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Ciliopathies are associated with wide spectrum of structural birth defects (SBDs), indicating important roles for cilia in development. Here, we provide novel insights into the temporospatial requirement for cilia in SBDs arising from deficiency in Ift140, an intraflagellar transport (IFT) protein regulating ciliogenesis. Ift140-deficient mice exhibit cilia defects accompanied by wide spectrum of SBDs including macrostomia (craniofacial defects), exencephaly, body wall defects, tracheoesophageal fistula (TEF), randomized heart looping, congenital heart defects (CHDs), lung hypoplasia, renal anomalies, and polydactyly. Tamoxifen inducible CAGGCre-ER deletion of a floxed Ift140 allele between E5.5 to 9.5 revealed early requirement for Ift140 in left-right heart looping regulation, mid to late requirement for cardiac outflow septation and alignment, and late requirement for craniofacial development and body wall closure. Surprisingly, CHD were not observed with 4 Cre drivers targeting different lineages essential for heart development, but craniofacial defects and omphalocele were observed with Wnt1-Cre targeting neural crest and Tbx18-Cre targeting epicardial lineage and rostral sclerotome through which trunk neural crest cells migrate. These findings revealed cell autonomous role of cilia in cranial/trunk neural crest-mediated craniofacial and body wall closure defects, while non-cell autonomous multi-lineage interactions underlie CHD pathogenesis, revealing unexpected developmental complexity for CHD associated with ciliopathies.
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Ciliopatias , Cardiopatias Congênitas , Animais , Camundongos , Cílios/metabolismo , Cardiopatias Congênitas/genética , Desenvolvimento Embrionário , Proteínas de Transporte/metabolismo , Crânio , Ciliopatias/genética , Ciliopatias/metabolismo , Ciliopatias/patologiaRESUMO
BACKGROUND: Little prior research focused on person-centred care and support (PCCS) for dementia in home, community or outpatient care. We aimed to describe what constitutes PCCS, how to implement it, and considerations for women who comprise the majority of affected persons (with dementia, carers). METHODS: We conducted a scoping review by searching multiple databases from 2000 inclusive to June 7, 2020. We extracted data on study characteristics and PCCS approaches, evaluation, determinants or the impact of strategies to implement PCCS. We used summary statistics to report data and interpreted findings with an existing person-centred care framework. RESULTS: We included 22 studies with qualitative (55%) or quantitative/multiple methods design (45%) involving affected persons (50%), or healthcare workers (50%). Studies varied in how PCCS was conceptualized; 59% cited a PCC definition or framework. Affected persons and healthcare workers largely agreed on what constitutes PCCS (e.g. foster partnership, promote autonomy, support carers). In 4 studies that evaluated care, barriers of PCCS were reported at the affected person (e.g. family conflict), healthcare worker (e.g. lack of knowledge) and organizational (e.g. resource constraints) levels. Studies that evaluated strategies to implement PCCS approaches were largely targeted to healthcare workers, and showed that in-person inter-professional educational meetings yielded both perceived (e.g. improved engagement of affected persons) and observed (e.g. use of PCCS approaches) beneficial outcomes. Few studies reported results by gender or other intersectional factors, and none revealed if or how to tailor PCCS for women. This synthesis confirmed and elaborated the PCC framework, resulting in a Framework of PCCS for Dementia. CONCLUSION: Despite the paucity of research on PCCS for dementia, synthesis of knowledge from diverse studies into a Framework provides interim guidance for those planning or evaluating dementia services in outpatient, home or community settings. Further research is needed to elaborate the Framework, evaluate PCCS for dementia, explore determinants, and develop strategies to implement and scale-up PCCS approaches. Such studies should explore how to tailor PCCS needs and preferences based on input from persons with dementia, and by sex/gender and other intersectional factors such as ethnicity or culture.
