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DOAJ Open Access 2026
Hidden in the Chest: Myocardial Bridging and Cardiovascular Response to Exercise

Dominik Kret, Wiktoria Szlachta, Daria Twardowska et al.

Myocardial bridging (MB) of the coronary arteries has long been considered a benign anatomical variant with no significant clinical relevance. However, the development of modern imaging and functional diagnostic methods indicates that its impact on myocardial perfusion may become apparent under conditions of increased hemodynamic load, especially during physical exertion. In the context of sports science, this issue is particularly important, as even subtle coronary flow disturbances can modulate the heart's response to training load and affect exercise tolerance.The aim of this study was to present the current state of knowledge on the anatomy, pathophysiology, clinical picture, diagnosis, and therapeutic management of myocardial bridges, with particular emphasis on their functional significance under conditions of stress typical of physical activity. The article is a narrative review of the literature based on a critical analysis of anatomical, observational, and imaging studies, as well as works devoted to functional assessment and treatment strategies. Available data indicate that MBs are a common structure, but heterogeneous in terms of morphology and hemodynamic significance. Although they remain asymptomatic in most people, in selected cases they may be associated with myocardial ischemia, arrhythmias, and reduced exercise tolerance. Myocardial bridges require individualized clinical and functional assessment, and their presence should not be automatically considered insignificant, especially in the context of exercise capacity assessment.

Sports, Sports medicine
DOAJ Open Access 2025
Gender differences in self-reported hearing loss and hearing aid use: a cross-national comparison

Anastasia Lam, Yana C Vierboom, Jessica S West

Background Objective measurements estimated that 1.57 billion people globally had hearing loss in 2019. However, where audiologists are sparse, self-reported measures have been suggested as alternatives to assess burden. Moreover, research suggests this number varies by gender, due to biological and social mechanisms. Further refining our knowledge of the global prevalence of hearing loss will provide better understanding of which groups are most affected and how to best allocate resources.Methods Using Gateway to Global Ageing data and the South African National Income Dynamics Study, we estimated the prevalence and men:women ratio of self-reported hearing loss and hearing aid use for 28 countries. Hearing loss was measured as having fair/poor hearing or reporting hearing aid use. We included 664 580 observations of individuals aged 50+ years.Results We found that the four countries with the highest levels of hearing loss (China 65%, South Korea 39%, Mexico 33%, Brazil 31%) also had the lowest reported hearing aid use (as low as 1% in China). Though men were more likely than women to report hearing loss in nearly all countries, especially in regions with higher hearing aid use (USA, Northern/Western Europe), China, South Korea and South Africa reported no gender difference. As the prevalence of hearing loss and hearing aid use increased with age, gender differences generally decreased.Conclusion International variation underscores the importance of country context in shaping perceived hearing and hearing aid use. Regions with high levels of hearing loss and low hearing aid use may be especially amenable to interventions.

Medicine (General), Infectious and parasitic diseases
DOAJ Open Access 2025
Diagnostic and therapeutic approach to acute blood pressure elevations: results of an international survey among excellence centres of the European society of hypertension

Giacomo Buso, Thomas Weber, Christos Fragoulis et al.

Background Acute blood pressure (BP) elevations are common in emergency settings and are traditionally classified into hypertensive urgencies (HU) and hypertensive emergencies (HE). Malignant hypertension (MHT) represents a severe form of HE characterised by small vessel damage. Although international guidelines provide clear definitions and treatment strategies, real-world data have shown persistent fragmentation and heterogeneity in the diagnosis and management of these patients.Methods A web-based, anonymous survey promoted by the European Society of Hypertension (ESH) was distributed among physicians from 18 European and 4 non-European countries. The questionnaire assessed definitions, diagnostic work-up, BP measurement practices, and therapeutic strategies for HU, HE, and MHT.Results Sixty–four participants in 56 centres completed the survey. HU was correctly defined as a severe BP elevation without acute clinically symptomatic hypertension-mediated organ damage (A-HMOD) by 45.3% of respondents. Small cuffs were available to 79.7% and extra-large cuffs to 70.3% of respondents.. Intravenous antihypertensive therapy was used for HE by 88.7% of participants, while 20.6% also used intravenous drugs for HU. Parenteral clonidine and sublingual nifedipine were prescribed by 29.7% and 26.6% of respondents, respectively. Definitions and therapeutic approaches for MHT varied substantially, with 62.9% adopting a recently proposed definition involving at least three target organ damages in patients with BP >200/120 mmHg.Conclusions This international survey highlights considerable variability in the definition, diagnostic work-up, and therapeutic management of acute BP elevations, emphasising the need for harmonised protocols and further education.

