The synthesis of solid supports carrying base labile linkers to generate 3'-phosphate oligonucleotides.

Oligonucleotides carrying 3'-terminal phosphates and conjugates are important tools in molecular biology and diagnostic purposes. We described the preparation of solid supports carrying the base labile linker 4-((2-hydroxyethyl)sulfonyl)benzamide for the solid-phase synthesis of 3'-phosphorylated oligonucleotides. These supports are fully compatible with the phosphoramidite chemistry yielding the desired 3'-phosphate oligonucleotides in excellent yields. The use of mild deprotection conditions allows the generation of partially protected DNA fragments.

Lunar Lithium-7 Sensing (δ7Li): Spectral Patterns and Artificial Intelligence Techniques.

Lithium, a critical natural resource integral to modern technology, has influenced diverse industries since its discovery in the 1950s. Of particular interest is lithium-7, the most prevalent lithium isotope on Earth, playing a vital role in applications such as batteries, metal alloys, medicine, and nuclear research. However, its extraction presents significant environmental and logistical challenges. This article explores the potential for lithium exploration on the Moon, driven by its value as a resource and the prospect of cost reduction due to the Moon's lower gravity, which holds promise for future space exploration endeavors. Additionally, the presence of lithium in the solar wind and its implications for material transport across celestial bodies are subjects of intrigue. Drawing from a limited dataset collected during the Apollo missions (Apollo 12, 15, 16, and 17) and leveraging artificial intelligence techniques and sample expansion through bootstrapping, this study develops predictive models for lithium-7 concentration based on spectral patterns. The study areas encompass the Aitken crater, Hadley Rima, and the Taurus-Littrow Valley, where higher lithium concentrations are observed in basaltic lunar regions. This research bridges lunar geology and the formation of the solar system, providing valuable insights into celestial resources and enhancing our understanding of space. The data used in this study were obtained from the imaging sensors (infrared, visible, and ultraviolet) of the Clementine satellite, which significantly contributed to the success of our research. Furthermore, the study addresses various aspects related to statistical analysis, sample quality validation, resampling, and bootstrapping. Supervised machine learning model training and validation, as well as data import and export, were explored. The analysis of data generated by the Clementine probe in the near-infrared (NIR) and ultraviolet-visible (UVVIS) spectra revealed evidence of the presence of lithium-7 (Li-7) on the lunar surface. The distribution of Li-7 on the lunar surface is non-uniform, with varying concentrations in different regions of the Moon identified, supporting the initial hypothesis associating surface Li-7 concentration with exposure to solar wind. While a direct numerical relationship between lunar topography and Li-7 concentration has not been established due to morphological diversity and methodological limitations, preliminary results suggest significant economic and technological potential in lunar lithium exploration and extraction.

Cortical microinfarcts in adults with Down syndrome assessed with 3T-MRI.

BACKGROUND: Cortical microinfarcts (CMI) were attributed to cerebrovascular disease and cerebral amyloid angiopathy (CAA). CAA is frequent in Down syndrome (DS) while hypertension is rare, yet no studies have assessed CMI in DS. METHODS: We included 195 adults with DS, 63 with symptomatic sporadic Alzheimer's disease (AD), and 106 controls with 3T magnetic resonance imaging. We assessed CMI prevalence in each group and CMI association with age, AD clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition in DS. RESULTS: CMI prevalence was 11.8% in DS, 4.7% in controls, and 17.5% in sporadic AD. In DS, CMI increased in prevalence with age and the AD clinical continuum, was clustered in the parietal lobes, and was associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. DISCUSSION: In DS, CMI are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic CAA phenotype. HIGHLIGHTS: This is the first study to assess cortical microinfarcts (assessed with 3T magnetic resonance imaging) in adults with Down syndrome (DS). We studied the prevalence of cortical microinfarcts in DS and its relationship with age, the Alzheimer's disease (AD) clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition. The prevalence of cortical microinfarcts was 11.8% in DS and increased with age and along the AD clinical continuum. Cortical microinfarcts were clustered in the parietal lobes, and were associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. In DS, cortical microinfarcts are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic phenotype of cerebral amyloid angiopathy.

