Increased expression of aggrecan and biglycan mRNA in Achilles tendinopathy

To determine the expression of mRNA encoding the proteoglycans aggrecan, versican, biglycan and decorin in mid-tendon samples of chronic painful Achilles tendinopathy and ruptured Achilles tendons, compared with normal tendons. Total RNA isolated from frozen tendon samples (14 normal, 13 painful, 14 ruptured) was assayed by relative quantitative reverse transcription polymerase chain reaction for aggrecan, versican, biglycan and decorin mRNA, normalized using 18S rRNA. Differences between sample groups were tested by univariate analysis of variance with age as co-variate. In normal tendon samples expression of each of the proteoglycan mRNA decreased with increasing age. Decorin mRNA was the most highly-expressed of the proteoglycan mRNA, while versican mRNA expression was higher (3.8-fold) than that of aggrecan. In painful tendinopathy both aggrecan and biglycan mRNA expression increased (more than 10-fold and 5-fold, respectively) compared with normal tendon samples, but levels of versican and decorin mRNA were not significantly changed. In ruptured tendons the levels of aggrecan, biglycan and versican mRNA were not changed compared with normal tendon samples, but decorin mRNA decreased markedly. Increased aggrecan and biglycan mRNA expression in painful tendinopathy resembles the pattern in fibrocartilaginous regions of tendon, and may reflect an altered mechanical environment at the site of the lesion. Increased aggrecan mRNA expression may underlie the increase in glycosaminoglycan observed in painful tendinopathy

Versican splice variant messenger RNA expression in normal human Achilles tendon and tendinopathies

Versican is the principal large proteoglycan expressed in mid-tendon, but its role in tendon pathology is unknown. Our objective was to define the expression of versican isoform splice variant messenger ribonucleic acid (mRNA) in normal Achilles tendons, in chronic painful tendinopathy and in ruptured tendons. Total RNA isolated from frozen tendon samples (normal n = 14; chronic painful tendinopathy n = 10; ruptured n = 8) was assayed by relative quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for total versican, versican variants V0, V1, V2, V3 and type I collagen a1 mRNA, normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Differences between sample groups were tested by Wilcoxon statistics. Painful and ruptured tendons showed a significant decrease (median 2-fold) in the expression of versican mRNA, in contrast to an increased expression (median 8-fold) of type I collagen a1 mRNA in painful tendons. Versican splice variants V0 and V1 mRNA were readily detected in normal samples, V3 levels were substantially lower, and V2 levels were more variable. Each of V1, V2 and V3 mRNA showed significant decreases in expression in painful and ruptured tendons, but V0 was not significantly changed. Changes in versican expression relative to that of collagen, and alterations in the balance of versican splice variants, may contribute to changes in matrix structure and function in tendinopathies

Secular changes in dietary patterns in the metropolitan areas of Brazil (1988-1996)