Diseases of the circulatory (Cardiovascular) system
DOAJ Open Access 2025
Impact of providing education on the recognition and differential diagnosis of angioedema among emergency department physicians

Derya Unal, MD, Semra Demir, MD, Sacide Rana Işik, MD et al.

Background: We aimed to assess knowledge of emergency department (ED) physicians regarding the classification and treatment of angioedema and to evaluate the impact of a training program on this knowledge base. Methods: A total of 11 questions about angioedema and its types were posed to ED physicians from various hospitals, either in person or via e-mail, before the implementation of an educational module on the subject (pre-test). Following a brief training period, the ED physicians were presented with the same set of questions once again (post-test). The reliability between the repeated tests were estimated using intraclass correlation coefficients (ICC). Item difficulty was calculated separately for each question in both the pre-test and post-test. Results: A total of 541 ED physicians participated in the pre-test survey, and 162 of them declined to participate in the post-test survey. The remaining 379 participated in the post-test survey as well. The ICC between the repeated tests indicated a moderate level of reliability (mean ICC = 0.5; 0.42–0.57; lower and upper 95% confidence intervals). The mean item difficulty was 0.36 in the pre-test, indicating that the items had an appropriate level of difficulty. In the post-test, the mean item difficulty increased to 0.57, suggesting that the items were generally easier, likely reflecting improved knowledge or skills following the intervention. The level of knowledge regarding the clinical features of different types of angioedema was found to be inadequate. Following the training period, there was a notable increase in the number of correct answers, with a statistically significant difference (p = 0.002). Similarly, a remarkable increase was observed in the number of respondents who indicated that bradykinin-mediated-angioedema should be considered in cases of unresponsiveness to antihistamine and-corticosteroid treatment (p < 0.001). Regarding queries about hereditary angioedema (HAE), the majority of ED physicians had no prior experience in treating a patient with HAE, and only a small number were familiar with the symptoms of HAE. Following the training ED physicians demonstrated enhanced knowledge of HAE symptoms and diagnostic criteria (p < 0.001). Similarly, a notable enhancement in familiarity with HAE attack treatments was observed when the inquiries related to these treatments were compared between the pre-test and post-test phases (p < 0.001). Conclusion: In light of the potential lethality of attacks mediated by bradykinin, a training program should include the recognition of rare types of angioedema, with a particular emphasis on HAE disease.

Immunologic diseases. Allergy
DOAJ Open Access 2024
The imaging features of ectopic spleen: which modality is more consistent? A cases series report and literature reviews

Mingyue Xiao, Jiayi Liang, Jie Ren et al.

Ectopic spleen (ES) is a rare condition. It is difficult to diagnose with conventional imaging modalities. In this case series, we presented the imaging features of three misdiagnosed ES cases in our hospital and previously reported cases to compare the consistency of enhancement patterns among different imaging modalities with varied phases. Finally, 22 cases were reviewed. We determined that variable arterial phase enhancement and persistent enhancement throughout the portal and delayed phases are present in contrast-enhanced ultrasound (CEUS) imaging of the ES and found the arterial phase of CEUS had the highest consistency compared with computerized tomography (CT) and magnetic resonance imaging (MRI).

Neoplasms. Tumors. Oncology. Including cancer and carcinogens
DOAJ Open Access 2023
Identification of serum micro-RNAs of early knee osteoarthritis in a cohort of Egyptian patients

Anna Abou-Raya, Mohamed Rizk, Eman AbdelGhani et al.