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Demência , Pacientes Ambulatoriais , Demência/terapia , Feminino , Pessoal de Saúde , Humanos , Assistência Centrada no Paciente , AutocuidadoRESUMO
BACKGROUND: Evidence indicates that emotions such as anger are associated with increased incidence of sudden cardiac death, but the biological mechanisms remain unclear. We tested the hypothesis that, in patients with sudden death vulnerability, anger would be associated with arrhythmic vulnerability, indexed by cardiac repolarization instability. METHODS: Patients with coronary artery disease (CAD) and an implantable cardioverter defibrillator (ICD; n = 41) and healthy controls (n = 26) gave an anger-inducing speech (anger recall), rated their current (state) anger, and completed measures of trait (chronic) levels of Anger and Hostility. Repolarization instability was measured using QT Variability Index (QTVI) at resting baseline and during anger recall using continuous ECG. RESULTS: ICD patients had significantly higher QTVI at baseline and during anger recall compared with controls, indicating greater arrhythmic vulnerability overall. QTVI increased from baseline to anger recall to a similar extent in both groups. In ICD patients but not controls, during anger recall, self-rated anger was related to QTVI (r = .44, p = .007). Trait (chronic) Anger Expression (r = .26, p = .04), Anger Control (r = -.26, p = .04), and Hostility (r = .25, p = .05) were each associated with the change in QTVI from baseline to anger recall (ΔQTVI). Moderation analyses evaluated whether psychological trait associations with ΔQTVI were specific to the ICD group. Results indicated that Hostility scores predicted ΔQTVI from baseline to anger recall in ICD patients (ß = 0.07, p = .01), but not in controls. CONCLUSIONS: Anger increases repolarization lability, but in patients with CAD and arrhythmic vulnerability, chronic and acute anger interact to trigger cardiac repolarization lability associated with susceptibility to malignant arrhythmias.
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Desfibriladores Implantáveis , Ira , Arritmias Cardíacas , Morte Súbita Cardíaca , Eletrocardiografia , HumanosRESUMO
BACKGROUND: Assessing the fidelity of an implementation strategy is important to understand why and how the strategy influences the uptake of evidence-based interventions. The present study aims to assess the fidelity of the two procedures for engaging primary care (PC) professionals and for the deployment of an implementation strategy for optimizing type 2 diabetes prevention in routine PC within the PREDIAPS randomized cluster implementation trial. METHOD: We conducted a mixed-method fidelity evaluation study of the PVS-PREDIAPS implementation strategy. Nine PC centers from the Basque Health Service (Osakidetza) were allocated to two different procedures to engage physicians and nurses and deploy a implementation strategy to model and adapt the clinical intervention and its implementation to their specific contexts: a Global procedure, promoting the cooperation of all healthcare professionals from the beginning; or a Sequential procedure, centered first on nurses who then pursued the pragmatic cooperation of physicians. Process indicators of the delivery and receipt of implementation strategy actions, documented modifications to the planned implementation strategy, and a structured group interview with centers' leaders were all used to assess the following components of fidelity: adherence, dose, quality of delivery, professionals' responsiveness and program differentiation. RESULTS: Generally, the procedures compared for professionals engagement and deployment of the implementation strategy were carried out with the planned differentiation. Nonetheless, some unexpected between-group differences were observed, the initial rate of collaboration of nurses being higher in the Sequential (93%) than in the Global (67%) groups. Exposure rate to the programed implementation actions (% of hours received out of those delivered) were similar in both groups by professional category, with nurses (86%) having a higher rate of exposure than physicians (75%). Professionals identified half of the planned discrete strategies and their rating of strategies' perceived usefulness was overwhelmingly positive, with few differences between Sequential and Global centers. CONCLUSIONS: The PVS-PREDIAPS implementation strategy has been implemented with high fidelity and minor unplanned reactive modifications. Professionals' exposure to the implementation strategy was high in both groups. The centers' organizational context (i.e., work overload) led to small mismatches between groups in participation and exposure of professionals to implementation actions. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03254979 . Registered 16 August 2017.
