Divergent transcriptomic profiles in depressed individuals with hyper- and hypophagia implicating inflammatory status.

Major Depressive Disorder (MDD) is a heterogenous and etiologically complex disease encompassing a broad spectrum of psychopathology, presumably arising from distinct pathophysiological mechanisms. Divergent appetitive phenotypes including Hyperphagic MDD (characterized by an increased appetite) and Hypophagic MDD (characterized by a decrease in appetite) are important clinical characteristics that are closely related to comorbidities, including cardiometabolic disorders. Prior evidence supports the notion that hyperphagia is associated with atypical depression, decreased stress-hormone signaling, a pro-inflammatory status, hypersomnia, and poorer clinical outcomes. Yet, our understanding of the underlying mechanisms of Hyperphagic and Hypophagic MDD is limited, and knowledge of associated biological correlates of these endophenotypes remain fragmented. We performed an exploratory study on peripheral blood RNA profiling using bulk RNAseq in unmedicated individuals with Hyperphagic and Hypophagic MDD (n=8 and n=13, respectively) and discovered individual genes and gene pathways associated with appetitive phenotypes. In addition, we used the Maastricht Acute Stress Task to uncover stress-related transcriptomic profiles in Hyper- and Hypophagic MDD.

Divergent transcriptomic profiles in depressed individuals with hyper- and hypophagia implicating inflammatory status.

Major Depressive Disorder (MDD) is a heterogenous and etiologically complex disease encompassing a broad spectrum of psychopathology, presumably arising from distinct pathophysiological mechanisms. Divergent appetitive phenotypes including Hyperphagic MDD (characterized by an increased appetite) and Hypophagic MDD (characterized by a decrease in appetite) are important clinical characteristics that are closely related to comorbidities, including cardiometabolic disorders. Prior evidence supports the notion that hyperphagia is associated with atypical depression, decreased stress-hormone signaling, a pro-inflammatory status, hypersomnia, and poorer clinical outcomes. Yet, our understanding of the underlying mechanisms of Hyperphagic and Hypophagic MDD is limited, and knowledge of associated biological correlates of these endophenotypes remain fragmented. We performed an exploratory study on peripheral blood RNA profiling using bulk RNAseq in unmedicated individuals with Hyperphagic and Hypophagic MDD (n=8 and n=13, respectively) and discovered individual genes and gene pathways associated with appetitive phenotypes. In addition, we used the Maastricht Acute Stress Task to uncover stress-related transcriptomic profiles in Hyper- and Hypophagic MDD.

Current European flood-rich period exceptional compared with past 500 years.

There are concerns that recent climate change is altering the frequency and magnitude of river floods in an unprecedented way1. Historical studies have identified flood-rich periods in the past half millennium in various regions of Europe2. However, because of the low temporal resolution of existing datasets and the relatively low number of series, it has remained unclear whether Europe is currently in a flood-rich period from a long-term perspective. Here we analyse how recent decades compare with the flood history of Europe, using a new database composed of more than 100 high-resolution (sub-annual) historical flood series based on documentary evidence covering all major regions of Europe. We show that the past three decades were among the most flood-rich periods in Europe in the past 500 years, and that this period differs from other flood-rich periods in terms of its extent, air temperatures and flood seasonality. We identified nine flood-rich periods and associated regions. Among the periods richest in floods are 1560-1580 (western and central Europe), 1760-1800 (most of Europe), 1840-1870 (western and southern Europe) and 1990-2016 (western and central Europe). In most parts of Europe, previous flood-rich periods occurred during cooler-than-usual phases, but the current flood-rich period has been much warmer. Flood seasonality is also more pronounced in the recent period. For example, during previous flood and interflood periods, 41 per cent and 42 per cent of central European floods occurred in summer, respectively, compared with 55 per cent of floods in the recent period. The exceptional nature of the present-day flood-rich period calls for process-based tools for flood-risk assessment that capture the physical mechanisms involved, and management strategies that can incorporate the recent changes in risk.