ABSTRACTBackground Osteoarthritis (OA), is a prevalent low-grade inflammatory synovial joint disease characterized by progressive cartilage degradation and alteration of the entire joint. Knee OA (KOA) is the commonest form of OA. Osteoarthritis is the 4th leading cause of disability worldwide with no cure and therefore identifying persons with early OA of the knee (KOA), is important to retard progression of the disease process. Several proinflammatory cytokines and microRNAs (miRNAs) are involved in OA pathogenesis.Objective The aim of the work was to investigate the serum miRNA-136 (miR-136) and miR-155-5p expression profile, IL-8 and IL-17 levels in subjects with early KOA and to further evaluate and compare the expression profile of these miRNAs, and level of serum IL-8 and IL-17 in subjects with early and severe KOA.Methods Serum miR-136 and miR-155-5p expression profile in 40 patients with early KOA were compared to 40 age and sex matched healthy controls and 10 patients with severe KOA. Clinical, laboratory, and disease parameters were assessed. Serum and synovial fluid miRNAs were assessed by real-time polymerase chain reaction. Levels of IL-17 and IL-8 levels were determined by the enzyme linked immunosorbent assay test.Results miR-155-5p in serum was significantly higher in early KOA patients compared to healthy controls and to patients with severe OA. Synovial miRNA-155-5p expression levels were significantly higher than serum miRNA-155-5p in severe KOA patients compared to early OA patients. When we compared the expression levels of miRNA-136 between cases and healthy controls, there was no statistical significant difference, p=0.413. Serum IL-8 levels were significantly higher in early OA patients compared to healthy controls.Conclusions Serum miR-155-5p and IL-8 levels are potential useful biomarkers for the early detection of OA and in particular, early KOA.

DOAJ Open Access 2022
Biobanking in LMIC settings for infectious diseases: Challenges and enablers

Sameera Ezzat, Ruzica Biga, Zisis Kozlakidis

Biobanking facilities are well established in high-income settings, where substantial funding has been invested in infrastructure. In contrast, such facilities are much less developed in resource-restricted settings. However, low-and middle-income countries (LMICs) still face a disproportionately high infectious diseases burden. Thus, the further development of infrastructure facilities, including biobanks is warranted as an important component of this unfolding clinical research environment. This perspective manuscript summarises the challenges and enablers for biobanking in LMICs, with a particular focus on infectious diseases, incorporating some of the lessons learned from the recent coronavirus disease 2019 (COVID-19) pandemic.

Infectious and parasitic diseases, Public aspects of medicine
DOAJ Open Access 2022
A Novel Prognostic Scoring Model for Myelodysplastic Syndrome Patients With SF3B1 Mutation

Liya Ma, Bin Liang, Huixian Hu et al.

The outcomes of myelodysplastic syndrome (MDS) patients with SF3B1 mutation, despite identified as a favorable prognostic biomarker, are variable. To comprehend the heterogeneity in clinical characteristics and outcomes, we reviewed 140 MDS patients with SF3B1 mutation in Zhejiang province of China. Seventy-three (52.1%) patients diagnosed as MDS with ring sideroblasts (MDS-RS) following the 2016 World Health Organization (WHO) classification and 118 (84.3%) patients belonged to lower risk following the revised International Prognostic Scoring System (IPSS-R). Although clonal hematopoiesis-associated mutations containing TET2, ASXL1 and DNMT3A were the most frequent co-mutant genes in these patients, RUNX1, EZH2, NF1 and KRAS/NRAS mutations had significant effects on overall survival (OS). Based on that we developed a risk scoring model as IPSS-R×0.4+RUNX1×1.1+EZH2×0.6+RAS×0.9+NF1×1.6. Patients were categorized into two subgroups: low-risk (L-R, score &lt;= 1.4) group and high risk (H-R, score &gt; 1.4) group. The 3-year OS for the L-R and H-R groups was 91.88% (95% CI, 83.27%-100%) and 38.14% (95% CI, 24.08%-60.40%), respectively (P&lt;0.001). This proposed model distinctly outperformed the widely used IPSS-R. In summary, we constructed and validated a personalized prediction model of MDS patients with SF3B1 mutation that can better predict the survival of these patients.

Neoplasms. Tumors. Oncology. Including cancer and carcinogens
DOAJ Open Access 2022
A case of NASH with genetic predisposition successfully treated with an SGLT2 inhibitor: a possible involvement of mitochondrial dysfunction

Rikako Nakajima, Motohiro Sekiya, Yasuhisa Furuta et al.

