Effects of repeated lysergic acid diethylamide (LSD) on the mouse brain endocannabinoidome and gut microbiome.

BACKGROUND AND PURPOSE: Psychedelics elicit prosocial, antidepressant and anxiolytic effects via neuroplasticity, neurotransmission and neuro-immunomodulatory mechanisms. Whether psychedelics affect the brain endocannabinoid system and its extended version, the endocannabinoidome (eCBome) or the gut microbiome, remains unknown. EXPERIMENTAL APPROACH: Adult C57BL/6N male mice were administered lysergic acid diethylamide (LSD) or saline for 7 days. Sociability was assessed in the direct social interaction and three chambers tests. Prefrontal cortex and hippocampal endocannabinoids, endocannabinoid-like mediators and metabolites were quantified via high-pressure liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Neurotransmitter levels were assessed via HPLC-UV/fluorescence. Gut microbiome changes were investigated by 16S ribosomal DNA sequencing. KEY RESULTS: LSD increased social preference and novelty and decreased hippocampal levels of the N-acylethanolamines N-linoleoylethanolamine (LEA), anandamide (N-arachidonoylethanolamine) and N-docosahexaenoylethanolamine (DHEA); the monoacylglycerol 1/2-docosahexaenoylglycerol (1/2-DHG); the prostaglandins D2 (PGD2 ) and F2α (PGF2α ); thromboxane 2 and kynurenine. Prefrontal eCBome mediator and metabolite levels were less affected by the treatment. LSD decreased Shannon alpha diversity of the gut microbiota, prevented the decrease in the Firmicutes:Bacteroidetes ratio observed in saline-treated mice and altered the relative abundance of the bacterial taxa Bifidobacterium, Ileibacterium, Dubosiella and Rikenellaceae RC9. CONCLUSIONS AND IMPLICATIONS: The prosocial effects elicited by repeated LSD administration are accompanied by alterations of hippocampal eCBome and kynurenine levels, and the composition of the gut microbiota. Modulation of the hippocampal eCBome and kynurenine pathway might represent a mechanism by which psychedelic compounds elicit prosocial effects and affect the gut microbiome.

Examining Racial, Ethnic, and Gender Disparities in the Treatment of Pain and Injury Emergencies.

Background: Racial, ethnic, and gender disparities in effective pain management have been well-documented across healthcare settings. However, discrepancies in the treatment of patients in prehospital pain management settings have not been well researched. The objective of this study was to determine whether Wyoming emergency medical service (EMS) providers' use of opioids to treat prehospital pain or injury varies by patient race/ethnicity or gender. Methods: This cross-sectional study of EMS records examined 27 448 patient care reports (PCRs) generated during emergency medical responses to pain/injury emergencies in the state of Wyoming between January 2016 and March 2019. We included PCRs in the sample when 1) the primary impression was pain or injury, 2) the type of service was a 911 response, 3) the patient received treatment from and was transported by the EMS unit completing the PCR, and 4) the responding unit included one or more providers authorized to administer opioids. Results: The analysis identified a disparity in opioid administration by EMS providers during emergency transport (N = 27 448). Logistic regression reveals that EMS providers administered opioids to American Indian/Alaska Native patients (AI/AN) [n = 1610; 5.9%; P < .001; OR = 0.44] and those of Hispanic ethnicity (n = 1351; 4.9%; P = .001; OR = 0.74) at statistically significant lower rates (n = 14 769; 53.8%; P = .004; OR = 0.90) than they administer opioids to White patients. The analysis found EMS providers administer opioids to females at significantly lower rates (P = .004) compared to males. Conclusion: Wyoming EMS providers administer opioids to White and male patients more often than non-White and female patients. Our results do not show a significant difference in the administration of opioids between White and Black patients. However, the data indicate a statistically significant difference between Hispanic, AI/AN, and White patients as well as between male and female patients.

Evidence Map and Systematic Review of Disinfection Efficacy on Environmental Surfaces in Healthcare Facilities.

