Burden of Ischemic and Hemorrhagic Stroke Across the US From 1990 to 2019.

Importance: Stroke is a leading cause of death and disability in the US. Accurate and updated measures of stroke burden are needed to guide public health policies. Objective: To present burden estimates of ischemic and hemorrhagic stroke in the US in 2019 and describe trends from 1990 to 2019 by age, sex, and geographic location. Design, Setting, and Participants: An in-depth cross-sectional analysis of the 2019 Global Burden of Disease study was conducted. The setting included the time period of 1990 to 2019 in the US. The study encompassed estimates for various types of strokes, including all strokes, ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs). The 2019 Global Burden of Disease results were released on October 20, 2020. Exposures: In this study, no particular exposure was specifically targeted. Main Outcomes and Measures: The primary focus of this analysis centered on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100 000 individuals. Results: In 2019, the US recorded 7.09 million prevalent strokes (4.07 million women [57.4%]; 3.02 million men [42.6%]), with 5.87 million being ischemic strokes (82.7%). Prevalence also included 0.66 million ICHs and 0.85 million SAHs. Although the absolute numbers of stroke cases, mortality, and DALYs surged from 1990 to 2019, the age-standardized rates either declined or remained steady. Notably, hemorrhagic strokes manifested a substantial increase, especially in mortality, compared with ischemic strokes (incidence of ischemic stroke increased by 13% [95% uncertainty interval (UI), 14.2%-11.9%]; incidence of ICH increased by 39.8% [95% UI, 38.9%-39.7%]; incidence of SAH increased by 50.9% [95% UI, 49.2%-52.6%]). The downturn in stroke mortality plateaued in the recent decade. There was a discernible heterogeneity in stroke burden trends, with older adults (50-74 years) experiencing a decrease in incidence in coastal areas (decreases up to 3.9% in Vermont), in contrast to an uptick observed in younger demographics (15-49 years) in the South and Midwest US (with increases up to 8.4% in Minnesota). Conclusions and Relevance: In this cross-sectional study, the declining age-standardized stroke rates over the past 3 decades suggest progress in managing stroke-related outcomes. However, the increasing absolute burden of stroke, coupled with a notable rise in hemorrhagic stroke, suggests an evolving and substantial public health challenge in the US. Moreover, the significant disparities in stroke burden trends across different age groups and geographic locations underscore the necessity for region- and demography-specific interventions and policies to effectively mitigate the multifaceted and escalating burden of stroke in the country.

Emergent Crisis of COVID-19 Pandemic: Mental Health Challenges and Opportunities.

Mental health is a fundamental human right and is part of the well-being of society. The public health burden of mental health disorders affects people's social and economic status around the world. Coronavirus's (COVID-19) negative impact on the economy and mental health worldwide is concerning. This is a worldwide emergency, and there is an urgent need for research about this topic to prevent long-lasting adverse effects on the population. Unpreparedness and inconsistencies in guidelines, lockdowns, containment strategies, unemployment, financial losses, physical distancing, isolation, chaos, and uncertainty are among factors that lead to a rise in emotional distress, anxiety, and depression. Governments' decisions affect the socioeconomic status of a country and the psychological well-being of the people. COVID-19 pandemic exposed disparities in multiple mental health care systems by having adverse mental health effects in people with pre-existing mental health disorders and previously healthy individuals. Aggregation of concurrent or cumulative comorbid risk factors for COVID-19 disease and its psychosocial sequelae could provide invaluable information for the public health stakeholders. This review aims to address the burden and the psychosocial impact of the COVID-19 pandemic, the challenges and opportunities facing mental health systems, and proposes new strategies to improve the mental health outcomes in the post-COVID era.

Burden of Neurological Disorders Across the US From 1990-2017: A Global Burden of Disease Study.