In this study, we herein describe a 47-year-old Japanese woman who manifested inheritable non-alcoholic steatohepatitis (NASH) and severe dyslipidemia. Interestingly, her NASH progression was ameliorated by treatment with a sodium– glucose co-transporter 2 (SGLT2) inhibitor. This inheritability prompted us to comprehensively decode her genomic information using whole-exome sequencing. We found the well-established I148M mutation in PNPLA3 as well as mutations in LGALS3 and PEMT for her NASH. Mutations in GCKR may contribute to both NASH and dyslipidemia. We further mined gene mutations potentially responsible for her manifestations that led to the identification of a novel M188fs mutation in MUL1 that may be causally associated with her mitochondrial dysfunction. Our case may provide some clues to better understand this spectrum of disease as well as the rationale for selecting medications.

Diseases of the endocrine glands. Clinical endocrinology
DOAJ Open Access 2021
A survey about sports investments in Iran: Comparison between 1998 & 2016 without inflation

Fariba Askarian

Background: Sports Investments is one of the most unique sports events, in the country dealing both with collectors and dealers.Aim: The purpose of this study was to compare the sports investment o Iran in 2016 and 1998. Therefore, we estimate the value of the sports investment sector and share of total investment, GDP, GDSP and compare with 1998 in Iran.Materials and Methods: In this study, national accounts were used. Most of the basic data fare available in a decentralized manner in the Statistics Center and the Program and Budget Organization of Iran. Due to achieving real changes in sports investment between 1998 and 2016, prices in 1998 was considered as the base year and were considered. Then using the price index of the desired years, the effects of inflation were eliminated and growth real was calculated.Results: The results indicate that investment in sport in 1998 was 360 billion Rials, which is 0.43% of total investment, 0.1% GDP, and 26.2% of GDSP. Also, investment in sport in 2016 was 15449 billion Rials, which is 0.46% of total investment, 0.11% GDP and, 73.38% of GDSP. Investment in sport in 2016 compared to 1998 had 2347% real growth.Conclusion: Although, investment in sport in 2016 compared to 1998 has grown, but it is very small compared to the total investments. Results also show the major share of the public sector and the low participation of the private sector.

Sports, Sports medicine
DOAJ Open Access 2021
DOUBLE HETEROZYGOTIC FV DEFECT WITH HETEROZYGOTIC FV LEIDEN MUTATION AND FV DEFICIENCY IN THROMBOSIS

İSMAİL ALTUĞ DEMİR, HATİCE DEMET KİPER ÜNAL, ŞERİFE SOLMAZ et al.

Objective: FV Leiden mutation causes activated protein C (APC) resistance and causes an increase in thrombin level. Although moderate bleeding is seen in severe factor V deficiency, less than 1% of patients experience bleeding. Cases in which thrombosis is prominent in the presence  FV Leiden mutation and FV deficiency have been reported. Here, we present a patient with FV deficiency with FV Leiden heterozygous mutation in the etiology of recurrent abortion. Case report: A 41-year-old female patient who applied to her primary care physician with bilateral lumbar pain upon finding INR: 1.43 (0.8-1.2) and APTT: 37.6 seconds (25-36.5), the patient was recommended to apply to our out patient clinic. The patient who described two spontaneous abortions (at the age of 25, the first in the 2nd trimester and the other in the 3rd trimester), also had a history of ecchymosis in the extremities caused by minor trauma at intervals. Methodology: PT, INR and APTT returned to normal with the mixing test performed on the patient (12.1 sEC, 1.03 and 28.6 sec, respectively).Afterwards, FV, which is one of the factors in the common pathway of coagulation, was found low in the examination repeated twice (12.3% and 10.2%) (N: 62-139%). The APCR studied twice in screening for thrombophilia was 1.4  and 2.4 (N: 2.61-3.32) Protein C, protein S, antithrombin III levels were within normal limits, LAC and APA were negative. Results: According to this result, FV Leiden heterozygous mutation was detected in the genetic thrombophilia panel. Also the patient had FV deficiency . Conclusion: Authors termed the coexistence of heterozygous FV Leiden mutation and type1 FV deficiency as pseudohomozygous FV Leiden mutation. In our and other studies, we concluded that thrombosis was clinically significant, where as bleeding was rare and mild. We think that prolonged PT and APTT results in patients with a history of thrombosis with FV Leidenmutation are also stimulating in evaluating FV activity.