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Diabetes Mellitus Tipo 2 , Médicos , Diabetes Mellitus Tipo 2/prevenção & controle , Pessoal de Saúde , Humanos , Atenção Primária à Saúde , Projetos de PesquisaRESUMO
Craniofacial development relies on coordinated tissue interactions that allow for patterning and growth of the face. We know a priori that the Wingless, fibroblast growth factor, Hedgehog and transforming growth factor-beta growth factor signaling pathways are required for the development of the face, but how they contribute to the shape of the face is largely untested. Here, we test how each signaling pathway contributes to the overall morphology of the zebrafish anterior neurocranium. We tested the contribution of each signaling pathway to the development of the ethmoid plate during three distinct time periods: the time of neural crest migration [10 hour post fertilization (hpf)]; once the neural crest is resident in the face (20 hpf); and finally at the time at which the cartilaginous condensations are being initiated (48 hpf). Using geometric morphometric analysis, we conclude that each signaling pathway contributes to the shape, size and morphology of the ethmoid plate in a dose-, and time-dependent fashion.
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Osso Etmoide/embriologia , Osso Etmoide/fisiologia , Fatores de Crescimento de Fibroblastos/fisiologia , Transdução de Sinais/fisiologia , Proteínas de Peixe-Zebra/fisiologia , Animais , Movimento Celular/fisiologia , Crista Neural/embriologia , Crista Neural/fisiologia , Peixe-ZebraRESUMO
BACKGROUND: Myofascial pain syndrome (MPS) of the shoulder girdle and cervical region is a common musculoskeletal problem that is often chronic or recurrent. Physical therapy (PT) and lidocaine injections (LI) are two treatments with demonstrated effectiveness compared to a control group, however little is known about their combined value. The objective of this study was to determine whether LI into trigger points combined with a PT program would be more effective than each separate treatment alone in improving pain, function, and quality of life in a group of patients with MPS of the shoulder girdle and cervical region. METHODS: A single-blind, randomized, controlled clinical trial (RCT) was conducted with three parallel groups in the Departments of Physical Medicine and Rehabilitation of two urban hospitals in Medellin, Colombia. One hundred and twenty seven patients with shoulder girdle MPS for more than 6 weeks and pain greater than 40 mm on the visual analog scale (VAS) were assigned to 1 of 3 intervention groups: PT, LI, or the combination of both (PT + LI). The primary outcome was VAS pain rating at 1-month post-treatment. The secondary outcomes included VAS pain rating at 3 months, and, at both 1 and 3 months post-treatment: (a) function, evaluated by hand-back maneuver and the hand-mouth maneuver, (b) quality of life, as measured by sub-scales of the Short Form - 36 (SF-36), and (c) depressive symptoms, as measured by the Patient Health Questionnaire - 9 (PHQ-9). Independent t-tests were used to compare outcomes between groups at 1 month and 3 months post-treatment. RESULTS: In the per protocol analysis, there were no significant intergroup differences in VAS at 1 month PT + LI, 40.8 [25.3] vs. PT, 37.8 [21.9], p = 0.560 and vs. LI, 44.2 [24.9], p = 0.545. There were also no differences between groups on secondary outcomes except that the PT and PT + LI groups had higher right upper limb hand-back maneuver scores compared to the LI alone group at both 1 and 3 months (p = 0.013 and p = 0.016 respectively). CONCLUSIONS: The results of this RCT showed that no differences in pain ratings were observed between the individual treatments (PT or LI) compared to the combined treatment of PT and LI. In general, no difference in primary or secondary outcomes was observed between treatments. TRIAL REGISTRATION: NTC01250184 November 27, 2010.