Importance: Accurate and up-to-date estimates on incidence, prevalence, mortality, and disability-adjusted life-years (burden) of neurological disorders are the backbone of evidence-based health care planning and resource allocation for these disorders. It appears that no such estimates have been reported at the state level for the US. Objective: To present burden estimates of major neurological disorders in the US states by age and sex from 1990 to 2017. Design, Setting, and Participants: This is a systematic analysis of the Global Burden of Disease (GBD) 2017 study. Data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of major neurological disorders were derived from the GBD 2017 study of the 48 contiguous US states, Alaska, and Hawaii. Fourteen major neurological disorders were analyzed: stroke, Alzheimer disease and other dementias, Parkinson disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus. Exposures: Any of the 14 listed neurological diseases. Main Outcome and Measure: Absolute numbers in detail by age and sex and age-standardized rates (with 95% uncertainty intervals) were calculated. Results: The 3 most burdensome neurological disorders in the US in terms of absolute number of DALYs were stroke (3.58 [95% uncertainty interval [UI], 3.25-3.92] million DALYs), Alzheimer disease and other dementias (2.55 [95% UI, 2.43-2.68] million DALYs), and migraine (2.40 [95% UI, 1.53-3.44] million DALYs). The burden of almost all neurological disorders (in terms of absolute number of incident, prevalent, and fatal cases, as well as DALYs) increased from 1990 to 2017, largely because of the aging of the population. Exceptions for this trend included traumatic brain injury incidence (-29.1% [95% UI, -32.4% to -25.8%]); spinal cord injury prevalence (-38.5% [95% UI, -43.1% to -34.0%]); meningitis prevalence (-44.8% [95% UI, -47.3% to -42.3%]), deaths (-64.4% [95% UI, -67.7% to -50.3%]), and DALYs (-66.9% [95% UI, -70.1% to -55.9%]); and encephalitis DALYs (-25.8% [95% UI, -30.7% to -5.8%]). The different metrics of age-standardized rates varied between the US states from a 1.2-fold difference for tension-type headache to 7.5-fold for tetanus; southeastern states and Arkansas had a relatively higher burden for stroke, while northern states had a relatively higher burden of multiple sclerosis and eastern states had higher rates of Parkinson disease, idiopathic epilepsy, migraine and tension-type headache, and meningitis, encephalitis, and tetanus. Conclusions and Relevance: There is a large and increasing burden of noncommunicable neurological disorders in the US, with up to a 5-fold variation in the burden of and trends in particular neurological disorders across the US states. The information reported in this article can be used by health care professionals and policy makers at the national and state levels to advance their health care planning and resource allocation to prevent and reduce the burden of neurological disorders.

The Burden of Skin and Subcutaneous Diseases in the United States From 1990 to 2017.

Importance: Skin and subcutaneous diseases affect the health of millions of individuals in the US. Data are needed that highlight the geographic trends and variations of skin disease burden across the country to guide health care decision-making. Objective: To characterize trends and variations in the burden of skin and subcutaneous tissue diseases across the US from 1990 to 2017. Design, Setting, and Participants: For this cohort study, data were obtained from the Global Burden of Disease (GBD), a study with an online database that incorporates current and previous epidemiological studies of disease burden, and from GBD 2017, which includes more than 90 000 data sources such as systematic reviews, surveys, population-based disease registries, hospital inpatient and outpatient data, cohort studies, and autopsy data. The GBD separated skin conditions into 15 subcategories according to incidence, prevalence, adequacy of data, and standardized disease definitions. GBD 2017 also estimated the burden from melanoma of the skin and keratinocyte carcinoma. Data analysis for the present study was conducted from September 9, 2019, to March 31, 2020. Main Outcomes and Measures: Primary study outcomes included age-standardized disability-adjusted life-years (DALYs), incidence, and prevalence. The data were stratified by US states with the highest and lowest age-standardized DALY rate per 100 000 people, incidence, and prevalence of each skin condition. The percentage change in DALY rates in each state was calculated from 1990 to 2017. Results: Overall, age-standardized DALY rates for skin and subcutaneous diseases increased from 1990 (821.6; 95% uncertainty interval [UI], 570.3-1124.9) to 2017 (884.2; 95% UI, 614.0-1207.9) in all 50 states and the District of Columbia. The degree of increase varied according to geographic location, with the largest percentage change of 0.12% (95% UI, 0.09%-0.15%) in New York and the smallest percentage change of 0.04% (95% UI, 0.02%-0.07%) in Colorado, 0.04% (95% UI, 0.01%-0.06%) in Nevada, 0.04% (95% UI, 0.02%-0.07%) in New Mexico, and 0.04% (95% UI, 0.02%-0.07%) in Utah. The age-standardized DALY rate, incidence, and prevalence of specific skin conditions differed among the states. New York had the highest age-standardized DALY rate for skin and subcutaneous disease in 2017 (1097.0 [95% UI, 764.9-1496.1]), whereas Wyoming had the lowest age-standardized DALY rate (672.9 [95% UI, 465.6-922.3]). In all 50 states and the District of Columbia, women had higher age-standardized DALY rates for overall skin and subcutaneous diseases than men (women: 971.20 [95% UI, 676.76-1334.59] vs men: 799.23 [95% UI, 559.62-1091.50]). However, men had higher DALY rates than women for malignant melanoma (men: 80.82 [95% UI, 51.68-123.18] vs women: 42.74 [95% UI, 34.05-70.66]) and keratinocyte carcinomas (men: 37.56 [95% UI, 29.35-49.52] vs women: 14.42 [95% UI, 10.01-20.66]). Conclusions and Relevance: Data from the GBD suggest that the burden of skin and subcutaneous disease was large and that DALY rate trends varied across the US; the age-standardized DALY rate for keratinocyte carcinoma appeared greater in men. These findings can be used by states to target interventions and meet the needs of their population.

