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1.
Int J Equity Health ; 23(1): 58, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38491541

RESUMEN

BACKGROUND: The Government of North Macedonia's Primary Health Care reform is committed to leaving no one behind on the path to Universal health Coverage (UHC). During mid-2022 to March 2023, the World Health Organization (WHO) collaborated with the Government and other national stakeholders for an assessment of barriers to effective coverage with health services experienced by adult citizens, with a specific focus on rural areas and subpopulations in situations of vulnerability. METHODS: This study constituted the piloting of a draft forthcoming WHO handbook on assessing barriers for health services, grounded in the Tanahashi framework for effective coverage with health services. In North Macedonia, the convergent parallel mixed methods study involved four sources. These were: a nationally representative Computer Assisted Telephone Interview Survey (1,139 respondents); 24 key informant interviews with representatives from government, professional associations, non-governmental and civil society organizations, and development partners; 12 focus groups in four regions with adults from vulnerable/high risk groups in rural areas and small urban settlements and an additional focus group with persons with disabilities; and a literature review. Instrument design was underpinned by the Tanahashi framework, which also orientated data triangulation and deductive analysis. The research team synergistically incorporated emerging themes in an inductive way. A key component of the assessment was participatory design of the study protocol with inputs from national stakeholders as well as participatory deliberation of the results and the ways forward. RESULTS: Despite considerable progress towards UHC in North Macedonia, the assessment elucidated remaining challenges. These included: insufficient numbers of health workers, in general and particularly in the more disadvantaged regions of the country; inadequate number of outpatient medicines covered by health insurance; distance and transportation obstacles, including indirect travel costs, particularly in rural areas; adverse gender norms and relations for both women and men inhibiting timely treatment seeking; perceived discrimination by providers on multiple grounds; bottlenecks including waiting times to get appointments for specialist referrals; and lack of patient adherence, due several factors including costs of medicines and health products. CONCLUSIONS: The outputs from this study of barriers to effective coverage with health services for adult citizens of North Macedonia are feeding into the ongoing Primary Health Care reform, and provide evidence for equity-related actions in the forthcoming National Development Strategy.


Asunto(s)
Reforma de la Atención de Salud , Servicios de Salud , Masculino , Adulto , Humanos , Femenino , República de Macedonia del Norte , Seguro de Salud , Grupos Focales
2.
Health Policy ; 139: 104966, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38101148

RESUMEN

Over three years since the first COVID-19 vaccine was approved, many countries still have suboptimal vaccination rates despite holding great amounts of vaccines. Overall, there is little evidence on which policies are more effective to encourage vaccination, particularly in countries where a large share of the population remains unvaccinated. In this study, we examine the effectiveness of a community-based intervention carried out in March 2022 in North Macedonia, a country with a large and persistent share of the population that remains unvaccinated. The intervention, spearheaded by the Ministry of Health and supported by the World Health Organization and UNICEF, consisted of a mobile caravan offering vaccination and public health advice to different locations across the country on different days. Results from our staggered difference-in-difference model show that the mobile vaccination caravan increased daily vaccination rates by 7.7 vaccines per 100,000 inhabitants during the three weeks after the day of the caravan visit. This corresponds to a 35 % increase with respect to pre-intervention vaccination rates. We estimate a cost-effectiveness of 25.4 US dollars (USD) per additional vaccination induced. These results point to mobile caravan vaccines as an effective and cost-effective strategy to increase COVID-19 vaccination rates, even in a context of persistently suboptimal uptake.


Asunto(s)
COVID-19 , Vacunas , Humanos , Vacunas contra la COVID-19 , Salud Pública , República de Macedonia del Norte , COVID-19/prevención & control , Vacunación
3.
Cancer Med ; 12(13): 14806-14819, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37212529

