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1.
BMJ Glob Health ; 9(4)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38599663

RESUMO

Non-communicable diseases (NCDs) are a leading health and development challenge worldwide. Since 2015, WHO and the United Nations Development Programme have provided support to governments to develop national NCD investment cases to describe the socioeconomic dimensions of NCDs. To assess the impact of the investment cases, semistructured interviews and a structured process for gathering written feedback were conducted between July and October 2022 with key informants in 13 countries who had developed a national NCD investment case between 2015 and 2020. Investment cases describe: (1) the social and economic costs of NCDs, including their distribution and projections over time; (2) priority areas for scaled up action; (3) the cost and returns from investing in WHO-recommended measures to prevent and manage NCDs; and (4) the political dimensions of NCD responses. While no country had implemented all the recommendations set out in their investment case reports, actions and policy changes attributable to the investment cases were identified, across (1) governance; (2) financing; and (3) health service access and delivery. The pathways of these changes included: (1) stronger collaboration across government ministries and partners; (2) advocacy for NCD prevention and control; (3) grounding efforts in nationally owned data and evidence; (4) developing mutually embraced 'language' across health and finance; and (5) elevating the priority accorded to NCDs, by framing action as an investment rather than a cost. The assessment also identified barriers to progress on the investment case implementation, including the influence of some private sector entities on sectors other than health, the impact of the COVID-19 pandemic, and changes in senior political and technical government officials. The results suggest that national NCD investment cases can significantly contribute to catalysing the prevention and control of NCDs through strengthening governance, financing, and health service access and delivery.


Assuntos
Doenças não Transmissíveis , Humanos , Doenças não Transmissíveis/epidemiologia , Doenças não Transmissíveis/prevenção & controle , Pandemias , Política de Saúde , Formulação de Políticas , Governo
2.
Sci Rep ; 14(1): 2797, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38307876

RESUMO

Hepatic fibrosis remains a significant clinical challenge due to ineffective treatments. 4-methylumbelliferone (4MU), a hyaluronic acid (HA) synthesis inhibitor, has proven safe in phase one clinical trials. In this study, we aimed to ameliorate liver fibrosis by inhibiting HA synthesis. We compared two groups of mice with CCl4-induced fibrosis, treated with 4-methylumbelliferone (4MU) and hyaluronan synthase 2 (HAS2) targeting siRNA (siHAS2). The administration of 4MU and siHAS2 significantly reduced collagen and HA deposition, as well as biochemical markers of hepatic damage induced by repeated CCl4 injections. The transcriptomic analysis revealed converging pathways associated with downstream HA signalling. 4MU- and siHAS2-treated fibrotic livers shared 405 upregulated and 628 downregulated genes. These genes were associated with xenobiotic and cholesterol metabolism, mitosis, endoplasmic reticulum stress, RNA processing, and myeloid cell migration. The functional annotation of differentially expressed genes (DEGs) in siHAS2-treated mice revealed attenuation of extracellular matrix-associated pathways. In comparison, in the 4MU-treated group, DEGs were related to lipid and bile metabolism pathways and cell cycle. These findings confirm that HAS2 is an important pharmacological target for suppressing hepatic fibrosis using siRNA.


Assuntos
Ácido Hialurônico , Himecromona , Animais , Camundongos , Perfilação da Expressão Gênica , Hialuronan Sintases/genética , Hialuronan Sintases/metabolismo , Ácido Hialurônico/metabolismo , Himecromona/farmacologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/genética , RNA Interferente Pequeno
3.
Brain Res ; 1829: 148792, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38325559