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

BACKGROUND: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. METHODS: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. RESULTS: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. CONCLUSIONS: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

Falls in older aged adults in 22 European countries: incidence, mortality and burden of disease from 1990 to 2017.

INTRODUCTION: Falls in older aged adults are an important public health problem. Insight into differences in fall-related injury rates between countries can serve as important input for identifying and evaluating prevention strategies. The objectives of this study were to compare Global Burden of Disease (GBD) 2017 estimates on incidence, mortality and disability-adjusted life years (DALYs) due to fall-related injury in older adults across 22 countries in the Western European region and to examine changes over a 28-year period. METHODS: We performed a secondary database descriptive study using the GBD 2017 results on age-standardised fall-related injury in older adults aged 70 years and older in 22 countries from 1990 to 2017. RESULTS: In 2017, in the Western European region, 13 840 per 100 000 (uncertainty interval (UI) 11 837-16 113) older adults sought medical treatment for fall-related injury, ranging from 7594 per 100 000 (UI 6326-9032) in Greece to 19 796 per 100 000 (UI 15 536-24 233) in Norway. Since 1990, fall-related injury DALY rates showed little change for the whole region, but patterns varied widely between countries. Some countries (eg, Belgium and Netherlands) have lost their favourable positions due to an increasing fall-related injury burden of disease since 1990. CONCLUSIONS: From 1990 to 2017, there was considerable variation in fall-related injury incidence, mortality, DALY rates and its composites in the 22 countries in the Western European region. It may be useful to assess which fall prevention measures have been taken in countries that showed continuous low or decreasing incidence, death and DALY rates despite ageing of the population.

The burden of unintentional drowning: global, regional and national estimates of mortality from the Global Burden of Disease 2017 Study.

BACKGROUND: Drowning is a leading cause of injury-related mortality globally. Unintentional drowning (International Classification of Diseases (ICD) 10 codes W65-74 and ICD9 E910) is one of the 30 mutually exclusive and collectively exhaustive causes of injury-related mortality in the Global Burden of Disease (GBD) study. This study's objective is to describe unintentional drowning using GBD estimates from 1990 to 2017. METHODS: Unintentional drowning from GBD 2017 was estimated for cause-specific mortality and years of life lost (YLLs), age, sex, country, region, Socio-demographic Index (SDI) quintile, and trends from 1990 to 2017. GBD 2017 used standard GBD methods for estimating mortality from drowning. RESULTS: Globally, unintentional drowning mortality decreased by 44.5% between 1990 and 2017, from 531 956 (uncertainty interval (UI): 484 107 to 572 854) to 295 210 (284 493 to 306 187) deaths. Global age-standardised mortality rates decreased 57.4%, from 9.3 (8.5 to 10.0) in 1990 to 4.0 (3.8 to 4.1) per 100 000 per annum in 2017. Unintentional drowning-associated mortality was generally higher in children, males and in low-SDI to middle-SDI countries. China, India, Pakistan and Bangladesh accounted for 51.2% of all drowning deaths in 2017. Oceania was the region with the highest rate of age-standardised YLLs in 2017, with 45 434 (40 850 to 50 539) YLLs per 100 000 across both sexes. CONCLUSIONS: There has been a decline in global drowning rates. This study shows that the decline was not consistent across countries. The results reinforce the need for continued and improved policy, prevention and research efforts, with a focus on low- and middle-income countries.

