Living with obesity in Ireland: determinants, policy and future perspectives.

Globally, the prevalence of those living with obesity (≥30 kg/m2) is rising, with this trend expected to continue if firm and decisive policy interventions are not introduced. Across Europe, despite many consecutive policies aiming to reverse rising trends in weight status over recent decades, no country is currently on track to halt and reverse current trends in the coming years. This is evident in Ireland too, whereby the reporting of nationally representative weight status data show that targets have not been achieved since reporting began. The aim of this review is to critically appraise recent evidence relating to the key determinants of obesity including weight status, diet quality and physical activity with an emphasis on socioeconomic inequalities. And to consider these in the context of respective policy measures and propose future-focused recommendations. Furthermore, as with the complex nature of obesity, multifaceted approaches that shift the focus from the individual and place responsibility at a societal level will be reviewed.

Satisfacción estética y funcional tras reducción cerrada de fracturas nasales: implementación de la escala NOSE / Aesthetic and functional satisfaction after closed reduction of nasal fractures: implementation of the NOSE scale

Introducción y objetivo: La fractura nasal es la lesión facial más común y más del 50 % de todas las fracturas faciales en adultos. Debido a que en muchas ocasiones no es diagnosticada y tratada oportunamente, puede generar diferentes grados de limitación funcional y resultados estéticos indeseables. Pocos estudios evalúan la satisfacción de los pacientes tratados con técnica cerrada de reducción de fractura nasal. Nuestro objetivo es valorar la satisfacción funcional y estética posterior a reducción cerrada de fractura de huesos nasales en un hospital de Colombia, mediante la escala de evaluación de síntomas de obstrucción nasal (NOSE, por sus siglas en inglés - nasal obstruction symptom evaluation) y la escala estética subjetiva. Material y método: Estudio observacional analítico prospectivo de pacientes con fractura nasal llevados a reducción cerrada en el Hospital Universitario de Santander, Colombia. Se registraron las puntuaciones de las escalas NOSE y estética subjetiva, antes y 2 meses después de la cirugía. Resultados: Evaluamos 55 pacientes, 90.9% hombres. La mediana de edad fue de 31 años (RIC 24-48). El contexto de lesión principal fue violencia física (40%), seguido de accidente de tránsito (32.7%). Tras el procedimiento, los pacientes presentaron mejoría de obstrucción nasal medida con la escala NOSE (p<0.001); antes de la cirugía el 89% presentaba obstrucción nasal moderada-severa, posteriormente descendió a 14.5%. La escala NOSE mostró fabilidad por consistencia interna con alfa de Cronbach de 0.8317. Tras la cirugía hubo aumento de la satisfacción respecto al aspecto nasal (p<0.001). Conclusiones: En nuestro estudio, el cuestionario NOSE permitió cuantificar la mejora de síntomas de obstrucción nasal en pacientes con reducción cerrada por fractura de huesos nasales. Observamos mejoría de síntomas obstructivos nasales y aumento de satisfacción estética.Nivel de evidencia científica 4c Terapéutico.(AU)

Background and objective: Nasal fracture is the most common facial injury, accounting for more than 50% of all facial fractures in adults. Because it is often not diagnosed and treated promptly, it can generate different degrees of functional limitation and undesirable aesthetic results. Few studies evaluate the satisfaction of patients treated with the closed nasal fracture reduction technique. Our objective is to evaluate functional and aesthetic satisfaction after closed reduction of a nasal bone fracture in a hospital in Colombia, using the nasal obstruction symptom evaluation (NOSE) and subjective aesthetic scales. Methods: Prospective analytical observational study of patients with nasal fractures undergoing closed reduction at the University Hospital of Santander, Colombia. The scores of the NOSE scales and subjective aesthetics were recorded, before and 2 months after surgery. Results: We evaluated 55 patients, 90.9% men. Median age 31 years (IQR 24-48). The main injury context was physical violence (40%), followed by traffic accident (32.7%). After the procedure, the patients presented improvement in nasal obstruction measured with the NOSE scale (p<0.001); before surgery, 89% had moderate-severe nasal obstruction, later it decreased to 14.5%. The NOSE scale showed reliability due to internal consistency with Cronbach's alpha of 0.8317. After surgery, there was an increase in satisfaction regarding the nasal appearance (p<0.001). Conclusions: The NOSE questionnaire allows us to quantify the improvement of nasal obstruction symptoms in patients with closed reduction due to nasal bone fracture. Improvement of nasal obstructive symptoms and increased aesthetic satisfaction was observed.Level of evidence 4c Terapeutic.(AU)