OBJECTIVE: A new family budget survey carried out in the mid-nineties in Brazil allows an update of the secular trends (1962-1988) of dietary patterns of Brazilian population living in metropolitan areas. METHODS: Data sources are IBGE Institute of Statistics family budget surveys carried out from March 1987 to February 1988 (13,611 households) and from October 1995 to September 1996 (16,014 households) in all metropolitan areas of Brazil. The daily food availability per capita for each household was calculated dividing the total food acquired in a month by the number of individuals living in a household and the month's number of days. Dietary patterns were characterized according to the amount of selected food groups and nutrients relative to the diet caloric input. Comparisons between the two surveys included the metropolitan area population as a whole and subgroups from less (North and Northeast) and more developed (Mid-west, Southeast and South) regions. RESULTS: It was observed an increase in consumption of meat and dairy products (except for butter) and a reduction in eggs consumption in both less and more developed regions. Beans, roots and tubers consumption showed a steady decline in the whole country while cereals consumption remained the same (higher in developed regions) or had a slight increase (in less developed regions). The proportional consumption of vegetal oils and margarine remained constant in the less developed regions but their consumption was greatly reduced in the more developed ones. CONCLUSIONS: An increase in the diet's lipid content in less developed regions and of saturated fat in the country as a whole, associated with a decrease or even no consumption of beans, vegetables, fruits and complex carbohydrates, and a further increase in the excessive sugar consumption are the negative aspects of the trend observed from 1988 to 1996. Changes that may indicate a growing awareness of the population toward a healthier diet, such as a decline in egg intake and a slight reduction in diets with a high total lipid content, were found only in more developed regions.OBJETIVO: Atualizar a tendência secular (1962-1988) da composição e da adequação nutricional da dieta familiar praticada nas áreas metropolitanas do Brasil, com base em nova pesquisa sobre orçamentos familiares realizada em meados da década de 90. MÉTODOS: Utilizaram-se como fontes de dados as pesquisas sobre orçamentos familiares (POF) da Fundação IBGE, realizadas entre março de 1987 e fevereiro de 1988 (13.611 domicílios) e entre outubro de 1995 e setembro de 1996 (16.014 domicílios), tendo ambas como universo de estudo as áreas metropolitanas do Brasil. Nas duas pesquisas chegou-se à disponibilidade domiciliar diária per capita de alimentos, dividindo-se o total de alimentos adquiridos no mês pelo número de pessoas residentes no domicílio e pelo número de dias do mês. O padrão alimentar foi caracterizado com base na participação relativa de grupos selecionados de alimentos e de nutrientes na disponibilidade calórica total. A comparação entre as duas pesquisas levou em conta o conjunto das áreas metropolitanas do País e estratos dessas áreas correspondentes às regiões menos desenvolvidas (Norte e Nordeste) e mais desenvolvidas (Centro-Oeste, Sudeste e Sul). RESULTADOS: Observou-se intensificação do consumo relativo de carnes, de leites e de seus derivados (exceto manteiga) em todas as áreas metropolitanas, enquanto o consumo de ovos passou a declinar, sobretudo no Centro-Sul do País. Leguminosas, raízes e tubérculos prosseguiram sua trajetória descendente, mas cereais e derivados tenderam a se estabilizar no Centro-Sul ou mesmo a se elevar ligeiramente no Norte-Nordeste. A participação relativa de açúcar refinado e refrigerantes cresceu em todas as áreas, sendo que a participação de óleos e gorduras vegetais manteve-se constante no Norte-Nordeste e declinou intensamente no Centro-Sul. CONCLUSÕES: A tendência ascendente da participação relativa de lipídios na dieta do Norte e do Nordeste, o aumento no consumo de ácidos graxos saturados em todas as áreas metropolitanas do País, ao lado da redução do consumo de carboidratos completos, da estagnação ou da redução do consumo de leguminosas, verduras, legumes e frutas e do aumento no consumo já excessivo de açúcar são os traços marcantes e negativos da evolução do padrão alimentar entre 1988 e 1996. Mudanças que podem indicar a adesão da população a dietas mais saudáveis -- declínio no consumo de ovos e recuo discreto da elevada proporção de calorias lipídicas -- foram registradas apenas no Centro-Sul do País.Universidade de São Paulo Faculdade de Saúde Pública Departamento de NutriçãoUniversidade Federal de São Paulo (UNIFESP) Departamento de Medicina PreventivaUniversidade de São Paulo Núcleo de Pesquisas Epidemiológicas em Nutrição e SaúdeUNIFESP, Depto. de Medicina PreventivaSciEL