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Lidocaína/administração & dosagem , Síndromes da Dor Miofascial/diagnóstico , Síndromes da Dor Miofascial/terapia , Modalidades de Fisioterapia , Dor de Ombro/diagnóstico , Dor de Ombro/terapia , Adulto , Terapia Combinada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes da Dor Miofascial/epidemiologia , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Dor de Ombro/epidemiologia , Método Simples-Cego , Resultado do Tratamento , Pontos-Gatilho/patologiaRESUMO
BACKGROUND: Major depression is an independent predictor of increased mortality in patients presenting with acute coronary syndromes (ACS). There have been several mechanisms proposed to explain the link between depression and ischemic heart disease. Both abnormal platelet physiology and inflammation have been suggested as potential confounding variables. OBJECTIVE: We set out to examine platelet activation, inflammation, and levels of depression in hospitalized patients presenting with ACS. METHODS: We enrolled 28 patients with ACS and assessed levels of depression by PHQ-9. Platelet activation was assessed by the measurement of platelet microparticle levels and platelet aggregation to adenosine diphosphate and serotonin. Inflammatory markers were assessed by the measurement of TNF alpha, IL-6, and CRP. RESULTS: We found that ACS patients with moderate depressive symptoms who had higher TNF alpha, IL-6, and CRP levels had higher levels of platelet microparticles. We also found that ACS patients with PHQ-9 ≥ 10 had higher platelet aggregation to ADP. CONCLUSION: Our results suggest that patients hospitalized for the treatment of an ACS who have moderate depression have increased platelet aggregation. These patients also have a positive association between elevated inflammatory markers and platelet activation, thus suggesting a pro-inflammatory component in ACS patients with depressive symptoms that may alter platelet function. These results are intriguing in that a potential pathway to explain the connection between depression, inflammation, and increased cardiovascular thrombosis might be found when both platelet activation and inflammation are measured.
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Síndrome Coronariana Aguda/sangue , Proteína C-Reativa/imunologia , Micropartículas Derivadas de Células , Depressão/sangue , Interleucina-6/imunologia , Fator de Necrose Tumoral alfa/imunologia , Síndrome Coronariana Aguda/imunologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Plaquetas , Depressão/imunologia , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Ativação PlaquetáriaRESUMO
Olfactory ensheathing cells (OECs) are a unique class of glial cells with exceptional translational potential because of their ability to support axon regeneration in the central nervous system. Although OECs are similar in many ways to immature and nonmyelinating Schwann cells, and can myelinate large-diameter axons indistinguishably from myelination by Schwann cells, current dogma holds that OECs arise from the olfactory epithelium. Here, using fate-mapping techniques in chicken embryos and genetic lineage tracing in mice, we show that OECs in fact originate from the neural crest and hence share a common developmental heritage with Schwann cells. This explains the similarities between OECs and Schwann cells and overturns the existing dogma on the developmental origin of OECs. Because neural crest stem cells persist in adult tissue, including skin and hair follicles, our results also raise the possibility that patient-derived neural crest stem cells could in the future provide an abundant and accessible source of autologous OECs for cell transplantation therapy for the injured central nervous system.
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Linhagem da Célula , Crista Neural/citologia , Neuroglia/citologia , Mucosa Olfatória/citologia , Animais , Transplante de Células , Embrião de Galinha , Técnicas Citológicas , Humanos , Camundongos , Medicina Regenerativa/métodos , Células de SchwannRESUMO
Ciliopathies are associated with wide spectrum of structural birth defects (SBD), indicating important roles for cilia in development. Here we provide novel insights into the temporospatial requirement for cilia in SBDs arising from deficiency in Ift140 , an intraflagellar transport protein regulating ciliogenesis. Ift140 deficient mice exhibit cilia defects accompanied by wide spectrum of SBDs including macrostomia (craniofacial defects), exencephaly, body wall defects, tracheoesophageal fistula, randomized heart looping, congenital heart defects (CHD), lung hypoplasia, renal anomalies, and polydactyly. Tamoxifen inducible CAG-Cre deletion of a floxed Ift140 allele between E5.5 to 9.5 revealed early requirement for Ift140 in left-right heart looping regulation, mid to late requirement for cardiac outflow septation and alignment, and late requirement for craniofacial development and body wall closure. Surprisingly, CHD was not observed with four Cre drivers targeting different lineages essential for heart development, but craniofacial defects and omphalocele were observed with Wnt1-Cre targeting neural crest and Tbx18-Cre targeting epicardial lineage and rostral sclerotome through which trunk neural crest cells migrate. These findings revealed cell autonomous role of cilia in cranial/trunk neural crest mediated craniofacial and body wall closure defects, while non-cell autonomous multi-lineage interactions underlie CHD pathogenesis, revealing unexpected developmental complexity for CHD associated with ciliopathy.