Remains Containment Considerations for Death in Low-Earth Orbit.

BACKGROUND: Maintenance and disposition of decedent remains during spaceflight require the isolation of biohazardous products of decomposition in microgravity and in the absence of refrigeration. Containment and isolation options would preferably offer sufficient time to enable crew and ground support teams to determine appropriate disposition of remains and even potentially return remains to the Earth. The pilot study described herein undertook an effort to develop a postmortem containment unit for the isolation and maintenance of decedent remains in a microgravity environment.METHODS: Commercial off-the-shelf containment units were modified to meet the needs of a microgravity spaceflight environment and to offer the best likelihood of successful containment and management of remains. A subsequent evaluation of modified containment unit performance was undertaken utilizing human cadavers, with measurement and analysis of volatile off-gassing over time followed by impact testing of the units containing cadaverous remains in a simulated spaceflight vehicle seat.RESULTS: Modifications were implemented without significant negative design impact. Failure was observed in one modified unit after 9 d and attributed to improper filter application. The remaining unit successfully contained remains beyond the intended endpoint of the study.DISCUSSION: These pilot efforts offer important insight into the development of effective postmortem containment options for future spaceflight. Further study is needed to ensure repeatability of the findings and to further characterize the failure modes of the modified units evaluated, the impact of microgravity conditions, and the identification of additional modifications that would improve remains disposition.Houser T, Lindgren KN, Mazuchowski EL II, Barratt MR, Haines DC, Jayakody M, Blue RS, Bytheway JA, Stepaniak PC. Remains containment considerations for death in low-Earth orbit. Aerosp Med Hum Perform. 2023; 94(5):368-376.

Associations Between Positive Childhood Experiences and Adult Smoking and Alcohol Use Behaviors in a Large Statewide Sample.

Childhood experiences are linked to myriad indices of health and wellbeing in adulthood, including substance use behaviors. Increasingly, there has been a paradigm shift in prevention science focused on healthy outcomes of positive experiences. The current study examined associations between retrospective reports of positive childhood experiences and patterns of smoking and alcohol use in adulthood. Data were from the 2019 Montana Behavioral Risk Factor Surveillance System survey (N = 6,495; Mage = 55.9 years; 49% male as assigned at birth). Outcomes examined with regard to positive childhood experiences included lifetime smoking (> 100 cigarettes), current smoking status, and past-month alcohol use indices (i.e., total drinks, typical quantity, heavy episodic drinking, and peak drinking occasion). Positive childhood experience scores were inversely associated with both smoking outcomes (AORs = 0.66 and 0.61). Curiously, positive childhood experiences were positively associated with any past-month alcohol use (AOR = 1.12), but among respondents who did use alcohol in the past month, positive childhood experiences were inversely associated with all indices of alcohol use patterns: total drinks (CR = 0.94), drinks per occasion (CR = 0.95), heavy episodic occasions (AOR = 0.91), and peak drinking (AOR = 0.95). Findings generally indicated that positive childhood experiences may be protective against cigarette and high-risk alcohol use behaviors in adulthood. Item-by-item analyses identified specific childhood experiences that may be particularly protective, which may inform prevention efforts and policy (prevention recommendations are discussed below).

Comparing the quantitative fit-testing results of half-mask respirators with various skin barriers in a crossover study design: a pilot study.

