their timing within each condition.


Assuntos
Análise de Alimentos , Arcada Osseodentária/fisiologia , Mastigação/fisiologia , Sus scrofa/fisiologia , Animais , Fenômenos Biomecânicos , Comportamento Alimentar , Feminino , Movimento , Periodicidade
7.
J Med Internet Res ; 20(7): e10480, 2018 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-30001997

RESUMO

BACKGROUND: Remote measurement technology refers to the use of mobile health technology to track and measure change in health status in real time as part of a person's everyday life. With accurate measurement, remote measurement technology offers the opportunity to augment health care by providing personalized, precise, and preemptive interventions that support insight into patterns of health-related behavior and self-management. However, for successful implementation, users need to be engaged in its use. OBJECTIVE: Our objective was to systematically review the literature to update and extend the understanding of the key barriers to and facilitators of engagement with and use of remote measurement technology, to guide the development of future remote measurement technology resources. METHODS: We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines involving original studies dating back to the last systematic review published in 2014. We included studies if they met the following entry criteria: population (people using remote measurement technology approaches to aid management of health), intervention (remote measurement technology system), comparison group (no comparison group specified), outcomes (qualitative or quantitative evaluation of the barriers to and facilitators of engagement with this system), and study design (randomized controlled trials, feasibility studies, and observational studies). We searched 5 databases (MEDLINE, IEEE Xplore, EMBASE, Web of Science, and the Cochrane Library) for articles published from January 2014 to May 2017. Articles were independently screened by 2 researchers. We extracted study characteristics and conducted a content analysis to define emerging themes to synthesize findings. Formal quality assessments were performed to address risk of bias. RESULTS: A total of 33 studies met inclusion criteria, employing quantitative, qualitative, or mixed-methods designs. Studies were conducted in 10 countries, included male and female participants, with ages ranging from 8 to 95 years, and included both active and passive remote monitoring systems for a diverse range of physical and mental health conditions. However, they were relatively short and had small sample sizes, and reporting of usage statistics was inconsistent. Acceptability of remote measurement technology according to the average percentage of time used (64%-86.5%) and dropout rates (0%-44%) was variable. The barriers and facilitators from the content analysis related to health status, perceived utility and value, motivation, convenience and accessibility, and usability. CONCLUSIONS: The results of this review highlight gaps in the design of studies trialing remote measurement technology, including the use of quantitative assessment of usage and acceptability. Several processes that could facilitate engagement with this technology have been identified and may drive the development of more person-focused remote measurement technology. However, these factors need further testing through carefully designed experimental studies. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42017060644; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=60644 (Archived by WebCite at http://www.webcitation.org/70K4mThTr).


Assuntos
Participação do Paciente/métodos , Tecnologia de Sensoriamento Remoto/métodos , Telemedicina/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
8.
Arch Biochem Biophys ; 535(2): 215-26, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23603314

RESUMO

ADP-Glc pyrophosphorylase (AGPase), a rate-limiting enzyme in starch biosynthesis, is controlled by thermostability and allosteric regulation. Previous studies suggested that redox affects turnover number and heat stability of AGPases. Here, we investigated how allostery and redox state affect kinetic mechanisms of the reduced, heat labile and the oxidized, heat stable potato tuber enzymes; the heat labile maize endosperm enzyme and a chimeric maize/potato heat stable enzyme that lacks the cysteine responsible for redox changes. With 3-PGA, all AGPases followed a Theorell-Chance Bi Bi mechanism with ATP binding first and ADP-Glc releasing last. 3-PGA increases the binding affinity for both substrates with little effect on velocity for the maize and MP isoforms. By contrast, 3-PGA increases the velocity and the affinity for G-1-P for the potato enzymes. Redox state does not affect kcat of the two potato isoforms. Without 3-PGA the oxidized potato enzyme exhibits a rapid equilibrium random Bi Bi mechanism with a dead end ternary complex. This fundamental change from rapid, ordered binding with little buildup of intermediates to a mechanism featuring relatively slow, random binding is unique to the oxidized potato tuber enzyme. Finally, ADP-Glc the physiologically relevant product of this enzyme has complex, isoform-specific effects on catalysis.