Multi-century trends to wetter winters and drier summers in the England and Wales precipitation series explained by observational and sampling bias in early records.

Globally, few precipitation records extend to the 18th century. The England Wales Precipitation (EWP) series is a notable exception with continuous monthly records from 1766. EWP has found widespread use across diverse fields of research including trend detection, evaluation of climate model simulations, as a proxy for mid-latitude atmospheric circulation, a predictor in long-term European gridded precipitation data sets, the assessment of drought and extremes, tree-ring reconstructions and as a benchmark for other regional series. A key finding from EWP has been the multi-centennial trends towards wetter winters and drier summers. We statistically reconstruct seasonal EWP using independent, quality-assured temperature, pressure and circulation indices. Using a sleet and snow series for the UK derived by Profs. Gordon Manley and Elizabeth Shaw to examine winter reconstructions, we show that precipitation totals for pre-1870 winters are likely biased low due to gauge under-catch of snowfall and a higher incidence of snowfall during this period. When these factors are accounted for in our reconstructions, the observed trend to wetter winters in EWP is no longer evident. For summer, we find that pre-1820 precipitation totals are too high, likely due to decreasing network density and less certain data at key stations. A significant trend to drier summers is not robustly present in our reconstructions of the EWP series. While our findings are more certain for winter than summer, we highlight (a) that extreme caution should be exercised when using EWP to make inferences about multi-centennial trends, and; (b) that assessments of 18th and 19th Century winter precipitation should be aware of potential snow biases in early records. Our findings underline the importance of continual re-appraisal of established long-term climate data sets as new evidence becomes available. It is also likely that the identified biases in winter EWP have distorted many other long-term European precipitation series.

Changing climate both increases and decreases European river floods.

Climate change has led to concerns about increasing river floods resulting from the greater water-holding capacity of a warmer atmosphere1. These concerns are reinforced by evidence of increasing economic losses associated with flooding in many parts of the world, including Europe2. Any changes in river floods would have lasting implications for the design of flood protection measures and flood risk zoning. However, existing studies have been unable to identify a consistent continental-scale climatic-change signal in flood discharge observations in Europe3, because of the limited spatial coverage and number of hydrometric stations. Here we demonstrate clear regional patterns of both increases and decreases in observed river flood discharges in the past five decades in Europe, which are manifestations of a changing climate. Our results-arising from the most complete database of European flooding so far-suggest that: increasing autumn and winter rainfall has resulted in increasing floods in northwestern Europe; decreasing precipitation and increasing evaporation have led to decreasing floods in medium and large catchments in southern Europe; and decreasing snow cover and snowmelt, resulting from warmer temperatures, have led to decreasing floods in eastern Europe. Regional flood discharge trends in Europe range from an increase of about 11 per cent per decade to a decrease of 23 per cent. Notwithstanding the spatial and temporal heterogeneity of the observational record, the flood changes identified here are broadly consistent with climate model projections for the next century4,5, suggesting that climate-driven changes are already happening and supporting calls for the consideration of climate change in flood risk management.

Developing the methods and questionnaire (VOICES-SF) for a national retrospective mortality follow-back survey of palliative and end-of-life care in England.

The National Survey of Bereaved People was conducted by the Office for National Statistics on behalf of NHS England for the first time in 2011, and repeated annually thereafter. It is thought to be the first time that nationally representative data have been collected annually on the experiences of all people who have died, regardless of cause and setting, and made publicly available informing palliative and end-of-life policy, service provision and development, and practice. This paper describes the development of the questionnaire used in the survey, VOICES-SF, a short-form of the VOICES (Views Of Informal Carers-Evaluation of Services) questionnaire, adapted specifically to address the aims of the national survey. The pilot study to refine methods for the national survey is also described. The paper also reports on the development of the retrospective, after-death or mortality follow-back method in palliative and end-of-life care, and reviews its strengths and weaknesses.