RESUMEN

BACKGROUND: While adherence to cancer prevention recommendations is linked to lower risk of colorectal cancer (CRC), few have studied associations across the entire spectrum of colorectal carcinogenesis. Here, we studied the relationship of the standardized 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score for cancer prevention recommendations with detection of colorectal lesions in a screening setting. As a secondary objective, we examined to what extent the recommendations were being followed in an external cohort of CRC patients. METHODS: Adherence to the seven-point 2018 WCRF/AICR Score was measured in screening participants receiving a positive fecal immunochemical test and in CRC patients participating in an intervention study. Dietary intake, body fatness and physical activity were assessed using self-administered questionnaires. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for screen-detected lesions. RESULTS: Of 1486 screening participants, 548 were free from adenomas, 524 had non-advanced adenomas, 349 had advanced lesions and 65 had CRC. Adherence to the 2018 WCRF/AICR Score was inversely associated with advanced lesions; OR 0.82 (95% CI 0.71, 0.94) per score point, but not with CRC. Of the seven individual components included in the score, alcohol, and BMI seemed to be the most influential. Of the 430 CRC patients included in the external cohort, the greatest potential for lifestyle improvement was seen for the recommendations concerning alcohol and red and processed meat, where 10% and 2% fully adhered, respectively. CONCLUSIONS: Adherence to the 2018 WCRF/AICR Score was associated with lower probability of screen-detected advanced precancerous lesions, but not CRC. Although some components of the score seemed to be more influential than others (i.e., alcohol and BMI), taking a holistic approach to cancer prevention is likely the best way to prevent the occurrence of precancerous colorectal lesions.


Asunto(s)
Neoplasias Colorrectales , Cooperación del Paciente , Humanos , Estados Unidos/epidemiología , Estilo de Vida , Ejercicio Físico , Carcinogénesis , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiología , Dieta , Factores de Riesgo
4.
Front Physiol ; 14: 1054169, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36733907

RESUMEN

Introduction: The ribosomal protein L3-like (RPL3L) is a heart and skeletal muscle-specific ribosomal protein and paralogue of the more ubiquitously expressed RPL3 protein. Mutations in the human RPL3L gene are linked to childhood cardiomyopathy and age-related atrial fibrillation, yet the function of RPL3L in the mammalian heart remains unknown. Methods and Results: Here, we observed that mouse cardiac ventricles express RPL3 at birth, where it is gradually replaced by RPL3L in adulthood but re-expressed with induction of hypertrophy in adults. Rpl3l gene-deleted mice were generated to examine the role of this gene in the heart, although Rpl3l -/- mice showed no overt changes in cardiac structure or function at baseline or after pressure overload hypertrophy, likely because RPL3 expression was upregulated and maintained in adulthood. mRNA expression analysis and ribosome profiling failed to show differences between the hearts of Rpl3l null and wild type mice in adulthood. Moreover, ribosomes lacking RPL3L showed no differences in localization within cardiomyocytes compared to wild type controls, nor was there an alteration in cardiac tissue ultrastructure or mitochondrial function in adult Rpl3l -/- mice. Similarly, overexpression of either RPL3 or RPL3L with adeno-associated virus -9 in the hearts of mice did not cause discernable pathology. However, by 18 months of age Rpl3l -/- null mice had significantly smaller hearts compared to wild type littermates. Conclusion: Thus, deletion of Rpl3l forces maintenance of RPL3 expression within the heart that appears to fully compensate for the loss of RPL3L, although older Rpl3l -/- mice showed a mild but significant reduction in heart weight.

5.
Cardiovasc Res ; 119(3): 802-812, 2023 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-36125329

RESUMEN

AIMS: The adult mammalian heart is a post-mitotic organ. Even in response to necrotic injuries, where regeneration would be essential to reinstate cardiac structure and function, only a minor percentage of cardiomyocytes undergo cytokinesis. The gene programme that promotes cell division within this population of cardiomyocytes is not fully understood. In this study, we aimed to determine the gene expression profile of proliferating adult cardiomyocytes in the mammalian heart after myocardial ischaemia, to identify factors to can promote cardiac regeneration. METHODS AND RESULTS: Here, we demonstrate increased 5-ethynyl-2'deoxyuridine incorporation in cardiomyocytes 3 days post-myocardial infarction in mice. By applying multi-colour lineage tracing, we show that this is paralleled by clonal expansion of cardiomyocytes in the borderzone of the infarcted tissue. Bioinformatic analysis of single-cell RNA sequencing data from cardiomyocytes at 3 days post ischaemic injury revealed a distinct transcriptional profile in cardiomyocytes expressing cell cycle markers. Combinatorial overexpression of the enriched genes within this population in neonatal rat cardiomyocytes and mice at postnatal day 12 (P12) unveiled key genes that promoted increased cardiomyocyte proliferation. Therapeutic delivery of these gene cocktails into the myocardial wall after ischaemic injury demonstrated that a combination of thymosin beta 4 (TMSB4) and prothymosin alpha (PTMA) provide a permissive environment for cardiomyocyte proliferation and thereby attenuated cardiac dysfunction. CONCLUSION: This study reveals the transcriptional profile of proliferating cardiomyocytes in the ischaemic heart and shows that overexpression of the two identified factors, TMSB4 and PTMA, can promote cardiac regeneration. This work indicates that in addition to activating cardiomyocyte proliferation, a supportive environment is a key for regeneration to occur.