Characterization of white matter hyperintensities in Down syndrome.

INTRODUCTION: In Down syndrome (DS), white matter hyperintensities (WMHs) are highly prevalent, yet their topography and association with sociodemographic data and Alzheimer's disease (AD) biomarkers remain largely unexplored. METHODS: In 261 DS adults and 131 euploid controls, fluid-attenuated inversion recovery magnetic resonance imaging scans were segmented and WMHs were extracted in concentric white matter layers and lobar regions. We tested associations with AD clinical stages, sociodemographic data, cerebrospinal fluid (CSF) AD biomarkers, and gray matter (GM) volume. RESULTS: In DS, total WMHs arose at age 43 and showed stronger associations with age than in controls. WMH volume increased along the AD continuum, particularly in periventricular regions, and frontal, parietal, and occipital lobes. Associations were found with CSF biomarkers and temporo-parietal GM volumes. DISCUSSION: WMHs increase 10 years before AD symptom onset in DS and are closely linked with AD biomarkers and neurodegeneration. This suggests a direct connection to AD pathophysiology, independent of vascular risks. HIGHLIGHTS: White matter hyperintensities (WMHs) increased 10 years before Alzheimer's disease symptom onset in Down syndrome (DS). WMHs were strongly associated in DS with the neurofilament light chain biomarker. WMHs were more associated in DS with gray matter volume in parieto-temporal areas.

Effect of Obstructive Sleep Apnea during Pregnancy on Fetal Development: Gene Expression Profile of Cord Blood.

Obstructive sleep apnea (OSA) is quite prevalent during pregnancy and is associated with adverse perinatal outcomes, but its potential influence on fetal development remains unclear. This study investigated maternal OSA impact on the fetus by analyzing gene expression profiles in whole cord blood (WCB). Ten women in the third trimester of pregnancy were included, five OSA and five non-OSA cases. WCB RNA expression was analyzed by microarray technology to identify differentially expressed genes (DEGs) under OSA conditions. After data normalization, 3238 genes showed significant differential expression under OSA conditions, with 2690 upregulated genes and 548 downregulated genes. Functional enrichment was conducted using gene set enrichment analysis (GSEA) applied to Gene Ontology annotations. Key biological processes involved in OSA were identified, including response to oxidative stress and hypoxia, apoptosis, insulin response and secretion, and placental development. Moreover, DEGs were confirmed through qPCR analyses in additional WCB samples (7 with OSA and 13 without OSA). This highlighted differential expression of several genes in OSA (EGR1, PFN1 and PRKAR1A), with distinct gene expression profiles observed during rapid eye movement (REM)-OSA in pregnancy (PFN1, UBA52, EGR1, STX4, MYC, JUNB, and MAPKAP). These findings suggest that OSA, particularly during REM sleep, may negatively impact various biological processes during fetal development.

Cross-sectional versus longitudinal cognitive assessments for the diagnosis of symptomatic Alzheimer's disease in adults with Down syndrome.

BACKGROUND: Down syndrome (DS) is a genetic form of Alzheimer's disease (AD). However, clinical diagnosis is difficult, and experts emphasize the need for detecting intra-individual cognitive decline. OBJECTIVE: To compare the performance of baseline and longitudinal neuropsychological assessments for the diagnosis of symptomatic AD in DS. METHODS: Longitudinal cohort study of adults with DS. Individuals were classified as asymptomatic, prodromal AD, or AD dementia. We performed receiver operating characteristic curve analyses to compare baseline and longitudinal changes of CAMCOG-DS and mCRT. RESULTS: We included 562 adults with DS. Baseline assessments showed good to excellent diagnostic performance for AD dementia (AUCs between 0.82 and 0.99) and prodromal AD, higher than the 1-year intra-individual cognitive decline (area under the ROC curve between 0.59 and 0.79 for AD dementia, lower for prodromal AD). Longer follow-ups increased the diagnostic performance of the intra-individual cognitive decline. DISCUSSION: Baseline cognitive assessment outperforms the 1-year intra-individual cognitive decline in adults with DS.

