Miracle-dz/UniFAR-FTUs huggingface dataset:
Diurnal rhythm of melatonin action on sexual maturation of male rats.

Immature male Wistar rats with a 12:12 h light-dark cycle received daily s.c. melatonin injections of 100 micrograms from 20 to 40 days of age. Melatonin administration during the late photophase (9 h after the onset of light) or during the late scotophase (9 h after the onset of darkness) caused reduced weights of testes and seminal vesicles, lowered plasma levels of testosterone, LH and FSH, and decreased number of pituitary GnRH receptors, a series of observations which reflects delayed sexual maturation at 40 days. In contrast, no effect was observed when melatonin was injected during the early photophase of scotophase (5 h after the onset of light or darkness, respectively). In order to better investigate the night hours, melatonin action was studied in rats that were born and raised with a shifted 12:12 h light-dark cycle. When the light phase was shifted by 5 and 17 h 1 week before the animals were born, sensitivity to melatonin action was unchanged. The responsiveness of the neuroendocrine-reproductive axis to exogenous melatonin was then studied throughout the day-night cycle. The inhibitory influence of melatonin increased gradually during the late photophase and reached a peak just before the onset of darkness. No effect was observed during the first 7 h of the dark phase; however, melatonin injected 9 h after the onset of darkness again had an inhibitory influence equivalent to about 50% of that observed in the late photophase , whereas administration 2 h later remained without effect. These results demonstrate that the time of administration of melatonin within the day-night cycle is critical for melatonin action. (ABSTRACT TRUNCATED AT 250 WORDS)
Food sources of fat may clarify the inconsistent role of dietary fat intake for incidence of type 2 diabetes.

BACKGROUND Dietary fats could affect glucose metabolism and obesity development and, thereby, may have a crucial role in the cause of type 2 diabetes (T2D). Studies indicated that replacing saturated with unsaturated fats might be favorable, and plant foods might be a better choice than animal foods. Nevertheless, epidemiologic studies suggested that dairy foods are protective. OBJECTIVE We hypothesized that, by examining dietary fat and its food sources classified according to fat type and fat content, some clarification regarding the role of dietary fat in T2D incidence could be provided. DESIGN A total of 26,930 individuals (61% women), aged 45-74 y, from the Malmö Diet and Cancer cohort were included in the study. Dietary data were collected by using a modified diet-history method. During 14 y of follow-up, 2860 incident T2D cases were identified. RESULTS Total intake of high-fat dairy products (regular-fat alternatives) was inversely associated with incident T2D (HR for highest compared with lowest quintiles: 0.77; 95% CI: 0.68, 0.87; P-trend < 0.001). Most robust inverse associations were seen for intakes of cream and high-fat fermented milk (P-trend < 0.01) and for cheese in women (P-trend = 0.02). High intake of low-fat dairy products was associated with increased risk, but this association disappeared when low- and high-fat dairy were mutually adjusted (P-trend = 0.18). Intakes of both high-fat meat (P-trend = 0.04) and low-fat meat (P-trend < 0.001) were associated with increased risk. Finally, we did not observe significant association between total dietary fat content and T2D (P-trend = 0.24), but intakes of saturated fatty acids with 4-10 carbons, lauric acid (12:0), and myristic acid (14:0) were associated with decreased risk (P-trend < 0.01). CONCLUSIONS Decreased T2D risk at high intake of high- but not of low-fat dairy products suggests that dairy fat partly could have contributed to previously observed protective associations between dairy intake and T2D. Meat intake was associated with increased risk independently of the fat content.
White matter integrity in obstructive sleep apnea before and after treatment.