Epidemiology of injuries from fire, heat and hot substances: global, regional and national morbidity and mortality estimates from the Global Burden of Disease 2017 study.

BACKGROUND: Past research has shown how fires, heat and hot substances are important causes of health loss globally. Detailed estimates of the morbidity and mortality from these injuries could help drive preventative measures and improved access to care. METHODS: We used the Global Burden of Disease 2017 framework to produce three main results. First, we produced results on incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years from 1990 to 2017 for 195 countries and territories. Second, we analysed these results to measure mortality-to-incidence ratios by location. Third, we reported the measures above in terms of the cause of fire, heat and hot substances and the types of bodily injuries that result. RESULTS: Globally, there were 8 991 468 (7 481 218 to 10 740 897) new fire, heat and hot substance injuries in 2017 with 120 632 (101 630 to 129 383) deaths. At the global level, the age-standardised mortality caused by fire, heat and hot substances significantly declined from 1990 to 2017, but regionally there was variability in age-standardised incidence with some regions experiencing an increase (eg, Southern Latin America) and others experiencing a significant decrease (eg, High-income North America). CONCLUSIONS: The incidence and mortality of injuries that result from fire, heat and hot substances affect every region of the world but are most concentrated in middle and lower income areas. More resources should be invested in measuring these injuries as well as in improving infrastructure, advancing safety measures and ensuring access to care.

Challenges and perspectives of child labor.

Child labor is one of the oldest problems in our society and still an ongoing issue. During the time, child labor evolved from working in agriculture or small handicraft workshops to being forced into work in factories in the urban setting as a result of the industrial revolution. Children were very profitable assets since their pay was very low, were less likely to strike, and were easy to be manipulated. Socioeconomic disparities and lack of access to education are among others contributing to the child labor. Religious and cultural beliefs can be misguiding and concealing in delineating the limits of child labor. Child labor prevents physical, intellectual, and emotional development of children. To date, there is no international agreement to fully enforced child labor. This public health issue demands a multidisciplinary approach from the education of children and their families to development of comprehensive child labor laws and regulations.

Ki67 Labeling Correlated With Invasion But Not With Recurrence.

Pituitary adenomas account for 10% to 15% of intracranial neoplasms. Multiple factors had been introduced for tumor recurrence. MIB-1 monoclonal antibody, a marker of the proliferative index, has been introduced in various tumors, but unfortunately, the usefulness of MIB-1 in predicting the behavior of pituitary adenoma has been debated recently. Hence, the aim of this study was to evaluate its role in the recurrence and the invasiveness of pituitary adenomas. In a cross-sectional study conducted between 2005 and 2010, patients with a diagnosis of pituitary adenoma, referred to 2 medical centers (Arad and Iran Mehr hospital) in Tehran, were enrolled. Clinical and laboratory data were gathered. Immunostaining for MIB-1 monoclonal antibody was performed for each slide and scored blindly by 2 pathologists. A total of 176 surgically treated patients met the inclusion criteria. Thirty-six of 176 cases had recurrent episodes. Eleven of 176 patients had invasive tumors. The mean Ki67 index was 2.7%±3.96% in recurrent cases and 2.24%±2.35% in nonrecurring cases, with no statistically significant difference between them (P>0.05). Ten of 11 invasive pituitary tumors had a Ki67>3%, and a statistically significant difference was observed between invasive and noninvasive tumors (P<0.05). Hence, the Ki67 index seems to be suitable for predicting invasion, but it failed to show any correlation between Ki67 and tumor recurrence.

Validation of Oxford Classification of Immunoglobulin A Nephropathy: an Iranian Experience.