Healthcare-associated infections (HAIs) contribute to patient morbidity and mortality with an estimated 1.7 million infections and 99,000 deaths costing USD $28-34 billion annually in the United States alone. There is little understanding as to if current environmental surface disinfection practices reduce pathogen load, and subsequently HAIs, in critical care settings. This evidence map includes a systematic review on the efficacy of disinfecting environmental surfaces in healthcare facilities. We screened 17,064 abstracts, 635 full texts, and included 181 articles for data extraction and study quality assessment. We reviewed ten disinfectant types and compared disinfectants with respect to study design, outcome organism, and fourteen indictors of study quality. We found important areas for improvement and gaps in the research related to study design, implementation, and analysis. Implementation of disinfection, a determinant of disinfection outcomes, was not measured in most studies and few studies assessed fungi or viruses. Assessing and comparing disinfection efficacy was impeded by study heterogeneity; however, we catalogued the outcomes and results for each disinfection type. We concluded that guidelines for disinfectant use are primarily based on laboratory data rather than a systematic review of in situ disinfection efficacy. It is critically important for practitioners and researchers to consider system-level efficacy and not just the efficacy of the disinfectant.

Preliminary Findings on a Novel Behavioural Approach for the Assessment of Pain and Analgesia in Lambs Subject to Routine Husbandry Procedures.

The identification and assessment of pain in sheep under field conditions are important, but, due to their stoic nature, are fraught with many challenges. In Australia, various husbandry procedures that are documented to cause pain are routinely performed at lamb marking, including ear tagging, castration, mulesing, and tail docking. This study evaluated the validity of a novel methodology to assess pain in lambs: qualitative behavioural assessment (QBA) was used to compare the behavioural expression of control lambs (CONTROL) with that of lambs subject to these procedures that received either a saline placebo 15 min before procedures (PLACEBO), or were administered meloxicam 15 min before procedures in addition to the standard analgesic Tri-Solfen at the time of procedures, as per the manufacturer's recommendations (ANALGESIC TREATMENT; AT). In terms of behavioural expression, it was expected that: CONTROL ≠ PLACEBO, AT = CONTROL, and PLACEBO ≠ AT. Video footage of the 6-8-week-old lambs (n = 10 for each treatment) was captured approximately 1.5 h postprocedure and was presented, in a random order, to 19 observers for assessment using the Free-Choice Profiling (FCP) approach to QBA. There was significant consensus (p < 0.001) among the observers in their assessment of the lambs, with two main dimensions of behavioural expression explaining 69.2% of the variation. As expected, observers perceived differences in the demeanour of lambs in the first dimension, scoring all lambs subject to the routine husbandry procedures as significantly more 'dull' and 'uneasy' compared to the control lambs (p < 0.05). Contrary to expectations, the results also suggested that analgesic treatment did not provide relief at the time of observation. Further investigations to validate the relationship between behavioural expression scores and pain are necessary, but these results suggest that painful husbandry procedures alter the behavioural expression of lambs and these differences can be captured using QBA methodology.

Diabetes-related sex differences in the brain endothelin system following ischemia in vivo and in human brain endothelial cells in vitro.

The endothelin (ET) system has been implicated to contribute to the pathophysiology of cognitive impairment and stroke in experimental diabetes. Our goals were to test the hypotheses that (1) circulating and (or) periinfarct ET-1 levels are elevated after stroke in both sexes and this increase is greater in diabetes, (2) ET receptors are differentially regulated in the diabetic brain, (3) brain microvascular endothelial cells (BMVEC) of female and male origin express the ETA receptor subtype, and (4) diabetes- and stroke-mimicking conditions increase ET-1 levels in BMVECs of both sexes. Control and diabetic rats were randomized to sham or stroke surgery. BMVECs of male (hBEC5i) and female (hCMEC/D3) origin, cultured under normal and diabetes-mimicking conditions, were exposed to normoxia or hypoxia. Circulating ET-1 levels were higher in diabetic animals and this was more pronounced in the male cohort. Stroke did not further increase plasma ET-1. Tissue ET-1 levels were increased after stroke only in males, whereas periinfarct ET-1 increased in both control and diabetic females. Male BMVECs secreted more ET-1 than female cells and hypoxia increased ET-1 levels in both cell types. There was sexually dimorphic regulation of ET receptors in both tissue and cell culture samples. There are sex differences in the stroke- and diabetes-mediated changes in the brain ET system at the endothelial and tissue levels.

Exploring the Relationship between Teacher Knowledge and Active-Learning Implementation in Large College Biology Courses.