STUDY OBJECTIVES Obstructive sleep apnea (OSA) is commonly associated with cognitive and functional deficits, some of which are resolved after continuous positive airway pressure (CPAP) treatment. The investigation of brain structural changes before and after treatment could provide deep insights into the pathogenesis and the reversibility of this disorder. We hypothesized that severe OSA patients would have altered white matter (WM) integrity and cognition and that treatment would improve both the structural damage and the cognitive impairment. DESIGN Prospective clinical study. SETTING The Sleep Disorders Center and the Center of Excellence in High-Field Magnetic Resonance Imaging at Vita-Salute San Raffaele University, Milan, Italy. PARTICIPANTS Seventeen never-treated consecutive OSA patients were evaluated before and after treatment (after 3 and 12 months) and compared to 15 matched healthy controls. INTERVENTION CPAP. MEASUREMENTS WM integrity measured by diffusion tensor imaging (DTI) and cognitive performance (measured with neuropsychological testing) before and after 3 and 12 months of CPAP. RESULTS Results in pre-treatment OSA patients showed impairments in most cognitive areas, mood and sleepiness that were associated with diffuse reduction of WM fiber integrity reflected by diminished fractional anisotropy (FA) and mean diffusivity (MD) in multiple brain areas. After 3 months of CPAP, only limited changes of WM were found. However, over the course of 12 months CPAP treatment, an almost complete reversal of WM abnormalities in all the affected regions was observed in patients who were compliant with treatment. Significant improvements involving memory, attention, and executive-functioning paralleled WM changes after treatment. CONCLUSIONS Changes of WM DTI "signatures" of brain pathology in OSA patients are appreciable over the course of 12-month treatment with CPAP in most of the regions involved. Recovery of cognitive deficits after treatment is consistent with the presence of a reversible structural neural injury in OSA in patients who were compliant with treatment.
Peripheral blood HIV DNA is associated with atrophy of cerebellar and subcortical gray matter

Objective: We evaluated regional brain volumes and cerebral metabolite levels as correlates of HIV DNA in peripheral blood mononuclear cells (PBMCs). Methods: In this cross-sectional study, 35 HIV+ subjects aged ≥40 years (25 with detectable PBMC HIV DNA; 10 with HIV DNA <10 copies/106 cells, the threshold of detection) and 12 seronegative controls underwent structural brain MRI and magnetic resonance spectroscopy at 3 T. HIV+ subjects were on combination antiretroviral therapy ≥1 year; all but 1 had plasma HIV RNA <50 copies/mL. We used logistic regression to evaluate relationships of likely predictor variables to the outcome of PBMC HIV DNA detectability in the HIV+ subjects. Effects of serostatus and HIV DNA on regional brain volumes (normalized to intracranial volume) and on metabolite ratios over creatine were evaluated by analyses of covariance, controlling for age. Results: Relative to the HIV+ group with undetectable HIV DNA, subjects with detectable HIV DNA demonstrated decreased volumes of cerebellar (−14%, p = 0.020) and total subcortical (−10%, p = 0.024) gray matter. Compared to healthy controls, only the detectable HIV DNA group showed significant (p < 0.05) enlargement of lateral ventricles and volumetric reductions of caudate, putamen, thalamus, hippocampus, nucleus accumbens, brainstem, total cortical gray matter, and cerebral white matter. Detectable HIV DNA was not associated with significantly altered cerebral metabolite levels. Conclusion: Inability to clear peripheral blood of HIV DNA is associated with regional brain atrophy in well-controlled HIV infection, supporting the involvement of peripheral viral reservoirs in the neuropathogenesis of persistent HIV-related neurocognitive disorders.
Tandem transplants with different high‐dose regimens improve the complete remission rates in multiple myeloma. Results of a Grupo Español de Síndromes Linfoproliferativos/Trasplante Autólogo de Médula Ósea phase II trial