Basal forebrain atrophy along the Alzheimer's disease continuum in adults with Down syndrome.

BACKGROUND: Basal forebrain (BF) degeneration occurs in Down syndrome (DS)-associated Alzheimer's disease (AD). However, the dynamics of BF atrophy with age and disease progression, its impact on cognition, and its relationship with AD biomarkers have not been studied in DS. METHODS: We included 234 adults with DS (150 asymptomatic, 38 prodromal AD, and 46 AD dementia) and 147 euploid controls. BF volumes were extracted from T-weighted magnetic resonance images using a stereotactic atlas in SPM12. We assessed BF volume changes with age and along the clinical AD continuum and their relationship to cognitive performance, cerebrospinal fluid (CSF) and plasma amyloid/tau/neurodegeneration biomarkers, and hippocampal volume. RESULTS: In DS, BF volumes decreased with age and along the clinical AD continuum and significantly correlated with amyloid, tau, and neurofilament light chain changes in CSF and plasma, hippocampal volume, and cognitive performance. DISCUSSION: BF atrophy is a potentially valuable neuroimaging biomarker of AD-related cholinergic neurodegeneration in DS.

Metabolite Signature of Alzheimer's Disease in Adults with Down Syndrome.

OBJECTIVE: The purpose of this study was to examine the Alzheimer's disease metabolite signature through magnetic resonance spectroscopy in adults with Down syndrome and its relation with Alzheimer's disease biomarkers and cortical thickness. METHODS: We included 118 adults with Down syndrome from the Down Alzheimer Barcelona Imaging Initiative and 71 euploid healthy controls from the Sant Pau Initiative on Neurodegeneration cohort. We measured the levels of myo-inositol (a marker of neuroinflammation) and N-acetyl-aspartate (a marker of neuronal integrity) in the precuneus using magnetic resonance spectroscopy. We investigated the changes with age and along the disease continuum (asymptomatic, prodromal Alzheimer's disease, and Alzheimer's disease dementia stages). We assessed the relationship between these metabolites and Aß42 /Aß40 ratio, phosphorylated tau-181, neurofilament light (NfL), and YKL-40 cerebrospinal fluid levels as well as amyloid positron emission tomography uptake using Spearman correlations controlling for multiple comparisons. Finally, we computed the relationship between cortical thickness and metabolite levels using Freesurfer. RESULTS: Asymptomatic adults with Down syndrome had a 27.5% increase in the levels of myo-inositol, but equal levels of N-acetyl-aspartate compared to euploid healthy controls. With disease progression, myo-inositol levels increased, whereas N-acetyl-aspartate levels decreased in symptomatic stages of the disease. Myo-inositol was associated with amyloid, tau, and neurodegeneration markers, mainly at symptomatic stages of the disease, whereas N-acetyl-aspartate was related to neurodegeneration biomarkers in symptomatic stages. Both metabolites were significantly associated with cortical thinning, mainly in symptomatic participants. INTERPRETATION: Magnetic resonance spectroscopy detects Alzheimer's disease related inflammation and neurodegeneration, and could be a good noninvasive disease-stage biomarker in Down syndrome. ANN NEUROL 2021;90:407-416.

Isolation of human fibroadipogenic progenitors and satellite cells from frozen muscle biopsies.

Skeletal muscle contains multiple cell types that work together to maintain tissue homeostasis. Among these, satellite cells (SC) and fibroadipogenic progenitors cells (FAPs) are the two main stem cell pools. Studies of these cells using animal models have shown the importance of interactions between these cells in repair of healthy muscle, and degeneration of dystrophic muscle. Due to the unavailability of fresh patient muscle biopsies, similar analysis of interactions between human FAPs and SCs is limited especially among the muscular dystrophy patients. To address this issue here we describe a method that allows the use of frozen human skeletal muscle biopsies to simultaneously isolate and grow SCs and FAPs from healthy or dystrophic patients. We show that while the purified SCs differentiate into mature myotubes, purified FAPs can differentiate into adipocytes or fibroblasts demonstrating their multipotency. We find that these FAPs can be immortalized and the immortalized FAPs (iFAPs) retain their multipotency. These approaches open the door for carrying out personalized analysis of patient FAPs and interactions with the SCs that lead to muscle loss.