Asunto(s)
Lesiones Cardíacas , Timosina , Ratones , Animales , Ratas , Proliferación Celular , Corazón/fisiología , Miocitos Cardíacos/metabolismo , Lesiones Cardíacas/metabolismo , Timosina/genética , Timosina/metabolismo , Regeneración , Mamíferos
6.
Int J Integr Care ; 22(3): 6, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36043027

RESUMEN

Introduction: In addition to the functional aspects of healthcare integration, an understanding of its normative aspects is needed. This study explores the importance of values underpinning integrated, people-centred health services, and examines similarities and differences among the values prioritised by actors across Europe. Methods: Explorative cross-sectional design with quantitative analysis. A questionnaire of 18 values was conducted across Europe. A total of 1,013 respondents indicated the importance of each of the values on a nine-point scale and selected three most important values. Respondents were clustered in four actor groups, and countries in four European sub-regions. Results: The importance scores of values ranged from 7.62 to 8.55 on a nine-point scale. Statistically significant differences among actor groups were found for ten values. Statistically significant differences across European sub-regions were found for six values. Our analysis revealed two clusters of values: 'people related' and 'governance and organisation'. Discussion and conclusion: The study found that all 18 values in the set are considered important by the respondents. Additionally, it revealed distinctions in emphasis among the values prioritised by actor groups and across sub-regions. The study uncovered two clusters of values that contribute to a conceptually based definition of integrated, people-centred health services.

7.
Euro Surveill ; 27(29)2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35866437

RESUMEN

Technical advances in diagnostic techniques have permitted the possibility of multi-disease-based approaches for diagnosis and treatment monitoring of several infectious diseases, including tuberculosis (TB), human immunodeficiency virus (HIV), viral hepatitis and sexually transmitted infections (STI). However, in many countries, diagnosis and monitoring, as well as disease response programs, still operate as vertical systems, potentially causing delay in diagnosis and burden to patients and preventing the optimal use of available resources. With countries facing both human and financial resource constraints, during the COVID-19 pandemic even more than before, it is important that available resources are used as efficiently as possible, potential synergies are leveraged to maximise benefit for patients, continued provision of essential health services is ensured. For the infectious diseases, TB, HIV, hepatitis C (HCV) and STI, sharing devices and integrated services starting with rapid, quality-assured, and complete diagnostic services is beneficial for the continued development of adequate, efficient and effective treatment strategies. Here we explore the current and future potential (as well as some concerns), importance, implications and necessary implementation steps for the use of platforms for multi-disease testing for TB, HIV, HCV, STI and potentially other infectious diseases, including emerging pathogens, using the example of the COVID-19 pandemic.


Asunto(s)
COVID-19 , Infecciones por VIH , Hepatitis C , Enfermedades de Transmisión Sexual , Tuberculosis , Infecciones por VIH/epidemiología , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Humanos , Pandemias , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/prevención & control , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Organización Mundial de la Salud
8.
Prim Health Care Res Dev ; 22: e81, 2021 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-34911588