Diseases of the blood and blood-forming organs
DOAJ Open Access 2020
Identification of Plasma Glycosphingolipids as Potential Biomarkers for Prostate Cancer (PCa) Status

Ashley J. Snider, Michael C. Seeds, Laurel Johnstone et al.

Prostate cancer (PCa) is the most common male cancer and the second leading cause of cancer death in United States men. Controversy continues over the effectiveness of prostate-specific antigen (PSA) for distinguishing aggressive from indolent PCa. There is a critical need for more specific and sensitive biomarkers to detect and distinguish low- versus high-risk PCa cases. Discovery metabolomics were performed utilizing ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) on plasma samples from 159 men with treatment naïve prostate cancer participating in the North Carolina-Louisiana PCa Project to determine if there were metabolites associated with aggressive PCa. Thirty-five identifiable plasma small molecules were associated with PCa aggressiveness, 15 of which were sphingolipids; nine common molecules were present in both African-American and European-American men. The molecules most associated with PCa aggressiveness were glycosphingolipids; levels of trihexosylceramide and tetrahexosylceramide were most closely associated with high-aggressive PCa. The Cancer Genome Atlas was queried to determine gene alterations within glycosphingolipid metabolism that are associated with PCa and other cancers. Genes that encode enzymes associated with the metabolism of glycosphingolipids were altered in 12% of PCa and >30% of lung, uterine, and ovarian cancers. These data suggest that the identified plasma (glyco)sphingolipids should be further validated for their association with aggressive PCa, suggesting that specific sphingolipids may be included in a diagnostic signature for PCa.

DOAJ Open Access 2017
Metastização óssea de carcinoma hepatocelular – A propósito de um caso clínico

Sónia Martins, Ana Sanches

O carcinoma hepatocelular (CHC) é o tumor hepático mais frequente, com uma incidência crescente ao longo dos anos. A metastização extra-hepática após terapêutica loco-regional é pouco frequente, sendo o osso um local pouco afetado. Os autores apresentam o caso de um doente de 72 anos, com antecedentes pessoais de CHC (controlado sob radiofrequência), que recorreu ao Serviço de Urgência por dor no membro superior direito com início após mau posicionamento. A radiografia mostrou fratura da extremidade distal do úmero, tendo realizado radiografia de controlo após 2 meses que apresentava ausência de osso no local onde tinha ocorrido a fratura, agora substituído por lesão expansiva. Após estudo complementar admitiu-se tratar-se de metástase óssea do CHC. O doente faleceu 1 mês após o diagnóstico. O caso apresentado alerta para a importância da exclusão de fraturas patológicas em doentes com antecedentes pessoais de neoplasia, o que, caso se verifique, poderá alterar a abordagem e prognóstico destes doentes. Hepatocellular carcinoma (HCC) is the most frequent liver tumor, with an increasing incidence over the years. Extrahepatic metastasis after locoregional therapy is infrequent, with bone being a poorly affected site. The authors present the case of a 72 year-old man, with a personal history of HCC (controlled under radiofrequency) who appealed to the Emergency Department for pain in the upper right limb after poor positioning. The radiograph showed fracture of the distal end of the humerus, and a control radiograph was performed after 2 months, which showed no bone at the site where the fracture had occurred, now replaced by an expansive lesion. After a complementary study it is admitted that bone metastasis of HCC is involved. The patient died 1 month after diagnosis. The present case alerts to the importance of the exclusion of pathological fractures in patients with a personal history of neoplasia, which, if happens, could alter the approach and prognosis of these patients.

Medicine, Internal medicine
DOAJ Open Access 2017
Lipids characterization of ultrasound and microwave processed germinated sorghum

Sadia Hassan, Muhammad Imran, Nazir Ahmad et al.