Cerebral venous thrombosis: an unexpected complication from spinal surgery

PURPOSE: To provide new insights into the pathophysiology, prevention and diagnosis of cerebral venous thrombosis (CVT) associated with iatrogenic cerebrospinal fluid (CSF) leaks and/or external CSF drainage. METHODS: Case report and literature review. RESULTS: We describe the case of a 30-year-old woman who developed a CSF fistula after lumbar spinal surgery. The treatment included rest, hydration, caffeine, and continuous lumbar CSF drainage. After closure of the fistula, the patient complained of severe orthostatic headache. Thrombosis involving the superior sagittal sinus, the right transverse sinus, the right sigmoid sinus, and the right jugular vein was diagnosed after neurological deterioration. CONCLUSION: A few reports have associated CVT with various forms of spinal meningeal injury. However, it has been rarely documented following spinal surgery complicated by accidental durotomy and/or external lumbar CSF drainage. CSF hypovolemia may precipitate CVT in patients having prothrombotic risk factors. Patients who have or had CSF leaks and/or lumbar CSF drains who present with symptoms of intracranial CSF hypotension should remain in the horizontal position to prevent CVT. In that context, the diagnosis of CVT depends on a high degree of suspicion

Mudanças na composição e adequação nutricional da dieta familiar nas áreas metropolitanas do Brasil (1988-1996)

OBJECTIVE: A new family budget survey carried out in the mid-nineties in Brazil allows an update of the secular trends (1962-1988) of dietary patterns of Brazilian population living in metropolitan areas. METHODS: Data sources are IBGE Institute of Statistics family budget surveys carried out from March 1987 to February 1988 (13,611 households) and from October 1995 to September 1996 (16,014 households) in all metropolitan areas of Brazil. The daily food availability per capita for each household was calculated dividing the total food acquired in a month by the number of individuals living in a household and the month's number of days. Dietary patterns were characterized according to the amount of selected food groups and nutrients relative to the diet caloric input. Comparisons between the two surveys included the metropolitan area population as a whole and subgroups from less (North and Northeast) and more developed (Mid-west, Southeast and South) regions. RESULTS: It was observed an increase in consumption of meat and dairy products (except for butter) and a reduction in eggs consumption in both less and more developed regions. Beans, roots and tubers consumption showed a steady decline in the whole country while cereals consumption remained the same (higher in developed regions) or had a slight increase (in less developed regions). The proportional consumption of vegetal oils and margarine remained constant in the less developed regions but their consumption was greatly reduced in the more developed ones. CONCLUSIONS: An increase in the diet's lipid content in less developed regions and of saturated fat in the country as a whole, associated with a decrease or even no consumption of beans, vegetables, fruits and complex carbohydrates, and a further increase in the excessive sugar consumption are the negative aspects of the trend observed from 1988 to 1996. Changes that may indicate a growing awareness of the population toward a healthier diet, such as a decline in egg intake and a slight reduction in diets with a high total lipid content, were found only in more developed regions.OBJETIVO: Atualizar a tendência secular (1962-1988) da composição e da adequação nutricional da dieta familiar praticada nas áreas metropolitanas do Brasil, com base em nova pesquisa sobre orçamentos familiares realizada em meados da década de 90. MÉTODOS: Utilizaram-se como fontes de dados as pesquisas sobre orçamentos familiares (POF) da Fundação IBGE, realizadas entre março de 1987 e fevereiro de 1988 (13.611 domicílios) e entre outubro de 1995 e setembro de 1996 (16.014 domicílios), tendo ambas como universo de estudo as áreas metropolitanas do Brasil. Nas duas pesquisas chegou-se à disponibilidade domiciliar diária per capita de alimentos, dividindo-se o total de alimentos adquiridos no mês pelo número de pessoas residentes no domicílio e pelo número de dias do mês. O padrão alimentar foi caracterizado com base na participação relativa de grupos selecionados de alimentos e de nutrientes na disponibilidade calórica total. A comparação entre as duas pesquisas levou em conta o conjunto das áreas metropolitanas do País e estratos dessas áreas correspondentes às regiões menos desenvolvidas (Norte e Nordeste) e mais desenvolvidas (Centro-Oeste, Sudeste e Sul). RESULTADOS: Observou-se intensificação do consumo relativo de carnes, de leites e de seus derivados (exceto manteiga) em todas as áreas metropolitanas, enquanto o consumo de ovos passou a declinar, sobretudo no Centro-Sul do País. Leguminosas, raízes e tubérculos prosseguiram sua trajetória descendente, mas cereais e derivados tenderam a se estabilizar no Centro-Sul ou mesmo a se elevar ligeiramente no Norte-Nordeste. A participação relativa de açúcar refinado e refrigerantes cresceu em todas as áreas, sendo que a participação de óleos e gorduras vegetais manteve-se constante no Norte-Nordeste e declinou intensamente no Centro-Sul. CONCLUSÕES: A tendência ascendente da participação relativa de lipídios na dieta do Norte e do Nordeste, o aumento no consumo de ácidos graxos saturados em todas as áreas metropolitanas do País, ao lado da redução do consumo de carboidratos completos, da estagnação ou da redução do consumo de leguminosas, verduras, legumes e frutas e do aumento no consumo já excessivo de açúcar são os traços marcantes e negativos da evolução do padrão alimentar entre 1988 e 1996. Mudanças que podem indicar a adesão da população a dietas mais saudáveis -- declínio no consumo de ovos e recuo discreto da elevada proporção de calorias lipídicas -- foram registradas apenas no Centro-Sul do País