RESUMEN

AIMS: The aim of this paper is to introduce an operational checklist to serve as a tool for policymakers in the WHO European Region to strengthen primary health care (PHC) services and address the COVID-19 pandemic more effectively and to present the results from piloting the tool in Armenia. BACKGROUNDS: PHC has the potential to play a fundamental role in countries' responses to COVID-19. However, this potential remains unrealized in many countries. To assist countries, the WHO Regional Office for Europe developed a guidance document - Strengthening the Health Systems Response to COVID-19: Adapting Primary Health Care Services to more Effectively Address COVID-19 - that identifies strategic actions countries can take to strengthen their PHC response to the pandemic. Based on this guidance document, an operational checklist was developed to serve as a tool for policymakers to operationalize the recommended actions. METHODS: The operational checklist was developed by transforming key points in the guidance document into questions in order to identify potentially modifiable factors to strengthen PHC in response to COVID-19. The operational checklist was then piloted in Armenia in June 2020 as part of a WHO mission to provide technical advice on strengthening Armenia's PHC response to COVID-19. Two WHO experts performed semi-structured, face-to-face interviews with nine key informants (both facility managers and clinical staff) in three PHC facilities (two in a rural and one in an urban area). The data collected were analyzed to identify underlying challenges limiting PHC providers' ability to effectively and efficiently respond to COVID-19 and maintain essential health services. FINDINGS: The paper finds that making adjustments only to health services delivery will be insufficient to address most of the challenges identified by PHC providers in the context of COVID-19 in Armenia. In particular, strategic responses to the pandemic were missed, due, in part, to the absence of COVID-19 management teams at the facility level. Furthermore, the absence of PHC experts in Armenia's national pandemic response team meant that health system issues identified at the facility level could not easily be communicated to or addressed by policymakers. The checklist therefore helps policymakers identify critical challenges - at both the facility and health system level - that need to be addressed to strengthen the PHC response to the COVID-19 pandemic.


Asunto(s)
COVID-19 , Armenia , Humanos , Pandemias , Atención Primaria de Salud , SARS-CoV-2
9.
Acta Neurol Scand ; 144(4): 394-399, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34021596

RESUMEN

OBJECTIVES: The purpose of this study is twofold, first to present a new method based on head laser tracking designed to measure head or hand movements and second to further investigate if patients suffering from chronic whiplash or tension-type headache have impaired motor control of neck muscles. MATERIAL AND METHODS: A new laser tracking instrument was designed to measure the ability of a test person to track a reference point moving on the wall by a laser fixed to the forehead or held in the hand. The reference point to be tracked moves in runs of a circle or a square at three different speeds 10, 20, or 30 cm/s. We used a 1 × 1 ×1 m setup geometry to provide head movements well below pain release. Groups of 22 patients diagnosed with chronic whiplash-associated disorder grade 2, 19 patients diagnosed with chronic tension-type headache, and 37 control persons were compared. RESULTS: A small but highly significant dyscoordination of head movements was observed in both patient groups and in whiplash also of the hand. CONCLUSIONS: Our study presents a new method based on laser tracking for precision quantitative measurements of head or hand movements during standardized conditions. The results confirm that motor control of head movements is impaired in both chronic whiplash and tension-type headache, and in whiplash also of the hand. This suggests involvement of the central nervous system in the pathology of these diseases.


Asunto(s)
Cefalea de Tipo Tensional , Lesiones por Latigazo Cervical , Movimientos de la Cabeza , Humanos , Músculos del Cuello , Dolor , Cefalea de Tipo Tensional/etiología , Lesiones por Latigazo Cervical/complicaciones
10.
J Dairy Sci ; 104(6): 6598-6608, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33773791

RESUMEN

This study aimed to investigate the production of acid-coagulated fresh cheese by using slightly acid diafiltered (DF) microfiltered (MF) casein concentrates (8% protein). Three different acidifying agents were tested during DF: carbon dioxide, lactic acid, and citric acid. Fresh cheese was manufactured using acid-DF casein concentrates, or casein concentrates DF with just water, and compared with cheese manufactured using MF casein concentrates without DF. The fresh cheeses were characterized for composition, rheological, and sensorial properties. Acid-DF casein concentrates improved acidification kinetics during cheesemaking and reduced casein leakage to cheese whey, compared with cheese from regular MF casein concentrate. Among the rheological properties investigated in this study, the storage modulus of the fresh cheese was higher when DF of the casein concentrate was performed with nonacidified DF water or when DF water was acidified with citric acid. However, fresh cheese made from casein concentrate diafiltered with DF water acidified by citric acid was most liked in a sensory ranking test.


