An assessment of prospective memory retrieval in women with chronic fatigue syndrome using a virtual-reality environment: an initial study

People with chronic fatigue syndrome (CFS) have increased rates of depression, anxiety, and illness intrusiveness; they may also suffer from cognitive problems such as retrospective memory (RM) deficits and concentration difficulties that can stem from diminished information-processing capability. We predicted that this diminished capacity may also lead to deficits in other cognitive functions, such as prospective memory (ProM). Event-, time-, and activity-based ProM was assessed in 11 women with CFS and 12 healthy women using a computer-generated virtual environment (VE). RM was assessed using a free-recall test, and subjective assessment of both ProM and RM was assessed by questionnaire. Groups were equivalent in age and measures of IQ. People with CFS performed slightly worse than healthy controls on both the event- and time-based ProM measures, although these were not statistically significant. However, the CFS group performed significantly worse than the healthy controls on both the free recall-task and on subjective assessment of both RM and ProM. Women with CFS do have some subtle decrements in memory, particularly RM. However, it is possible that the decrements found in the present sample would be greater in real life. Further studies utilizing both healthy controls and illness controls are now needed to ascertain how sensitive the VE measure is and to inform the development of tasks in the VE that place progressively increasing demands on working memory capacity

Activity distribution of comet 67P/Churyumov-Gerasimenko from combined measurements of non-gravitational forces and torques

Aims. Understanding the activity is vital for deciphering the structure, formation, and evolution of comets. We investigate models of cometary activity by comparing them to the dynamics of 67P/Churyumov-Gerasimenko. Methods. We matched simple thermal models of water activity to the combined Rosetta datasets by fitting to the total outgassing rate and four components of the outgassing induced non-gravitational force and torque, with a final manual adjustment of the model parameters to additionally match the other two torque components. We parametrised the thermal model in terms of a distribution of relative activity over the surface of the comet, and attempted to link this to different terrain types. We also tested a more advanced thermal model based on a pebble structure. Results. We confirm a hemispherical dichotomy and non-linear water outgassing response to insolation. The southern hemisphere of the comet and consolidated terrain show enhanced activity relative to the northern hemisphere and dust-covered, unconsolidated terrain types, especially at perihelion. We further find that the non-gravitational torque is especially sensitive to the activity distribution, and to fit the pole-axis orientation in particular, activity must be concentrated (in excess of the already high activity in the southern hemisphere and consolidated terrain) around the south pole and on the body and neck of the comet over its head. This is the case for both the simple thermal model and the pebble-based model. Overall, our results show that water activity cannot be matched by a simple model of sublimating surface ice driven by the insolation alone, regardless of the surface distribution, and that both local spatial and temporal variations are needed to fit the data. Conclusions. Fully reconciling the Rosetta outgassing, torque, and acceleration data requires a thermal model that includes both diurnal and seasonal effects and also structure with depth (dust layers or ice within pebbles). This shows that cometary activity is complex. Nonetheless, non-gravitational dynamics provides a useful tool for distinguishing between different thermophysical models and aids our understanding

Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome: a prospective, community-based study