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The cranial vault in humans is highly variable, clinically relevant, and heritable, yet its genetic architecture remains poorly understood. Here, we conduct a joint multi-ancestry and admixed multivariate genome-wide association study on 3D cranial vault shape extracted from magnetic resonance images of 6772 children from the ABCD study cohort yielding 30 genome-wide significant loci. Follow-up analyses indicate that these loci overlap with genomic risk loci for sagittal craniosynostosis, show elevated activity cranial neural crest cells, are enriched for processes related to skeletal development, and are shared with the face and brain. We present supporting evidence of regional localization for several of the identified genes based on expression patterns in the cranial vault bones of E15.5 mice. Overall, our study provides a comprehensive overview of the genetics underlying normal-range cranial vault shape and its relevance for understanding modern human craniofacial diversity and the etiology of congenital malformations.
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Craniossinostoses , Estudo de Associação Genômica Ampla , Criança , Humanos , Animais , Camundongos , Crânio/diagnóstico por imagem , Craniossinostoses/genética , Ossos Faciais , Encéfalo/diagnóstico por imagemRESUMO
Purpose of Review: Preparing for pandemics requires a degree of interdisciplinary work that is challenging under the current paradigm. This review summarizes the challenges faced by the field of pandemic science and proposes how to address them. Recent Findings: The structure of current siloed systems of research organizations hinders effective interdisciplinary pandemic research. Moreover, effective pandemic preparedness requires stakeholders in public policy and health to interact and integrate new findings rapidly, relying on a robust, responsive, and productive research domain. Neither of these requirements are well supported under the current system. Summary: We propose a new paradigm for pandemic preparedness wherein interdisciplinary research and close collaboration with public policy and health practitioners can improve our ability to prevent, detect, and treat pandemics through tighter integration among domains, rapid and accurate integration, and translation of science to public policy, outreach and education, and improved venues and incentives for sustainable and robust interdisciplinary work.
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OBJECTIVE: Insufficient levels of physical activity are a well-known modifiable risk factor for a number of chronic conditions including obesity, type 2 diabetes, cardiovascular diseases and certain malignancies. Little is known about the status of physical activity and its associated factors among adults in low-income countries, including Ethiopia. Therefore, this study aimed to assess the level of physical activity and its associated factors among adults in southeast Ethiopia. DESIGN: Analytical cross-sectional study. SETTING: Community setting in southeast Ethiopia. PARTICIPANTS: 641 adults aged 18-64 years. PRIMARY OUTCOME: Level of physical activity assessed via the Global Physical Activity Questionnaire (GPAQ). RESULTS: The overall prevalence of insufficient physical activity in this study was 29.48% (95% CI: 25.78 to 33.18). Women were more likely to report insufficient physical activity compared with men (39.0% for women and 12.3% for men, p<0.001). Being: a women (adjusted OR (AOR)=3.99, 95% CI: 2.15 to 7.40)), overweight/obese (AOR=1.95, 95% CI: 1.23 to 3.09), ever-married (AOR=2.13, 95% CI: 1.01 to 4.47), a person with no formal education (AOR=1.94, 95% CI: 1.05 to 3.56), a housewife (AOR=3.04, 95% CI: 1.75 to 5.29) and unemployed (AOR=3.30, 95% CI: 1.55 to 7.02) were significantly associated with insufficient physical activity. CONCLUSION: The study revealed that three in 10 adults did not achieve the recommended level of physical activity. For chronic disease prevention in Ethiopia, the Ethiopian Ministry of Health and other stakeholders should pay special attention to strategies to improve the population's physical activity especially among women, housewives, people with no formal education, and married, unemployed and overweight/obese adults.