Asunto(s)
Queso , Animales , Caseínas , Queso/análisis , Manipulación de Alimentos , Leche/química , Suero Lácteo/química , Proteína de Suero de Leche/análisis
11.
J Dairy Sci ; 103(9): 7927-7938, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32684480

RESUMEN

Cheese made from microfiltration (MF) retentate may suffer from textural defects due to a high Ca concentration. The reduction of colloidal minerals by the acidification of milk before MF at pH below 6.0 has been well documented in the literature. This process, however, creates less valuable side streams to the MF process and induces changes in the casein micelles that negatively affect their coagulation properties. The objective of this study was to determine whether a minor reduction in pH by using different acidifiers in the diafiltration (DF) water could induce changes in composition and renneting properties of the MF retentate. A 2-stage filtration process was used, with the first designed to increase the casein concentration to 8% and the second to slightly reduce the casein concentrate by 0.1 pH unit by DF, without influencing the total protein concentration. Four acidifying agents were tested during DF: lactic acid, hydrochloric acid, citric acid, and carbon dioxide. Diafiltration with water was used as a reference. At the start of DF, the retentates of acid DF had a slightly reduced pH, with an average of 0.09, whereas the pH of the reference retentate increased by an average of 0.07 unit. The reference retentate regained its starting pH by the end of DF. The carbonated retentate gradually increased in pH during processing, whereas the pH of the lactic, hydrochloric, and citric acid retentates remained constant. The permeate from the lactic acid and carbonated treatments had a reduced whey protein content compared with the reference. The total P and inorganic phosphate were lowered in the retentate by using carbonation. The total amount of Mg and Na were lowered in the retentate by using citric acid. The ionic Ca content in the retentate increased with use of lactic or hydrochloric acid. The type of acidifier used reduced the rennet clotting time. Combined acidified diafiltration with a slight reduction affects the permeate composition and improves the retentate clotting time despite the minimal mineral modification.


Asunto(s)
Caseínas/química , Queso/análisis , Quimosina/química , Manipulación de Alimentos , Animales , Filtración/métodos , Manipulación de Alimentos/métodos , Concentración de Iones de Hidrógeno , Micelas , Leche/química , Agua , Proteína de Suero de Leche/análisis
12.
Eur J Public Health ; 30(6): 1072-1077, 2020 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-32601680

RESUMEN

BACKGROUND: Health 2020 is the regional health policy framework of the World Health Organization (WHO) Regional Office for Europe. The goals of Health 2020 are to improve health and well-being, reduce health inequalities and strengthen public health. To gain insight into the Health 2020 targets needing extra attention in coming years, we assessed progress under Health 2020 in the WHO European Region. METHODS: Quantitative methods were used to assess progress in 50 out of 53 Member States of the WHO European Region in 2005, 2010 and 2015. The 16 quantitative Health 2020 indicators were rescaled from 1 to 100, with 1 indicating poor performance and 100 indicating good performance. The geometric mean of all 16 rescaled indicators was taken by Health 2020 target to compose a Health 2020 index. RESULTS: The Health 2020 index (2015) ranged from 82.8 in Sweden to 30.0 in Turkmenistan. A clear east-west gradient was observed in the WHO European Region, with countries in western parts performing relatively better than countries in eastern parts. Indicators with the largest increase between 2005 and 2015 were premature mortality, mortality external causes, life expectancy and infant mortality. However, all quintiles showed a decline on overweight. CONCLUSIONS: The Health 2020 index gives a relative overview regarding the past and present performance on the Health 2020 policy framework of countries in the WHO European Region. Although improvements have been observed between 2005 and 2015, challenges remain to improve health for all in the context of the United Nations 2030 Agenda for Sustainable Development.