BACKGROUND: Clinicians around the world are experiencing skin breakdown due to the prolonged usage of masks while working long hours to treat patients with COVID-19. The skin damage is a result of the increased friction and pressure at the mask-skin barrier. Throughout the COVID-19 pandemic, clinicians have been applying various skin barriers to prevent and ameliorate skin breakdown. However, there are no studies to our knowledge that assess the safety and efficacy of using these skin barriers without compromising a sufficient mask-face seal. AIM: To conduct the largest study to date of various skin barriers and seal integrity with quantitative fit testing (QNFT). METHODS: This pilot study explored whether the placement of a silicone scar sheet (ScarAway®), Cavilon™, or Tegaderm™ affects 3M™ half-face mask respirator barrier integrity when compared to no barrier using QNFT. Data were collected from nine clinicians at an academic level 1 trauma centre in New Jersey. FINDINGS: The silicone scar sheet resulted in the lowest adequate fit, whereas Cavilon provided the highest fit factor when compared to other interventions (P < 0.05). CONCLUSION: These findings help inform clinicians considering barriers for comfort when wearing facemasks during the COVID-19 pandemic and for future pandemics.

Animal and translational models of SARS-CoV-2 infection and COVID-19.

COVID-19 is causing a major once-in-a-century global pandemic. The scientific and clinical community is in a race to define and develop effective preventions and treatments. The major features of disease are described but clinical trials have been hampered by competing interests, small scale, lack of defined patient cohorts and defined readouts. What is needed now is head-to-head comparison of existing drugs, testing of safety including in the background of predisposing chronic diseases, and the development of new and targeted preventions and treatments. This is most efficiently achieved using representative animal models of primary infection including in the background of chronic disease with validation of findings in primary human cells and tissues. We explore and discuss the diverse animal, cell and tissue models that are being used and developed and collectively recapitulate many critical aspects of disease manifestation in humans to develop and test new preventions and treatments.

Characterizing rhizome bud dormancy in Polygonatum kingianum: Development of novel chill models and determination of dormancy release mechanisms by weighted correlation network analysis.

This study was conducted to explore specific chill models and the mechanisms underlying rhizome bud dormancy break in Polygonatum kingianum. Rhizome buds were subjected to various chilling temperatures for different duration and then transferred to warm conditions for germination and subsequent evaluation of their response to temperature and chilling requirements. A CUkingianum model was constructed to describe the contribution of low temperature to the chill unit, and it was suggested that 2.97°C was the optimum temperature and that 11.54°C was the upper limit for bud release. The CASkingianum model showed the relationship between chilling accumulation and sprouting percentage; therefore, rhizome bud development could be predicted through the model. Weighted correlation network analysis (WGCNA) of transcriptomic data of endo-, eco- and nondormant rhizome buds generated 33 gene modules, 6 of which were significantly related to bud sprouting percentage. In addition, 7 significantly matched transcription factors (TFs) were identified from the promoters of 17 "real" hub genes, and DAG2 was the best matched TF that bound to AAAG element to regulate gene expression. The current study is valuable for developing a highly efficient strategy for seedling cultivation and provides strong candidates for key genes related to rhizome bud dormancy in P. kingianum.

Refined diagnostic criteria for the bipolar disorders: phase two of the AREDOC project.

OBJECTIVE: As limitations exist across DSM criteria sets for defining and differentiating the bipolar disorders generally and their component bipolar I (BP-1) and bipolar II (BP-II) sub-types, we sought to generate empirically based criteria. METHOD: We formed an international Task Force (TF) comprising members with bipolar disorder expertise, and who recruited 74 patients with a TF-diagnosed bipolar I and 104 with a bipolar II condition (with patients responding to definitional queries and symptom questionnaires), while 33 unipolar depressed patients recruited by the first author also completed the symptom questionnaire. A factor analysis sought to determine granular hypo/manic constructs. RESULTS: The bipolar disorder subjects strongly affirmed a new general definition of a bipolar disorder (capturing both manic and hypomanic episodes). While DSM-5 requires impaired functioning, we established that a high percentage of individuals with a BP-I or a BP-II disorder reported improved functioning and therefore modified this criterion. Analyses identified syptoms with differential high rates in individuals with bipolar disorder and its sub-types (and thus not simply capturing happiness), while a factor analysis generated seven symptom constructs both linked with and differing from DSM-5 bipolar symptom criteria. CONCLUSION: This second-stage report details a new set of criteria for differentiating the bipolar disorders from unipolar depressive conditions, while arguing for BP-I and BP-II disorders being differentiated principally by the respective presence or absence of psychotic features. Future studies will evaluate whether further modifications are required and examine for differential treatment benefits for those with a BP-I versus a BP-II condition.

