Miracle-dz/UniFAR-FTUs huggingface dataset:
A single night of sleep loss impairs objective but not subjective working memory performance in a sex‐dependent manner

Acute sleep deprivation can lead to judgement errors and thereby increases the risk of accidents, possibly due to an impaired working memory. However, whether the adverse effects of acute sleep loss on working memory are modulated by auditory distraction in women and men are not known. Additionally, it is unknown whether sleep loss alters the way in which men and women perceive their working memory performance. Thus, 24 young adults (12 women using oral contraceptives at the time of investigation) participated in two experimental conditions: nocturnal sleep (scheduled between 22:30 and 06:30 hours) versus one night of total sleep loss. Participants were administered a digital working memory test in which eight‐digit sequences were learned and retrieved in the morning after each condition. Learning of digital sequences was accompanied by either silence or auditory distraction (equal distribution among trials). After sequence retrieval, each trial ended with a question regarding how certain participants were of the correctness of their response, as a self‐estimate of working memory performance. We found that sleep loss impaired objective but not self‐estimated working memory performance in women. In contrast, both measures remained unaffected by sleep loss in men. Auditory distraction impaired working memory performance, without modulation by sleep loss or sex. Being unaware of cognitive limitations when sleep‐deprived, as seen in our study, could lead to undesirable consequences in, for example, an occupational context. Our findings suggest that sleep‐deprived young women are at particular risk for overestimating their working memory performance.
Coordination of end-of-life care for patients with lung cancer and those with advanced COPD: are there transferable lessons? A longitudinal qualitative study

Background: Care coordination is defined as good communication between professionals to enable access to services based on need. Aims: To explore patients' experience of care coordination in order to inform current debates on how best to coordinate care and deliver services in end-of-life for patients with lung cancer and those with chronic obstructive pulmonary disease (COPD). Methods: A qualitative study involving serial interviews was performed in 18 patients recruited from three hospital outpatient clinics situated in a hospital. Interviews were transcribed verbatim and data were analysed thematically. Results: Data comprised 38 interviews. Patients experiencing services related to lung cancer reported good access enabled by the involvement of a keyworker. This contrasted with COPD patients' experiences of services. The keyworker coordinated care between and within clinical settings, referred patients to community palliative care services, helped them with financial issues, and provided support. Conclusions: For patients with lung cancer, the keyworker's role augmented access to various services and enabled care based on their needs. The experiences of patients with COPD highlight the importance of providing a keyworker for this group of patients in both secondary and primary care.
New therapeutic agents for the treatment of bone diseases

Bisphosphonates have demonstrated important clinical benefits for patients with malignant bone disease, metabolic bone diseases, such as Paget’s disease, and postmenopausal osteoporosis. The introduction of nitrogen-containing bisphosphonates with high affinity for hydroxyapatite in bone represents an important advancement. These agents are now a standard of care for osteoporosis, Paget’s disease, osteogenesis imperfecta, primary bone lesions from multiple myeloma and bone metastases from breast cancer. Moreover, the recent clinical development of zoledronic acid (4 mg by 15-minute intravenous infusion) has expanded the benefits of bisphosphonate therapy to patients with bone metastases from any solid tumour. Bisphosphonates are also being investigated at present for the prevention of bone loss resulting from cancer therapy. In addition, a variety of novel biologic agents, receptor activator of nuclear factor-κB (RANK) ligand antibodies, osteoprotegerin and cathepsin K inhibitors are being investigated at present for the treatment of malignant bone disease. The management of bone health is an important area of active research, and the armamentarium and role of bone-specific therapies continue to expand.
Variable Influence of Kaempferol and Myricetin on in vitro Hepatocellular Cholesterol Biosynthesis