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Diabetes Mellitus Tipo 2 , Sobrepeso , Adulto , Masculino , Humanos , Feminino , Estudos Transversais , Sobrepeso/epidemiologia , Sobrepeso/complicações , Etiópia/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Exercício Físico , Obesidade/epidemiologia , Obesidade/complicaçõesRESUMO
BACKGROUND: Obesity and overweight are known public health problems that affect populations across the world. These conditions have been associated with a wide range of chronic diseases including type 2 diabetes mellitus, cardiovascular disease, and cancers. In Ethiopia, the literature regarding the burden of central (abdominal) obesity is scarce. This study aimed to fill this gap by assessing the prevalence and risk factors associated with central obesity among adults in Ethiopia. METHODS: From May to July 2021, a community-based cross-sectional survey was conducted on a sample of 694 adults aged ≥18 years in administrative towns of Bale zone, Southeast Ethiopia. Multi-stage sampling followed by systematic random sampling was employed to identify study participants. Waist and hip circumferences were measured using standard protocols. The World Health Organization STEPS wise tool was used to assess risk factors associated with central obesity. Bi-variable and multi-variable binary logistic regression were used to identify factors associated with central obesity. Adjusted odds ratios (AOR) and their corresponding 95% confidence intervals (CI) have been reported to estimate the strength of associations. RESULTS: The overall prevalence of central obesity using waist circumference was 39.01% [(95% CI: 35.36-42.76; 15.44% for men and 53.12% for women)]. Multi-variable binary logistic regression analysis revealed that female sex (AOR = 12.93, 95% CI: 6.74-24.79), Age groups: 30-39 years old (AOR = 2.8, 95% CI: 1.59-4.94), 40-49 years (AOR = 7.66, 95% CI: 3.87-15.15), 50-59 years (AOR = 4.65, 95% CI: 2.19-9.89), ≥60 years (AOR = 12.67, 95% CI: 5.46-29.39), occupational status like: housewives (AOR = 5.21, 95% CI: 1.85-14.62), self-employed workers (AOR = 4.63, 95% CI: 1.62-13.24), government/private/non-government employees (AOR = 4.68, 95% CI: 1.47-14.88), and skipping breakfast (AOR = 0.46, 95% CI: 0.23-0.9) were significantly associated with central obesity. CONCLUSIONS: Abdominal obesity has become an epidemic in Bale Zone's towns in Southeastern Ethiopia. Female sex, age, being employed were positively associated with central obesity, while skipping breakfast was a protective factor.
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Diabetes Mellitus Tipo 2 , Obesidade Abdominal , Adolescente , Adulto , Estudos Transversais , Etiópia/epidemiologia , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Obesidade Abdominal/epidemiologia , Prevalência , Fatores de RiscoRESUMO
The vertebrate head is an extremely complicated structure: development of the head requires tissue-tissue interactions between derivates of all the germ layers and coordinated morphogenetic movements in three dimensions. In this review, we highlight a number of recent embryological studies, using chicken, frog, zebrafish and mouse, which have identified crucial signaling centers in the embryonic face. These studies demonstrate how small variations in growth factor signaling can lead to a diversity of phenotypic outcomes. We also discuss novel genetic studies, in human, mouse and zebrafish, which describe cell biological mechanisms fundamental to the growth and morphogenesis of the craniofacial skeleton. Together, these findings underscore the complex interactions leading to species-specific morphology. These and future studies will improve our understanding of the genetic and environmental influences underlying human craniofacial anomalies.
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Ossos Faciais/embriologia , Crânio/embriologia , Animais , HumanosRESUMO
BACKGROUND: Person-Centered Care (PCC) is a promising approach towards improved quality of care and cost containment within health systems. It has been evaluated in Sweden and England. This feasibility study examines initial PCC implementation in a rehabilitation hospital for children in Poland. METHODS: The WE-CARE Roadmap of enablers was used to guide implementation of PCC for patients with moderate scoliosis. A multi-disciplinary team of professionals were trained in the PCC approach and the hospital Information Technology (IT) system was modified to enhance PCC data capture. Semi-structured interviews were conducted with the nine health care professionals involved in the pilot study and three patients/parents receiving care. Transcribed data were analyzed via content analysis. RESULTS: 51 patients and their families were treated via a PCC approach. High proportions of new PCC data fields were completed by the professionals. The professionals were able to implement the three core PCC routines and perceived benefits using the PCC approach. Patients and their families also perceived improved quality care. The WE-CARE framework enablers facilitated PCC implementation in this setting. CONCLUSIONS: This feasibility pilot study indicates that the Gothenburg PCC approach can be successfully transferred to a rehabilitation hospital in Poland with favorable perceptions of implementation by both professionals and patients/their families.