RESUMO

Temporal lobe epilepsy (TLE) development is associated with dysregulation of glutamatergic transmission in the hippocampus; however, detailed molecular mechanisms of pathological changes are still poorly understood. In the present study, we performed the complex analysis of glutamatergic system in the hippocampus of Krushinsky-Molodkina (KM) rats genetically prone to audiogenic seizures (AGS). Daily AGS stimulations (audiogenic kindling) were used to reproduce the dynamics of TLE development. Naïve KM rats were used as a control. After 14 AGS, at the stage of developing TLE, KM rats demonstrated significant upregulation of extracellular signal-regulated kinases (ERK) 1 and 2, cAMP response element-binding protein (CREB), and c-Fos in the hippocampus indicating activation of the hippocampal cells. These changes were accompanied with an increase in glutaminase and vesicular glutamate transporter (VGLUT) 2 suggesting the activation of glutamate production and loading into the synaptic vesicles. After 21 AGS, when TLE was fully-established, alterations were similar but more pronounced, with higher activation of glutaminase, increase in glutamate production, upregulation of VGLUT1 and 2, and Fos-related antigen 1 (Fra-1) along with c-Fos. Analysis of glutamate receptors showed variable changes. Thus, after 14 AGS, simultaneous increase in metabotropic glutamate receptor mGluR1 and decrease in ionotropic N-methyl-D-aspartate (NMDA) receptors could reflect compensatory anti-epileptic mechanism, while further kindling progression induced upregulation of ionotropic receptors, probably, contributing to the hippocampal epileptization. However, we revealed practically no alterations in the expression of synaptic proteins. Altogether, obtained results suggested that overactivation of glutamate production in the hippocampus strongly contributed to TLE development in KM rats.


Assuntos
Epilepsia Reflexa , Epilepsia do Lobo Temporal , Excitação Neurológica , Ratos , Animais , Glutaminase/metabolismo , Hipocampo/metabolismo , Epilepsia Reflexa/metabolismo , Excitação Neurológica/fisiologia , Epilepsia do Lobo Temporal/metabolismo , Predisposição Genética para Doença , Ácido Glutâmico/metabolismo , Convulsões/metabolismo , Estimulação Acústica
4.
Ther Adv Ophthalmol ; 15: 25158414231189080, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37528899

RESUMO

Background: A number of articles report the association of polypoidal lesions and choroidal nevi; however, the relationship between choroidal nevi and pachychoroidal disorders has not been studied. Objectives: To study the prevalence of choroidal nevi in central serous chorioretinopathy (CSCR) patients and to elucidate potential differences in the clinical characteristics of CSCR in patients with and without choroidal nevi. Design: Case-control study. Methods: This study included a retrospective analysis of medical records and multimodal imaging data of CSCR patients and a prospective evaluation of the prevalence of the choroidal nevi in age- and sex-matched healthy controls. All participants received comprehensive ophthalmic examination and multimodal imaging including infrared scanning laser ophthalmoscopy in dark-field mode to detect choroidal nevi in the central 40° × 60° region. Results: A total of 199 CSCR patients (160 males and 39 females, 47.9 ± 9.4 years) and 184 age-matched healthy individuals (139 males and 45 females, 44.8 ± 12.5 years) were included. Choroidal nevi were detected in 24 (12.1%) CSCR patients and 10 (5.4%) healthy controls (p = 0.01). CSCR patients with choroidal nevi had statistically significantly higher subfoveal choroidal thickness, lower best-corrected visual acuity, and lower central retinal thickness (p < 0.05) than CSCR patients without choroidal nevi. The odds ratio for the presence of chronic CSCR in patients with choroidal nevi was 27.0 (95% CI: 3.1-231.9, p = 0.003). Conclusion: The prevalence of choroidal nevi among patients with CSCR is higher than in age- and sex-matched healthy population. Choroidal nevi may be associated with chronic CSCR.

5.
Front Health Serv ; 3: 1214885, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37533704

RESUMO

Introduction: Despite the increasing interest in and political commitment to mental health service development in many regions of the world, there remains a very low level of financial commitment and corresponding investment. Assessment of the projected costs and benefits of scaling up the delivery of effective mental health interventions can help to promote, inform and guide greater investment in public mental health. Methods: A series of national mental health investment case studies were carried out (in Bangladesh, Kenya, Nepal, Philippines, Uganda, Uzbekistan and Zimbabwe), using standardized guidance developed by WHO and UNDP and implemented by a multi-disciplinary team. Intervention costs and the monetized value of improved health and production were computed in national currency units and, for comparison, US dollars. Benefit-cost ratios were derived. Findings: Across seven countries, the economic burden of mental health conditions was estimated at between 0.5%-1.0% of Gross Domestic Product. Delivery of an evidence-based package of mental health interventions was estimated to cost US$ 0.40-2.40 per capita per year, depending on the country and its scale-up period. For most conditions and country contexts there was a return of >1 for each dollar or unit of local currency invested (range: 0.0-10.6 to 1) when productivity gains alone are included, and >2 (range: 0.4-30.3 to 1) when the intrinsic economic value of health is also considered. There was considerable variation in benefit-cost ratios between intervention areas, with population-based preventive measures and treatment of common mental, neurological and conditions showing the most attractive returns when all assessed benefits are taken into account. Discussion and Conclusion: Performing a mental health investment case can provide national-level decision makers with new and contextualized information on the outlays and returns that can be expected from renewed local efforts to enhance access to quality mental health services. Economic evidence from seven low- and middle-income countries indicates that the economic burden of mental health conditions is high, the investment costs are low and the potential returns are substantial.

