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Sleep disorders are very prevalent in late life, though they are often unrecognized, underdiagnosed, and poorly treated. Epidemiological evidence suggests that over 50% of elderly people suffer from one of several different sleep disorders, with the most common sleep disorders being insomnia and sleep apnea. Both insomnia and sleep apnea carry many serious negative physical, mental, and social consequences. Epidemiology, diagnosis, and treatment management for both insomnia and sleep apnea in older adults are reviewed. Diagnosis of insomnia in older adults is based on self-report, while sleep apnea diagnosis requires a sleep study. Treatment of insomnia in late life is guided by behavioral and cognitive principles, with the gold-standard treatment approach being cognitive-behavioral therapy or CBT. Positive airway pressure (PAP) therapy is the recommended treatment approach for sleep apnea. Contextual factors that complicate the diagnosis and management of insomnia and sleep apnea in late life are reviewed with the aim of providing practical information for the medical professional working with older patients.
Carbon reduction is an important process for Earth-like origins of life events and of great interest to the astrobiology community. In this paper, we have collected experimental results, field work and modelling data on CO and CO2 reduction in order to summarize the research that has been carried out particularly in relation to the early Earth and Mars. By having a database of this work, researchers will be able to clearly survey the parameters tested and find knowledge gaps wherein more experimentation would be most beneficial. We focused on reviewing the modelling parameters, field work and laboratory conditions relevant to Mars and the early Earth. We highlight important areas addressed as well as suggest future work needed, including identifying relevant parameters to test in both laboratory and modelling work. We also discuss the utility of organizing research results in such a database in astrobiology.
Maternal experiences of childhood adversity can increase the risk of emotional and behavioural problems in their children. This systematic review and meta-analysis provide the first narrative and quantitative synthesis of the mediators and moderators involved in the link between maternal childhood adversity and children's emotional and behavioural development. We searched EMBASE, PsycINFO, Medline, Cochrane Library, grey literature and reference lists. Studies published up to February 2021 were included if they explored mediators or moderators between maternal childhood adversity and their children's emotional and behavioural development. Data were synthesised narratively and quantitatively by meta-analytic approaches. The search yielded 781 articles, with 74 full-text articles reviewed, and 41 studies meeting inclusion criteria. Maternal mental health was a significant individual-level mediator, while child traumatic experiences and insecure maternal–child attachment were consistent family-level mediators. However, the evidence for community-level mediators was limited. A meta-analysis of nine single-mediating analyses from five studies indicated three mediating pathways: maternal depression, negative parenting practices and maternal insecure attachment, with pooled indirect standardised effects of 0.10 [95% CI (0.03–0.17)), 0.01 (95% CI (−0.02 to 0.04)] and 0.07 [95% CI (0.01–0.12)], respectively. Research studies on moderators were few and identified some individual-level factors, such as child sex (e.g. the mediating role of parenting practices being only significant in girls), biological factors (e.g. maternal cortisol level) and genetic factors (e.g. child's serotonin-transporter genotype). In conclusion, maternal depression and maternal insecure attachment are two established mediating pathways that can explain the link between maternal childhood adversity and their children's emotional and behavioural development and offer opportunities for intervention.
Invasive species pose a threat not only to biodiversity because they displace or compete with native fauna, but also because of the pathogens they can host. The Canary Islands are an Atlantic biodiversity hotspot threatened by increasing numbers of invasive species, including the California kingsnake Lampropeltis californiae, which was recently introduced to Gran Canaria. Seventy-seven snakes were examined for gastrointestinal parasites in 2019–2020. Sporocysts of Sarcocystis sp. were detected in 10 of them; detection of gamogonia stages in histological sections of 3 snakes confirmed the snake as a definitive host. Partial ssrDNA was amplified using SarcoFext/SarcoRext primers; an additional sequence of Sarcocystis was obtained from the tail muscle of the endemic Gran Canaria giant lizard Gallotia stehlini for a comparison. Identical ssrDNA sequences of unknown Sarcocystis sp. were obtained from 5 different snakes. Phylogenetic analysis showed that Sarcocystis sp. isolated from invasive California kingsnakes is unrelated to Sarcocystis provisionally considered S. stehlini from the endemic lizard. The dixenous coccidia are rarely reported to invade new predator–prey systems. However, the present data suggest that previously unknown Sarcocystis sp. is circulating among invasive snakes and as yet unknown vertebrate intermediate hosts, with undetermined consequences for the Gran Canaria ecosystem.