OBJECTIVE: To assess medium-term organ impairment in symptomatic individuals following recovery from acute SARS-CoV-2 infection. DESIGN: Baseline findings from a prospective, observational cohort study. SETTING: Community-based individuals from two UK centres between 1 April and 14 September 2020. PARTICIPANTS: Individuals ≥18 years with persistent symptoms following recovery from acute SARS-CoV-2 infection and age-matched healthy controls. INTERVENTION: Assessment of symptoms by standardised questionnaires (EQ-5D-5L, Dyspnoea-12) and organ-specific metrics by biochemical assessment and quantitative MRI. MAIN OUTCOME MEASURES: Severe post-COVID-19 syndrome defined as ongoing respiratory symptoms and/or moderate functional impairment in activities of daily living; single-organ and multiorgan impairment (heart, lungs, kidneys, liver, pancreas, spleen) by consensus definitions at baseline investigation. RESULTS: 201 individuals (mean age 45, range 21-71 years, 71% female, 88% white, 32% healthcare workers) completed the baseline assessment (median of 141 days following SARS-CoV-2 infection, IQR 110-162). The study population was at low risk of COVID-19 mortality (obesity 20%, hypertension 7%, type 2 diabetes 2%, heart disease 5%), with only 19% hospitalised with COVID-19. 42% of individuals had 10 or more symptoms and 60% had severe post-COVID-19 syndrome. Fatigue (98%), muscle aches (87%), breathlessness (88%) and headaches (83%) were most frequently reported. Mild organ impairment was present in the heart (26%), lungs (11%), kidneys (4%), liver (28%), pancreas (40%) and spleen (4%), with single-organ and multiorgan impairment in 70% and 29%, respectively. Hospitalisation was associated with older age (p=0.001), non-white ethnicity (p=0.016), increased liver volume (p<0.0001), pancreatic inflammation (p<0.01), and fat accumulation in the liver (p<0.05) and pancreas (p<0.01). Severe post-COVID-19 syndrome was associated with radiological evidence of cardiac damage (myocarditis) (p<0.05). CONCLUSIONS: In individuals at low risk of COVID-19 mortality with ongoing symptoms, 70% have impairment in one or more organs 4 months after initial COVID-19 symptoms, with implications for healthcare and public health, which have assumed low risk in young people with no comorbidities. TRIAL REGISTRATION NUMBER: NCT04369807; Pre-results

Bilobate comet morphology and internal structure controlled by shear deformation

Bilobate comets—small icy bodies with two distinct lobes—are a common configuration among comets, but the factors shaping these bodies are largely unknown. Cometary nuclei, the solid centres of comets, erode by ice sublimation when they are sufficiently close to the Sun, but the importance of a comet’s internal structure on its erosion is unclear. Here we present three-dimensional analyses of images from the Rosetta mission to illuminate the process that shaped the Jupiter-family bilobate comet 67P/Churyumov–Gerasimenko over billions of years. We show that the comet’s surface and interior exhibit shear-fracture and fault networks, on spatial scales of tens to hundreds of metres. Fractures propagate up to 500 m below the surface through a mechanically homogeneous material. Through fracture network analysis and stress modelling, we show that shear deformation generates fracture networks that control mechanical surface erosion, particularly in the strongly marked neck trough of 67P/Churyumov–Gerasimenko, exposing its interior. We conclude that shear deformation shapes and structures the surface and interior of bilobate comets, particularly in the outer Solar System where water ice sublimation is negligible.Additional co-authors: M. A. Barucci, J.-L. Bertaux, I. Bertini, D. Bodewits, G. Cremonese, V. Da Deppo, S. Debei, M. De Cecco, J. Deller, S. Fornasier, M. Fulle, P. J. Gutiérrez, C. Güttler, W.-H. Ip, H. U. Keller, L. M. Lara, F. La Forgia, M. Lazzarin, A. Lucchetti, J. J. López-Moreno, F. Marzari, M. Massironi, S. Mottola, N. Oklay, M. Pajola, L. Penasa, F. Preusker, H. Rickman, F. Scholten, X. Shi, I. Toth, C. Tubiana & J.-B. Vincen

Post-COVID-19 assessment in a specialist clinical service: a 12-month, single-centre, prospective study in 1325 individuals