Flavonoids, e. g. , quercetin, luteolin, and taxifolin, are known to inhibit hepatocellular cholesterol biosynthesis. Surprisingly, we found that some flavonoids, namely kaempferol and myricetin, are able to considerably stimulate cholesterol biosynthesis, particularly within a low concentration range (between 0.1 and 10 microM), while they show a variable degree of inhibition at higher concentrations. Kaempferol 3-glucoside even stimulated cholesterol synthesis up to 100 microM. In contrast, kaempferol 7-neohesperidoside was ineffective. These effects were more pronounced in rat hepatocytes than in HepG2 cells except for myricetin which acted stimulatory even at high concentrations in HepG2 cells. These opposing effects on cholesterol biosynthesis are exerted in an indirect manner and seem possible though differential modulation of the complex regulation of HMGCoA reductase.
Sympathetic nerve discharge in normal pregnancy and pregnancy‐induced hypertension

Background Microneurographic assessment of processed bursts that represent multi-unit nerve discharge has suggested that sympathetic hyperactivity occurs in pregnancy induced hypertension and preeclampsia in comparison with normal pregnancy. Objective To examine the differences between peripheral sympathetic outputs in pregnancy-induced hypertension and normal pregnancy by directly measuring single impulses of neural discharge. Design We compared the sympathetic neural discharge at rest and its reflex responses in subjects with pregnancy-induced hypertension and normal pregnancy and re-examined their progress at least 6 weeks post partum. The patients with pregnancy-induced hypertension were hospital in-patients for whom the diagnosis could be strictly defined and the normally pregnant women were recruited to match the former. Methods Standard microneurography was performed to quantify single impulses of action potentials, together with the processed multi-unit bursts from fibres innervating the leg muscles. We measured neural discharge with vascular vasoconstrictive properties, heart rate and finger arterial blood pressure at rest and their responses to standard isometric hand-grip exercise and cold pressor tests. Results As expected, patients with pregnancy-induced hypertension (n = 13) had higher levels of finger arterial blood pressure than did women with normal pregnancies (n = 11). The number of single impulses of action potentials (per min and per 100 cardiac beats) in resting patients with pregnancy-induced hypertension was more than three times greater than that in resting women with normal pregnancies, and the number of multi-unit bursts was twofold greater. After delivery of their child, sympathetic activity and heart rate in nine patients decreased, but finger arterial blood pressure decreased in patients with pregnancy-induced hypertension only. Conclusions From results of cross-sectional and longitudinal studies, pregnancy-induced hypertension is associated with a greater resting sympathetic output than that of women with normal pregnancies. Follow-up data after parturition suggest that this hyperactivity is not the only cause of hypertension. J Hypertens 16:617–624 © 1998 Lippincott-Raven Publishers.
APOE and spatial navigation in amnestic MCI: results from a computer-based test.

OBJECTIVE We investigated the association between APOE ε4 status and spatial navigation in patients with amnestic mild cognitive impairment (aMCI) and assessed the role of hippocampal volume in this association. METHOD Participants were 74 patients with clinically confirmed aMCI (33 APOE ε4 noncarriers, 26 heterozygous, and 15 homozygous ε4 carriers). Body-centered (egocentric) and world-centered (allocentric) spatial navigation in a computerized human analogue of the Morris Water Maze was assessed. Brain MRI with subsequent automated hippocampal volumetry was included. RESULTS Groups were similar in neuropsychological profile. Controlling for age, sex, education, and free memory recall, the APOE ε4 carriers performed more poorly on all spatial navigation subtasks (ps < .05). APOE ε4 homozygotes performed worse than heterozygotes (p = .021). Right hippocampal volume accounted for the differences in allocentric and delayed subtasks (ps > .05), but not in the egocentric subtask (p < .001). CONCLUSIONS Using an easy-to-use, computer-based tool to assess spatial navigation, we found spatial navigation deficits to worsen in a dose-dependent manner as a function of APOE ε4 status. This was at least partially due to differences in right hippocampal volume.
Regulation of gluconeogenesis by insulin and glucagon in the neonatal bovine.

