Drugs

Throughout history, intoxicants were an important part of the war experience. The First World War was by no means an exception in that respect: its main "war drugs" were alcohol (mostly beer, brandy, rum, schnapps, wine, and vodka), morphine, and cocaine. These were both "prescribed" by military authorities and "self-prescribed" by soldiers. As in the past, the reasons for using drugs varied: from purely medical (killing the pain, anesthetizing, and energizing) to performance enhancement, from raising the fighting spirit to alleviating combat trauma, from strengthening bonds between companions to mitigating the fear of battle. Simultaneously and paradoxically, in many states temperance ideas gained in popularity and prohibitionist regulations were adopted

Black, Hispanic, and White Women's Perception of Heart Disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73200/1/j.0889-7204.2007.05698.x.pd

Physical activity levels and patterns of 19-month-old children

Purpose: It is a commonly held perception that most young children are naturally active and meet physical activity recommendations. However, there is no scientific evidence available on which to confirm or refute such perceptions. The purpose of this study was to describe the physical activity levels and patterns of Australian toddlers. Methods: Physical activity and demographic data of two hundred ninety-five 19-month-old children from the Melbourne InFANT Program were measured using accelerometers and parent surveys. Validated cut points of 192&ndash;1672 and &gt;1672 counts per minute were used to determine time spent in light- (LPA) and moderate-to-vigorous- (MVPA) intensity physical activity, respectively. To be included in the analysis, children were required to have four valid days of accelerometer data to provide an acceptable (&gt;0.70) reliability estimate of LPA and MVPA. Physical activity data for different periods of the day were examined. Results: On average, toddlers engaged in 184 min of LPA and 47 min of MVPA daily, and 90.5% met the current Australian physical activity recommendations for 0- to 5-yr-olds (180 min of LPA/MVPA per day). Physical activity levels during mid morning and mid afternoon were higher than those during other periods. Physical activity patterns for boys and girls were similar, although boys engaged in more physical activity during the morning hours than girls did. Conclusions: Most children meet the physical activity recommendations, although the majority of activity undertaken in the study was of light intensity. Boys were more active than girls were in the morning hours, but there were no differences between sexes over the entire day. Certain periods of the day may hold more promise for intervention implementation than others do. <br /

Evaluation of the effect of patient education on rates of falls in older hospital patients: Description of a randomised controlled trial

Background. Accidental falls by older patients in hospital are one of the most commonly reported adverse events. Falls after discharge are also common. These falls have enormous physical, psychological and social consequences for older patients, including serious physical injury and reduced quality of life, and are also a source of substantial cost to health systems worldwide. There have been a limited number of randomised controlled trials, mainly using multifactorial interventions, aiming to prevent older people falling whilst inpatients. Trials to date have produced conflicting results and recent meta-analyses highlight that there is still insufficient evidence to clearly identify which interventions may reduce the rate of falls, and falls related injuries, in this population. Methods and design. A prospective randomised controlled trial (n = 1206) is being conducted at two hospitals in Australia. Patients are eligible to be included in the trial if they are over 60 years of age and they, or their family or guardian, give written consent. Participants are randomised into three groups. The control group continues to receive usual care. Both intervention groups receive a specifically designed patient education intervention on minimising falls in addition to usual care. The education is delivered by Digital Video Disc (DVD) and written workbook and aims to promote falls prevention activities by participants. One of the intervention groups also receives follow up education training visits by a health professional. Blinded assessors conduct baseline and discharge assessments and follow up participants for 6 months after discharge. The primary outcome measure is falls by participants in hospital. Secondary outcome measures include falls at home after discharge, knowledge of falls prevention strategies and motivation to engage in falls prevention activities after discharge. All analyses will be based on intention to treat principle. Discussion. This trial will examine the effect of a single intervention (specifically designed patient education) on rates of falls in older patients in hospital and after discharge. The results will provide robust recommendations for clinicians and researchers about the role of patient education in this population. The study has the potential to identify a new intervention that may reduce rates of falls in older hospital patients and could be readily duplicated and applied in a wide range of clinical settings. Trial Registration. ACTRN12608000015347

Genes and gene clusters related to genotype and drought induced variation in saccharification potential, lignin content, and wood anatomical traits in Populus nigra:Saccharification, Wood Anatomy and Gene Clusters

Wood is a renewable resource that can be employed for the production of second generation biofuels by enzymatic saccharification and subsequent fermentation. Knowledge on how the saccharification potential is affected by genotype-related variation of wood traits and drought is scarce. Here, we used three Populus nigra genotypes from habitats differing in water availability to (i) investigate the relationships between wood anatomy, lignin content and saccharification and (ii) identify genes and co-expressed gene clusters related to genotype and drought-induced variation in wood traits and saccharification potential. The three poplar genotypes differed in wood anatomy, lignin content and saccharification potential. Drought resulted in reduced cambial activity, decreased vessel and fibre lumina, and increased the saccharification potential. The saccharification potential was unrelated to lignin content as well as to most wood anatomical traits. RNA sequencing of the developing xylem revealed that 1.5% of the analysed genes were differentially expressed in response to drought, while 67% differed among the genotypes. Weighted gene correlation network analysis identified modules of co-expressed genes correlated with saccharification potential. These modules were enriched in gene ontology terms related to cell wall polysaccharide biosynthesis and modification and vesicle transport, but not to lignin biosynthesis. Among the most strongly saccharification-correlated genes, those with regulatory functions, especially kinases were prominent. We further identified transcription factors whose transcript abundances differed among genotypes, and which were co45 regulated with genes for biosynthesis and modifications of hemicelluloses and pectin. Overall, our study suggests that the regulation of pectin and hemicellulose metabolism is a promising target for improving wood quality of second generation bioenergy crops. The causal relationship of the identified genes and pathways with saccharification potential needs to be validated in further experiments.publishersversionPeer reviewe