INTRODUCTION: Post-COVID-19 complications require simultaneous characterisation and management to plan policy and health system responses. We describe the 12-month experience of the first UK dedicated post-COVID-19 clinical service to include hospitalised and non-hospitalised patients. METHODS: In a single-centre, observational analysis, we report the demographics, symptoms, comorbidities, investigations, treatments, functional recovery, specialist referral and rehabilitation of 1325 individuals assessed at the University College London Hospitals post-COVID-19 service between April 2020 and April 2021, comparing by referral route: posthospitalised (PH), non-hospitalised (NH) and post emergency department (PED). Symptoms associated with poor recovery or inability to return to work full time were assessed using multivariable logistic regression. RESULTS: 1325 individuals were assessed (PH: 547, 41.3%; PED: 212, 16%; NH: 566, 42.7%). Compared with the PH and PED groups, the NH group were younger (median 44.6 (35.6-52.8) years vs 58.3 (47.0-67.7) years and 48.5 (39.4-55.7) years), more likely to be female (68.2%, 43.0% and 59.9%), less likely to be of ethnic minority (30.9%, 52.7% and 41.0%) or seen later after symptom onset (median (IQR): 194 (118-298) days, 69 (51-111) days and 76 (55-128) days; all p<0.0001). All groups had similar rates of onward specialist referral (NH 18.7%, PH 16.1% and PED 18.9%, p=0.452) and were more likely to require support for breathlessness (23.7%, 5.5% and 15.1%, p<0.001) and fatigue (17.8%, 4.8% and 8.0%, p<0.001). Hospitalised patients had higher rates of pulmonary emboli, persistent lung interstitial abnormalities and other organ impairment. 716 (54.0%) individuals reported <75% optimal health (median 70%, IQR 55%-85%). Less than half of employed individuals could return to work full time at first assessment. CONCLUSION: Post-COVID-19 symptoms were significant in PH and NH patients, with significant ongoing healthcare needs and utilisation. Trials of interventions and patient-centred pathways for diagnostic and treatment approaches are urgently required

Nucleotide supplementation: a randomised double-blind placebo controlled trial of IntestAidIB in people with Irritable Bowel Syndrome [ISRCTN67764449]

BACKGROUND: Dietary nucleotide supplementation has been shown to have important effects on the growth and development of cells which have a rapid turnover such as those in the immune system and the gastrointestinal tract. Work with infants has shown that the incidence and duration of diarrhoea is lower when nucleotide supplementation is given, and animal work shows that villi height and crypt depth in the intestine is increased as a result of dietary nucleotides. Dietary nucleotides may be semi-essential under conditions of ill-health, poor diet or stress. Since people with Irritable Bowel Syndrome tend to fulfil these conditions, we tested the hypothesis that symptoms would be improved with dietary nucleotide supplementation. METHODS: Thirty-seven people with a diagnosis of Irritable Bowel gave daily symptom severity ratings for abdominal pain, diarrhoea, urgency to have a bowel movement, incomplete feeling of evacuation after a bowel movement, bloating, flatulence and constipation for 28 days (baseline). They were then assigned to either placebo (56 days) followed by experimental (56 days) or the reverse. There was a four week washout period before crossover. During the placebo and experimental conditions participants took one 500 mg capsule three times a day; in the experimental condition the capsule contained the nutroceutical substances. Symptom severity ratings and psychological measures (anxiety, depression, illness intrusiveness and general health) were obtained and analysed by repeated measures ANOVAs. RESULTS: Symptom severity for all symptoms (except constipation) were in the expected direction of baseline>placebo>experimental condition. Symptom improvement was in the range 4 – 6%. A feeling of incomplete evacuation and abdominal pain showed the most improvement. The differences between conditions for diarrhoea, bloating and flatulence were not significant at the p < .05 level. There were no significant differences between the conditions for any of the psychological measures. CONCLUSION: Dietary nucleotide supplementation improves some of the symptoms of irritable bowel above baseline and placebo level. As expected, placebo effects were high. Apart from abdominal pain and urgency to have a bowel movement, the improvements, while consistent, are modest, and were not accompanied by improvements in any of the psychological measures. We suggest that the percentage improvement over and above the placebo effect is a physiological effect of the nucleotide supplement on the gut. The mechanisms by which these effects might improve symptoms are discussed

Limits to modern contraceptive use among young women in developing countries: a systematic review of qualitative research