6.
Ther Adv Ophthalmol ; 15: 25158414231160689, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36970709

RESUMO

Background: The photoreceptor outer segment (PROS) layer demonstrates focal thinning above the fluorescein leakage in acute central serous chorioretinopathy (CSC); however, the nature of this phenomenon is not known. Objectives: To study the relationship between the PROS layer and thickness of the outer retinal layers above the fluorescein leakage in newly diagnosed acute CSC. Design: Single-center retrospective study. Methods: All participants received multimodal imaging, including fluorescein angiography and optical coherence tomography. Thickness of PROS, outer nuclear layer (ONL), and ONL-outer plexiform layer (OPL) complex was measured above the leakage and outside the leakage within the area of neurosensory detachment. The number of intraretinal hyperreflective foci of the outer retina was counted. The correlation between PROS thickness and ONL, OPL-ONL complex thickness, and the number of intraretinal hyperreflective foci was calculated. Results: Fifty eyes of 48 patients (38 males and 10 females, 43.8 ± 10.6 years) with a mean symptom duration of 1.4 ± 1.3 months were included. PROS thickness above the fluorescein leakage showed a statistically significant correlation with ONL thickness, OPL-ONL complex thickness, and the number of hyperreflective foci in the outer retina, 0.57, 0.60, and -0.46, respectively (p < 0.001). Measuring the extent of PROS thinning above the leakage in newly diagnosed CSC allowed to predict self-resolution of subretinal fluid. The greatest linear dimension of PROS thinning showed an area under the receiver operating curve (ROC) curve of 0.98. The cases without PROS thinning had the fastest resolution of subretinal fluid. Conclusion: PROS thinning above the fluorescein leakage in acute CSC is associated with thinning of the outer retinal layers and reveals mild outer retinal atrophy. The absence of PROS thinning predicts faster resolution of CSC.

7.
Epilepsy Behav ; 134: 108846, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35849865

RESUMO

Audiogenic seizures (AGS) (audiogenic kindling) in genetically selected audiogenic rodents are a reliable model of temporal lobe epilepsy (TLE). Temporal lobe epilepsy is accompanied with neurodegeneration in the hippocampus, but how the cells die is not fully understood. We analyzed the dynamics and mechanisms of cell loss in the hippocampus of audiogenic Krushinsky-Molodkina (KM) rats during the development of TLE. Audiogenic kindling of different durations was carried out to reproduce TLE progression in KM rats. Behavioral analysis showed the development of post-tonic clonus, the main indicator of TLE, by the 14th AGS. The severity and duration of post-tonic clonus positively correlated with the increase in the number of AGS. Temporal lobe epilepsy development was accompanied with two peaks of cell loss. The first peak was detected after 7 AGS in the dentate gyrus (DG) granular layer and associated with activation of p53- and mitochondria-dependent apoptosis. After a 7-day rest period, activation of autophagy and restoration of cell number were revealed. The second peak occurred after 14 AGS, affected both granular and hilar mossy cells and persisted further after 21 AGS, but no compensation was observed. Thus, activation of autophagy probably plays a neuroprotective role and supports survival of hippocampal cells at the beginning of epileptogenesis, but exacerbation of limbic seizures during TLE development causes irreversible neurodegeneration.