Hepatocyte monolayers from neonatal calves were used to determine the effects of glucagon and insulin on incorporation of carbon from [2-14C]propionate, [1-14C]lactate, [U-14C]lactate, and [1,3-14C]glycerol into glucose and glycogen. Glucagon increased gluconeogenesis (nmol substrate incorporated into glucose or glycogen.micrograms DNA-1.h-1) from propionate and lactate but not from glycerol. Insulin decreased gluconeogenesis from [2-14C]propionate but was without effect on gluconeogenesis from [U-14C]lactate or [1,3-14C]glycerol. Net de novo glycogenesis (nmol substrate retained in cell glycogen.micrograms DNA-1.h-1) from propionate, lactate, and glycerol was decreased by glucagon and increased by insulin. Glucagon effects on gluconeogenesis, but not glycogenesis, were mimicked by dibutyryl adenosine 3',5'-cyclic monophosphate. Lactate flux through pyruvate carboxylase accounts for > or = 91% of lactate carbon flux to glucose, and this proportion was unchanged by glucagon or insulin. Gluconeogenesis from propionate and lactate is regulated by substrate concentration and glucagon in bovine hepatocyte monolayers. The data indicate that, in neonatal bovine liver, glucagon acts on a process common to lactate and propionate to increase gluconeogenesis, and insulin opposes these effects on gluconeogenesis from propionate but not lactate.
Differential Expression and Activity of 11β-Hydroxysteroid Dehydrogenase in Human Placenta and Fetal Membranes from Pregnancies with Intrauterine Growth Restriction

Objectives: To study the expression and the function of the 11β-hydroxysteroid dehydrogenase enzyme 1 (11β-HSD1) and 2 (11β-HSD2) in placenta and the fetal membranes from pregnancies with intrauterine growth restriction (IUGR) and from controls. Methods: Amnion, chorion, decidua and cotyledon were separated from placenta; mRNA was analyzed by TaqMan real-time technology and proteins by Western blot; enzyme activities were measured by the conversion of 3H-cortisol to 3H-cortisone and vice versa. Results: Predominant mRNA expression (p < 0.001) was found for 11β-HSD1 in chorion and for 11β-HSD2 in decidua and cotyledon. In pregnancies with IUGR, 11β-HSD1 was upregulated in chorion (mean ΔCt 11β-HSD:18S mRNA 193.5 vs. 103.0 in controls respectively, p < 0.05) and 11β-HSD2 was downregulated in decidua (mean ΔCt 11β-HSD2:18S mRNA 0.18 vs. 15.88 in controls respectively, p < 0.05). 11β-HSD1 protein levels were reduced in amnion and 11β-HSD1 and 11β-HSD2 oxidase activity in decidua and cotyledon were reduced from pregnancies with IUGR. Conclusion: Reduced synthesis or activity of 11β-HSD1 or 2 in cases of IUGR is shown in some but not in all tissues. The local mRNA expression of 11β-HSD1 in chorion may reflect a mechanism on the post-transcriptional gene regulation to stimulate the formation of cortisone in IUGR. To provoke increasing activity with oxidase stimulators could be a future therapy in cases of IUGR.
Phase III randomized multicenter trial of surgical resection, BCNU-impregnated wafers, and irradiation versus surgical resection and irradiation alone for treatment of operable, solitary brain metastasis from systemic cancer.

11513 Background: Metastatic brain tumors (MBT) are the most frequent complication of systemic cancer. With conventional radiotherapy, survival remains poor, ranging from 24 to 32 weeks. Recent randomized trials suggest that surgical resection and irradiation of solitary MBT can extend survival and improve neurological quality of life. However, the role of chemotherapy remains unclear. A phase I/II trial demonstrated that interstitial chemotherapy with BCNU-impregnated wafers was well tolerated in this cohort, with an extended median survival and infrequent local recurrences. METHODS A randomized, multicenter phase III trial was begun to evaluate the ability of BCNU-impregnated wafers to improve survival and local time to progression in comparison to surgical resection and irradiation alone, with an expected accrual of 170 patients. Eligible patients were adults with systemic cancer of the lung or breast, with a solitary, accessible MBT that did not cross the midline or violate the ventricular system. RESULTS A total of 22 patients (female - 14; 20 with lung cancer), median age 60 years (range 39-77), were enrolled and randomized before the study was closed due to slow accrual. Each patient had undergone maximal surgical resection of the MBT and radiation therapy (35 Gy); wafers were placed in 12 patients (range 2-8 wafers). The median overall survival for the wafer and non-wafer groups were 35.0 and 47.4 weeks, respectively (log rank test, p = 0.54), with a 6-month survival rate of 67% and 56%, respectively (Fishers exact test, p = 0.67). Wafer placement was well tolerated. CONCLUSIONS In this small cohort limited by slow accrual, the use of BCNU-impregnated wafers did not improve survival over surgical resection and irradiation alone. The wafers were well tolerated and did not adversely impact on quality of life. Although animal studies and phase I/II data are suggestive of activity, a large, multicenter, phase III comparative trial will be necessary to determine the efficacy of BCNU-impregnated wafers in patients with solitary, resectable MBT. [Table: see text].
Impact of a school-based physical activity intervention on fitness and bone in adolescent females.