Assuntos
Glucose-1-Fosfato Adenililtransferase/química , Proteínas de Plantas/química , Regulação Alostérica , Endosperma/enzimologia , Ativação Enzimática , Ativadores de Enzimas/química , Estabilidade Enzimática , Glucose-1-Fosfato Adenililtransferase/genética , Ácidos Glicéricos/química , Temperatura Alta , Cinética , Oxirredução , Fosfatos/química , Proteínas de Plantas/genética , Tubérculos/enzimologia , Subunidades Proteicas/química , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Solanum tuberosum/enzimologia , Zea mays/enzimologia
9.
Compr Psychiatry ; 54(1): 41-5, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22534033

RESUMO

OBJECTIVE AND METHODS: The Work and Social Adjustment Scale (WSAS) assesses patients' perceptions of impairment in everyday functioning and has been reported as a simple and reliable self-report measure in different psychiatric disorders. This study compared WSAS data from an anorexia nervosa (AN) patient group with that from healthy controls (HCs) and published data from other patient groups. A total of 160 female participants (AN, 77; HC, 83) completed the WSAS as well as measures of eating disorder symptom severity and brief assessments of anxiety and depression. RESULTS: Work and Social Adjustment Scale scores for the AN group were found to be in the severely impaired range, whereas the scores for those within the HC group indicated very little, or no impairment. Total WSAS scores in the AN group were significantly correlated with severity of clinical symptoms, and eating disorder-specific symptoms were the best predictor of social and occupational functional impairment. The greatest impairment in the AN group was reported in the realm of social leisure. CONCLUSIONS: Consistent with reports in other clinical populations, it is suggested that the WSAS could be an extremely useful and meaningful measure to assess social and occupational functioning in people with eating disorders, in addition to eating disorder-specific assessments.


Assuntos
Anorexia Nervosa/psicologia , Emprego/psicologia , Ajustamento Social , Trabalho/psicologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Relações Interpessoais , Atividades de Lazer , Autorrelato , Inquéritos e Questionários , Adulto Jovem
10.
Am J Cardiol ; 193: 70-74, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36878055

RESUMO

ß-blockers are commonly used in heart failure with preserved ejection fraction (HFpEF), even in the absence of a compelling indication and despite the potential to cause harm. Identifying reasons for ß-blocker prescription in HFpEF could permit the development of strategies to reduce unnecessary use and potentially improve medication prescribing patterns in this vulnerable population. We administered an online survey regarding ß-blocker prescribing behavior to physicians trained in internal medicine or geriatrics (noncardiology physicians) and to cardiologists at 2 large academic medical centers. The survey assessed the reasons for ß-blocker initiation, agreement regarding initiation and/or continuation of ß-blockers by another clinician, and deprescribing behavior. The response rate was 28.2% (n = 231). Among respondents, 68.2% reported initiating ß-blockers in patients with HFpEF. The most common reason for initiating a ß-blocker was for treatment of an atrial arrhythmia. Notably, 23.7% of physicians reported initiating a ß-blocker without an evidence-based indication. When a ß-blocker was considered not necessary, 40.1% of physicians reported they were rarely or never willing to deprescribe. The most common reason for not deprescribing a ß-blocker when the physician felt that a ß-blocker was unnecessary was the concern about interfering with another physicians' treatment plan (76.6%). In conclusion, a significant proportion of noncardiology physicians and cardiologists report prescribing ß-blockers to patients with HFpEF, even when evidence-based indications are absent, and rarely deprescribe ß-blockers in these scenarios.