Not all instructors implement active-learning strategies in a way that maximizes student outcomes. One potential explanation for variation in active-learning effectiveness is variation in the teaching knowledge an instructor draws upon. Guided by theoretical frameworks of pedagogical content knowledge and pedagogical knowledge, this study investigated the teaching knowledge instructors used in planning, implementing, and reflecting on active-learning lessons in large courses. We used a preinstruction interview, video footage of a target class session, and a postinstruction interview with stimulated recall to elicit the teaching knowledge participants used. We then conducted qualitative content analysis to describe and contrast teaching knowledge employed by instructors implementing active learning that required students to generate their own understandings (i.e., generative instruction) and active learning largely focused on activity and recall (i.e., active instruction). Participants engaging in generative instruction exhibited teaching knowledge distinct from that of participants focused on activity. Those using generative instruction drew on pedagogical knowledge to design lessons focused on students generating reasoning; integrated pedagogical content knowledge and pedagogical knowledge to plan lessons to target student difficulties; and created opportunities to develop new pedagogical content knowledge while teaching. This work generated hypotheses about the teaching knowledge necessary for effective, generative active-learning instruction.

Remote Identification of Sheep with Flystrike Using Behavioural Observations.

Flystrike is a major problem affecting sheep in Australia. Identification of 'flystruck' individuals is crucial for treatment; but requires labour-intensive physical examination. As the industry moves toward more low-input systems; there is a need for remote methods to identify flystruck individuals. The aim of this study was to investigate the behaviour of sheep with breech flystrike within a paddock setting. Video footage of sixteen Merino sheep; eight later confirmed with flystrike and eight without; was collected as they moved freely within the paddock with conspecifics. Quantitative behavioural measurements and a qualitative behavioural assessment (QBA) were conducted and compared to their breech conditions (i.e., faecal/urine staining; flystrike severity). Both qualitative and quantitative assessments indicated behavioural differences between flystruck and non-flystruck animals. Flystruck sheep had a behavioural profile characterised by restless behaviour; abnormal postures and reduced grazing time (p < 0.05). Furthermore; flystruck sheep were scored to have a more 'exhausted/irritated' demeanour using QBA (p < 0.05). The behavioural responses also corresponded to the flystrike severity scores and condition of the breech area. We conclude that remotely assessed behaviour of flystruck sheep diverges markedly from non-flystruck sheep; and thus could be a low-input method for identifying and treating affected animals.

Increasing Active Transportation Through E-Bike Use: Pilot Study Comparing the Health Benefits, Attitudes, and Beliefs Surrounding E-Bikes and Conventional Bikes.

BACKGROUND: The emergence of electric pedal-assist bicycles (e-bikes) presents an opportunity to increase active transportation by minimizing personal barriers of engaging in physical activity. OBJECTIVES: The aim of this study was to assess the beliefs of individuals using e-bikes for active transport and report preliminary biometric measurements while using e-bikes for physical activity compared with conventional bikes. METHODS: Participants used both conventional bicycles and e-bikes to compare energy expenditure while riding on the study route. Apple smart watches were used to track each participant's heart rate, distance, speed, and time while riding both bicycles. A total of 3 survey instruments were used to estimate beliefs: one administered before riding the bicycles, a second administered after riding a conventional bike, and the final survey completed after riding an e-bike. Survey instruments were constructed using constructs from the theory of planned behavior. RESULTS: The study sample (N=33) included adults aged between 19 and 28 years. Paired t test analysis revealed that participants believed a conventional bike was more likely than an e-bike to benefit their physical health (P=.002) and save them money (P=.005), while an e-bike was perceived to be more likely than a conventional bike to save them time (P<.001). Paired t test analysis revealed participants significantly agreed more with the statement that they could ride an e-bike most days (P=.006) compared with a conventional bike. After participants traveled approximately 10 miles on each type of bicycle, participants' mean average heart rate while riding the e-bike was 6.21 beats per minute lower than when riding the conventional bike (P=.04), but both were significantly higher than resting heart rate (P<.001). CONCLUSIONS: This pilot study suggests that e-bikes are an active form of transportation capable of providing much of the cardiovascular health benefits obtained during conventional bike use. E-bikes may help reduce some of the obstacles to conventional bike use, such as increased transportation time, decreased convenience, and physical fatigue.

Home availability of fruit and vegetables and obesogenic foods as an indicator of nutrient intake in 50 year olds from Canterbury, New Zealand.