Summary. Between 1994 and 1999, 88 multiple myeloma (MM) patients were included in a phase II study to evaluate a tandem autologous stem cell transplantation (ASCT) programme. The first was conditioned with melphalan 200 mg/m2 (MEL200‐ASCT1), and the second with cyclophosphamide, etoposide and BCNU (CBV‐ASCT2). All patients were in response after MEL200‐ASCT1. A control group of MM patients with response to a single ASCT was selected to compare outcomes. After MEL200‐ASCT1, 26 patients (30%) achieved complete remission (CR). Of the remaining 48 evaluable patients, 16 (33%) achieved CR with CBV‐ASCT2. The final CR rate was 48%. The 5‐year survival (OS) was 55%[95% confidence interval (CI) 43–67%] while the event‐free survival (EFS) was 28% (95% CI 15–39%). CR status after CBV‐ASCT2 was the most important prognostic factor for OS and EFS (P = 0·00001), although no differences in outcomes were detected when the patients in CR after MEL200‐ASCT1 were compared with those who obtained CR after CBV‐ASCT2. Univariate and multivariate analyses showed improved OS and EFS for the tandem series as compared with the control series treated with a single MEL200‐ASCT. However, in a stratified comparison by response, there were no prognostic differences between tandem patients and control patients treated with a single ASCT. In summary, our study suggests that the benefit of a second high‐dose therapy course depends on its capacity to result in CR for MM patients who have not attained CR after ASCT1.
Differentiation and Injury-Repair Signals Modulate the Interaction of E2F and pRB Proteins with Novel Target Genes in Keratinocytes

E2F transcription factors are central to epidermal morphogenesis and regeneration afterinjury. The precise nature of E2F target genes involved in epidermal formation and repair has yetto be determined. Identification of these genes is essential to understand how E2F proteinsregulate fundamental aspects of epidermal homeostasis and transformation. We have conducted agenome-wide screen using CpG island microarray analysis to identify novel promoters bound byE2F3 and E2F5 in human keratinocytes. We further characterized several of these genes, anddetermined that multiple E2F and retinoblastoma (pRb) family proteins associate with them inexponentially proliferating cells. We also assessed the effect on E2F and pRb binding to thosegenes in response to differentiation induced by bone morphogenetic protein-6 (BMP-6), or toactivation of repair mechanisms induced by transforming growth factor-β (TGF-β). Thesestudies demonstrate promoter- and cytokine-specific changes in binding profiles of E2F and/orpRb family proteins. For example, E2F1, 3, 4 and p107 were recruited to the N-myc promoter incells treated with BMP-6, whereas E2F1, 3, 4, 5, p107 and p130 were bound to this promoter inthe presence of TGF-β. Functionally, these different interactions resulted in transcriptionalrepression by BMP-6 and TGF-β of the N-myc gene, via mechanisms that involved E2F bindingto the promoter and association with pRb-family proteins. Thus, multiple combinations of E2Fand pRb family proteins may associate with and transcriptionally regulate a given target promoterin response to differentiation and injury-repair stimuli in epidermal keratinocytes.
The biomarket

Abstract Political analysis can enrich our understanding of the interface between health and society. Here, a theoretical framework called ‘the biomarket’ is proposed, one that describes the interaction between life, power and the market, and the progressive institutionalisation of this dynamic by state actors. This framework expands upon ‘biopower’, a social concept developed by Michel Foucault. The role of the biomarket is illustrated by analysis of a range of cases, namely the relationships between global health and the pharmaceutical and tobacco industries. The potential adverse consequences of the biomarket are demonstrated, revealing how in some instances, important social measures of welfare are discarded for the sake of economic efficiency and profit. The authors conclude that the biomarket may serve to deepen our understanding of the authority and control exerted by corporations over life, positing that the biomarket must be further regulated for sustainable advances in global health.
Predictors of Nosocomial Bloodstream Infections Among Critically Ill Adult Trauma Patients

Abstract Objective: To identify the independent predictors of nosocomial bloodstream infections (BSIs) among critically ill adult trauma patients. Design: A prospective, cohort design was used to study patients who met predetermined inclusion criteria. Basic descriptive and univariate statistical analyses were performed to identify unadjusted predictors. A forward stepwise multivariate logistic regression analysis was then conducted to identify independent predictors of nosocomial BSI. Setting: Level I university-affiliated shock trauma center. Patients: Three hundred sixty-one critically ill adult trauma patients, 55 of whom developed nosocomial BSIs (15.2%). Results: Data analysis of 45 variables indicated that only 9 were independent predictors of nosocomial BSI: presence of a chest tube, use of immunosuppressive agents, presence of microbial resistance, length of stay, presence of preexisting infection, percentage change of serum albumin levels, patient disposition, transfusion of 10 or more units of blood, and number of central venous catheters (CVCs) for patients who had 4 or more. The classification index of the final regression model at a cut-off point of 0.5 had a specificity of 97.4%, a sensitivity of 60%, a positive predictive value of 76.7%, a negative predictive value of 93%, and an overall precision of 91%. Conclusion: In this study, only 9 variables were independent predictors of nosocomial BSI. Our findings are specific to critically ill adult trauma patients and should be interpreted within the context of this particular population.
Magneto-optical and field-metric evaluation of the punching effect on magnetic properties of electrical steels with varying alloying content and grain size