Combined anodal transcranial direct current stimulation and behavioural naming treatment improves language performance in patients with post-stroke aphasia.

PRIMARY OBJECTIVE: During the last decade, studies using anodal transcranial Direct Current Stimulation (atDCS) have yielded promising results in patients with aphasia. The main aim of the present pilot study was to assess the effects of combined atDCS over the left posterior perisylvian region and behavioral naming training on the behavioral outcomes of language comprehension and production of patients with post-stroke aphasia. RESEARCH DESIGN: A 2 × 2 quasi-experimental design was conducted, optimal to compare changes after treatment in experimental versus control group. METHODS AND PROCEDURES: Ten patients with post-stroke aphasia were enrolled in this study: half received atDCS on the left posterior perisylvian region while they underwent a 2-week behavioral naming training. The other half received sham stimulation. The outcomes were measured using the abbreviated form of the Boston Diagnostic Aphasia Examination and analyzed using ANOVAs. MAIN OUTCOMES AND RESULTS: Both groups improved their performance in Oral comprehension, Narrative writing and Language Competence Index, but only those that received anodal tDCS presented better results in the Naming category after the treatment. CONCLUSIONS: AtDCS on the left posterior perisylvian area seems to be a promising tool for boosting the outcomes of behavioral naming therapy in patients with post-stroke aphasia.

Sustainable Protocol for the Synthesis of 2',3'-Dideoxynucleoside and 2',3'-Didehydro-2',3'-dideoxynucleoside Derivatives.

An improved protocol for the transformation of ribonucleosides into 2',3'-dideoxynucleoside and 2',3'-didehydro-2',3'-dideoxynucleoside derivatives, including the anti-HIV drugs stavudine (d4T), zalcitabine (ddC) and didanosine (ddI), was established. The process involves radical deoxygenation of xanthate using environmentally friendly and low-cost reagents. Bromoethane or 3-bromopropanenitrile was the alkylating agent of choice to prepare the ribonucleoside 2',3'-bisxanthates. In the subsequent radical deoxygenation reaction, tris(trimethylsilyl)silane and 1,1'-azobis(cyclohexanecarbonitrile) were used to replace hazardous Bu3SnH and AIBN, respectively. In addition, TBAF was substituted for camphorsulfonic acid in the deprotection step of the 5'-O-silyl ether group, and an enzyme (adenosine deaminase) was used to transform 2',3'-dideoxyadenosine into 2',3'-dideoxyinosine (ddI) in excellent yield.

Clinical and biomarker changes of Alzheimer's disease in adults with Down syndrome: a cross-sectional study.

