Lipoatrophy of the footpad in HIV-treated patients is associated with increased PAI-1

Purpose: To describe lipoatrophy of the plantar pedis fat pads in HIV patients with or without long-term antiretroviral therapy (ART); to compare the characteristics of ART patients with and without plantar pedis lipoatrophy; and to examine the effects of HIV and metabolic/cardiovascular risk parameters and treatment history on plantar pedis lipoatrophy. Design: One hundred and thirty four patients who started PI-ART in 1996 and 49 treatment naïve patients, recruited 2004, were examined and graded for lipoatrophy of five body compartments including the plantar fat pads eight years after start of ART. Baseline HIV- and ART-related factors were documented together with follow up metabolic/cardiovascular risk parameters. Results: Plantar pedis lipoatrophy occurred more often among ART patients (60%) than among treatment naïve patients (12%; p <0.001). ART patients with plantar lipoatrophy were older, had higher PAI-1 values, a higher prevalence of lipoatrophy in other body compartments, and longer stavudine and didanosine treatment history as compared to patients without plantar lipoatrophy. In multiple logistic regression, the best predictive model for plantar lipoatrophy was increased PAI-1 when HIV and metabolic/cardiovascular risk parameters were studied and treatment with didanosine when treatment history was studied. Increased PAI-1 was not associated to lioatrophy in any other location. Conclusions: Plantar lipoatrophy is common among patients on long-term ART and, although often overlooked, may cause significant discomfort. The association to PAI-1, a well known marker of increased cardiovascular risk, is intriguing and further focuses on the need of an active approach to evaluating and lowering cardiovascular risk factors in long-term HIV treatment

Serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in relation to markers of reproductive function in young males from the general Swedish population.

A time-related deterioration in male reproductive function caused by exposure to endocrine disrupters, including persistent organochlorines (POCs), has been hypothesized. In animal studies, POCs were found to have adverse effects on male reproductive function. However, little is known about the impact of POC exposure on reproductive parameters in men. In a study of 305 young Swedish men 18-21 years old from the general population, we correlated lipid-adjusted serum levels of 2,2',4,4',5,5' -hexachlorobiphenyl (CB-153)--an index substance for POC exposure--to markers of male reproductive function: testis size assessed by ultrasound, sperm concentration, total sperm count, sperm motility assessed manually and with a computer-aided sperm analyzer (CASA), and serum levels of follicle-stimulating hormone, inhibin B, testosterone, sexual hormone-binding globulin (SHBG), luteinizing hormone, and estradiol. We found weak but statistically significant, negative correlations between CB-153 levels and both the testosterone:SHBG ratio (r = -0.25, p < 0.001)--a measure of the biologically active free testosterone fraction--and CASA sperm motility (r = -0.13, p = 0.02). No statistically significant association with other seminal, hormonal, or clinical markers of male reproductive function was found. In previous studies of more highly POC-exposed groups of adult men, the correlation between POC exposure, including CB-153, and free testosterone levels was not statistically significant. The present study gives some tentative support for weak negative effects of CB-153 exposure on sperm motility and free testosterone levels in young men, but further semen studies on more highly exposed groups may give more firm conclusions on the hazard for male reproductive function from dietary POC exposure

Industrins utveckling mot netto-nollutsläpp 2050

Sverige har en vision om ”netto-noll” utsläpp av växthusgaser till 2050 och är på god väg att nå utsatta delmål för utsläppsreduktioner till 2020. Klimatfrågan är dock långsiktig och det under klimatkonventionen antagna 2-gradersmålet innebär utsläppsåtaganden som sträcker sig till år 2050 och bortom. En långsiktigt effektiv klimatpolitik ska därför utvärderas både efter vilka långsiktiga utvecklingsmöjligheter den skapar likväl som efter de utsläppsreduktioner som nås till lägsta kostnad på kort sikt. Detta betyder ett ökat fokus på styrning och åtgärder som inte ger direkta utsläppsreduktioner idag men som på lång sikt skapar förutsättningar i form av infrastruktur, kunskap, teknikutveckling och grönt entreprenörskap. På lång sikt måste klimatpolitiken även fortsätta med bredare ekonomiska ansatser som grön skatteväxling för att styra mot klimatsmartart konsumtion. För tillverkningsindustrin bör staten skapa bra generella förutsättningar för innovation och industriell utveckling för att underlätta tillverkningsindustrins omställning till nya ”gröna” marknadskrav. För basindustrin behöver dock staten ta ett särskilt ansvar och ha en sammanhängande innovationspolitik som mer riktat styr mot att utveckla nya tekniska lösningar för att klara långsiktiga klimatmål. Forskning och utveckling är redan idag en viktig del av svensk klimatpolitik men det saknas en sammanhållen svensk strategi för basindustrin. För att utveckla de rätta institutionella förutsättningarna föreslår vi två uppdrag som bör utvecklas och sedan permanentas inom myndigheterna. I. Ett uppdrag att utveckla kapaciteten att analysera och utvärdera strukturomvandlingen mot grönare sektorer i ekonomin II. Ett uppdrag att utveckla branschvisa färdplaner för industrin Bägge uppdrag syftar till att stärka myndigheternas förmåga att effektivt implementera en långsiktig klimatpolitik med ett fokus på industri- och teknikutvecklin