A Rare Case of Vasospastic Angina Presenting with Inferior Lead ST-segment Elevation and Ventricular Fibrillation in the Absence of Coronary Obstruction: A Case Report.

Vasospastic angina (VSA) is a variant form of angina pectoris, which occurs at night or at rest, with transient electrocardiogram modifications and preserved exercise capacity. Its association with stable angina, sudden cardiac death, acute coronary syndrome, arrhythmia, and syncope has previously been established. Its presentation can occur with or without existing coronary artery disease and may present with focal or diffuse alteration and dysfunction of the coronary vasculature. VSA diagnosis involves patient response to nitrates, transient ischemic electrocardiogram (ECG) changes, and coronary artery spasms. The mechanisms proposed to constitute the substrate for susceptibility to VSA include vascular smooth muscle cell hyperreactivity, endothelial dysfunction, magnesium deficiency, low-grade inflammation, altered autonomic nervous system response, hypothyroidism, and oxidative stress. Herein, we present the rare case of a patient with ST-segment elevation in the inferior leads, increased troponin, and an episode of ventricular fibrillation initially thought to be due to lateral wall ST-elevation myocardial infarction (STEMI), although it was revealed to be vasospastic angina. We will also review the literature. Vasospastic angina remains underdiagnosed and a timely diagnosis is crucial to prevent major cardiac events. In patients with diffuse ST-segment elevation on ECG (independently of angiographic findings), VSA should be considered as one of the differential diagnoses and treated if found to be the cause of pathological changes.

Metastatic biphasic pleural mesothelioma presenting with cauda equina syndrome.

Patient with previous asbestos exposure on a watchful wait and watch regime presents acutely with cauda equina syndrome. Radiological imaging confirmed a mass with direct invasion of the spinal cord. Histology confirmed metastatic pleural mesothelioma.

Changing climate shifts timing of European floods.

A warming climate is expected to have an impact on the magnitude and timing of river floods; however, no consistent large-scale climate change signal in observed flood magnitudes has been identified so far. We analyzed the timing of river floods in Europe over the past five decades, using a pan-European database from 4262 observational hydrometric stations, and found clear patterns of change in flood timing. Warmer temperatures have led to earlier spring snowmelt floods throughout northeastern Europe; delayed winter storms associated with polar warming have led to later winter floods around the North Sea and some sectors of the Mediterranean coast; and earlier soil moisture maxima have led to earlier winter floods in western Europe. Our results highlight the existence of a clear climate signal in flood observations at the continental scale.

Outbreak of Botulism Due to Illicit Prison-Brewed Alcohol: Public Health Response to a Serious and Recurrent Problem.

Background: Botulism is a rare, sometimes lethal neuroparalytic illness. On 2 October 2011, an inmate at prison A developed symptoms compatible with botulism after drinking pruno, an illicit, prison-brewed alcoholic beverage. Additional illnesses were identified within several days. We conducted an investigation to determine the cause and extent of the outbreak. Methods: A case was defined as signs or symptoms of botulism in a prison A inmate with onset during 30 September-9 October 2011. Cases were identified through medical evaluations and interviews with inmates about recent pruno consumption. Laboratory testing was performed for Clostridium botulinum and botulinum neurotoxin. Ingredients, preparation, and sharing of the implicated pruno were investigated. Results: Eight prisoners developed botulism; all drank pruno made with a potato. Three received mechanical ventilation. Culture of fluid from a sock that inmates reported using to filter the implicated pruno yielded C. botulinum type A. The implicated batch may have been shared between cells during delivery of meal trays. Challenges of the investigation included identifying affected inmates, overcoming inaccuracies in histories, and determining how the illicit beverage was shared. Costs to taxpayers were nearly $500000 in hospital costs alone. Conclusions: Pruno made with potato has emerged as an important cause of botulism in the United States. This public health response illustrates the difficulties of investigating botulism in correctional facilities and lessons learned for future investigations.