Prediction of lithium response using clinical data.

OBJECTIVE: Promptly establishing maintenance therapy could reduce morbidity and mortality in patients with bipolar disorder. Using a machine learning approach, we sought to evaluate whether lithium responsiveness (LR) is predictable using clinical markers. METHOD: Our data are the largest existing sample of direct interview-based clinical data from lithium-treated patients (n = 1266, 34.7% responders), collected across seven sites, internationally. We trained a random forest model to classify LR-as defined by the previously validated Alda scale-against 180 clinical predictors. RESULTS: Under appropriate cross-validation procedures, LR was predictable in the pooled sample with an area under the receiver operating characteristic curve of 0.80 (95% CI 0.78-0.82) and a Cohen kappa of 0.46 (0.4-0.51). The model demonstrated a particularly low false-positive rate (specificity 0.91 [0.88-0.92]). Features related to clinical course and the absence of rapid cycling appeared consistently informative. CONCLUSION: Clinical data can inform out-of-sample LR prediction to a potentially clinically relevant degree. Despite the relevance of clinical course and the absence of rapid cycling, there was substantial between-site heterogeneity with respect to feature importance. Future work must focus on improving classification of true positives, better characterizing between- and within-site heterogeneity, and further testing such models on new external datasets.

Understanding Police Performance Under Stress: Insights From the Biopsychosocial Model of Challenge and Threat.

We examine when and how police officers may avoid costly errors under stress by leveraging theoretical and empirical work on the biopsychosocial (BPS) model of challenge and threat. According to the BPS model, in motivated performance contexts (e.g., test taking, athletics), the evaluation of situational and task demands in relation to one's perceived resources available to cope with those demands engenders distinct patterns of peripheral physiological responding. Individuals experience more challenge-like states in which blood circulates more efficiently in the periphery when they evaluate their coping resources as meeting or exceeding the task demands. Conversely, individuals experience more threat-like states in which blood circulates less efficiently in the periphery when they view the situation or task demands as exceeding their coping resources. Patterns of response consistent with challenge and threat states have been shown to predict important performance and decision-making outcomes in stressful contexts, and repeated experiences of threat-like patterns of physiological activity are thought to have detrimental effects on long-term cardiovascular health. To date, however, research has not used the biopsychosocial model to understand police decision-making under stress. Here, we review relevant empirical work from the perspective of the BPS model concerning how minority status and power can shape challenge and threat responding and contribute to decision-making under stress. We then detail a research agenda aimed at improving the translational value of research being conducted within the BPS model for understanding complex performance and decision-making in the real world, including among law enforcement personnel.

Semi-Synthesis and Evaluation of Sargahydroquinoic Acid Derivatives as Potential Antimalarial Agents.

Background: Malaria continues to present a major health problem, especially in developing countries. The development of new antimalarial drugs to counter drug resistance and ensure a steady supply of new treatment options is therefore an important area of research. Meroditerpenes have previously been shown to exhibit antiplasmodial activity against a chloroquinone sensitive strain of Plasmodium falciparum (D10). In this study we explored the antiplasmodial activity of several semi-synthetic analogs of sargahydroquinoic acid. Methods: Sargahydroquinoic acid was isolated from the marine brown alga, Sargassum incisifolium and converted, semi-synthetically, to several analogs. The natural products, together with their synthetic derivatives were evaluated for their activity against the FCR-3 strain of Plasmodium falciparum as well as MDA-MB-231 breast cancer cells. Results: Sarganaphthoquinoic acid and sargaquinoic acid showed the most promising antiplasmodial activity and low cytotoxicity. Conclusions: Synthetic modification of the natural product, sargahydroquinoic acid, resulted in the discovery of a highly selective antiplasmodial compound, sarganaphthoquinoic acid.