Tungsten (W) films have many applications in the semiconducting industry for sensor technology. Deposition conditions can significantly impact the resulting W films in terms of the phases present (α-BCC or β-A12), microstructural grain orientation (texture), and residual strain. Tilt-A-Whirl methodology has been employed for the evaluation of a W film showing both texture and residual strain. Sin2(ψ) analysis of the film was performed to quantify the strongly tensile in-plane strain (+0.476%) with an estimated in-plane tensile stress of ~1.9 GPa. The 3D dataset was also evaluated qualitatively via 3D visualization. Visualization of 3D texture/strain data poses challenges due to peak broadening resulting from defocusing of the beam at high ψ tilt angles. To address this issue, principal component analysis (PCA) was employed to diagnose, model, and remove the broadening component from the diffraction data. Evaluation of the raw data and subsequent corrected data (after removal of defocusing effects) has been performed through projection of the data into a virtual 3D environment (via CAD2VR software) to qualitatively detect the impact of residual strain on the observed pole figure.
The hippocampus of mammals, birds, reptiles, and amphibians is a fundamental brain structure for certain forms of relational memory. We review here the experimental evidence indicating that the hippocampal pallium of teleost fish, like the hippocampus of land vertebrates, is involved in relational map-like spatial memory, endowing fish behavior with the capability for allocentric navigation and allowing the flexible expression of spatial memory. In addition, recent evidence suggests that the teleost fish hippocampal pallium plays an important role in the processing of the temporal dimensions of relational memory. The functional similarities in the hippocampal pallium of taxa that diverged millions of years ago suggest the possibility that some features of the hippocampal networks allowing the processing of the spatial as well the temporal dimensions of relational associative memories appeared early in vertebrate evolution and were conserved through phylogenesis.
Based on probability theory, a methodology that allows diagnosing neonatal cardiac dynamics was previously developed; however, diagnostic applications of this method are required to validate it to the neonatal cardiac dynamics was conducted, allowing to differentiate normal from pathological dynamics. The hourly maximum and minimum heart rate values from 39 continuous and ambulatory electrocardiographic records with a minimum length of 21 hours were taken, from newborns between 0 and 10 days of life, 9 clinically within normality limits and 30 with cardiac pathologies. The probability of occurrence of heart rates in ranges of 5 beats/minute was calculated. The distributions of probability were analysed, and finally the diagnosis was determined by the physical-mathematical methodology. Then, a statistical validation of sensitivity, specificity, and diagnostic agreement was performed. Normal registries showed probability distributions with absent or minimal presence of heart rates of the ranges between 125 and 135 beats/minute, while the abnormal ones had values within these ranges, as well as absence or minimal presence of heart rates from 75 beats/minute to 85 beats/minute. The sensitivity and specificity were 100%, and the Kappa coefficient had a value of 1. Hereby, it is concluded that through an application of a physical–mathematical methodology of neonatal cardiac diagnosis, it is possible to differentiate normality from disease.