A Survey of Social Media Use and Preferences in Patients with Inflammatory Bowel Disease.

BACKGROUND: With the recent increase in the use of social media, patients with chronic illnesses are using the Internet as a resource for disease management. As the peak incidence of inflammatory bowel disease (IBD) occurs in patients between the ages of 15 and 30, IBD is a suitable condition to study social media use. The aim of this study was to assess social media usage and preferences in patients with IBD. METHODS: We administered a survey to 118 patients with IBD at our outpatient practice at the Boston Medical Center (BMC), Center for Digestive Disorders, and the University of Southern Alabama (USA) between November 1, 2015, and March 9, 2016. RESULTS: The most frequently used IBD-specific social media website was the CCFA (86%). High-frequency social media users were more likely to agree that "social media is useful for managing my IBD," compared with low-frequency social media users (OR 3.23, 0.3-10.1, P = 0.199). Fifty-five percent of respondents were interested in obtaining patient-with-IBD education through social media, or organizations such as the CCFA, whereas 45% did not express interest. Sixty-two percent of patients would be interested in following a social media account established by their gastroenterologist. Privacy and/or confidentiality issues were the primary barriers to social media use. Last, most patients were unsure of the quality of IBD information posted online. CONCLUSIONS: The results of this study suggest that patients who frequently use social media are highly interested in using social media in the management of their IBD. Most patients with IBD in our study were interested in receiving IBD information from their gastroenterologist and other patient-related organizations through social media. Most patients are unsure of the quality of IBD information posted on social media. Gastroenterologists should be aware that their patients may use social media to obtain disease education. Future studies should assess the quality of IBD information on social media and the effectiveness of communication through social media as a means to improve patient education and outcomes.

Place of death in the population dying from diseases indicative of palliative care need: a cross-national population-level study in 14 countries.

BACKGROUND: Studying where people die across countries can serve as an evidence base for health policy on end-of-life care. This study describes the place of death of people who died from diseases indicative of palliative care need in 14 countries, the association of place of death with cause of death, sociodemographic and healthcare availability characteristics in each country and the extent to which these characteristics explain country differences in the place of death. METHODS: Death certificate data for all deaths in 2008 (age ≥1 year) in Belgium, Canada, the Czech Republic, England, France, Hungary, Italy, Mexico, the Netherlands, New Zealand, South Korea, Spain (Andalusia), the USA and Wales caused by cancer, heart/renal/liver failure, chronic obstructive pulmonary disease, diseases of the nervous system or HIV/AIDS were linked with national or regional healthcare statistics (N=2,220,997). RESULTS: 13% (Canada) to 53% (Mexico) of people died at home and 25% (the Netherlands) to 85% (South Korea) died in hospital. The strength and direction of associations between home death and cause of death, sociodemographic and healthcare availability factors differed between countries. Differences between countries in home versus hospital death were only partly explained by differences in these factors. CONCLUSIONS: The large differences between countries in and beyond Europe in the place of death of people in potential need of palliative care are not entirely attributable to sociodemographic characteristics, cause of death or availability of healthcare resources, which suggests that countries' palliative and end-of-life care policies may influence where people die.

A Qualitative Inquiry About Pruno, an Illicit Alcoholic Beverage Linked to Botulism Outbreaks in United States Prisons.

OBJECTIVES: Since 2011, 3 outbreaks of botulism in US prisons have been attributed to pruno, which is an alcoholic beverage made by inmates. Following 1 outbreak, we conducted a qualitative inquiry to understand pruno brewing and its social context to inform outbreak prevention measures. METHODS: We interviewed staff, inmates, and parolees from 1 prison about pruno production methods, the social aspects of pruno, and strategies for communicating the association between botulism and pruno. RESULTS: Twenty-seven inmates and parolees and 13 staff completed interviews. Pruno is fermented from water, fruit, sugar, and miscellaneous ingredients. Knowledge of pruno making was widespread among inmates; staff were familiar with only the most common ingredients and supplies inmates described. Staff and inmates described inconsistent consequences for pruno possession and suggested using graphic health messages from organizations external to the prison to communicate the risk of botulism from pruno. CONCLUSIONS: Pruno making was frequent in this prison. Improved staff recognition of pruno ingredients and supplies might improve detection of brewing activities in this and other prisons. Consistent consequences and clear messages about the association between pruno and botulism might prevent outbreaks.