Disruption of the MDM2–p53 interaction strongly potentiates p53-dependent apoptosis in cisplatin-resistant human testicular carcinoma cells via the Fas/FasL pathway

Wild-type p53 has a major role in the response and execution of apoptosis after chemotherapy in many cancers. Although high levels of wild-type p53 and hardly any TP53 mutations are found in testicular cancer (TC), chemotherapy resistance is still observed in a significant subgroup of TC patients. In the present study, we demonstrate that p53 resides in a complex with MDM2 at higher cisplatin concentrations in cisplatin-resistant human TC cells compared with cisplatin-sensitive TC cells. Inhibition of the MDM2–p53 interaction using either Nutlin-3 or MDM2 RNA interference resulted in hyperactivation of the p53 pathway and a strong induction of apoptosis in cisplatin-sensitive and -resistant TC cells. Suppression of wild-type p53 induced resistance to Nutlin-3 in TC cells, demonstrating the key role of p53 for Nutlin-3 sensitivity. More specifically, our results indicate that p53-dependent induction of Fas membrane expression (∼threefold) and enhanced Fas/FasL interactions at the cell surface are important mechanisms of Nutlin-3-induced apoptosis in TC cells. Importantly, an analogous Fas-dependent mechanism of apoptosis upon Nutlin-3 treatment is executed in wild-type p53 expressing Hodgkin lymphoma and acute myeloid leukaemia cell lines. Finally, we demonstrate that Nutlin-3 strongly augmented cisplatin-induced apoptosis and cell kill via the Fas death receptor pathway. This effect is most pronounced in cisplatin-resistant TC cells

A Ligand Channel through the G Protein Coupled Receptor Opsin

The G protein coupled receptor rhodopsin contains a pocket within its seven-transmembrane helix (TM) structure, which bears the inactivating 11-cis-retinal bound by a protonated Schiff-base to Lys296 in TM7. Light-induced 11-cis-/all-trans-isomerization leads to the Schiff-base deprotonated active Meta II intermediate. With Meta II decay, the Schiff-base bond is hydrolyzed, all-trans-retinal is released from the pocket, and the apoprotein opsin reloaded with new 11-cis-retinal. The crystal structure of opsin in its active Ops* conformation provides the basis for computational modeling of retinal release and uptake. The ligand-free 7TM bundle of opsin opens into the hydrophobic membrane layer through openings A (between TM1 and 7), and B (between TM5 and 6), respectively. Using skeleton search and molecular docking, we find a continuous channel through the protein that connects these two openings and comprises in its central part the retinal binding pocket. The channel traverses the receptor over a distance of ca. 70 Å and is between 11.6 and 3.2 Å wide. Both openings are lined with aromatic residues, while the central part is highly polar. Four constrictions within the channel are so narrow that they must stretch to allow passage of the retinal β-ionone-ring. Constrictions are at openings A and B, respectively, and at Trp265 and Lys296 within the retinal pocket. The lysine enforces a 90° elbow-like kink in the channel which limits retinal passage. With a favorable Lys side chain conformation, 11-cis-retinal can take the turn, whereas passage of the all-trans isomer would require more global conformational changes. We discuss possible scenarios for the uptake of 11-cis- and release of all-trans-retinal. If the uptake gate of 11-cis-retinal is assigned to opening B, all-trans is likely to leave through the same gate. The unidirectional passage proposed previously requires uptake of 11-cis-retinal through A and release of photolyzed all-trans-retinal through B

Translations equations to compare ActiGraph GT3X and Actical accelerometers activity counts

Background: This study aimed to develop a translation equation to enable comparison between Actical and ActiGraph GT3X accelerometer counts recorded minute by minute. Methods: Five males and five females of variable height, weight, body mass index and age participated in this investigation. Participants simultaneously wore an Actical and an ActiGraph accelerometer for two days. Conversion algorithms and R2 were calculated day by day for each subject between the omnidirectional Actical and three different ActiGraph (three-dimensional) outputs: 1) vertical direction, 2) combined vector, and 3) a custom vector. Three conversion algorithms suitable for minute/minute conversions were then calculated from the full data set. Results: The vertical ActiGraph activity counts demonstrated the closest relationship with the Actical, with consistent moderate to strong conversions using the algorithm: y = 0.905x, in the day by day data (R2 range: 0.514 to 0.989 and average: 0.822) and full data set (R2 = 0.865). Conclusions: The Actical is most sensitive to accelerations in the vertical direction, and does not closely correlate with three-dimensional ActiGraph output. Minute by minute conversions between the Actical and ActiGraphvertical component can be confidently performed between data sets and might allow further synthesis of information between studies

The history of attention deficit hyperactivity disorder

The contemporary concept of attention deficit hyperactivity disorder (ADHD) as defined in the DSM-IV-TR (American Psychiatric Association 2000) is relatively new. Excessive hyperactive, inattentive, and impulsive children have been described in the literature since the nineteenth century. Some of the early depictions and etiological theories of hyperactivity were similar to current descriptions of ADHD. Detailed studies of the behavior of hyperactive children and increasing knowledge of brain function have changed the concepts of the fundamental behavioral and neuropathological deficits underlying the disorder. This article presents an overview of the conceptual history of modern-day ADHD