Asunto(s)
Mortalidad Infantil , Esperanza de Vida , Europa (Continente) , Humanos , Lactante , Suecia , Organización Mundial de la Salud
13.
Bull World Health Organ ; 98(5): 353-359, 2020 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32514200

RESUMEN

PROBLEM: Slovenia's model of primary health care relied on reactive, episodic care and was ill-equipped to address the country's burden of disease dominated by noncommunicable diseases. APPROACH: The government has developed a multidisciplinary, community-based, prevention-oriented service delivery model for primary health care. A compulsory family medicine residency programme was introduced in 2000, and from 2004 screening and control of chronic diseases were established in family medicine practices. Health promotion centres were established, providing group interventions to support healthy lifestyles. After 2011, registered nurses were introduced to conduct screening for chronic diseases, provide counselling and manage patients with stable noncommunicable diseases. LOCAL SETTING: In 1992, the government transformed Slovenia's health financing scheme to a social insurance system based on mandatory payroll taxes. The system enabled private provision of health services, although primary care was mostly provided by publicly funded community health centres. A strong gatekeeping role was introduced. RELEVANT CHANGES: Despite spending less on health than the European Union (EU) average, by 2013 Slovenia's life expectancy was higher than the average for EU countries. The increase was due in part to rapidly declining infant and under-five mortality and a faster decline in premature mortality due to chronic diseases. LESSONS LEARNT: Slovenia's approach was enabled by strong public health and governance structures, along with accountability mechanisms that monitored outcomes and took corrective action when necessary. New programmes were piloted, creating a strong evidence base that facilitated obtaining sustainable financing, while national roll-out was supported by regional branches of the National Institute of Public Health.


Asunto(s)
Servicios de Salud Comunitaria , Atención a la Salud , Reforma de la Atención de Salud , Atención Primaria de Salud , Atención a la Salud/métodos , Promoción de la Salud/métodos , Humanos , Esperanza de Vida , Calidad de la Atención de Salud , Eslovenia
14.
Nature ; 577(7790): 405-409, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31775156

RESUMEN

Clinical trials using adult stem cells to regenerate damaged heart tissue continue to this day1,2, despite ongoing questions of efficacy and a lack of mechanistic understanding of the underlying biological effect3. The rationale for these cell therapy trials is derived from animal studies that show a modest but reproducible improvement in cardiac function in models of cardiac ischaemic injury4,5. Here we examine the mechanistic basis for cell therapy in mice after ischaemia-reperfusion injury, and find that-although heart function is enhanced-it is not associated with the production of new cardiomyocytes. Cell therapy improved heart function through an acute sterile immune response characterized by the temporal and regional induction of CCR2+ and CX3CR1+ macrophages. Intracardiac injection of two distinct types of adult stem cells, cells killed by freezing and thawing or a chemical inducer of the innate immune response all induced a similar regional accumulation of CCR2+ and CX3CR1+ macrophages, and provided functional rejuvenation to the heart after ischaemia-reperfusion injury. This selective macrophage response altered the activity of cardiac fibroblasts, reduced the extracellular matrix content in the border zone and enhanced the mechanical properties of the injured area. The functional benefit of cardiac cell therapy is thus due to an acute inflammatory-based wound-healing response that rejuvenates the infarcted area of the heart.


Asunto(s)
Inmunidad Innata , Miocitos Cardíacos/inmunología , Trasplante de Células Madre , Células Madre , Animales , Diferenciación Celular , Femenino , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Miocitos Cardíacos/trasplante , Rejuvenecimiento
15.
16.
Genes Dev ; 33(21-22): 1457-1459, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31676733

RESUMEN

The Hippo pathway is an evolutionarily conserved kinase cascade that is fundamental for tissue development, homeostasis, and regeneration. In the developing mammalian heart, Hippo signaling regulates cardiomyocyte numbers and organ size. While cardiomyocytes in the adult heart are largely postmitotic, Hippo deficiency can increase proliferation of these cells and affect cardiac regenerative capacity. Recent studies have also shown that resident cardiac fibroblasts play a critical role in disease responsiveness and healing, and in this issue of Genes and Development, Xiao and colleagues (pp. 1491-1505) demonstrate that Hippo signaling also integrates the activity of fibroblasts in the heart. They show that Hippo signaling normally maintains the cardiac fibroblast in a resting state and, conversely, its inactivation during disease-related stress results in a spontaneous transition toward a myofibroblast state that underlies fibrosis and ventricular remodeling. This phenotypic switch is associated with increased cytokine signaling that promotes nonautonomous resident fibroblast and myeloid cell activation.