Abstract Background Cereal crops and oilseeds provide diverse pool of fatty acids with characteristic properties. Sorghum (Sorghum bicolor (L.) Moench) provides the staple food with serving as main source of energy and protein. Germination of sorghum generally increases the nutritive value of seeds and the effects of germination on lipids composition of seeds vary greatly with processing conditions. Therefore, the current study was conducted to compare the effect of emerging processing techniques such as ultrasound (US) and microwave (MW) on fatty acids composition and oil yield of sorghum seeds before and after germination. Methods Initially sorghum grains were soaked with 5% NaOCl (sodium hypochlorite) for surface sterilization. Afterwards, grains were soaked in excess water for 22 h at room temperature and were divided into four portions. The first portion (100 g grains) was subjected to germination without applying any microwave and ultrasonic treatment (T0). Second portion was further divided into four groups (T1, T2, T3, T4) (100 g of each group) and grains were subjected to ultrasonic treatments using two different ultrasonic intensities (US1: 40%; US2: 60%) within range of 0–100% and with two different time durations (tUS1: 5 min; tUS2: 10 min) at constant temperature. Third portion was also divided into four groups (T1, T2, T3, T4) (100 g of each group) and exposed to microwave treatments at two different power levels (MW1: 450 watt; MW2: 700 watt) within the range of 100-900 W for two different time durations (tMW1: 15 s; tMW2: 30s). Similarly, fourth portion was divided into four groups (T1, T2, T3, T4) (100 g of each group). Each group was exposed to both MW (MW1, MW2) (100–900 watt power) & US (US1, US2) (0–100% intensity) treatments at two different time levels (tUS, tMW). Then, germination was carried out and pre-treated raw and pre-treated germinated sorghum grains were analyzed for total oil yield, fatty acid composition and unsaturated fatty acids (Un-SFA)/saturated fatty acids (SFA) ratio by gas chromatography. Results The results revealed that oil yield in sorghum before and after germination ranged from 6.55 to 7.84% and 6.28 to 7.57%, respectively. All the microwave and ultrasound processed samples showed significant difference in oil yield than the raw sorghum grains. The highest tested yield was 7.84 ± 0.31% when combination of microwave power (700 W) and ultrasound intensity (60%) was applied for 30s and 10 min, respectively. The results further demonstrate that the raw sorghum contained palmitic (13.73 ± 0.10%), palmitoleic (0.43 ± 0.02%), stearic (1.07 ± 0.04%), oleic (37.15 ± 0.10%), linoleic (43.33 ± 0.21%), linolenic (1.55 ± 0.04%), arachidic acid (0.13 ± 0.01%) and eicosenoic acid (0.37 ± 0.02%), respectively. The highest fatty acid percentage for palmitic, stearic and arachidic acid was 13.75 ± 0.07%, 1.11 ± 0.09% and 0.15 ± 0.03% at 60% US intensity for 10 min (T4), respectively. Maximum amount observed was 1.60 ± 0.09% of linolenic acid while amount of eicosenoic acid decreased from 0.37 ± 0.02% to 0.31 ± 0.01% after processing. In case of applying combination of microwave and sonication treatments, the change in eicosenoic acid increased from 0.35 ± 0.02% to 0.40 ± 0.04% while there was no significant change in other fatty acids. The ungerminated sorghum oil possessed 14.93–15.05% and 82.83–83.12% of SFA and Un-SFA, respectively. After germination, percentage of saturated fatty acids increased (16.4–16.55%) while decreased for unsaturated fatty acids (80.13–80.56%) were noted. Conclusions The results of the present study conclude that the yield of oil from sorghum grains increased by emerging processing. Fatty acid analysis of sorghum oil suggested that pre-treatment strategies will not affect the quality of the oil with respect to essential fatty acids content. Overall, the composition of saturated fatty acid in germinated grain is improved than ungerminated grains after processing.