Assuntos
Epilepsia Reflexa , Epilepsia do Lobo Temporal , Excitação Neurológica , Estimulação Acústica , Animais , Hipocampo , Ratos , Convulsões
8.
BMJ Glob Health ; 7(6)2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35649631

RESUMO

BACKGROUND: While the non-communicable disease (NCD) burden in the countries of the Gulf Cooperation Council (GCC) (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and the United Arab Emirates) has surged over the past decades, the costs and return on investment (ROI) of implementing cost-effective, WHO-recommended NCD interventions have not been established. METHODS: We performed an economic analysis to estimate the ROI from scaling up four sets of NCD interventions over 15 years. We estimated the direct costs of the four main NCDs (cancer, diabetes, cardiovascular diseases and chronic respiratory diseases) using a prevalence-based, bottom-up cost-of-illness approach. We estimated indirect costs based on productivity loss due to absenteeism, presenteeism and premature deaths. We costed the scaling up of interventions using the WHO Costing Tool and assessed the health impact of interventions using the OneHealth Tool. We calculated ROI by comparing productivity and social benefits with the total costs of implementing the interventions. RESULTS: The four main NCDs cost the GCC economy nearly US$50 billion in 2019, equal to 3.3% of its gross domestic product. The indirect costs are estimated at US$20 billion or 40% of the total burden. Implementing the four modelled intervention packages in the six GCC countries over 15 years will cost US$14 billion, with an ROI of US$4.9 for every US$1 invested and significant health and social benefits, including 290 000 averted premature deaths. CONCLUSION: Based on the results of these six investment cases, we recommend actions to scale up current WHO-recommended cost-effective interventions, strengthen whole-of-government action, drive the NCD legislative agenda, build out the evidence base, generate additional advocacy material, and increase regional collaboration and data-sharing to establish best practices and monitor impact.


Assuntos
Doenças não Transmissíveis , Análise Custo-Benefício , Atenção à Saúde , Humanos , Kuweit , Doenças não Transmissíveis/prevenção & controle , Omã
9.
Epilepsy Behav ; 125: 108445, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34837844

RESUMO

Temporal lobe epilepsy is associated with considerable structural changes in the hippocampus. Pharmacological and electrical models of temporal lobe epilepsy in animals strongly suggest that hippocampal reorganization is based on seizure-stimulated aberrant neurogenesis but the data are often controversial and hard to interpret. The aim of the present study was to estimate neurogenesis and synaptic remodeling in the hippocampus of Krushinsky-Molodkina (KM) rats genetically prone to audiogenic seizures (AGS). In our experiments we exposed KM rats to audiogenic kindling of different durations (4, 14, and 21 AGS) to model different stages of epilepsy development. Naïve KM rats were used as a control. Our results showed that even 4 AGS stimulated proliferation in the subgranular layer of the dentate gyrus (DG) accompanied with increase in number of doublecortin (DCX)-positive immature granular cells. Elevated number of proliferating cells was also observed in the hilus indicating the enhancement of abnormal migration of neural progenitors. In contrast to the DG, all DCX-positive cells in the hilus expressed VGLUT1/2 and their number was increased indicating that seizure activity accelerates glutamatergic differentiation of ectopic hilar cells. 14-day kindling further stimulated proliferation, abnormal migration, and glutamatergic differentiation of new neurons both in the DG granular and subgranular layers and in the hilus. However, after 21 AGS increased proliferation was observed only in the DG, while the numbers of immature neurons expressed VGLUT1/2 were still enhanced in both hippocampal areas. Audiogenic kindling also stimulated sprouting of mossy fibers and enhanced expression of synaptopodin in the hippocampus indicating generation of new synaptic contacts between granular cells, mossy cells, and CA3 pyramid neurons. Thus, our data suggest that epilepsy progression is associated with exacerbation of aberrant neurogenesis and reorganization of hippocampal neural circuits that contribute to the enhancement and spreading of epileptiform activity.