The punching of electrical steel sheets to manufacture iron cores for electrical machines can influence drastically the final magnetic properties of stator and rotor cores. In this paper, the influence of punching on the magnetic properties is studied on 5 mm wide ring core samples. Six different fully processed non-oriented electrical steels with varying alloy content and varying grain size were investigated. Both global (integral) as well as local magnetic characterisation is carried out. The global magnetic properties are obtained by field-metric magnetic measurements. Punching leads to an increase in the global ring core losses: for the specific case of 5mm wide punched rings, this increase is in the range of 10% to 30% (for losses at 1 T and 400 Hz) depending on the investigated material (this range corresponds to a loss increase of 2.5 to 5.5 W/kg). The local magnetic degradation due to punching becomes more important when approaching the cutting edge. For local magnetic characterisation the magneto-optical Kerr-effect is used. The method allows the observation of the magnetic domain behaviour near the cut edge. Moreover this magneto-optical method allows for a quantitative analysis of the effect of punching on the local magnetic contrast as a function of distance from the cut edge. In addition also micro hardness measurements are performed near the cut edges to determine the mechanically affected zone. Furthermore the influence of punching on the investigated local and global magnetic properties is discussed as a function of the differences in alloying content and grain size of the investigated materials. For the high alloyed electrical steels, the material with medium grain size deteriorates less due to punching than the material with high grain size. This can be observed both from the dc magnetization curves which exhibit higher permeability and from the iron losses at medium frequency (400Hz) after punching. At 50Hz the losses remain lowest for the high grain sized material, even after punching.
Exercise‐induced rib stress fractures: influence of reduced bone mineral density

Exercise‐induced rib stress fractures have been reported frequently in elite rowers during the past decade. The etiology of rib stress fractures is unclear, but low bone mineral density (BMD) has been suggested to be a potential risk factor for stress fractures in weight‐bearing bones. The present study investigated BMD in seven Danish national team rowers with previous rib stress fracture (RSF) and 7 controls (C) matched for gender, age, height, weight and training experience. Total body scan and specific scans of the lumbar spine (L2–L4), femoral neck and distal radius were performed using a DEXA scanner. The RSF subjects showed significantly lower L2–L4 BMD: RSF: 1.22±0.05 g cm−2 (mean±SEM) (median 1.19 g cm−2, range 1.02–1.37 g cm−2) compared to C: 140±0.04 g cm−2 (median 1.41 g cm−2, range 1.27–1.57 g cm−2) (P=0.028). The present results suggest that low bone mineral density may be a potential risk factor for the development of exercise‐induced rib stress fractures in elite rowers.
Cholesterol induces renal vasoconstriction and anti-natriuresis by inhibiting nitric oxide production in anesthetized rats.