BACKGROUND Many female adolescents participate in insufficient physical activity to maintain cardiovascular fitness and promote optimal bone growth. This study evaluates the impact of a school-based intervention on fitness, activity, and bone among adolescent females. METHODS Subjects were assigned to an intervention (n = 63) or comparison (n = 59) group, and underwent assessments of cardiovascular fitness (VO2peak), physical activity, body composition, bone mineral density (BMD), bone mineral content (BMC), and serum markers of bone turnover at baseline and at the end of each of two school semesters. RESULTS The intervention increased physical activity, VO2peak, and BMC for the thoracic spine (P values < 0.05). Bone turnover markers were not affected. In longitudinal analyses of the combined groups, improvements in cardiovascular fitness predicted increased bone formation (P < 0.01) and bone resorption (P < 0.05). CONCLUSION A school-based intervention for adolescent females effectively increased physical activity, cardiovascular fitness, and thoracic spine BMC.
The use of indexes evaluating the adherence to the Mediterranean diet in epidemiological studies: a review

Abstract The purpose of this paper is to review some of the methods that several epidemiological studies use to evaluate the adherence of a population to the Mediterranean diet pattern. Among these methods, diet indexes attempt to make a global evaluation of the quality of the diet based on a traditional Mediterranean reference pattern, described as a priori, general and qualitative. The Mediterranean diet indexes, hence, summarise the diet by means of a single score that results from a function of different components, such as food, food groups or a combination of foods and nutrients. The reviewed evaluation methods can be classified into three categories depending on the way they are calculated: (1) those based on a positive or negative scoring of the components, (2) those that add or substract standardised components, and (3) those that are based on a ratio between components. Dietary scores have been used to explore the multiple associations between the Mediterranean diet, as an integral entity, and health parameters such as life expectancy or the incidence of obesity, cardiovascular diseases and some types of cancers. Moreover, these indexes are also useful tools to measure food consumption trends and to identify the involved factors, as well as to develop comprehensive public health nutrition recommendations. A more precise and quantitative definition of the Mediterranean diet is required if the adherence to such a dietary pattern is intended to be more accurately measured. Other aspects of the Mediterranean diet indexes should also be taken into account, like the inclusion of typical Mediterranean foods such as nuts and fish and the validation of the dietary pattern approach by using biomarkers.
Melatonin regulates neuronal plasticity in the hippocampus

The influence of melatonin on hippocampal evoked potentials initiated by low‐ and high‐frequency electrical stimulations and by two pulses applied in rapid succession was investigated. In confirmation of our previous studies, melatonin attenuated the population spike triggered by low‐frequency stimulation (0.03 Hz). High‐frequency stimulation (HFS; 100 Hz for 1 sec, three times every 10 sec), which in control slices permanently facilitated neuronal excitability (347% ± 32%), was also able to amplify the melatonin‐depressed potential (467.8% ± 59.6%). Because melatonin is a hydrophobic molecule, it was dissolved and applied in ethanol. Ethanol (0.4%) by itself reduced the magnitude of HFS‐induced potentiation (233.5% ± 16.8%). The slices stimulated with two pulses separated with a delay longer than 15 msec demonstrated a facilitation of the response to the second stimuli (paired‐pulse facilitation; PPF). The influence of melatonin (100 μM) on PPF was biphasic: Shortly after addition of melatonin, PPF was briefly (5–10 min) reversed to paired‐pulse inhibition (PPI), which gradually returned to a stable PPF. Ethanol (0.4%) applied without melatonin exerted only a marginal, facilitatory effect on PPF. The delay between two successively applied pulses, shorter than 13 msec, resulted in attenuation of the response to the second stimuli (PPI). Melatonin (100 μM) reversed the attenuation of the second potential within 15–20 min following its application. Ethanol applied by itself at the concentration of 0.4% temporarily (5–10 min), but significantly, depressed the second potential. These results demonstrate the ability of melatonin to modulate specific forms of plasticity in hippocampal pyramidal neurons. © 2003 Wiley‐Liss, Inc.
Uremia-related oxidative stress in leukocytes is not triggered by β2-microglobulin.