BACKGROUND AND OBJECTIVES: The home food environment is known to influence children's diet and selected health outcomes. However, similar research in adults is scarce. The home is arguably the most important food environment for New Zealand adults as the majority of food consumed is stored and prepared in the home. Therefore we investigated relationships between home food availability and nutrient intake in 50 year olds from Canterbury, New Zealand. METHODS AND STUDY DESIGN: A cross-sectional study where participants completed a home food inventory and a four-day estimated food diary. Regression analysis was used to investigate relationships between home availability of 'Fruit and Vegetables' and 'Obesogenic Foods' and intake of selected nutrients, adjusting for Body Mass Index and demographic factors. Men and women (n=216) aged 50 were randomly selected from Canterbury District Health Board area electoral rolls. RESULTS: Women with a high 'Obesogenic Foods' score were significantly more likely to have a high intake of saturated fat (OR 5.8, CI: 1.67, 19.6) and high sugar intake (OR 3.1, CI: 1.23, 7.58). Men with a high 'Obesogenic Foods' score were less likely to have high folate (OR 0.14, CI: 0.05, 0.40) and fibre intake (OR 0.21, CI: 0.07, 0.60). Men and women with a higher 'Fruit and Vegetables' score were more likely to have high vitamin C intake (OR 5.6 and 4.5 respectively). CONCLUSIONS: Home Food Inventory scores are associated with selected nutrient intakes, particularly in women, suggesting that they are useful for identifying those groups with less favourable nutrient intakes. Future research should investigate whether these scores can predict health outcomes.

Home food availability is associated with multiple socio-economic indicators in 50 year olds from Canterbury, New Zealand.

Financial restraints and poverty lead to poor diets and poor health outcomes. Limited research shows that socioeconomic status is related to home availability of certain foods. However, studies in this area have used different socio-economic indicators, which may not equally influence eating-related behaviors. Using multiple indicators of socio-economic status may provide a more accurate picture of these relationships. The aim of this study was to investigate whether several socio-economic indicators are independently associated with home availability of selected foods known to influence chronic disease risk in 50 year olds from Canterbury, New Zealand, participating in the CHALICE study. Participants were selected randomly from health research extracts from Canterbury. Data from 216 participants (110 females, 106 males) were included. The presence (but not quantity) of foods/beverages in the home was measured by a validated home food inventory. Linear regression analyses were performed for the following home food inventory scores: fruit, vegetables, lower fat dairy, obesogenic foods and sweetened beverages with household income, standard of living and education using multivariate models. Higher household income and standard of living were individually associated with a 2% to 3% higher fruit and vegetables (3 to 5 types/forms) and total food scores (6 to 9 types/forms) (p<0.03). Higher education level was associated with a 2.5% increase in fruit and vegetables score (4 types/forms) and an 8% decrease in sweetened beverages score (0.4 beverages) (p<0.02). These results suggest that using only one measure of socio-economic status cannot accurately capture the effects of social inequalities in food availability. Those experiencing the most social disadvantage had a lesser availability of fruit and vegetables which may be detrimental to good health.

New policies signal changing attitudes on sex differences research: an SWHR® perspective.

The Society for Women's Health Research has long advocated that research studies on diseases that impact men and women should consider sex as a fundamental variable. Thankfully, this attitude seems to be evolving. Recently, the National Institutes of Health (NIH) reported that it will issue new policies on the inclusion of female animals and cells in preclinical medical research. We look forward to working with the NIH and the Office of Research on Women's Health as they develop new policies that require grant applicants to report their plans for including a balance of male and female animals and cells in preclinical studies as appropriate.

Initial orthostatic hypotension and cerebral blood flow regulation: effect of α1-adrenoreceptor activity.