Nutritional diseases. Deficiency diseases
DOAJ Open Access 2014
Conditional expression of Parkinson's disease-related R1441C LRRK2 in midbrain dopaminergic neurons of mice causes nuclear abnormalities without neurodegeneration

Elpida Tsika, Meghna Kannan, Caroline Shi-Yan Foo et al.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset, autosomal dominant Parkinson's disease (PD). The clinical and neurochemical features of LRRK2-linked PD are similar to idiopathic disease although neuropathology is somewhat heterogeneous. Dominant mutations in LRRK2 precipitate neurodegeneration through a toxic gain-of-function mechanism which can be modeled in transgenic mice overexpressing human LRRK2 variants. A number of LRRK2 transgenic mouse models have been developed that display abnormalities in dopaminergic neurotransmission and alterations in tau metabolism yet without consistently inducing dopaminergic neurodegeneration. To directly explore the impact of mutant LRRK2 on the nigrostriatal dopaminergic pathway, we developed conditional transgenic mice that selectively express human R1441C LRRK2 in dopaminergic neurons from the endogenous murine ROSA26 promoter. The expression of R1441C LRRK2 does not induce the degeneration of substantia nigra dopaminergic neurons or striatal dopamine deficits in mice up to 2 years of age, and fails to precipitate abnormal protein inclusions containing alpha-synuclein, tau, ubiquitin or autophagy markers (LC3 and p62). Furthermore, mice expressing R1441C LRRK2 exhibit normal motor activity and olfactory function with increasing age. Intriguingly, the expression of R1441C LRRK2 induces age-dependent abnormalities of the nuclear envelope in nigral dopaminergic neurons including reduced nuclear circularity and increased invaginations of the nuclear envelope. In addition, R1441C LRRK2 mice display increased neurite complexity of cultured midbrain dopaminergic neurons. Collectively, these novel R1441C LRRK2 conditional transgenic mice reveal altered dopaminergic neuronal morphology with advancing age, and provide a useful tool for exploring the pathogenic mechanisms underlying the R1441C LRRK2 mutation in PD.

Neurosciences. Biological psychiatry. Neuropsychiatry
DOAJ Open Access 2010
Community response to artemisinin-based combination therapy for childhood malaria: a case study from Dar es Salaam, Tanzania

Nyato Daniel J, Kamat Vinay R

<p>Abstract</p> <p>Background</p> <p>New malaria treatment guidelines in Tanzania have led to the large-scale deployment of artemether-lumefantrine (Coartem<sup>®</sup>), popularly known as ALu or <it>dawa mseto</it>. Very little is known about how people in malaria endemic areas interpret policy makers' decision to replace existing anti-malarials, such as sulphadoxine-pyrimethamine (SP) with "new" treatment regimens, such as ALu or other formulations of ACT. This study was conducted to examine community level understandings and interpretations of ALu's efficacy and side-effects. The paper specifically examines the perceived efficacy of ALu as articulated by the mothers of young children diagnosed with malaria and prescribed ALu.</p> <p>Methods</p> <p>Participant observation, six focus group discussions in two large villages, followed by interviews with a random sample of 110 mothers of children less than five years of age, who were diagnosed with malaria and prescribed ALu. Additionally, observations were conducted in two village dispensaries involving interactions between mothers/caretakers and health care providers.</p> <p>Results</p> <p>While more than two-thirds of the mothers had an overall negative disposition toward SP, 97.5% of them spoke favourably about ALu, emphasizing it's ability to help their children to rapidly recover from malaria, without undesirable side-effects. 62.5% of the mothers reported that they were spending less money dealing with malaria than previously when their child was treated with SP. 88% of the mothers had waited for 48 hours or more after the onset of fever before taking their child to the dispensary. Mothers' knowledge and reporting of ALu's dosage was, in many cases, inconsistent with the recommended dosage schedule for children.</p> <p>Conclusion</p> <p>Deployment of ALu has significantly changed community level perceptions of anti-malarial treatment. However, mothers continue to delay seeking care before accessing ALu, limiting the impact of highly subsidized rollout of the drug. Implementation of ACT-based treatment guidelines must be complemented with educational campaigns to insure that mothers seek prompt help for their children within 24 hours of the onset of fever. Improved communication between health care providers and mothers of sick children can facilitate better adherence to ALu's recommended dosage. Community level interpretations of anti-malarials are multifaceted; integrating knowledge of local beliefs and practices surrounding consumption of anti-malarials into programmatic goals can help to significantly improve malaria control interventions.</p>

Arctic medicine. Tropical medicine, Infectious and parasitic diseases

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