Assuntos
Epilepsia Reflexa , Excitação Neurológica , Animais , Hipocampo , Fibras Musgosas Hipocampais , Neurogênese , Ratos , Convulsões
10.
Cancers (Basel) ; 13(5)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807574

RESUMO

A special problem in the surgery of rectal cancer is connected with a need for appropriate removal of intestine parts, along with the tumor, including the fragment close to the sphincter. To determine the length of fragments to remove, it is necessary to reveal areas without changes in molecule functioning, specific for tumor. The purpose of the present study was to investigate functioning the proteasomes, the main actors in protein hydrolysis, in patient rectal adenocarcinoma and different intestine locations. Chymotrypsin-like and caspase-like activities, open to complex influence of different factors, were analyzed in 43-54 samples by Suc-LLVY-AMC- and Z-LLE-AMC-hydrolysis correspondingly. Both activities may be arranged by the decrease in the location row: cancer→adjacent tissue→proximal (8-20 cm from tumor) and distal (2 and 4 cm from tumor) sides. These activities did not differ noticeably in proximal and distal locations. Similar patterns were detected for the activities and expression of immune subunits LMP2 and LMP7 and expression of 19S and PA28αß activators. The largest changes in tumor were related to proteasome subtype containing LMP2 and PA28αß that was demonstrated by native electrophoresis. Thus, the results indicate a significance of subtype LMP2-PA28αß for tumor and absence of changes in proteasome pool in distal fragments of 2-4 cm from tumor.

11.
Epilepsy Behav ; 113: 107526, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33161330

RESUMO

The hippocampus plays an important role in epilepsy progression even if it is not involved in seizure generalization. We hypothesized that abnormal development of the hippocampus may underlie epileptogenesis. Here we analyzed postnatal development of the hippocampus of Krushinsky-Molodkina (KM) rats, which are the animal model of reflex audiogenic epilepsy. KM rats are genetically prone to audiogenic seizures that are expressed in age-dependent manner. The study was performed on seizure-naïve KM rats at several days of postnatal development (P15, P30, P60, P120). Wistar rats of the corresponding ages were used as a control. We showed that at early stages (P15, P30), the hippocampus of KM rats was characterized by significantly smaller cell population, but the number of proliferated cells was increased in comparison with control Wistar rats. Only at P60 proliferation and the total number of the hippocampal cells reached a level equal to Wistar rats. These data suggest delayed postnatal development of the hippocampus of KM rats. Analysis of apoptosis demonstrated significantly increased number of TUNEL-positive cells in the dentate gyrus (DG) of KM rats at P30 that was accompanied with expression of p53, Bcl-2 and cleaved caspases 3 and 9. Additionally, at all analyzed stages in the hilus of KM rats, the number of new-born glutamatergic cells was significantly increased that suggests formation of hilar ectopic granular cells. Our data suggest that in the case of hereditary epilepsy aberrant neurogenesis may be genetically determined.


Assuntos
Epilepsia Reflexa , Estimulação Acústica , Animais , Modelos Animais de Doenças , Epilepsia Reflexa/genética , Hipocampo , Ratos , Ratos Wistar , Convulsões/genética
14.
Int J Mol Sci ; 20(24)2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31847129

RESUMO

4-methylumbelliferone (4MU) is an inhibitor of hyaluronan deposition and an active substance of hymecromone, a choleretic and antispasmodic drug. 4MU reported to be anti-fibrotic in mouse models; however, precise mechanism of action still requires further investigation. Here we describe the cellular and molecular mechanisms of 4MU action on CCl4-induced liver fibrosis in mice using NGS transcriptome, Q-PCR and immunohistochemical analysis. Collagen and hyaluronan deposition were prevented by 4MU. The CCl4 stimulated expression of Col1a and αSMA were reduced, while the expression of the ECM catabolic gene Hyal1 was increased in the presence of 4MU. Bioinformatic analysis identified an activation of TGF-beta and Wnt/beta-catenin signaling pathways, and inhibition of the genes associated with lipid metabolism by CCL4 treatment, while 4MU restored key markers of these pathways to the control level. Immunohistochemical analysis reveals the suppression of hepatic stellate cells (HSCs) transdifferentiation to myofibroblasts by 4MU treatment. The drug affected the localization of HSCs and macrophages in the sites of fibrogenesis. CCl4 treatment induced the expression of FSTL1, which was downregulated by 4MU. Our results support the hypothesis that 4MU alleviates CCl4-induced liver fibrosis by reducing hyaluronan deposition and downregulating FSTL1 expression, accompanied by the suppression of HSC trans-differentiation and altered macrophage localization.