We examined the hypothesis that α(1)-adrenergic blockade would lead to an inability to correct initial orthostatic hypotension (IOH) and cerebral hypoperfusion, leading to symptoms of presyncope. Twelve normotensive humans (aged 25 ± 1 yr; means ± SE) attempted to complete a 3-min upright stand, 90 min after the administration of either α(1)-blockade (prazosin, 1 mg/20 kg body wt) or placebo. Continuous beat-to-beat measurements of middle cerebral artery velocity (MCAv; Doppler), blood pressure (finometer), heart rate, and end-tidal Pco(2) were obtained. Compared with placebo, the α(1)-blockade reduced resting mean arterial blood pressure (MAP) (-15%; P < 0.01); MCAv remained unaltered (P ≥ 0.28). Upon standing, although the absolute level of MAP was lower following α(1)-blockade (39 ± 10 mmHg vs. 51 ± 14 mmHg), the relative difference in IOH was negligible in both trials (mean difference in MAP: 2 ± 2 mmHg; P = 0.50). Compared with the placebo trial, the declines in MCAv and Pet(CO(2)) during IOH were greater in the α(1)-blockade trial by 12 ± 4 cm/s and 4.4 ± 1.3 mmHg, respectively (P ≤ 0.01). Standing tolerance was markedly reduced in the α(1)-blockade trial (75 ± 17 s vs. 180 ± 0 s; P < 0.001). In summary, while IOH was little affected by α(1)-blockade, the associated decline in MCAv was greater in the blockade condition. Unlike in the placebo trial, the extent of IOH and cerebral hypoperfusion failed to recover toward baseline in the α(1)-blockade trial leading to presyncope. Although the development of IOH is not influenced by the α(1)-adrenergic receptor pathway, this pathway is critical in the recovery from IOH to prevent cerebral hypoperfusion and ultimately syncope.

An examination of the integration of certified peer specialists into community mental health centers.

The formal role of Certified Peer Specialist (CPS) is a recent addition to the mental health field. CPSs are people in recovery employed within the mental health system, mostly by community mental health centers, to provide support through sharing life experiences with those working toward recovery from mental illness. This brief report examines participant's experiences being a CPS, responsibilities and activities as a CPS, and integration into community mental health centers. Findings suggest that CPSs demonstrate high levels of communal orientation, job satisfaction, workplace integration and organizational support and are well received in mental health centers.

The effect of time-of-day and sympathetic α1-blockade on orthostatic tolerance.

Tolerance time to a standardized orthostatic stressor is markedly reduced in normotensive individuals in the morning. However, the physiological mechanisms that underpin this phenomenon are unknown. The purpose of this study was to examine the role of α(1)-adrenergic activity on orthostatic tolerance and associated cardiorespiratory and cerebrovascular responses, and to determine whether its endogenous modulation is important in the diurnal variation of orthostatic tolerance. In a four-trial, randomized placebo-controlled crossover experiment, 12 normotensive volunteers (aged 25 ± 1 yrs; mean ± SE) completed a 60° head-upward tilt (HUT; 15 min or until onset of presyncope) at 06:00 and 16:00 h, 90 min after the administration of either α(1)-blockade (prazosin, 1 mg/20 kg body weight) or placebo. Continuous beat-to-beat measurements of middle cerebral blood flow velocity (transcranial Doppler), blood pressure (Finometer), heart rate, stroke volume, cardiac output, and end-tidal carbon dioxide were obtained. Independent of time-of-day, α(1)-blockade markedly reduced the ability to tolerate a 15-min 60° HUT; tolerance time was 229% shorter compared with the placebo condition (p ≤ .0001). Moreover, a marked diurnal variation in orthostatic tolerance was evident following α(1)-adrenergic blockade; e.g., tolerance time in the morning (176 ± 30 s) was lower than in the afternoon (354 ± 75 s; p = .04). These findings highlight an important role of α(1)-sympathetic vasoconstrictor activity in acutely regulating blood pressure and offsetting syncope, especially in the early morning.

α1-Adrenoreceptor activity does not explain lower morning endothelial-dependent, flow-mediated dilation in humans.

Early morning reduction in endothelium-dependent, flow-mediated dilation (FMD) may contribute to the high incidence of sudden cardiac death at this time of day. The mechanisms underpinning diurnal variation in FMD are unclear, but potentially relate to a circadian rhythm in sympathetic nerve activity. We hypothesized that blockade of α(1)-mediated sympathetic nerve activity would act to attenuate the diurnal variation in FMD. In a randomized and placebo-controlled design, we measured brachial artery FMD in 12 participants (mean age = 26 yr, SD = 3) at 0600 and 1600 after ingestion of an α(1)-blocker (prazosin, 1 mg/20 kg body mass) or placebo. Arterial diameter and shear rate were assessed using edge-detection software. Heart rate and blood pressure were also measured. Data were analyzed using linear mixed modeling. Following placebo, FMD was 8 ± 2% in the morning compared with 10 ± 3% in the afternoon (P = 0.04). Blockade with prazosin led to a slight but nonsignificant increase in morning FMD (P = 0.24) and a significant (P = 0.04) decrease in afternoon FMD, resulting in no diurnal variation (P = 0.20). Shear rate did not differ in the morning or afternoon under either condition (P > 0.23). Blood pressure was lower following prazosin compared with placebo (P < 0.02), an effect that was similar at both times of day (P > 0.34). Heart rate and norepinephrine levels were higher in the afternoon following prazosin. These data indicate that α(1)-adrenoreceptor activity does not explain lower morning endothelium-dependent FMD.