INTRODUCTION: In 2009, the Oxford classification of immunoglobulin A (IgA) nephropathy was proposed by the working group of the International IgA Nephropathy Network and Renal Pathology Society. It established specific pathologic features that predict the risk of progression of disease. This study aimed to evaluate the interobserver reproducibility of the Oxford classification of IgA nephropathy between Iranian nephropathologists. MATERIALS AND METHODS: We included 100 patients with primary IgA nephropathy diagnosed between 2001 and 2011. Histologic slides were circulated among 4 pathologists. A score sheet was answered by each individual pathologist for each biopsy, according to the instruction of the Oxford classification. Reproducibility was determined for each variable, using intraclass correlation coefficient (ICC). RESULTS: The ICC values calculated for each major category of the Oxford classification were as follows: the highest score of 0.94 for tubular atrophy and interstitial fibrosis; 0.8 for glomerular basement membrane duplication, extracapillary proliferation, and segmental endocapillary proliferation; and 0.1 to 0.3 for arterial lesions, especially for hyalinosis of arterioles and intimal thickening of arcuate vessels and interlobar arteries. CONCLUSIONS: The Oxford classification of IgA nephropathy is a useful tool and evidenced-based method with high interobserver reproducibility in pathology reporting. Our data suggest that Oxford classification may be used as a model for classification of other renal pathologies in the future.

Diagnostic Accuracy of Fine Needle Aspiration Cytology versus Concurrent Core Needle Biopsy in Evaluation of Intrathoracic Lesions: a Retrospective Comparative Study.

BACKGROUND: Transthoracic fine needle aspiration (FNA) cytology and core needle biopsy (CNB) are two commonly used approaches for the diagnosis of suspected neoplastic intrathoracic lesions. This study compared the diagnostic accuracy of FNA cytology and concurrent CNB in the evaluation of intrathoracic lesions. MATERIALS AND METHODS: We studied FNA cytology and concurrent CNB specimens of 127 patients retrospectively, using hematoxylin and eosin (H and E), immunohistochemistry, and, on certain occasions cytochemistry. Information regarding additional tissue tests was derived from the electronic archives of the Department of Pathology and Laboratory Medicine as well as patient records. Diagnostic accuracy was calculated for each test. RESULTS: Of 127 cases, 22 were inconclusive and excluded from the study. The remaining 105 were categorized into 73 (69.5%) malignant lesions and 32 (30.5%) benign lesions. FNA and CNB findings were in complete agreement in 63 cases (60%). The accuracy and confidence intervals (CIs) of FNA and CNB for malignant tumors were 86.3% (CI: 79.3-90.7) and 93.2% (CI: 87.3- 96.0 ) respectively. For epithelial malignant neoplasms, a definitive diagnosis was made in 44.8% of cases by FNA and 80.6% by CNB. The diagnostic accuracy of CNB for nonepithelial malignant neoplasms was 83.3% compared with 50% for FNA. Of the 32 benign cases, we made specific diagnoses in 16 with diagnostic accuracy of 81.3% and 6.3% for CNB and FNA, respectively. CONCLUSIONS: Our findings suggest that FNA is comparable to CNB in the diagnosis of malignant epithelial lesions whereas diagnostic accuracy of CNB for nonepithlial malignant neoplasms is superior to that for FNA. Further, for histological typing of tumors and examining tumor origin, immunohistochemical work up plays an important role.

Avicenna's doctrine and institutional review board in international bio-medical research.

Avicenna, an outstanding Persian physician and philosopher (980 AD-1037 AD), established a clinical treaty, or doctrine, without which medical experimentation would not have progressed. This doctrine emphasizes the ultimate divine power of God or a higher being over healing and mandates the patients' well-being as the crucial aspect in all medical care and experiments. The Institutional Review Board, as the ethical body that oversees clinical research, is in line with this doctrine. However, the lack of a homogenous and internationally recognized code of ethics, the decentralized work of ethics oversight committees, the improper implementation of established ethical standards and a shortage of scientific auditing capacities have raised concerns over the possible exploitation of vulnerable populations.

FOXP3 expression in duodenal mucosa in pediatric patients with celiac disease.