BACKGROUND: Alzheimer's disease and its complications are the leading cause of death in adults with Down syndrome. Studies have assessed Alzheimer's disease in individuals with Down syndrome, but the natural history of biomarker changes in Down syndrome has not been established. We characterised the order and timing of changes in biomarkers of Alzheimer's disease in a population of adults with Down syndrome. METHODS: We did a dual-centre cross-sectional study of adults with Down syndrome recruited through a population-based health plan in Barcelona (Spain) and through services for people with intellectual disabilities in Cambridge (UK). Cognitive impairment in participants with Down syndrome was classified with the Cambridge Cognitive Examination for Older Adults with Down Syndrome (CAMCOG-DS). Only participants with mild or moderate disability were included who had at least one of the following Alzheimer's disease measures: apolipoprotein E allele carrier status; plasma concentrations of amyloid ß peptides 1-42 and 1-40 and their ratio (Aß1-42/1-40), total tau protein, and neurofilament light chain (NFL); tau phosphorylated at threonine 181 (p-tau), and NFL in cerebrospinal fluid (CSF); and one or more of PET with 18F-fluorodeoxyglucose, PET with amyloid tracers, and MRI. Cognitively healthy euploid controls aged up to 75 years who had no biomarker abnormalities were recruited from the Sant Pau Initiative on Neurodegeneration. We used a first-order locally estimated scatterplot smoothing curve to determine the order and age at onset of the biomarker changes, and the lowest ages at the divergence with 95% CIs are also reported where appropriate. FINDINGS: Between Feb 1, 2013, and June 28, 2019 (Barcelona), and between June 1, 2009, and Dec 31, 2014 (Cambridge), we included 388 participants with Down syndrome (257 [66%] asymptomatic, 48 [12%] with prodromal Alzheimer's disease, and 83 [21%] with Alzheimer's disease dementia) and 242 euploid controls. CSF Aß1-42/1-40 and plasma NFL values changed in individuals with Down syndrome as early as the third decade of life, and amyloid PET uptake changed in the fourth decade. 18F-fluorodeoxyglucose PET and CSF p-tau changes occurred later in the fourth decade of life, followed by hippocampal atrophy and changes in cognition in the fifth decade of life. Prodromal Alzheimer's disease was diagnosed at a median age of 50·2 years (IQR 47·5-54·1), and Alzheimer's disease dementia at 53·7 years (49·5-57·2). Symptomatic Alzheimer's disease prevalence increased with age in individuals with Down syndrome, reaching 90-100% in the seventh decade of life. INTERPRETATION: Alzheimer's disease in individuals with Down syndrome has a long preclinical phase in which biomarkers follow a predictable order of changes over more than two decades. The similarities with sporadic and autosomal dominant Alzheimer's disease and the prevalence of Down syndrome make this population a suitable target for Alzheimer's disease preventive treatments. FUNDING: Instituto de Salud Carlos III, Fundació Bancaria La Caixa, Fundació La Marató de TV3, Medical Research Council, and National Institutes of Health.

Oligonucleotides Containing 1-Aminomethyl or 1-Mercaptomethyl-2-deoxy-d-ribofuranoses: Synthesis, Purification, Characterization, and Conjugation with Fluorophores and Lipids.

Oligonucleotide conjugates are widely used as therapeutic drugs, gene analysis, and diagnostic tools. A critical step in the biologically relevant oligonucleotide conjugates is the design and synthesis of functional molecules that connect oligonucleotide with ligands. Here, we report the synthesis and application for oligonucleotide functionalization of novel tethers based on aminomethyl and mercaptomethyl sugar derivatives. Starting from a common cyano sugar precursor, three novel phosphoramidites have been prepared in the two α- and ß-anomeric forms. The mercaptomethyl sugar was protected with the S-acetyl group, while two different protecting groups have been developed for the aminomethyl sugar. These two protecting groups are orthogonal, as they can be removed independently using photolysis or ammonolysis. This combination allowed the introduction of two different ligands in a single oligonucleotide.

Coding valence in touchscreen interactions: hand dominance and lateral movement influence valence appraisals of emotional pictures.

The Body-Specificity Hypothesis postulates that the space surrounding the dominant hand is perceived as positive due to the motor fluency of this hand, whereas the space surrounding the non-dominant hand is perceived as negative. Experimental studies based on this theoretical framework also revealed associations between affective valence and hand dominance (i.e., dominant hand-positive; non-dominant hand-negative), or lateral movements of the hands (i.e., right hand toward the right space-positive; left hand toward the left space-positive). Interestingly, these associations have not been examined with regard to how lateral actions of the hands may influence affective experiences as, for example, in valence appraisals of affective objects that have been manipulated. The study presented here has considered this question in light of the emerging interest of embodied cognition approaches to interactive technologies, particularly in affective experiences with touchscreen interfaces. Accordingly, right-handed participants evaluated the valence of positive and negative emotional pictures after interacting with them either with the dominant right or with the non-dominant left hand. Specifically, they moved the pictures either from left to right or from right to left sides of a touchscreen monitor. The results indicated that a valence matching between the hand used for the interactions, the picture's valence category, and the movement's starting side reinforced the valence appraisals of the pictures (i.e., positive/negative pictures were more positively/negatively evaluated). The findings are discussed against the background of the Theory of Event Coding, which accounts for both the affective properties of the stimuli and the affective connotation of the related action.

Intergenerational Transmissible Meanings in Breastfeeding in Spain: A Phenomenological Study.