Estimated Lifetime Cardiovascular, Kidney, and Mortality Benefits of Combination Treatment With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Nonsteroidal MRA Compared With Conventional Care in Patients With Type 2 Diabetes and Albuminuria

BACKGROUND: Sodium glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and the nonsteroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone all individually reduce cardiovascular, kidney, and mortality outcomes in patients with type 2 diabetes and albuminuria. However, the lifetime benefits of combination therapy with these medicines are not known. METHODS: We used data from 2 SGLT2i trials (CANVAS [Canagliflozin Cardiovascular Assessment] and CREDENCE [Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation]), 2 ns-MRA trials (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease]), and 8 GLP-1 RA trials to estimate the relative effects of combination therapy versus conventional care (renin-angiotensin system blockade and traditional risk factor control) on cardiovascular, kidney, and mortality outcomes. Using actuarial methods, we then estimated absolute risk reductions with combination SGLT2i, GLP-1 RA, and ns-MRA in patients with type 2 diabetes and at least moderately increased albuminuria (urinary albumin:creatinine ratio ≥30 mg/g) by applying estimated combination treatment effects to participants receiving conventional care in CANVAS and CREDENCE. RESULTS: Compared with conventional care, the combination of SGLT2i, GLP-1 RA, and ns-MRA was associated with a hazard ratio of 0.65 (95% CI, 0.55–0.76) for major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death). The corresponding estimated absolute risk reduction over 3 years was 4.4% (95% CI, 3.0–5.7), with a number needed to treat of 23 (95% CI, 18–33). For a 50-year-old patient commencing combination therapy, estimated major adverse cardiovascular event–free survival was 21.1 years compared with 17.9 years for conventional care (3.2 years gained [95% CI, 2.1–4.3]). There were also projected gains in survival free from hospitalized heart failure (3.2 years [95% CI, 2.4–4.0]), chronic kidney disease progression (5.5 years [95% CI, 4.0–6.7]), cardiovascular death (2.2 years [95% CI, 1.2–3.0]), and all-cause death (2.4 years [95% CI, 1.4–3.4]). Attenuated but clinically relevant gains in event-free survival were observed in analyses assuming 50% additive effects of combination therapy, including for major adverse cardiovascular events (2.4 years [95% CI, 1.1–3.5]), chronic kidney disease progression (4.5 years [95% CI, 2.8–5.9]), and all-cause death (1.8 years [95% CI, 0.7–2.8]). CONCLUSIONS: In patients with type 2 diabetes and at least moderately increased albuminuria, combination treatment of SGLT2i, GLP-1 RA, and ns-MRA has the potential to afford relevant gains in cardiovascular and kidney event-free and overall survival