An update on the Enzyme Portal: an integrative approach for exploring enzyme knowledge.

14: Enzymes are a key part of life processes and are increasingly important for various areas of research such as medicine, biotechnology, bioprocessing and drug research. The goal of the Enzyme Portal is to provide an interface to all European Bioinformatics Institute (EMBL-EBI) data about enzymes (de Matos, P., et al. , (2013), BMC Bioinformatics , (1), 103). These data include enzyme function, sequence features and family classification, protein structure, reactions, pathways, small molecules, diseases and the associated literature. The sources of enzyme data are: the UniProt Knowledgebase (UniProtKB) (UniProt Consortium, 2015), the Protein Data Bank in Europe (PDBe), (Valenkar, S., et al ., Nucleic Acids Res. 2016; , D385-D395) Rhea-a database of enzyme-catalysed reactions (Morgat, A., et al .,  Nucleic Acids Res.  2015; , D459-D464), Reactome-a database of biochemical pathways (Fabregat, A., et al ., Nucleic Acids Res. 2016;  , D481-D487), IntEnz-a resource with enzyme nomenclature information (Fleischmann, A., et al ., Nucleic Acids Res.  2004 , D434-D437) and ChEBI (Hastings, J., et al .,  Nucleic Acids Res. 2013) and ChEMBL (Bento, A. P., et al ., Nucleic Acids Res.  2014 , 1083-1090)-resources which contain information about small-molecule chemistry and bioactivity. This article describes the redesign of Enzyme Portal and the increased functionality added to maximise integration and interpretation of these data. Use case examples of the Enzyme Portal and the versatile workflows its supports are illustrated. We welcome the suggestion of new resources for integration.

Latrophilin receptors: novel bronchodilator targets in asthma.

BACKGROUND: Asthma affects 300 million people worldwide. In asthma, the major cause of morbidity and mortality is acute airway narrowing, due to airway smooth muscle (ASM) hypercontraction, associated with airway remodelling. However, little is known about the transcriptional differences between healthy and asthmatic ASM cells. OBJECTIVES: To investigate the transcriptional differences between asthmatic and healthy airway smooth muscle cells (ASMC) in culture and investigate the identified targets using in vitro and ex vivo techniques. METHODS: Human asthmatic and healthy ASMC grown in culture were run on Affymetrix_Hugene_1.0_ST microarrays. Identified candidates were confirmed by PCR, and immunohistochemistry. Functional analysis was conducted using in vitro ASMC proliferation, attachment and contraction assays and ex vivo contraction of mouse airways. RESULTS: We suggest a novel role for latrophilin (LPHN) receptors, finding increased expression on ASMC from asthmatics, compared with non-asthmatics in vivo and in vitro, suggesting a role in mediating airway function. A single nucleotide polymorphism in LPHN1 was associated with asthma and with increased LPHN1 expression in lung tissue. When activated, LPHNs regulated ASMC adhesion and proliferation in vitro, and promoted contraction of mouse airways and ASMC. CONCLUSIONS: Given the need for novel inhibitors of airway remodelling and bronchodilators in asthma, the LPHN family may represent promising novel targets for future dual therapeutic intervention.

p16 Expression Is Not a Surrogate Marker for High-Risk Human Papillomavirus Infection in Periocular Sebaceous Carcinoma.