OBJECTIVES/GOALS: A functional precision medicine platform to identify therapeutic targets for a glioblastoma patient with Li Fraumeni syndrome was performed. Comparative transcriptomics identified druggable targets and patient derived organoids and a 3D-PREDICT drug screening assay was used to validate the pipeline and identify further therapeutic targets. METHODS/STUDY POPULATION: A comparative transcriptomics pipeline was used to identify druggable genes that are uniquely overexpressed in our patient of interest relative to a cancer compendium of 12,747 tumor RNA sequencing datasets including 200 GBMs. Mini-ring patient derived organoid-based drug viability assays were performed to validate the comparative transcriptomics data. Additionally, a spheroid-based drug screening assay (3D-PREDICT) was performed and used to identify further therapeutic targets. RESULTS/ANTICIPATED RESULTS: Using comparative transcriptomics STAT1 and STAT2 were found to be significantly overexpressed in our patient, indicating ruxolitinib, a Janus kinase 1 and 2 inhibitor, as a potential therapy. Druggable pathways predicted using comparative transcriptomics corresponded with ruxolitinib sensitivity in a panel of patient derived organoids screened with this compound. Cells from the LFS patient were among the most sensitive to ruxolitinib compared to patient-derived cells with lower STAT1 and STAT2 expression levels. Additionally, 3D-PREDICT screening identified the mTOR inhibitor everolimus as a potential candidate. These two targeted therapies were selected for our patient and resulted in radiographic disease stability. DISCUSSION/SIGNIFICANCE: This research illustrates the use of comparative transcriptomics to identify druggable pathways irrespective of actionable DNA mutations present. Our results are promising and serve to highlight the importance of functional precision medicine in tailoring treatment regimes to specific patients.
Large, conglomerate caves in north-eastern Iberia have been significant places since the Neolithic through to historical times; however, their significance during the Palaeolithic has barely been explored. This project is the first systematic study of the use of these iconic geological landmarks among Pleistocene hunter-gatherers.
To present the process evaluation of a curricular Cross-curricular Unit on Portion Size (CUPS) program that integrates nutrition and mathematics, describing teacher and student perspectives on the intervention.
Design:
Semi-structured interviews and focus groups were conducted following the implementation of the CUPS program during a pilot randomised controlled trial designed to evaluate efficacy for improved portion size estimation. Lessons involved experiential learning using food models and mathematics cubes and focussed on portion size, food groups, volume and capacity. Data were collected immediately post-intervention and analysed using an inductive thematic approach.
Setting:
Primary schools in Newcastle, Australia.
Participants:
Year 3 and/or 4 teachers (n 3) and their students (n 15).
Results:
Teachers believed the programme supported the learning of nutrition concepts, with the majority of students enjoying the lessons, cubes and food models. Teachers indicated most students were engaged and became more aware of healthy eating and serve size recommendation. Although teachers enjoyed and valued the lessons, they suggested that the integration of volume and capacity should be further improved in order to address the time barrier for teaching nutrition.
Conclusion:
The process evaluation reports on challenges and successes of implementing an integrative nutrition programme. This teaching approach could be useful and successful when aligned with teacher’ and student’ needs. Based on participant feedback, lessons could be refined to enhance integration of mathematics content and to support student learning.
Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case–control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD).
Methods
Participants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons.
Results
In case–control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case–case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54–0.92] and PRS-D (OR = 1.31, 95% CI 1.06–1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23–3.74).
Conclusions
Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases.
Longitudinal data on the mental health impact of the coronavirus disease 2019 (Covid-19) pandemic in healthcare workers is limited. We estimated prevalence, incidence and persistence of probable mental disorders in a cohort of Spanish healthcare workers (Covid-19 waves 1 and 2) -and identified associated risk factors.
Methods
8996 healthcare workers evaluated on 5 May–7 September 2020 (baseline) were invited to a second web-based survey (October–December 2020). Major depressive disorder (PHQ-8 ≥ 10), generalised anxiety disorder (GAD-7 ≥ 10), panic attacks, post-traumatic stress disorder (PCL-5 ≥ 7), and alcohol use disorder (CAGE-AID ≥ 2) were assessed. Distal (pre-pandemic) and proximal (pandemic) risk factors were included. We estimated the incidence of probable mental disorders (among those without disorders at baseline) and persistence (among those with disorders at baseline). Logistic regression of individual-level [odds ratios (OR)] and population-level (population attributable risk proportions) associations were estimated, adjusting by all distal risk factors, health care centre and time of baseline interview.