Assuntos
Cardiologistas , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico/fisiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Prescrições de Medicamentos
11.
Biology (Basel) ; 12(11)2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37998020

RESUMO

The three most important commercial bacterial insecticides are all derived from subspecies of Bacillus thuringiensis (Bt). Specifically, Bt subsp. kurstaki (Btk) and Bt subsp. aizawai (Bta) are used to control larval lepidopteran pests. The third, Bt subsp. israelensis (Bti), is primarily used to control mosquito and blackfly larvae. All three subspecies produce a parasporal body (PB) during sporulation. The PB is composed of insecticidal proteins that damage the midgut epithelium, initiating a complex process that results in the death of the insect. Among these three subspecies of Bt, Bti is unique as it produces the most complex PB consisting of three compartments. Each compartment is bound by a multilaminar fibrous matrix (MFM). Two compartments contain one protein each, Cry11Aa1 and Cyt1Aa1, while the third contains two, Cry4Aa1/Cry4Ba1. Each compartment is packaged independently before coalescing into the mature spherical PB held together by additional layers of the MFM. This distinctive packaging process is unparalleled among known bacterial organelles, although the underlying molecular biology is yet to be determined. Here, we present structural and molecular evidence that the MFM has a hexagonal pattern to which Bti proteins Bt152 and Bt075 bind. Bt152 binds to a defined spot on the MFM during the development of each compartment, yet its function remains unknown. Bt075 appears to be derived from a bacteriophage major capsid protein (MCP), and though its sequence has markedly diverged, it shares striking 3-D structural similarity to the Escherichia coli phage HK97 Head 1 capsid protein. Both proteins are encoded on Bti's pBtoxis plasmid. Additionally, we have also identified a six-amino acid motif that appears to be part of a novel molecular process responsible for targeting the Cry and Cyt proteins to their cytoplasmic compartments. This paper describes several previously unknown features of the Bti organelle, representing a first step to understanding the biology of a unique process of sorting and packaging of proteins into PBs. The insights from this research suggest a potential for future applications in nanotechnology.

12.
Integr Org Biol ; 3(1): obab012, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805747

RESUMO

As a muscular hydrostat, the tongue undergoes complex deformations during most oral behaviors, including chewing and drinking. During thesebehaviors, deformations occur in concert with tongue and jaw movements to position and transport the bolus. Moreover, the various parts of the tongue may move and deform at similar timepoints relative to the gape cycle or they may occur at different timepoints, indicating regional biomechanical and functional variation. The goal of this study is to quantify tongue deformations during chewing and drinking in pigs by characterizing intrinsic changes in tongue dimensions (i.e., length and width) across multiple regions simultaneously. Tongue deformations are generally larger during chewing cycles compared to drinking cycles. Chewing and drinking also differ in the timing, relative to the gape cycle, of regional length and width, but not total length, deformations. This demonstrates functional differences in the temporal dynamics of localized shape changes, whereas the global properties of jaw-tongue coordination are maintained. Finally, differences in the trade-off between length and width deformations demonstrate that the properties of a muscular hydrostat are observed at the whole tongue level, but biomechanical variation (e.g., changes in movements and deformations) at the regional level exists. This study provides new critical insights into the regional contributions to tongue deformations as a basis for future work on multidimensional shape changes in soft tissues.