PURPOSE: To evaluate the role of high-risk human papillomavirus (HR-HPV) infection in periocular sebaceous carcinoma (SC) using multiple methods of detection, and to determine whether p16 overexpression is present and can be used as a surrogate marker for HR-HPV. DESIGN: Retrospective observational case series with laboratory investigations. METHODS: Unstained paraffin sections of 35 cases of periocular SC were analyzed with immunohistochemistry for p16 and subjected to polymerase chain reaction (PCR) for HR-HPV. A subset of 18 lesions that were p16-positive was further studied with a novel method of mRNA in situ hybridization (ISH) for the detection of transcriptionally active HR-HPV, an advanced technique with an enhanced sensitivity and specificity. RESULTS: The clinical findings were in keeping with those of comparable earlier studies. Strong immunohistochemical p16 positivity (meeting the criterion of >70% nuclear and cytoplasmic staining) was present in 29 of 35 cases of periocular SC (82.9%). The selected 18 p16-positive cases tested were negative for HR-HPV using mRNA ISH. PCR yielded unequivocal results with adequate DNA isolated in 24 cases, 23 of which were negative for HR-HPV. One case was positive for HPV type 16, which was found to be a false positive as collaterally determined by mRNA ISH negativity. CONCLUSION: No evidence was found for HR-HPV as an etiologic agent in the development of periocular SC using multiple modalities to maximize sensitivity and specificity and reduce the limitations of any single test. p16 overexpression is common in periocular SC but unrelated to HR-HPV status. Although p16 may be used as a surrogate marker for HR-HPV status in other tissue sites, this interpretation of p16 positivity is not applicable to periocular SC.

Regulation and localization of vascular endothelial growth factor within the mammary glands during the transition from late gestation to lactation.

The vascular network within the developing mammary gland (MG) grows in concert with the epithelium to prepare for lactation, although the mechanisms coordinating this vascular development are unresolved. Vascular endothelial growth factor A (VEGF-A) mediates angiogenesis and vascular permeability in the MG during pregnancy and lactation, where its expression is upregulated by prolactin. Given our previous finding that late-gestational hyperprolactinemia induced by domperidone (DOM) increased subsequent milk yield from gilts, we sought to establish changes in vascular development during late gestation and lactation in the MGs of these pigs and determine whether DOM altered MG angiogenesis and the factors regulating it. Gilts received either no treatment (n = 6) or DOM (n = 6) during late gestation, then had their MG biopsied from late gestation through lactation to assess microvessel density, VEGF-A distribution and messenger RNA expression, and aquaporin (AQP) gene expression. Microvessel density in the MG was unchanged during gestation then increased between days 2 and 21 of lactation (P < 0.05). The local expression of messenger RNA for VEGF-A120, VEGF-A147, VEGF-A164, VEGF-A164b, VEGF-A188, VEGF receptors-1 and -2, and AQP1 and AQP3 all generally increased during the transition from gestation to lactation (P < 0.05). Immunostaining localized VEGF-A to the apical cytoplasm of secretory epithelial cells, consistent with a far greater concentration of VEGF-A in colostrum and/or milk vs plasma (P < 0.0001). There was no effect of DOM on any of the variables analyzed. In summary, we found that vascular development in the MG increases during lactation in first-parity gilts and that VEGF-A is a part of the mammary secretome. Although late-gestational hyperprolactinemia increases milk yield, there was no evidence that it altered vascular development.

Influence of birth cohort on age of onset cluster analysis in bipolar I disorder.

PURPOSE: Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database. METHODS: The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared. RESULTS: There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups. CONCLUSION: These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.

Neuroprotective effect of lithium on hippocampal volumes in bipolar disorder independent of long-term treatment response.