<p>Abstract</p> <p>Background</p> <p>Improving the reproductive health of young women in developing countries requires access to safe and effective methods of fertility control, but most rely on traditional rather than modern contraceptives such as condoms or oral/injectable hormonal methods. We conducted a systematic review of qualitative research to examine the limits to modern contraceptive use identified by young women in developing countries. Focusing on qualitative research allows the assessment of complex processes often missed in quantitative analyses.</p> <p>Methods</p> <p>Literature searches of 23 databases, including Medline, Embase and POPLINE^®, were conducted. Literature from 1970–2006 concerning the 11–24 years age group was included. Studies were critically appraised and meta-ethnography was used to synthesise the data.</p> <p>Results</p> <p>Of the 12 studies which met the inclusion criteria, seven met the quality criteria and are included in the synthesis (six from sub-Saharan Africa; one from South-East Asia). Sample sizes ranged from 16 to 149 young women (age range 13–19 years). Four of the studies were urban based, one was rural, one semi-rural, and one mixed (predominantly rural). Use of hormonal methods was limited by lack of knowledge, obstacles to access and concern over side effects, especially fear of infertility. Although often more accessible, and sometimes more attractive than hormonal methods, condom use was limited by association with disease and promiscuity, together with greater male control. As a result young women often relied on traditional methods or abortion. Although the review was limited to five countries and conditions are not homogenous for all young women in all developing countries, the overarching themes were common across different settings and contexts, supporting the potential transferability of interventions to improve reproductive health.</p> <p>Conclusion</p> <p>Increasing modern contraceptive method use requires community-wide, multifaceted interventions and the combined provision of information, life skills, support and access to youth-friendly services. Interventions should aim to counter negative perceptions of modern contraceptive methods and the dual role of condoms for contraception and STI prevention should be exploited, despite the challenges involved.</p

Impaired neural development in a zebrafish model for Lowe syndrome

Lowe syndrome, which is characterized by defects in the central nervous system, eyes and kidneys, is caused by mutation of the phosphoinositide 5-phosphatase OCRL1. The mechanisms by which loss of OCRL1 leads to the phenotypic manifestations of Lowe syndrome are currently unclear, in part, owing to the lack of an animal model that recapitulates the disease phenotype. Here, we describe a zebrafish model for Lowe syndrome using stable and transient suppression of OCRL1 expression. Deficiency of OCRL1, which is enriched in the brain, leads to neurological defects similar to those reported in Lowe syndrome patients, namely increased susceptibility to heat-induced seizures and cystic brain lesions. In OCRL1-deficient embryos, Akt signalling is reduced and there is both increased apoptosis and reduced proliferation, most strikingly in the neural tissue. Rescue experiments indicate that catalytic activity and binding to the vesicle coat protein clathrin are essential for OCRL1 function in these processes. Our results indicate a novel role for OCRL1 in neural development, and support a model whereby dysregulation of phosphoinositide metabolism and clathrin-mediated membrane traffic leads to the neurological symptoms of Lowe syndrome

The Re-Establishment of Desiccation Tolerance in Germinated Arabidopsis thaliana Seeds and Its Associated Transcriptome

The combination of robust physiological models with “omics” studies holds promise for the discovery of genes and pathways linked to how organisms deal with drying. Here we used a transcriptomics approach in combination with an in vivo physiological model of re-establishment of desiccation tolerance (DT) in Arabidopsis thaliana seeds. We show that the incubation of desiccation sensitive (DS) germinated Arabidopsis seeds in a polyethylene glycol (PEG) solution re-induces the mechanisms necessary for expression of DT. Based on a SNP-tile array gene expression profile, our data indicates that the re-establishment of DT, in this system, is related to a programmed reversion from a metabolic active to a quiescent state similar to prior to germination. Our findings show that transcripts of germinated seeds after the PEG-treatment are dominated by those encoding LEA, seed storage and dormancy related proteins. On the other hand, a massive repression of genes belonging to many other classes such as photosynthesis, cell wall modification and energy metabolism occurs in parallel. Furthermore, comparison with a similar system for Medicago truncatula reveals a significant overlap between the two transcriptomes. Such overlap may highlight core mechanisms and key regulators of the trait DT. Taking into account the availability of the many genetic and molecular resources for Arabidopsis, the described system may prove useful for unraveling DT in higher plants