BACKGROUND: The process of breastfeeding is linked to intergenerational influences based on attitudes and messages of grandmothers about their own experience, and this can reinforce or interfere with the experiences of future mothers in breastfeeding. The aim of this study was to explore the meanings transmissible to the next generation of nursing mothers, based on the experiences of grandmothers. METHODS: We report the findings of an interpretive phenomenological qualitative research based on the philosophy of Martin Heidegger. In-depth interviews were conducted in Madrid with 17 participants who breastfed before the age of 35 and more than 8 years ago (to ensure the settlement of transmissible meanings in remote memory). Data were analyzed by interpretive phenomenological analysis (IPA). FINDINGS: Two thematic categories were identified: "Breastfeeding: life experiences" and "Breastfeeding: body and mind process", which show that mothers want to convey the need for a balance that allows maintaining the role of women outside of stereotypes but that is also compatible with the rhythm of life, giving new meanings to attachment, weaning, and modesty. CONCLUSIONS: Meanings that future grandmothers wish to transmit to the next generation of nursing mothers are related to the search for a satisfactory experience for the mother, who must make an adjustment in her life, freeing herself of inflexible messages about attachment and the maternal role. PRACTICAL IMPLICATIONS: Strategies to promote breastfeeding and care for nursing mothers can improve the impact of trying to understand the meanings that are transmitted by the grandmothers in the family environment.

Snow Albedo Seasonality and Trend from MODIS Sensor and Ground Data at Johnsons Glacier, Livingston Island, Maritime Antarctica.

The aim of this work is to investigate whether snow albedo seasonality and trend under all sky conditions at Johnsons Glacier (Livingston Island, Antarctica) can be tracked using the Moderate Resolution Imaging Spectroradiometer (MODIS) snow albedo daily product MOD10A1. The time span is from December 2006 to February 2015. As the MOD10A1 snow albedo product has never been used in Antarctica before, we also assess the performance for the MOD10A1 cloud mask. The motivation for this work is the need for a description of snow albedo under all sky conditions (including overcast days) using satellite data with mid-spatial resolution. In-situ albedo was filtered with a 5-day windowed moving average, while the MOD10A1 data were filtered using a maximum filter. Both in-situ and MOD10A1 data follow an exponential decay during the melting season, with a maximum decay of 0.049/0.094 day-1 (in-situ/MOD10A1) for the 2006-2007 season and a minimum of 0.016/0.016 day-1 for the 2009-2010 season. The duration of the decay varies from 85 days (2007-2008) to 167 days (2013-2014). Regarding the albedo trend, both data sets exhibit a slight increase of albedo, which may be explained by an increase of snowfall along with a decrease of snowmelt in the study area. Annual albedo increases of 0.2% and 0.7% are obtained for in-situ and MOD10A1 data, respectively, which amount to respective increases of 2% and 6% in the period 2006-2015. We conclude that MOD10A1 can be used to characterize snow albedo seasonality and trend on Livingston Island when filtered with a maximum filter.

Screening for delirium with the Intensive Care Delirium Screening Checklist (ICDSC): Symptom profile and utility of individual items in the identification of delirium dependent on the level of sedation.

OBJECTIVE: The importance of the proper identification of delirium, with its high incidence and adversities in the intensive care setting, has been widely recognized. One common screening instrument is the Intensive Care Delirium Screening Checklist (ICDSC); however, the symptom profile and key features of delirium dependent on the level of sedation have not yet been evaluated. METHOD: In this prospective cohort study, the ICDSC was evaluated versus the Diagnostic and Statistical Manual, 4th edition, text revision, diagnosis of delirium set as standard with respect to the symptom profile, and correct identification of delirium. The aim of this study was to identify key features of delirium in the intensive care setting dependent on the Richmond Agitation and Sedation Scale levels of sedation: drowsiness versus alert and calmness.ResultThe 88 delirious patients of 225 were older, had more severe disease, and prolonged hospitalization. Irrespective of the level of sedation, delirium was correctly classified by items related to inattention, disorientation, psychomotor alterations, inappropriate speech or mood, and symptom fluctuation. In the drowsy patients, inattention reached substantial sensitivity and specificity, whereas psychomotor alterations and sleep-wake cycle disturbances were sensitive lacked specificity. The positive prediction was substantial across items, whereas the negative prediction was only moderate. In the alert and calm patient, the sensitivities were substantial for psychomotor alterations, sleep-wake cycle disturbances, and symptom fluctuations; however, these fluctuations were not specific. The positive prediction was moderate and the negative prediction substantial. Between the nondelirious drowsy and alert, the symptom profile was similar; however, drowsiness was associated with alterations in consciousness.Significance of resultsIn the clinical routine, irrespective of the level of sedation, delirium was characterized by the ICDSC items for inattention, disorientation, psychomotor alterations, inappropriate speech or mood and symptom fluctuation. Further, drowsiness caused altered levels of consciousness.