En tant qu'hydrostat musculaire, la langue subit des déformations complexes pendant la plupart des comportements oraux, en particulier au cours de la mastication et de l'ingestion de liquide. Au cours de ces comportements, les déformations se produisent de concert avec les mouvements de la langue et des mâchoires pour positionner et transporter le bolus. De plus, les différentes parties de la langue peuvent se déplacer et se déformer à des moments similaires ou différents par rapport au cycle d'ouverture de la bouche, indiquant une variation biomécanique et fonctionnelle régionale de la langue. L'objectif de cette étude est de quantifier les déformations de la langue pendant la mastication et l'ingestion d'eau chez le porc en caractérisant les changements intrinsèques des dimensions de la langue (i.e., longueur et largeur) des différentes régions de la langue simultanément. Les déformations de la langue sont généralement plus importantes pendant les cycles de mastication que pendant les cycles d'ingestion d'eau. La mastication et l'ingestion d'eau diffèrent également dans le timing (par rapport au cycle d'ouverture de la bouche) des déformations régionales de la langue en longueur et en largeur, mais pas en longueur totale. Cela démontre des différences fonctionnelles dans la dynamique temporelle des changements localisés de la forme de la langue alors que les propriétés globales de la coordination mâchoire-langue sont maintenues. Enfin, les différences dans le compromis mettant en jeu les déformations en longueur et en largeur démontrent que les propriétés d'un hydrostat musculaire sont observées au niveau de la langue entière, mais qu'il existe une variation biomécanique (par exemple, des changements dans les mouvements et les déformations) au niveau régional. Cette étude fournit de nouvelles informations essentielles sur les contributions régionales des déformations de la langue, qui serviront de base aux travaux futurs sur les changements multidimensionnels de forme dans les tissus mous.

13.
Front Public Health ; 9: 781572, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35155345

RESUMO

BACKGROUND: Construction work offers women economic advancement and self-fulfillment opportunities, but multiple barriers prevent their increased representation in the industry. This study used qualitative methods to identity key physical and psychosocial safety hazards affecting tradeswomen. METHODS: Three focus groups were held in 2015 with 19 tradeswomen in Washington State. Groups discussed workplace hazards and solutions to make the trades safer for women. Discussions were recorded, transcribed, and two independent reviewers analyzed themes. RESULTS: Participants identified myriad physical and psychosocial hazards including a dangerous work environment, inadequate personal protective equipment, gender discrimination, and fear of layoff for reporting concerns. Participants identified mentorship as a potential intervention to overcome some of these barriers. CONCLUSION: Findings suggest that the industry's work environment can be hostile and unsupportive for women, contributing to tradeswomen's injury risk and psychological distress. Future research and interventions should focus on understanding the relationships between and mediating the negative impact of women's physical and psychosocial workplace hazards. Results from these focus groups inspired a randomized control trial to study the impact mentorship has on decreasing physical and psychosocial hazards for women in construction, and improving retention.


Assuntos
Saúde Ocupacional , Feminino , Grupos Focais , Humanos , Washington , Local de Trabalho
14.
Cancer Immunol Res ; 9(7): 765-778, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33839688

RESUMO

The mechanisms behind the antitumor effects of exercise training (ExTr) are not fully understood. Using mouse models of established breast cancer, we examined here the causal role of CD8+ T cells in the benefit acquired from ExTr in tumor control, as well as the ability of ExTr to improve immunotherapy responses. We implanted E0771, EMT6, MMTV-PyMT, and MCa-M3C breast cancer cells orthotopically in wild-type or Cxcr3-/- female mice and initiated intensity-controlled ExTr sessions when tumors reached approximately 100 mm3 We characterized the tumor microenvironment (TME) using flow cytometry, transcriptome analysis, proteome array, ELISA, and immunohistochemistry. We used antibodies against CD8+ T cells for cell depletion. Treatment with immune checkpoint blockade (ICB) consisted of anti-PD-1 alone or in combination with anti-CTLA-4. ExTr delayed tumor growth and induced vessel normalization, demonstrated by increased pericyte coverage and perfusion and by decreased hypoxia. ExTr boosted CD8+ T-cell infiltration, with enhanced effector function. CD8+ T-cell depletion prevented the antitumor effect of ExTr. The recruitment of CD8+ T cells and the antitumor effects of ExTr were abrogated in Cxcr3-/- mice, supporting the causal role of the CXCL9/CXCL11-CXCR3 pathway. ExTr also sensitized ICB-refractory breast cancers to treatment. Our results indicate that ExTr can normalize the tumor vasculature, reprogram the immune TME, and enhance the antitumor activity mediated by CD8+ T cells via CXCR3, boosting ICB responses. Our findings and mechanistic insights provide a rationale for the clinical translation of ExTr to improve immunotherapy of breast cancer.