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Assistência Centrada no Paciente , Criança , Inglaterra , Estudos de Viabilidade , Humanos , Projetos Piloto , Polônia , SuéciaRESUMO
The expansion and growth of the endochondral skeleton requires organized cell behaviors that control chondrocyte maturation and oriented division. In other organs, these processes are accomplished through Wnt/planar cell polarity (Wnt/PCP) signaling pathway and require the protein-protein interactions of core components including Prickle1 (PK1) and Dishevelled (DVL). To determine the function of Wnt/PCP signaling in endochondral ossification of the cranial base and limb, we utilized the Prickle1Beetlejuice (Pk1Bj ) mouse line. The Pk1Bj allele has a missense mutation in the PK1 LIM1 domain that results in a hypomorphic protein. Similar to human patients with Robinow syndrome, the Prickle1Bj/Bj mouse mutants lack growth plate expansion resulting in shorter limbs and midfacial hypoplasia. Within the Prickle1Bj/Bj limb and cranial base growth plates we observe precocious maturation of chondrocytes and stalling of terminal differentiation. Intriguingly, we observed that the growth plate chondrocytes have randomized polarity based on the location of the primary cilia and the location of PRICKLE1, DVL2, and DVL3 localization. Importantly, mutant PK1Bj protein has decreased protein-protein interactions with both DVL2 and DVL3 in chondrocytes as revealed by in vivo co-immunoprecipitation and proximity ligation assays. Finally, we propose a model where the interaction between the Prickle1 LIM1 domain and DVL2 and DVL3 contributes to chondrocyte polarity and contributes to proximal-distal outgrowth of endochondral elements. © 2021 American Society for Bone and Mineral Research (ASBMR).
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Condrócitos , Osteogênese , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Polaridade Celular , Condrócitos/metabolismo , Proteínas Desgrenhadas , Lâmina de Crescimento/metabolismo , Humanos , Proteínas com Domínio LIM/genética , Proteínas com Domínio LIM/metabolismo , Camundongos , Proteínas Supressoras de Tumor , Via de Sinalização WntRESUMO
Primary care is especially well positioned to address prevention of non-communicable diseases. However, implementation of health promotion activities such as personalized dietary advice is challenging. The study aim was to understand barriers and facilitators of the personalized dietary advice component of a lifestyle intervention in primary care, as perceived by health center professionals and program participants. Thirteen focus groups were conducted with 49 professionals and 47 participants. Audio recordings were transcribed. Professional group text was coded using the Consolidated Framework for Implementation Research (CFIR). Participant group text was coded via an inductive approach with thematic analysis. Across most CFIR domains, both barriers and facilitators were equally present, except for 'characteristics of individuals', which were primarily facilitators. Intervention characteristics was the most important domain, with barriers in design and packaging (e.g., the ICT tool) and complexity. Facilitators included high evidence strength and quality, adaptability, and relative advantage. Participants described the importance of more personalized advice, the value of follow-up with feedback, and the need to see outcomes. Both professionals and patients stated that primary care was the place for personalized dietary advice intervention, but that lack of time, workload, and training were barriers to effective implementation. Implementation strategies targeting these modifiable barriers could potentially increase intervention adoption and intervention effectiveness.