Results
4809 healthcare workers participated at four months follow-up (cooperation rate = 65.7%; mean = 120 days s.d. = 22 days from baseline assessment). Follow-up prevalence of any disorder was 41.5%, (v. 45.4% at baseline, p < 0.001); incidence, 19.7% (s.e. = 1.6) and persistence, 67.7% (s.e. = 2.3). Proximal factors showing significant bivariate-adjusted associations with incidence included: work-related factors [prioritising Covid-19 patients (OR = 1.62)], stress factors [personal health-related stress (OR = 1.61)], interpersonal stress (OR = 1.53) and financial factors [significant income loss (OR = 1.37)]. Risk factors associated with persistence were largely similar.
Conclusions
Our study indicates that the prevalence of probable mental disorders among Spanish healthcare workers during the second wave of the Covid-19 pandemic was similarly high to that after the first wave. This was in good part due to the persistence of mental disorders detected at the baseline, but with a relevant incidence of about 1 in 5 of HCWs without mental disorders during the first wave of the Covid-19 pandemic. Health-related factors, work-related factors and interpersonal stress are important risks of persistence of mental disorders and of incidence of mental disorders. Adequately addressing these factors might have prevented a considerable amount of mental health impact of the pandemic among this vulnerable population. Addressing health-related stress, work-related factors and interpersonal stress might reduce the prevalence of these disorders substantially. Study registration number: NCT04556565
This study aimed to describe the shedding pattern of gastrointestinal parasite eggs by a wild population of desert bighorn sheep (DBS; Ovis canadensis) in northern Mexico. Seventy-five fresh faecal samples were collected from the ground in each season within an hour after being expelled by these animals. The generalized linear mixed model showed that eggs per gram of faeces were highest in winter (577 ± 399) and lowest in summer (260 ± 198). Generalized linear models revealed that Strongyloides spp. predominated during most seasons with a peak in summer (85% of faecal samples analysed) and the absence of this helminth in winter. Nematodirus spp. was another helminth present in three seasons, with the presence of this nematode in 35% of the faecal samples in spring and 0% in summer. Other parasites in DBS faeces included Bunostomun spp., Trichostrongylus spp., Cooperia spp., Mecistocirrus digitatus, Haemonchus contortus, Chabertia ovina and Eimeria ovinoidalis. There were differences among seasons in the percentage of these helminths and coccidia in faecal samples for all these parasites. It was concluded that helminths egg output in DBS in a semi-arid rangeland is lowest in summer and spring and highest in autumn and winter. Furthermore, it was shown that DBS in the study site do not suffer from severe parasite burden. Therefore, this nematode parasite burden is compatible with the conservation and well-being of this particular population.
In the present study, the nematicidal activity of a Moringa oleifera ethyl acetate leaf extract against the eggs and larvae of Haemonchus contortus and Nacobbus aberrans, nematodes of agricultural importance, was evaluated. The experimental design for the evaluation of the effects against both nematodes consisted of eight treatments (n = 4). Distilled water, Tween (4%) and a commercial anthelmintic agent (ivermectin, 5 mg/mL) were used as controls, and for treatments 4–8, the concentrations of the extract were 20, 10, 5, 2.5 and 1.25 mg/mL, respectively. Readings were taken at 12 h and 24 h for N. aberrans and 48 h and 72 h for H. contortus post-treatment under an optical microscope (10× and 40×). The data obtained were analysed by analysis of variance through a completely randomized factorial design using the SAS V9 program. The results show that, for H. contortus egg hatching, 85.88% inhibition was obtained at a concentration of 20 mg/mL at 48 h, while for third-stage larva (L3) mortality, the highest percentage was 68.19% at 1.25 mg/mL at 72 h. In the case of N. aberrans, the greatest inhibition of egg hatching was 90.69% at 5 mg/mL at 12 h post-treatment, and for larval mortality, it was 100% at 10 mg/mL at 24 h post-treatment. The main major compounds identified by qualitative analysis and by gas chromatography coupled to mass spectrometry were 9,12,15-octadecatrienoic acid, (Z,Z,Z)-, n-hexadecanoic acid and 2,4-di-tert-butylphenol, and the minor compounds included phytol, γ-sitosterol and α-tocopheryl acetate. It was demonstrated that the ethyl acetate leaf extract of M. oleifera Lam. shows great potential for combating agricultural nematodes.