Assuntos
Neoplasias da Mama/terapia , Linfócitos T CD8-Positivos/imunologia , Terapia por Exercício , Inibidores de Checkpoint Imunológico/farmacologia , Receptores CXCR3/metabolismo , Animais , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linhagem Celular Tumoral , Quimiocina CXCL11/metabolismo , Quimiocina CXCL9/metabolismo , Terapia Combinada/métodos , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/imunologia , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Camundongos , Camundongos Knockout , Condicionamento Físico Animal , Receptores CXCR3/genética , Transdução de Sinais/imunologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
15.
J Appl Physiol (1985) ; 128(4): 941-951, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32191597

RESUMO

During chewing, movements and deformations of the tongue are coordinated with jaw movements to manage and manipulate the bolus and avoid injury. Individuals with injuries to the lingual nerve report both tongue injuries due to biting and difficulties in chewing, primarily because of impaired bolus management, suggesting that jaw-tongue coordination relies on intact lingual afferents. Here, we investigate how unilateral lingual nerve (LN) transection affects jaw-tongue coordination in an animal model (pig, Sus scrofa). Temporal coordination between jaw pitch (opening-closing) and 1) anteroposterior tongue position (i.e., protraction-retraction), 2) anteroposterior tongue length, and 3) mediolateral tongue width was compared between pre- and post-LN transection using cross-correlation analyses. Overall, following LN transection, the lag between jaw pitch and the majority of tongue kinematics decreased significantly, demonstrating that sensory loss from the tongue alters jaw-tongue coordination. In addition, decrease in jaw-tongue lag suggests that, following LN transection, tongue movements and deformations occur earlier in the gape cycle than when the lingual sensory afferents are intact. If the velocity of tongue movements and deformations remains constant, earlier occurrence can reflect less pronounced movements, possibly to avoid injuries. The results of this study demonstrate that lingual afferents participate in chewing by assisting with coordinating the timing of jaw and tongue movements. The observed changes may affect bolus management performance and/or may represent protective strategies because of altered somatosensory awareness of the tongue.NEW & NOTEWORTHY Chewing requires coordination between tongue and jaw movements. We compared the coordination of tongue movements and deformation relative to jaw opening-closing movements pre- and post-lingual nerve transection during chewing in pigs. These experiments reveal that the timing of jaw-tongue coordination is altered following unilateral disruption of sensory information from the tongue. Therefore, maintenance of jaw-tongue coordination requires bilateral sensory information from the tongue.


Assuntos
Traumatismos do Nervo Lingual , Mastigação , Animais , Eletromiografia , Arcada Osseodentária , Movimento , Suínos , Língua
16.
PLoS One ; 15(2): e0228619, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32032365

RESUMO

Chewing is a rhythmic oral behavior that requires constant modifications of jaw movements in response to changes in food properties. The food-specific kinematic response is dependent on the potential for kinematic flexibility allowed by morphology and modulation of motor control. This study investigates the effects of food toughness and stiffness on the amplitude and variability of jaw movements during chewing in a typical omnivorous mammalian model (pigs). Jaw movements were reconstructed using X-ray Reconstruction Of Moving Morphology (XROMM) and kinematic data associated with the amplitude of jaw pitch (opening-closing) and jaw yaw (mediolateral rotation) were extracted for each cycle. Between-food differences were tested for the amplitude of jaw movements during each phase of the gape cycle, as well as in their respective within-food variability, or stereotypy, as indicated by coefficients of variation. With increasing toughness, jaw pitch amplitude is decreased during fast close, larger and more stereotyped during slow close, smaller but more variable during slow open, and more variable during fast open. In addition, when chewing on tougher foods, the amplitude of jaw yaw during slow close only increases in a subset of individuals, but all become less variable (i.e., more stereotyped). In contrast, increasing food stiffness has no effect on the amplitude or the variability of jaw pitch, whereas jaw yaw increases significantly in the majority of individuals studied. Our data demonstrate that food stiffness and toughness both play a role in modulating gape cycle dynamics by altering the trajectory of jaw movements, especially during the slow-close phase and tooth-food-tooth contact, albeit differently. This highlights how a generalist oral morphology such as that of pigs (e.g., bunodont teeth lacking precise occlusion, permissive temporomandibular joint allowing extensive condylar displacements in 3 dimensions) enables organisms to not only adjust chewing movements in their amplitude, but also in their variability.