OBJECTIVE: It was the aim of this study to evaluate the number of 2 lymphoid subpopulations, CD8(+) cells and FOXP3(+), in the duodenum mucosa from pediatric celiac patients. METHODS: Tissue sections prepared from paraffin-embedded biopsies of the descending duodenum of 61 celiac patients with Marsh grade 1 (M1), M2 and M3 disease and biopsies from 21 age-matched non-celiac (NC) patients were immunohistostained with anti-CD8 or FOXP3 antibodies. RESULTS: The histological Marsh grade correlated with the mean number of FOXP3(+) cells in the lamina propria (LP) mucosa (8.9 ± 1.1, 6.8 ± 2.4, 24.5 ± 2.6 and 31.1 ± 2.8 for NC, M1, M2 and M3 biopsies, respectively; p < 0.001). Using a cutoff point of 15 cells, 95% of NC and 88% of M1 biopsies had a mean of <15 FOXP3(+) cells compared with 14% for M2 and 13% for M3 biopsies. The number of FOXP3(+) cells in the epithelial mucosa also correlated with transglutaminase type 2 serum levels from the celiac patients. Unlike the FOXP3(+) cells, CD8(+) lymphocytes were present in both LP and surface epithelial mucosa and significantly different only in the LP mucosa of the M2 and M3 groups. CONCLUSION: The number of FOXP3(+) cells is substantially increased in the mucosa of celiac patients at advanced stages. Characterization of the activity of these cells in celiac and in other inflammatory bowel diseases will enable us to understand the significance of these cells in celiac disease.

Galectin-3 expression in pouchitis in patients with ulcerative colitis who underwent ileal pouch-anal anastomosis (IPAA).

Galectin-3, an endogenous pleiotropic beta-galactoside-binding protein, which is expressed by various malignant and normal cells, regulates many biological and pathological processes, including inflammation. In the present study, we tested a possible correlation between the severity of pouchitis in patients with ulcerative colitis who underwent ileal pouch-anal anastomosis (IPAA) and the presence of galectin-3(+) macrophages in pouch mucosa. Paraffin-embedded pouch biopsies from patients with normal pouch function or chronic and recurrent acute pouchitis were immunohistostained with galectin-3, CD68, and smooth muscle actin (SMA) antibodies. Microscopic examination was performed in a blinded fashion. There was a significant decrease in the staining index of galectin-3 in the subepithelial macrophages in patients with chronic pouchitis (0.53, P=0.001; n=12) or recurrent acute pouchitis (0.43, P=0.008; n=10) when compared to patients with no clinical manifestations of pouchitis (0.63, n=12). No significant differences were noted in the lamina propria of small intestine biopsies from the same patients (from 0.63 to 0.68, P=0.24). Galectin-3 staining was restricted to CD68(+) macrophages and not present in myofibroblasts. Clinical manifestation of pouchitis is inversely correlated with galectin-3 expression in the pouches' subepithelial lamina propria macrophages.

Rosiglitazone improves aortic arginine transport, through inhibition of PKCalpha, in uremic rats.

Peroxisome proliferator-activated receptor (PPAR) agonists were shown to inhibit atherosclerosis through augmentation of endothelial nitric oxide synthase (eNOS) activity. In addition, rosiglitazone exerts a beneficial effect in chronic renal failure (CRF). Since l-arginine transport by CAT-1 (the specific arginine transporter for eNOS) is inhibited in uremia, we aimed to explore the effect of rosiglitazone on arginine transport in CRF. Arginine uptake by aortic rings was studied in control animals, rats, 6 wk following 5/6 nephrectomy (CRF) and rats with CRF treated with rosiglitazone. The decrease of arginine transport in CRF was prevented by rosiglitazone. Immunobloting revealed that CAT-1 protein was decreased in CRF but remained unchanged following rosiglitazone administration. Protein content of the membrane fraction of PKCalpha and phosphorylated CAT-1 increased significantly in CRF, effects that were prevented by rosiglitazone. PKCalpha phosphorylation was unchanged but significantly attenuated by rosiglitazone in CRF. Ex vivo administration of phorbol-12-myristate-13-acetate to rosiglitazone-treated CRF rats significantly attenuated the effect of rosiglitazone on arginine uptake. The decrease in cGMP response to carbamyl-choline (eNOS agonist) was significantly attenuated by rosiglitazone in CRF. Western blotting and immunohistochemistry analysis revealed that protein nitration was intensified in the endothelium of CRF rats and this was attenuated by rosiglitazone. In conclusion, rosiglitazone prevents the decrease in arginine uptake in CRF through both depletion and inactivation of PKCalpha. These findings are associated with restoration of eNO generation and attenuation of protein nitration and therefore may serve as a novel mechanism to explain the beneficial effects of rosiglitazone on endothelial function in uremia.