Asunto(s)
Negociación , Proteínas Serina-Treonina Quinasas , Animales , Proliferación Celular , Fibroblastos , Fibrosis , Miocitos Cardíacos
18.
JCI Insight ; 4(15): e128722, 2019 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-31393098

RESUMEN

Collagen production in the adult heart is thought to be regulated by the fibroblast, although cardiomyocytes and endothelial cells also express multiple collagen mRNAs. Molecular chaperones are required for procollagen biosynthesis, including heat shock protein 47 (Hsp47). To determine the cell types critically involved in cardiac injury­induced fibrosis theHsp47 gene was deleted in cardiomyocytes, endothelial cells, or myofibroblasts. Deletion ofHsp47 from cardiomyocytes during embryonic development or adult stages, or deletion from adult endothelial cells, did not affect cardiac fibrosis after pressure overload injury. However, myofibroblast-specific ablation of Hsp47; blocked fibrosis and deposition of collagens type I, III, and V following pressure overload as well as significantly reduced cardiac hypertrophy. Fibroblast-specific Hsp47-deleted mice showed lethality after myocardial infarction injury, with ineffective scar formation and ventricular wall rupture. Similarly, only myofibroblast-specific deletion of Hsp47reduced fibrosis and disease in skeletal muscle in a mouse model of muscular dystrophy. Mechanistically, deletion of Hsp47 from myofibroblasts reduced mRNA expression of fibrillar collagens and attenuated their proliferation in the heart without affecting paracrine secretory activity of these cells. The results show that myofibroblasts are the primary mediators of tissue fibrosis and scar formation in the injured adult heart, which unexpectedly affects cardiomyocyte hypertrophy.


Asunto(s)
Colágeno/metabolismo , Proteínas del Choque Térmico HSP47/metabolismo , Ventrículos Cardíacos/patología , Distrofia Muscular de Cinturas/patología , Infarto del Miocardio/patología , Miofibroblastos/patología , Animales , Línea Celular , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Fibrosis , Perfilación de la Expresión Génica , Proteínas del Choque Térmico HSP47/genética , Ventrículos Cardíacos/citología , Humanos , Masculino , Ratones , Músculo Esquelético/citología , Distrofia Muscular de Cinturas/genética , Infarto del Miocardio/etiología , Miocitos Cardíacos/metabolismo , Miofibroblastos/metabolismo , Cultivo Primario de Células , Ratas , Sarcoglicanos/genética , Remodelación Ventricular
19.
J Cardiovasc Dev Dis ; 6(3)2019 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-31434209

RESUMEN

During the postnatal period in mammals, the heart undergoes significant remodeling and cardiac cells progressively lose their embryonic characteristics. At the same time, notable changes in the extracellular matrix (ECM) composition occur with a reduction in the components considered facilitators of cellular proliferation, including fibronectin and periostin, and an increase in collagen fiber organization. Not much is known about the postnatal cardiac fibroblast which is responsible for producing the majority of the ECM, but during the days after birth, mammalian hearts can regenerate after injury with only a transient scar formation. This phenomenon has also been described in adult urodeles and teleosts, but relatively little is known about their cardiac fibroblasts or ECM composition. Here, we review the pre-existing knowledge about cardiac fibroblasts and the ECM during the postnatal period in mammals as well as in regenerative environments.

20.
Food Chem X ; 1: 100007, 2019 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-31432007

RESUMEN

Wine fraud leaves wineries vulnerable to damage in reputation and potential lost revenue. To reduce this risk for wines from Washington State (WA), USA, advanced analytical instrumentation and statistical methods were employed to geographically classify 133 wines from 4 major wine producing regions, including 70 wines from WA. Analyses of 37 elements and 2 water isotopes were performed with Triple Quadrupole Inductively Coupled Plasma Mass Spectrometry and Cavity Ring-Down Spectroscopy, respectively. Linear discriminant analysis resulted in 96.2% discrimination, achieved with 11 parameters (Mn, Zn, Pb, Ni, As, D/H, La, Ce, Si, Zr and Sr) that were linearly combined into 3 functions. WA wines were uniquely distinguished in large part with low D/H ratios and Mn concentrations derived from the isotopically light precipitation and volcanic loess soils encountered in this region, respectively. This study is the first of its kind to focus on the authentication of WA wines.

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