The objective of this study was to investigate whether glycated hemoglobin (HbA1c) is a valid surrogate for evaluating the effectiveness of antihyperglycemic drugs in diabetes mellitus (DM) trials.
Methods
We conducted a systematic review of placebo-controlled randomized clinical trials (RCTs) evaluating the effect of a treatment on HbA1c (mean difference between groups) and clinical outcomes (relative risk of mortality, myocardial infarction, stroke, heart failure, and/or kidney injury) in patients with DM. Then, we investigated the association between treatment effects on HbA1c and clinical outcomes using regression analysis at the trial level. Lastly, we interpreted the correlation coefficients (R) using the cut-off points suggested by the Institute for Quality and Efficiency in Healthcare (IQWiG). HbA1c was considered a valid surrogate if it demonstrated a strong association: lower limit of the 95 percent confidence interval (95 percent CI) of R greater than or equal to .85.
Results
Nineteen RCTs were identified. All studies included adults with type 2 DM. None of the associations evaluated was strong enough to validate HbA1c as a surrogate for any clinical outcome: mortality (R = .34; 95 percent CI −.14 to .69), myocardial infarction (R = .20; −.30 to .61), heart failure (R = .08; −.40 to .53), kidney injury (R = −.04; −.52 to .47), and stroke (R = .81; .54 to .93).
Conclusions
The evidence from multiple placebo-controlled RCTs does not support the use of HbA1c as a surrogate to measure the effectiveness of antihyperglycemic drugs in DM studies.
From public health to political campaigns, numerous attempts to encourage behavior begin with the spread of information. Of course, seeding new information does not guarantee action, especially when it is difficult for receivers to verify this information. We use a novel design that introduced valuable, actionable information in rural Uganda and reveals the intermediate process that led many in the village to hear the information but only some to act on it. We find that the seeded information spread easily through word of mouth via a simple contagion process. However, acting on the information spread less easily; this process relied instead on endogenously created social information that served to vet, verify, and pass judgment. Our results highlight an important wedge between information that a policy intervention can best control and the behavior that ultimately results.
To examine the patterns of care for octogenarian head and neck cancer patients.
Methods
All newly diagnosed patients aged 80 years or older, who presented at our centre between June 2018 and October 2020, were included.
Results
The total number of patients was 42. The median Charlson Comorbidity Index was 5 (range, 4–9). The larynx was the most common subsite (n = 12). Twenty-nine patients (66 per cent) were diagnosed at disease stage IV. Squamous cell carcinoma was the most common histology (86 per cent). Twenty-six patients (62 per cent) had radical treatment and 16 (38 per cent) had palliative treatment. The estimated six-month and one-year overall survival rates for the radical and palliative treatment cohorts were 92.3 per cent and 42.9 per cent (p = 0.001) and 65.4 per cent and 15.4 per cent (p = 0.003), respectively.
Conclusion
This study provides useful information on octogenarian patients with head and neck cancer. This information may help in conducting prospective studies, especially those focusing on older patients with head and neck cancer, in order to define the ideal care of this patient population.
The valorization of plant genetic resources and their direct use in local markets can make a significant contribution to the preservation of agrobiodiversity, while also contributing to the sustainability of rural communities. Indeed, plant genetic resources are a precious source of genes, and they represent an important crop heritage for the quality and sensory characteristics that are required by both farmers and consumers. However, an efficient strategy of agrobiodiversity conservation is strictly connected to product marketability and to consumer preferences. In the present study, choice experiments that involved 920 consumers were carried out to determine their willingness to pay for ancient local tomato varieties (landraces) rather than commercial varieties based on their preferences, and to determine how much they valued these products. The results obtained indicate that consumers are willing to pay premium prices for ancient local tomato varieties (an additional €0.90 kg−1), thus demonstrating their increasing attention to sustainable food and the willingness to contribute to agrobiodiversity conservation and enhancement. These results provide the basis for planning strategies and programs to support the cultivation of these landraces and the development of regional and national markets to acknowledge their characteristics, which will considerably increase the effectiveness and efficiency of conservation strategies.