Although hypercholesterolemia is implicated in the pathophysiology of many renal disorders as well as hypertension, its direct actions in the kidney are not yet clearly understood. In the present study, we evaluated renal responses to administration of cholesterol (8 microg x min(-1). 100 g body wt(-1); bound by polyethylene glycol) into the renal artery of anesthetized male Sprague-Dawley rats. Total renal blood flow (RBF) was measured by a Transonic flow probe, and glomerular filtration rate (GFR) was determined by Inulin clearance. In control rats (n = 8), cholesterol induced reductions of 10 +/- 2% in RBF [baseline (b) 7.6 +/- 0.3 microg x min(-1). 100 g(-1)], 17 +/- 3% in urine flow (b, 10.6 +/- 0.9 microg x min(-1). 100 g(-1)), 29 +/- 3% in sodium excretion (b, 0.96 +/- 0.05 mumol.min(-1). 100 g(-1)) and 24 +/- 2% in nitrite/nitrate excretion (b, 0.22 +/- 0.01 nmol.min(-1). 100 g(-1)) without an appreciable change in GFR (b, 0.87 +/- 0.03 ml.min(-1). 100 g(-1)). These renal vasoconstrictor and anti-natriuretic responses to cholesterol were absent in rats pretreated with nitric oxide (NO) synthase inhibitor, nitro-l-arginine methylester (0.5 microg x min(-1). 100 g(-1); n = 6). In rats pretreated with superoxide (O(2)(-)) scavenger tempol (50 microg x min(-1). 100 g(-1); n = 6), the cholesterol-induced renal responses remained mostly unchanged, although there was a slight attenuation in anti-natriuretic response. This anti-natriuretic response to cholesterol was abolished in furosemide-pretreated rats (0.3 microg x min(-1). 100 g(-1); n = 6) but remained unchanged in amiloride-pretreated rats (0.2 microg x min(-1). 100 g(-1); n = 5), indicating that Na(+)/K(+)/2Cl(-) cotransport is the dominant mediator of this effect. These data demonstrate that cholesterol-induced acute renal vasoconstrictor and antinatriuretic responses are mediated by a decrease in NO production. These data also indicate that tubular effect of cholesterol on sodium reabsorption is mediated by the furosemide sensitive Na(+)/K(+)/2Cl(-) cotransporter.
TAF4/4b·TAF12 Displays a Unique Mode of DNA Binding and Is Required for Core Promoter Function of a Subset of Genes*

The major core promoter-binding factor in polymerase II transcription machinery is TFIID, a complex consisting of TBP, the TATA box-binding protein, and 13 to 14 TBP-associated factors (TAFs). Previously we found that the histone H2A-like TAF paralogs TAF4 and TAF4b possess DNA-binding activity. Whether TAF4/TAF4b DNA binding directs TFIID to a specific core promoter element or facilitates TFIID binding to established core promoter elements is not known. Here we analyzed the mode of TAF4b·TAF12 DNA binding and show that this complex binds DNA with high affinity. The DNA length required for optimal binding is ∼70 bp. Although the complex displays a weak sequence preference, the nucleotide composition is less important than the length of the DNA for high affinity binding. Comparative expression profiling of wild-type and a DNA-binding mutant of TAF4 revealed common core promoter features in the down-regulated genes that include a TATA-box and an Initiator. Further examination of the PEL98 gene from this group showed diminished Initiator activity and TFIID occupancy in TAF4 DNA-binding mutant cells. These findings suggest that DNA binding by TAF4/4b-TAF12 facilitates the association of TFIID with the core promoter of a subset of genes.
Cryptic diversity and gene flow among three African agricultural pests: Ceratitis rosa, Ceratitis fasciventris and Ceratitis anonae (Diptera, Tephritidae)

The ‘Ceratitis FAR complex’ is a species complex of African fruit flies (Diptera, Tephritidae) including the major agricultural pest Ceratitis rosa and the morphologically similar Ceratitis fasciventris and Ceratitis anonae. To resolve their intra‐ and interspecific genetic relationships and to estimate gene flow within this complex, we surveyed allelic variation at 16 microsatellite loci in 27 African populations of the three morphospecies. Interpopulation genetic distances and individual Bayesian assignments distinguished five genotypic clusters: two involving C. rosa (R1, R2; that may occur in sympatry), two involving C. fasciventris (F1, F2; with parapatric distributions) and one involving C. anonae (A). Intra‐ and interspecific patterns of genetic differentiation were not hierarchically structured and genetic differentiation between conspecific clusters (F1–F2 and R1–R2) was higher or comparable with differentiation between heterospecific clusters (e.g. F1‐A or R2‐A). In some cases, gene flow estimates among morphospecies or among heterospecific genotypic clusters were significantly different from zero, showing the lack of reproductive isolation. Genetic differentiation between genotypic clusters was partly supported by morphological differences observed a posteriori in male secondary sexual characters. These results suggest important revisions to current models of ecological niche requirements and invasion risk of the major agricultural pest C. rosa and provide a basis for a taxonomic re‐interpretation of the FAR complex.