Characterization of NAC domain transcription factors implicated in control of vascular cell differentiation in Arabidopsis and Populus.

Wood has a wide variety of uses and is arguably the most important renewable raw material. The composition of xylem cell types in wood determines the utility of different types of wood for distinct commercial applications. Using expression profiling and phylogenetic analysis, we identified many xylem-associated regulatory genes that may control the differentiation of cells involved in wood formation in Arabidopsis and poplar. Prominent among these are NAC domain transcription factors (NACs). We studied NACs with putative involvement as negative (XND1 from Arabidopsis and its poplar orthologs PopNAC118, PopNAC122, PopNAC128, PopNAC129), or positive (SND2 and SND3 from Arabidopsis and their poplar orthologs PopNAC105, PopNAC154, PopNAC156, PopNAC157) regulators of secondary cell wall synthesis. Using quantitative PCR and in situ hybridization, we evaluated expression of these Populus NACs in a developmental gradient and in association with reaction wood and found that representatives from both groups were associated with wood-forming tissue and phloem fibers. Additionally, XND1 orthologs were expressed in mesophyll cells of developing leaves. We prepared transgenic Arabidopsis and poplar plants for overexpression of selected NACs. XND1 overexpression in poplar resulted in severe stunting. Additionally, poplar XND1 overexpressors lacked phloem fibers and showed reductions in cell size and number, vessel number, and frequency of rays in the xylem. Overexpression of PopNAC122, an XND1 ortholog, yielded an analogous phenotype in Arabidopsis. Overexpression of PopNAC154 in poplar reduced height growth and increased the relative proportion of bark versus xylem.

The impact of home-based physiotherapy interventions on breathlessness during activities of daily living in severe COPD: a systematic review.

OBJECTIVES: To conduct a systematic review and meta-analysis to determine the impact of home-based physiotherapy interventions on breathlessness during activities of daily living (ADL) in severe chronic obstructive disease (COPD). DATA SOURCES: The electronic databases AMED, CINAHL, Cochrane Central Register of Controlled Trials, Embase, Medline and Physiotherapy Evidence Database (PEDro) were searched from their inception to Week 20 2008. Bibliographies of all potentially relevant retrieved studies, identified relevant systematic reviews and international guidelines were searched by hand. REVIEW METHODS: Inclusion criteria consisted of individuals over 18 years of age with severe COPD (defined as forced expiratory volume in 1 second < or = 50% predicted) without cardiovascular co-morbidities, home-based interventions and valid, reliable breathlessness ADL outcome measures. The PEDro scale assessed methodological quality. Data extraction included baseline characteristics, treatment intervention, frequency of training, level of supervision, breathlessness ADL outcome measure and results. Where possible, a random-effects meta-analysis was applied to appropriate trial data to produce overall quantitative results. RESULTS: Seven studies, providing nine data sets, met the inclusion criteria. Trial PEDro scores ranged from 4 to 7 out of 10. Studies were homogenous at baseline regarding age and COPD severity, although subjects were predominantly male. Five studies investigated inspiratory or expiratory muscle training, and two studies investigated exercises. Statistically significant breathlessness ADL outcome improvements were reported for all interventions except expiratory muscle training. Five studies demonstrated clinical significance (four for inspiratory muscle training and one for exercise). However, due to heterogeneity among study interventions and outcomes, meta-analysis was only considered clinically appropriate on one occasion to pool three inspiratory muscle training studies in relation to breathlessness score. The random-effects meta-analysis indicated that, on average, inspiratory muscle training improved the breathlessness score significantly by 2.36 (95% confidence interval 0.76 to 3.96) compared with controls. CONCLUSION: Inspiratory muscle training and exercise are home-based physiotherapy interventions that may improve breathlessness during ADL in severe COPD. Administration can only be advocated tentatively in outpatient services and primary care at this stage because further higher quality, more homogeneous research with larger sample sizes is required to substantiate the current findings.