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PURPOSE: This study aims to elucidate the health care organization, management and policy barriers and facilitators associated with implementation of an evidence-based health promotion intervention in primary care centers in the Basque Country, Spain. DESIGN/METHODOLOGY/APPROACH: Seven focus groups were conducted with 49 health professionals from six primary care centers participating in the Prescribing Healthy Life program. Text was analyzed using the Consolidated Framework for Implementation Research (CFIR) focusing on those constructs related to health care organization, management and policy. FINDINGS: The health promotion intervention was found to be compatible with the values of primary care professionals. However, professionals at all centers reported barriers to implementation related to: (1) external policy and incentives, (2) compatibility with existing workflow and (3) available resources to carry out the program. Specific barriers in these areas related to lack of financial and political support, consultation time constraints and difficulty managing competing day-to-day demands. Other barriers and facilitators were related to the constructs networks and communication, culture, relative priority and leadership engagement. A set of six specific barrier-facilitator pairs emerged. ORIGINALITY/VALUE: Implementation science and, specifically, the CFIR constructs were used as a guide. Barriers and facilitators related to the implementation of a health promotion program in primary care were identified. Healthcare managers and policy makers can modify these factors to foster a more propitious implementation environment. These factors should be appropriately monitored, both in pre-implementation phases and during the implementation process, in order to ensure effective integration of health promotion into the primary care setting.
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Atenção à Saúde , Atenção Primária à Saúde , Pessoal de Saúde , Promoção da Saúde , Humanos , Pesquisa QualitativaRESUMO
BACKGROUND: Overweight and obesity have become a serious public health problem in both developed and developing countries, particularly in urban areas. However, there are limited studies conducted to identify the risk factors of overweight and obesity in Ethiopia, especially among men. Therefore, this study aimed to assess individual and community level determinants of overweight and obesity among urban men in Ethiopia. METHODS: This study used the 2016 Ethiopian Demographic and Health Survey (EDHS) data. A weighted sample of 2259 urban men aged 15-59 years were included in this analysis. A multilevel logistic regression model was used to assess the determinants of overweight and obesity among the study participants. RESULTS: Men aged 30-44 years old (AOR = 3.1, 95% CI: 2.3-4.11), 45-59 years old (AOR = 4.8, 95% CI: 3.4-6.9), married (AOR = 1.7, 95% CI: 1.3-2.2), with secondary education (AOR = 2.7, 95% CI: 1.6-4.7), with higher education (AOR = 3.6, 95% CI: 2.1-6.2), watching television at least once a week (AOR = 1.7, 95% CI: 1.1-2.7), being from high rich communities (AOR = 2.4, 95% CI: 1.5-3.7), and living in three metropolises (Addis Ababa, Harari, Diredawa) were more likely to be overweight or obese (AOR = 1.8, 95% CI: 1.1-2.9). However, currently unemployed men were less likely to be overweight or obese (AOR = 0.5, 95% CI: 0.3-0.7). CONCLUSION: Being older age, being married, having higher educational status, having higher frequency of watching television, being residents of three metropolises (Addis Ababa, Harari, and Diredawa), and being from high rich communities were found to be predictors of overweight and obesity in Ethiopian men. Therefore, it is essential to design strategies and programs to reduce or prevent overweight and obesity with special focus on the identified risk factors.
Assuntos
Obesidade/epidemiologia , Sobrepeso/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Estudos Transversais , Etiópia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multinível , Fatores Socioeconômicos , População Urbana , Adulto JovemRESUMO
The resilience of health systems has received considerable attention as of late, yet little is known about what a resilience test might look like. We develop a resilience test concept and methodology. We describe key components of a toolkit and a 5-phased approach to implementation of resilience testing that can be adapted to individual health systems. We develop a methodology for a test that is balanced in terms of standardization and system-specific characteristics/needs. We specify how to work with diverse stakeholders from the health ecosystem via participatory processes to assess and identify recommendations for health system strengthening. The proposed resilience test toolkit consists of "what if" adverse scenarios, a menu of health system performance elements and indicators based on an input-output-outcomes framework, a discussion guide for each adverse scenario, and a traffic light scorecard template. The five phases of implementation include Phase 0, a preparatory phase to adapt the toolkit materials; Phase 1: facilitated discussion groups with stakeholders regarding the adverse scenarios; Phase 2: supplemental data collection of relevant quantitative indicators; Phase 3: summarization of results; Phase 4: action planning and health system transformation. The toolkit and 5-phased approach can support countries to test resilience of health systems, and provides a concrete roadmap to its implementation.