Increased mRNA Levels of TCF7L2 and MYC of the Wnt Pathway in Tg-ArcSwe Mice and Alzheimer's Disease Brain

Several components in the Wnt pathway, including β-catenin and glycogen synthase kinase 3 beta, have been implied in AD pathogenesis. Here, mRNA brain levels from five-month-old tg-ArcSwe and nontransgenic mice were compared using Affymetrix microarray analysis. With surprisingly small overall changes, Wnt signaling was the most affected pathway with altered expression of nine genes in tg-ArcSwe mice. When analyzing mRNA levels of these genes in human brain, transcription factor 7-like 2 (TCF7L2) and v-myc myelocytomatosis viral oncogene homolog (MYC), were increased in Alzheimer's disease (AD) (P < .05). Furthermore, no clear differences in TCF7L2 and MYC mRNA were found in brains with frontotemporal lobar degeneration, suggesting that altered regulation of these Wnt-related genes could be specific to AD. Finally, mRNA levels of three neurogenesis markers were analyzed. Increased mRNA levels of dihydropyrimidinase-like 3 were observed in AD brain, suggesting that altered Wnt pathway regulation may signify synaptic rearrangement or neurogenesis

Increased mRNA Levels of TCF7L2 and MYC of the Wnt Pathway in Tg-ArcSwe Mice and Alzheimer's Disease Brain

Several components in the Wnt pathway, including β-catenin and glycogen synthase kinase 3 beta, have been implied in AD pathogenesis. Here, mRNA brain levels from five-month-old tg-ArcSwe and nontransgenic mice were compared using Affymetrix microarray analysis. With surprisingly small overall changes, Wnt signaling was the most affected pathway with altered expression of nine genes in tg-ArcSwe mice. When analyzing mRNA levels of these genes in human brain, transcription factor 7-like 2 (TCF7L2) and v-myc myelocytomatosis viral oncogene homolog (MYC), were increased in Alzheimer's disease (AD) (P < .05). Furthermore, no clear differences in TCF7L2 and MYC mRNA were found in brains with frontotemporal lobar degeneration, suggesting that altered regulation of these Wnt-related genes could be specific to AD. Finally, mRNA levels of three neurogenesis markers were analyzed. Increased mRNA levels of dihydropyrimidinase-like 3 were observed in AD brain, suggesting that altered Wnt pathway regulation may signify synaptic rearrangement or neurogenesis

Factors effecting the induction of rat forestomach hyperplasia induced by Swedish oral smokeless tobacco (snus)

Long term exposure to oral smokeless tobacco may induce lesions in the oral cavity characterized by a hyperplastic epithelium. The possible role of nicotine and the physical properties of oral tobacco for developing these lesions, as well as of dysplasia and neoplasia is unclear. Low nitrosamine Swedish snus as well as non-genotoxic butylated hydroxyanisole induces increased cellular proliferation in the rat forestomach epithelia. Using this model, we report here on the effects of nicotine, pH, and particle size. Snus with different properties had no impact on oxidative stress as determined by 8-oxo-7,8-dihydro-2′-deoxyguanosine, or on interleukin IL-1b. Whereas BHA boosted IL-6, probably due to the presence of nicotine. there was no significant enhancement of cell divisions with increasing particle size, although in individual samples the variations in proliferation rates increased greatly with increasing particle size. Conforming to human experience, the enhanced cell proliferation caused by snus was found to be completely reversible. A cacao bean extract had a protective action similar to that previously found for blueberries. The main cause of the observed tobacco induced cell proliferation could be mechanical irritation, possibly in combination with nicotine, whereas within the studied range, pH did not affect the rate of cell division. © 201

Clinical categories of patients and encounter rates in primary health care – a three-year study in defined populations

BACKGROUND: The objective was to estimate the proportion of inhabitants with a diagnosis-registered encounter with a general practitioner, and to elucidate annual variations of clinical categories of patients in terms of their individual comorbidity. METHODS: A three-year retrospective study of encounter data from electronic patient records, with an annual-based application of the Johns Hopkins Adjusted Clinical Groups (ACG) system. Data were retrieved from every patient with a diagnosis-registered encounter with a GP during the period 2001–2003 at 13 publicly managed primary health care centres in Blekinge county, southeastern Sweden, with about 150000 inhabitants. Main outcome measures: Proportions of inhabitants with a diagnosis-registered encounter, and ranges of the annual proportions of categories of patients according to ACGs. RESULTS: The proportion of inhabitants with a diagnosis-registered encounter ranged from about 64.0% to 90.6% for the primary health care centres, and averaged about 76.5% for all inhabitants. In a three-year perspective the average range of categories of patients was about 0.4% on the county level, and about 0.9% on the primary health care centre level. About one third of the patients each year had a constellation of two or more types of morbidity. CONCLUSION: About three fourths of all inhabitants had one or more diagnosis-registered encounters with a general practitioner during the three-year period. The annual variation of categories of patients according to ACGs was small on both the county and the primary health care centre level. The ACG system seems useful for demonstrating and predicting various aspects of clinical categories of patients in Swedish primary health care