Assuntos
Ração Animal , Arcada Osseodentária/fisiologia , Mastigação , Suínos/fisiologia , Animais , Fenômenos Biomecânicos , Comportamento Alimentar , Movimento , Dente/fisiologia
17.
JMIR Mhealth Uhealth ; 8(6): e15086, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32519975

RESUMO

BACKGROUND: Remote measurement technology (RMT), including the use of mobile phone apps and wearable devices, may provide the opportunity for real-world assessment and intervention that will streamline clinical input for years to come. In order to establish the benefits of this approach, we need to operationalize what is expected in terms of a successful measurement. We focused on three clinical long-term conditions where a novel case has been made for the benefits of RMT: major depressive disorder (MDD), multiple sclerosis (MS), and epilepsy. OBJECTIVE: The aim of this study was to conduct a consultation exercise on the clinical end point or outcome measurement priorities for RMT studies, drawing on the experiences of people with chronic health conditions. METHODS: A total of 24 participants (16/24 women, 67%), ranging from 28 to 65 years of age, with a diagnosis of one of three chronic health conditions-MDD, MS, or epilepsy-took part in six focus groups. A systematic thematic analysis was used to extract themes and subthemes of clinical end point or measurement priorities. RESULTS: The views of people with MDD, epilepsy, and MS differed. Each group highlighted unique measurements of importance, relevant to their specific needs. Although there was agreement that remote measurement could be useful for tracking symptoms of illness, some symptoms were specific to the individual groups. Measuring signs of wellness was discussed more by people with MDD than by people with MS and epilepsy. However, overlap did emerge when considering contextual factors, such as life events and availability of support (MDD and epilepsy) as well as ways of coping (epilepsy and MS). CONCLUSIONS: This is a unique study that puts patients' views at the forefront of the design of a clinical study employing novel digital resources. In all cases, measuring symptom severity is key; people want to know when their health is getting worse. Second, symptom severity needs to be placed into context. A holistic approach that, in some cases, considers signs of wellness as well as illness, should be the aim of studies employing RMT to understand the health of people with chronic conditions.


Assuntos
Transtorno Depressivo Maior , Aplicativos Móveis , Doença Crônica , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/terapia , Exercício Físico , Feminino , Humanos , Tecnologia
18.
Plant Biotechnol J ; 7(8): 733-43, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19702647

RESUMO

The texture of maize (Zea mays L.) seeds is important to seed processing properties, and soft dent maize is preferred for both wet-milling and livestock feed applications. The puroindoline genes (Pina and Pinb) are the functional components of the wheat (Triticum aestivum L.) Hardness locus and together function to create soft grain texture in wheat. The PINs (PINA and PINB) are believed to act by binding to lipids on the surface of starch granules, preventing tight adhesion between starch granules and the surrounding protein matrix during seed maturation. Here, maize kernel structure and wet milling properties were successfully modified by the endosperm-specific expression of wheat Pins (Pina and Pinb). Pins were introduced into maize under the control of a maize gamma-Zein promoter. Three Pina/Pinb expression positive transgenic lines were evaluated over two growing seasons. Textural analysis of the maize seeds indicated that the expression of PINs decreased adhesion between starch and protein matrix and reduced maize grain hardness significantly. Reduction in pressure required to fracture kernels ranged from 15.65% to 36.86% compared with control seeds. Further, the PINs transgenic maize seeds had increased levels of extractable starch as characterized by a small scale wet milling method. Starch yield was increased by 4.86% on average without negatively impacting starch purity. The development of softer maize hybrids with higher starch extractability would be of value to maize processors.