Assuntos
Proteínas Relacionadas à Folistatina/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Hialurônico/biossíntese , Himecromona/farmacologia , Cirrose Hepática , Via de Sinalização Wnt/efeitos dos fármacos , Actinas/biossíntese , Animais , Intoxicação por Tetracloreto de Carbono/metabolismo , Intoxicação por Tetracloreto de Carbono/patologia , Intoxicação por Tetracloreto de Carbono/prevenção & controle , Transdiferenciação Celular/efeitos dos fármacos , Feminino , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Hialuronoglucosaminidase/biossíntese , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Cirrose Hepática/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Miofibroblastos/metabolismo , Miofibroblastos/patologia
15.
PLoS One ; 14(10): e0223412, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31584979

RESUMO

Noncommunicable diseases (NCDs) are a broad challenge for decision-makers. NCDs account for seven out of every 10 deaths globally, with 42 percent occurring prematurely in individuals under age 70. Despite their heavy toll, NCDs are underfunded, with only around two percent of global funding dedicated to the disease set. Country governments are responsible for funding targeted actions to reduce the NCD burden, but among other priorities, many have yet to invest in the health-system interventions and policy measures that can reduce the burden. This article examines "investment cases" as a potential mechanism for catalyzing attention to-and funding for-NCDs. In Jamaica, using the UN inter-agency OneHealth Tool, we conducted an economic analysis to estimate the return-on-investment from scaling up strategic clinical interventions, and from implementing or intensifying policy measures that target NCD risk factors. In addition, we conducted an institutional and context (ICA) analysis, interviewing stakeholders across sectors to take stock of promising policy pathways (e.g., areas of general consensus, political appetite and opportunity) as well as challenges to implementation. The economic analysis found that scaling up clinical interventions that target CVD, diabetes, and mental health disorders, and policy measures that target tobacco and alcohol use, would save over 6,600 lives between 2017-2032, and avert JMD 81.3 billion (USD 640 million) in direct and indirect economic costs that result from mortality and morbidity linked to NCDs. The ICA uncovered government economic growth targets and social priorities that would be aided by increased attention to NCDs, and it linked these targets and priorities to the economic analysis.

16.
Epilepsy Behav ; 99: 106494, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31493733

RESUMO

Krushinsky-Molodkina (KM) rats genetically prone to audiogenic seizure are characterized by age-dependent expression of audiogenic seizures (AGS). It is known that the critical period of enhanced seizure susceptibility in rodents occurs at 2nd-3rd weeks of postnatal development. However, KM rats do not express AGS at this time-point, but start to demonstrate a stable AGS only after the age of 3 months. We hypothesized that this delay in AGS susceptibility in KM rats is genetically determined and may depend on some alterations in the development of the hippocampal glutamatergic system during the early postnatal period. We analyzed the expression and activity of seizure-related proteins, such as vesicular glutamate transporter 2 (VGLUT2), extracellular signal-regulated kinases 1 and 2 (ERK1/2), synapsin I, and NR2B subunit of the N-methyl-d-aspartate (NMDA) receptor (NR2B) in the hippocampus of KM rats during postnatal development. A significantly higher activity of ERK1/2 in KM rats was observed at 14th, 30th, and 60th days of postnatal development (P14, P30, P60) in comparison with control Wistar rats of the corresponding ages, while in adult (P120) KM rats it was at the same level with Wistar rats. Despite the increased activity of ERK1/2 at P14 and P30, the phosphorylation of synapsin I at Ser62/67 was significantly lower in the hippocampus of KM rats than in Wistar rats of the same ages; however, at P60 and P120, the phosphorylation of synapsin I was enhanced. Our data also revealed the increase of VGLUT2 and NR2B expression at P14, which dramatically decreased at the later stages. Our data indicate that a genetically determined increase in ERK1/2 kinase activity during postnatal ontogenesis in KM rats may be associated with the disturbances in synthesis and activity of the proteins, which are responsible for glutamatergic transmission in the KM rat hippocampus during the seizure susceptibility development.