Stellar Population Diagnostics of Elliptical Galaxy Formation

Major progress has been achieved in recent years in mapping the properties of passively-evolving, early-type galaxies (ETG) from the local universe all the way to redshift ~2. Here, age and metallicity estimates for local cluster and field ETGs are reviewed as based on color-magnitude, color-sigma, and fundamental plane relations, as well as on spectral-line indices diagnostics. The results of applying the same tools at high redshifts are then discussed, and their consistency with the low-redshift results is assessed. Most low- as well as high-redshift (z~1) observations consistently indicate 1) a formation redshift z>~3 for the bulk of stars in cluster ETGs, with their counterparts in low-density environments being on average ~1-2 Gyr younger, i.e., formed at z>~1.5-2, 2) the duration of the major star formation phase anticorrelates with galaxy mass, and the oldest stellar populations are found in the most massive galaxies. With increasing redshift there is evidence for a decrease in the number density of ETGs, especially of the less massive ones, whereas existing data appear to suggest that most of the most-massive ETGs were already fully assembled at z~1. Beyond this redshift, the space density of ETGs starts dropping significantly, and as ETGs disappear, a population of massive, strongly clustered, starburst galaxies progressively becomes more and more prominent, which makes them the likely progenitors to ETGs.Comment: To appear on Annual Review of Astronomy & Astrophysics, Vol. 44 (2006). 46 pages with 16 figures. Replaced version includes updated references, few typos less, and replaces Fig. 11 and Fig. 16 which had been skrewed u

Heterogeneities in leishmania infantum infection : using skin parasite burdens to identify highly infectious dogs

Background: The relationships between heterogeneities in host infection and infectiousness (transmission to arthropod vectors) can provide important insights for disease management. Here, we quantify heterogeneities in Leishmania infantum parasite numbers in reservoir and non-reservoir host populations, and relate this to their infectiousness during natural infection. Tissue parasite number was evaluated as a potential surrogate marker of host transmission potential. Methods: Parasite numbers were measured by qPCR in bone marrow and ear skin biopsies of 82 dogs and 34 crab-eating foxes collected during a longitudinal study in Amazon Brazil, for which previous data was available on infectiousness (by xenodiagnosis) and severity of infection. Results: Parasite numbers were highly aggregated both between samples and between individuals. In dogs, total parasite abundance and relative numbers in ear skin compared to bone marrow increased with the duration and severity of infection. Infectiousness to the sandfly vector was associated with high parasite numbers; parasite number in skin was the best predictor of being infectious. Crab-eating foxes, which typically present asymptomatic infection and are non-infectious, had parasite numbers comparable to those of non-infectious dogs. Conclusions: Skin parasite number provides an indirect marker of infectiousness, and could allow targeted control particularly of highly infectious dogs

Neural development features: Spatio-temporal development of the Caenorhabditis elegans neuronal network

The nematode Caenorhabditis elegans, with information on neural connectivity, three-dimensional position and cell linage provides a unique system for understanding the development of neural networks. Although C. elegans has been widely studied in the past, we present the first statistical study from a developmental perspective, with findings that raise interesting suggestions on the establishment of long-distance connections and network hubs. Here, we analyze the neuro-development for temporal and spatial features, using birth times of neurons and their three-dimensional positions. Comparisons of growth in C. elegans with random spatial network growth highlight two findings relevant to neural network development. First, most neurons which are linked by long-distance connections are born around the same time and early on, suggesting the possibility of early contact or interaction between connected neurons during development. Second, early-born neurons are more highly connected (tendency to form hubs) than later born neurons. This indicates that the longer time frame available to them might underlie high connectivity. Both outcomes are not observed for random connection formation. The study finds that around one-third of electrically coupled long-range connections are late forming, raising the question of what mechanisms are involved in ensuring their accuracy, particularly in light of the extremely invariant connectivity observed in C. elegans. In conclusion, the sequence of neural network development highlights the possibility of early contact or interaction in securing long-distance and high-degree connectivity