Assuntos
Proteínas de Plantas/metabolismo , Sementes/metabolismo , Amido/metabolismo , Triticum/genética , Zea mays/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Regiões Promotoras Genéticas , Sementes/genética , Transformação Genética , Zea mays/genética
19.
Arch Oral Biol ; 98: 226-237, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30522042

RESUMO

OBJECTIVE: This study evaluates the effect of unilateral lingual sensory loss on the spatial and temporal dynamics of jaw movements during pig chewing. DESIGN: X-ray Reconstruction of Moving Morphology (XROMM) was used to reconstruct the 3-dimensional jaw movements of 6 pigs during chewing before and after complete unilateral lingual nerve transection. The effect of the transection were evaluated at the temporal and spatial level using Multiple Analysis of Variance. Temporal variables include gape cycle and phase durations, and the corresponding relative phase durations. Spatial variables include the amplitude of jaw opening, jaw yaw, and mandibular retraction-protraction. RESULTS: The temporal and spatial dynamics of jaw movements did not differ when chewing ipsilateral versus contralateral to the transection. When compared to pre-transection data, 4 of the 6 animals showed significant changes in temporal characteristics of the gape cycle following the transection, irrespective of chewing side, but the specific response to the lesion was highly dependent on the animal. On the other hand, in affected individuals the amplitude of jaw movements was altered similarly in all 3 dimensions: jaw opening and protraction-retraction increased whereas jaw yaw decreased. CONCLUSION: The variable impact of this injury in this animal model suggests that individuals use different compensatory strategies to adjust or maintain the temporal dynamics of the gape cycle. Because the amplitude of jaw movements are more adversely affected than their timing, results suggest that maintaining the tongue-jaw coordination is critical and this can come at the expense of bolus handling and masticatory performance.


Assuntos
Arcada Osseodentária/fisiologia , Traumatismos do Nervo Lingual/complicações , Mastigação/fisiologia , Animais , Fenômenos Biomecânicos , Eletromiografia , Mandíbula/fisiologia , Movimento , Suínos
20.
Mult Scler Relat Disord ; 32: 123-132, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31125754

RESUMO

BACKGROUND: Smartphone apps and wearable devices could augment clinical practice by detecting changes in health status for multiple sclerosis (MS). This study sought to investigate potential barriers and facilitators for uptake and sustained use in (i) people with both relapsing remitting MS (RRMS) and progressive MS (PMS) and (ii) across different countries. METHODS: Twenty four participants with MS took part in four focus groups held in three countries (2 in the UK, 1 in Spain, and 1 in Italy) to investigate potential barriers and facilitators for mHealth technology. A systematic thematic analysis was used to extract themes and sub-themes. RESULTS: Facilitators and barriers were organised into functional technology-related factors and non-functional health-related and user-related factors. Twelve themes captured all requirements across the three countries for both RRMS and PMS. Key requirements included accommodation for varying physical abilities, providing information and memory aids. Potential negative effects on mood and providing choice and control as part of overcoming practical challenges were identified. CONCLUSIONS: We took a cross-national perspective and found many similarities between three European countries across people with RRMS and PMS. Future provision should accommodate the key requirements identified to engage people with MS in scalable mHealth interventions.


Assuntos
Diversidade Cultural , Gerenciamento Clínico , Progressão da Doença , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla Recidivante-Remitente/etnologia , Telemedicina/métodos , Adulto , Estudos Transversais , Feminino , Grupos Focais , Humanos , Itália/etnologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/etnologia , Esclerose Múltipla/psicologia , Esclerose Múltipla Recidivante-Remitente/psicologia , Espanha/etnologia , Reino Unido/etnologia
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