XND1, a member of the NAC domain family in Arabidopsis thaliana, negatively regulates lignocellulose synthesis and programmed cell death in xylem.

Members of the large Arabidopsis NAC domain transcription factor family are regulators of meristem development, organ elongation and separation, and deposition of patterned secondary cell walls. XYLEM NAC DOMAIN 1 (XND1) is highly expressed in xylem. Changes observed for XND1 knockout plants compared with wild-type Arabidopsis thaliana included a reduction in both plant height and tracheary element length and an increase in metaxylem relative to protoxylem in roots of plants treated with the proteasome inhibitor MG132. Overexpression of XND1 resulted in extreme dwarfism associated with the absence of xylem vessels and little or no expression of tracheary element marker genes. In contrast, phloem marker-gene expression was not altered and phloem-type cells still formed. Transmission electron microscopy showed that parenchyma-like cells in the incipient xylem zone in hypocotyls of XND1 overexpressors lacked secondary wall thickenings and retained their cytoplasmic content. Considered together, these findings suggest that XND1 affects tracheary element growth through regulation of secondary wall synthesis and programmed cell death.

Hypertrophy with unilateral resistance exercise occurs without increases in endogenous anabolic hormone concentration.

We aimed to gain insight into the role that the transitory increases in anabolic hormones play in muscle hypertrophy with unilateral resistance training. Ten healthy young male subjects (21.8 +/- 0.4 years, 1.78 +/- 0.04 m, 75.6 +/- 2.9 kg; mean +/- SE) engaged in unilateral resistance training for 8 week (3 days/week). Exercises were knee extension and leg press performed at 80-90% of the subject's single repetition maximum (1RM). Blood samples were collected in the acute period before and after the first training bout and following the last training bout and analyzed for total testosterone, free-testosterone, luteinizing hormone, sex hormone binding globulin, growth hormone, cortisol, and insulin-like growth factor-1. Thigh muscle cross sectional area (CSA) and muscle fibre CSA by biopsy (vastus lateralis) were measured pre- and post-training. Acutely, no changes in systemic hormone concentrations were observed in the 90 min period following exercise and there was no influence of training on these results. Training-induced increases were observed in type IIx and IIa muscle fibre CSA of 22 +/- 3 and 13 +/- 2% (both P < 0.001). No changes were observed in fibre CSA in the untrained leg (all P > 0.5). Whole muscle CSA increased by 5.4 +/- 0.9% in the trained leg (P < 0.001) and remained unchanged in the untrained leg (P = 0.76). Isotonic 1RM increased in the trained leg for leg press and for knee extension (P < 0.001). No changes were seen in the untrained leg. In conclusion, unilateral training induced local muscle hypertrophy only in the exercised limb, which occurred in the absence of changes in systemic hormones that ostensibly play a role in muscle hypertrophy.

Strain variation in an emerging iridovirus of warm-water fishes.

Although iridoviruses vary widely within and among genera with respect to their host range and virulence, variation within iridovirus species has been less extensively characterized. This study explores the nature and extent of intraspecific variation within an emerging iridovirus of North American warm-water fishes, largemouth bass virus (LMBV). Three LMBV isolates recovered from three distinct sources differed genetically and phenotypically. Genetically, the isolates differed in the banding patterns generated from amplified fragment length polymorphism analysis but not in their DNA sequences at two loci of different degrees of evolutionary stability. In vitro, the isolates replicated at identical rates in cell culture, as determined by real-time quantitative PCR of viral particles released into suspension. In vivo, the isolates varied over fivefold in virulence, as measured by the rate at which they induced mortality in juvenile largemouth bass. This variation was reflected in the viral loads of exposed fish, measured using real-time quantitative PCR; the most virulent viral strain also replicated to the highest level in fish. Together, these results justify the designation of these isolates as different strains of LMBV. Strain variation in iridoviruses could help explain why animal populations naturally infected with iridovirus pathogens vary so extensively in their clinical responses to infection. The results of this study are especially relevant to emerging iridoviruses of aquaculture systems and wildlife.