BACKGROUND: Neuroimaging studies have demonstrated an association between lithium (Li) treatment and brain structure in human subjects. A crucial unresolved question is whether this association reflects direct neurochemical effects of Li or indirect effects secondary to treatment or prevention of episodes of bipolar disorder (BD). METHOD: To address this knowledge gap, we compared manually traced hippocampal volumes in 37 BD patients with at least 2 years of Li treatment (Li group), 19 BD patients with <3 months of lifetime Li exposure over 2 years ago (non-Li group) and 50 healthy controls. All BD participants were followed prospectively and had at least 10 years of illness and a minimum of five episodes. We established illness course and long-term treatment response to Li using National Institute of Mental Health (NIMH) life charts. RESULTS: The non-Li group had smaller hippocampal volumes than the controls or the Li group (F 2,102 = 4.97, p = 0.009). However, the time spent in a mood episode on the current mood stabilizer was more than three times longer in the Li than in the non-Li group (t(51) = 2.00, p = 0.05). Even Li-treated patients with BD episodes while on Li had hippocampal volumes comparable to healthy controls and significantly larger than non-Li patients (t(43) = 2.62, corrected p = 0.02). CONCLUSIONS: Our findings support the neuroprotective effects of Li. The association between Li treatment and hippocampal volume seems to be independent of long-term treatment response and occurred even in subjects with episodes of BD while on Li. Consequently, these effects of Li on brain structure may generalize to patients with neuropsychiatric illnesses other than BD.

The energy cost of playing active video games in children with obesity and children of a healthy weight.

BACKGROUND: Increasing physical activity and reducing sedentary behaviour form a large part of the treatment of paediatric obesity. However, many children today spend prolonged periods of time playing sedentary video games. Active video games (AVGs) represent a novel and child friendly form of physical activity. OBJECTIVES: To measure the energy cost of playing two AVGs in children with obesity and healthy age- and gender-matched children. METHODS: The energy cost of gaming and heart rates achieved during gaming conditions were compared between groups. RESULTS: AVG play can result in light-to-moderate intensity physical activity (2.7-5.4 metabolic equivalents). When corrected for fat-free mass those with obesity expended significantly less energy than healthy weight peers playing Nintendo Wii Fit Free Jogging (P = 0.017). No significant difference was seen between groups in the energy cost of playing Boxing. CONCLUSION: Certain AVGs, particularly those that require lower limb movement, could be used to increase total energy expenditure, replace more sedentary activities, or achieve moderate intensity physical activity among children with obesity. There seems to be some differences in how children with obesity and children of a healthy weight play AVGs. This could result in those with obesity expending less energy than their lean peers during AVG play.

Prostaglandin E2 elicits greater bronchodilation than salbutamol in mouse intrapulmonary airways in lung slices.

BACKGROUND: Current asthma therapy may not adequately target contraction of smaller intrapulmonary airways, which are a major site of airway obstruction and inflammation. The aim of this study was to characterise responses of mouse intrapulmonary airways to prostaglandin E(2) (PGE(2)) and compare its dilator efficacy with the ß(2)-adrenoceptor agonist salbutamol in situ, using lung slices. METHODS: Lung slices (150 µm) were prepared from male Balb/C mice. Changes in intrapulmonary airway lumen area were recorded and analysed by phase-contrast microscopy. Relaxation to PGE(2) and salbutamol were assessed following various levels of pre-contraction with methacholine, serotonin or endothelin-1, as well as following overnight incubation with PGE(2) or salbutamol. The mechanism of PGE(2)-mediated relaxation was explored using selective EP antagonists (EP(1/2) AH6809; EP(4) L-161982) and Ca(2+)-permeabilized slices, where airway responses are due to regulation of Ca(2+)-sensitivity alone. RESULTS: PGE2 elicited EP(1/2)-mediated relaxation of intrapulmonary airways. PGE(2) was more potent than salbutamol in opposing submaximal pre-contraction to all constrictors tested, and only PGE(2) opposed maximal pre-contraction with endothelin-1. Relaxation to PGE(2) was maintained when contraction to methacholine was mediated via increased Ca(2+)-sensitivity alone. PGE(2) was less sensitive to homologous or heterologous desensitization of its receptors than salbutamol. CONCLUSION: The greater efficacy and potency of PGE(2) compared to salbutamol in mouse intrapulmonary airways supports further investigation of the mechanisms underlying this improved dilator responsiveness for the treatment of severe asthma.