BACKGROUND Chronic kidney disease (CKD) is characterized by low-grade inflammation and increased risk for cardiovascular disease. The interest in β2-microglobulin (B2M) as a marker for cardiovascular outcome with and without CKD has grown. Clinical studies suggested that B2M could be involved in the pathogenesis of vascular disease, for which chronic leukocyte activation is a pathogenic factor. We investigated whether B2M is proinflammatory by inducing oxidative burst in leukocytes. METHODS Oxidative burst was measured at baseline and after stimulation with N-formyl-methionine-leucine-phenylalanine (fMLP), Escherichia coli, or phorbol-12-myristate-acetate (PMA) in the whole blood of healthy volunteers in the absence (saline) and presence of human B2M (hB2M; 10 and 50 mg/L) versus uremic whole blood. Because of suspicion of contamination, hB2M was dialyzed for purification and purified B2M (dB2M) and dialysates were tested in the burst test. As a comparator, reactive oxygen species (ROS) in response to lipopolysaccharide (LPS) was measured. RESULTS Unpurified hB2M strongly enhanced ROS in monocytes and granulocytes after E. coli and PMA and moderately after fMLP stimulation compared with control (P < .01) and uremia (P < .01) whereas at baseline hB2M only induced ROS in granulocytes (P < .05). After purification, dB2M no longer increased burst activity, suggesting that contamination was responsible for the initial effect. An endotoxin concentration of less than 1.5 EU/mL, as observed in hB2M, could not induce oxidative stress. CONCLUSION This study suggests that B2M, a traditional marker for middle molecule retention and a novel marker for cardiovascular outcome, may not by itself cause vascular damage by influencing inflammatory response due to induction of leukocyte free radical production. However, an effect on other cell types involved cannot be excluded. Our data further reveal that this type of research might be skewed by non-LPS contaminants, and that care should be taken to exclude this bias.
Substance use and cognition in early psychosis.

OBJECTIVE To determine the relation between substance use and cognition in individuals experiencing their first episode of psychosis. DESIGN Prospective cross-sectional and longitudinal study. SETTING An Early Psychosis Treatment and Prevention Program, an outpatient clinic in a psychiatry department at a university-affiliated hospital. PARTICIPANTS Individuals with a psychotic illness who were admitted to an Early Psychosis Program; 266 patients were assessed at initial presentation, 159 at 1 year and 90 at 2 years. Most were outpatients. MEASURES The effects of substance use (alcohol, cannabis, hallucinogens, cocaine, stimulants) on cognition were assessed. Substance use was determined by DSM-IV criteria, and the Case Manager Rating Scale was used to determine the level of substance use. A comprehensive cognitive battery of tests was used, and the Positive and Negative Syndrome Scale for schizophrenia was administered to all subjects to determine levels of positive and negative symptoms. RESULTS Overall, both cross-sectionally and longitudinally, there were no significant associations between cognitive functioning and the use of various substances. Substance use was associated with higher positive symptoms. CONCLUSIONS Individuals with psychotic disorders who show mild-to-moderate abuse of substances, in particular alcohol and cannabis, do not exhibit more cognitive impairment than those who do not do use the substances. However, substance use may have other detrimental effects on the process of the psychotic illness.