Turbocharged bilateral pedicled DIEP flap for reconstruction of thigh defect without recipient vessels: A case report.

Reconstruction of thigh defects is usually straightforward, but in cases of poor soft tissue quality, free flap reconstruction is not possible due to the absence of recipient vessels. The turbocharge technique may increase the viable, vascularized area of a flap. In this report we present a case of the use of a turbocharged bilateral pedicled DIEP flap for reconstruction of thigh defect without recipient vessels. A 29-year-old woman who underwent neoadjuvant chemotherapy plus radiation therapy for a leiomyosarcoma on the left thigh. Six weeks later, complete tumor excision and a femoropopliteal bypass with contralateral saphenous vein was performed. In the following days the wound had dehiscence, infection, necrosis of the surrounding muscles and exposure of femoropopliteal bypass. No recipient vessels were available for free flap and critical limb ischemia due to bypass thrombosis was detected. The reconstruction of a large thigh defect (30 × 12 cm) and the coverage of a femoropopliteal bypass with a turbocharged bilateral pedicled DIEP flap was performed. A flap including the entire infraumbilical tissue was designed and the anastomosis of the proximal stump of the right inferior epigastric vessels with the distal ends of the inferior left epigastric vessels was performed to increase the viable area. The flap survived without any complications during the postoperative period. At 12-month follow up, coverage was stable with no tumor recurrence. Our result suggests that a turbocharged bilateral pedicled DIEP flap may be an option for reconstructing large tissue defects when no recipient vessels are available for free flap.

Sustainability assessment in forest management based on individual preferences.

This paper presents a methodology to elicit the preferences of any individual in the assessment of sustainable forest management at the stand level. The elicitation procedure was based on the comparison of the sustainability of pairs of forest locations. A sustainability map of the whole territory was obtained according to the individual's preferences. Three forest sustainability indicators were pre-calculated for each point in a study area in a Scots pine forest in the National Park of Sierra de Guadarrama in the Madrid Region in Spain to obtain the best management plan with the sustainability map. We followed a participatory process involving fifty people to assess the sustainability of the forest management and the methodology. The results highlighted the demand for conservative forest management, the usefulness of the methodology for managers, and the importance and necessity of incorporating stakeholders into forestry decision-making processes.

Placing joy, surprise and sadness in space: a cross-linguistic study.

The valence-space metaphor posits that emotion concepts map onto vertical space such that positive concepts are in upper locations and negative in lower locations. Whilst previous studies have demonstrated this pattern for positive and negative emotions e.g. 'joy' and 'sadness', the spatial location of neutral emotions, e.g. 'surprise', has not been investigated, and little is known about the effect of linguistic background. In this study, we first characterised the emotions joy, surprise and sadness via ratings of their concreteness, imageability, context availability and valence before examining the allocation of these emotions in vertical space. Participants from six linguistic groups completed either a rating task used to characterise the emotions or a word allocation task to implicitly assess where these emotions are positioned in vertical space. Our findings suggest that, across languages, gender, handedness, and ages, positive emotions are located in upper spatial locations and negative emotions in lower spatial locations. In addition, we found that the neutral emotional valence of surprise is reflected in this emotion being mapped mid-way between upper and lower locations onto the vertical plane. This novel finding indicates that the location of a concept on the vertical plane mimics the concept's degree of emotional valence.