Assuntos
Epilepsia Reflexa/metabolismo , Epilepsia Reflexa/fisiopatologia , Hipocampo/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Masculino , Ratos , Ratos Wistar
18.
Копенгаген; Всемирная организация здравоохранения. Европейское региональное бюро; 2019. (WHO/EURO:2019-3643-43402-60940).
em Russo | WHO IRIS | ID: who-346423

RESUMO

Неинфекционные заболевания (НИЗ), такие как рак, сердечно-сосудистые заболевания, диабет и хронические респираторные заболевания, а также их факторы риска, являются растущей проблемой в области развития и общественного здравоохранения в Казахстане. В настоящем докладе предлагаются фактические данные, полученные в результате трех проведенных анализов, подтверждающие, что НИЗ способствуют сокращению объемов производства; в нем также рассматриваются возможные варианты мер, направленных на решение этой проблемы, с обзором относительного возврата инвестиций для каждой меры. Анализ экономического ущерба показал, что экономические потери, обусловленные НИЗ (прямые затраты и потери для экономики), составляют 2,3 трлн. тенге, что эквивалентно 4,5% валового внутреннего продукта страны за 2017 год. В рамках проведения расчета затрат на осуществление вмешательств были предварительно оценены объемы финансирования, необходимые для реализации комплекса профилактических мер и клинических вмешательств. В ходе проведения анализа экономической эффективности затраты на осуществление вмешательств были сопоставлены с прогнозируемым улучшением показателей здоровья, а также определены пакеты мер, дающие максимальный возврат инвестиций. Например, коэффициент соотношения затрат и выгод для пакета мер, направленных на сокращение потребления соли, составляет 118,4 за 15-летний период. Это прибыль в размере более 118 тенге на каждый инвестированный тенге.


Assuntos
Doenças não Transmissíveis , Doença Crônica , Atenção à Saúde , Financiamento da Assistência à Saúde , Planos de Sistemas de Saúde , Cazaquistão
19.
Copenhagen; World Health Organization. Regional Office for Europe; 2019. (WHO/EURO:2019-3643-43402-60941).
em Inglês | WHO IRIS | ID: who-346422

RESUMO

Noncommunicable diseases (NCDs) such as cancer, cardiovascular disease, diabetes and chronic respiratory diseases and their risk factors are an increasing public health and development challenge in Kazakhstan. This report provides evidence through three analyses that NCDs reduce economic output and discusses potential options in response, outlining details of their relative returns on investment. An economic burden analysis shows that economic losses from NCDs (direct and indirect costs) comprise 2.3 trillion tenge, equivalent to 4.5% of gross domestic product in 2017. An intervention costing analysis provides an estimate of the funding required to implement a set of policy interventions for prevention and clinical interventions. A cost–benefit analysis compares these implementation costs with the estimated health gains and identifies which policy packages would give the greatest returns on investment. For example, the salt policy package achieved a benefit-to-cost ratio of 118.4 over 15 years, a return of more than 118 tenge for every 1 tenge invested.


Assuntos
Doenças não Transmissíveis , Doença Crônica , Atenção à Saúde , Financiamento da Assistência à Saúde , Planos de Sistemas de Saúde , Cazaquistão
20.
Copenhagen; World Health Organization. Regional Office for Europe; 2019. (WHO/EURO:2019-3642-43401-60939).
em Inglês | WHO IRIS | ID: who-346420

RESUMO

Noncommunicable diseases (NCDs) such as cancer, cardiovascular disease, diabetes and chronic respiratory diseases and their risk factors are an increasing public health and development challenge in Armenia.This report provides evidence through three analyses that NCDs reduce economic output and discusses potential options in response, outlining details of their relative returns on investment. An economic burden analysis shows that economic losses from NCDs (direct and indirect costs) comprise 362.7 billion dram, equivalent to 6.5% of gross domestic product in 2017. An intervention costing analysis provides an estimate of the funding required to implement a set of policy interventions for prevention and clinical interventions.A cost–benefit analysis compares these implementation costs with the estimated health gains and identifies which policy packages would give the greatest returns on investment. For example, the tobacco policy package achieved a return of more than 14.5 dram over 15 years for every 1 dram invested, and for a salt reduction package the equivalent return on investment was more than 14.2 dram for every 1 dram invested.


Assuntos
Doenças não Transmissíveis , Doença Crônica , Atenção à Saúde , Financiamento da Assistência à Saúde , Planos de Sistemas de Saúde , Armênia
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