'You can't say, "what about me?" I'm not the one with cancer': information and support needs of relatives.

OBJECTIVE: The aims of this study were to explore relatives' experiences of talking about cancer within the family and to identify their information and support needs. METHOD: A cross-sectional in-depth interview study with relatives and partners (n = 22) of cancer patients recruited through community settings was conducted. A thematic approach was used for analysis. RESULTS: Information sharing and communication within families operated within a context of cancer-related uncertainty. Discussion about cancer was generally viewed as beneficial, but relatives faced dilemmas, which inhibited information exchange. Participants often devised strategies to manage the challenges faced to fulfil their needs for information and support. This was deemed important as talking about cancer allowed relatives to support patients' preferences for care, deal with practical demands and come to terms with difficult issues. Lack of information was perceived to affect the quality of care participants could provide. CONCLUSION: Participants did not always want to know everything about the patient's illness, suggesting the importance of tailoring information to individual needs. Offering a range of different kinds of support directly to relatives may improve patient care and emotional well-being.

International variation in place of death of older people who died from dementia in 14 European and non-European countries.

OBJECTIVES: The objective of this study was to examine variation in place of death of older people dying from dementia in countries across 4 continents. DESIGN: Study of death certificate data. METHODS: We included deaths of older (65 + years) people whose underlying cause of death was a dementia-related disease (ICD-10: F01, F02, F03, G30) in Belgium, the Netherlands, England, Wales, France, Italy, Spain, Czech Republic, Hungary, New Zealand, United States, Canada, Mexico and South Korea. We examined associations between place of death and sociodemographic factors, social support, and residential and health care system factors. RESULTS: Overall, 4.8% of all deaths were from a dementia-related disease, ranging from 0.4% in Mexico to 6.9% in Canada. Of those deaths, the proportion occurring in hospital varied from 1.6% in the Netherlands to 73.6% in South Korea. When controlling for potential confounders, hospital death was more likely for men, those younger than 80, and those married or living in a region with a higher availability of long-term care beds, although this could not be concluded for each country. Hospital death was least likely in the Netherlands compared with other countries. CONCLUSIONS: Place of death of older people who died from a dementia-related disease differs substantially between countries, which might point to organizational differences in end-of-life care provision. Increasing the availability of long-term care beds might be important to reduce the number of hospital deaths, while focusing specialized end-of-life care services on married people or those aged 65 to 79 might be crucial for achieving home death. However, proper end-of-life care needs to be ensured in hospitals, should this be the most appropriate end-of-life care setting.

Increasing river floods: fiction or reality?

There has been a surprisingly large number of major floods in the last years around the world, which suggests that floods may have increased and will continue to increase in the next decades. However, the realism of such changes is still hotly discussed in the literature. This overview article examines whether floods have changed in the past and explores the driving processes of such changes in the atmosphere, the catchments and the river system based on examples from Europe. Methods are reviewed for assessing whether floods may increase in the future. Accounting for feedbacks within the human-water system is important when assessing flood changes over lead times of decades or centuries. It is argued that an integrated flood risk management approach is needed for dealing with future flood risk with a focus on reducing the vulnerability of the societal system. WIREs Water 2015, 2:329-344. doi: 10.1002/wat2.1079 For further resources related to this article, please visit the WIREs website.

The JACS prospective cohort study of newly diagnosed women with breast cancer investigating joint and muscle pain, aches, and stiffness: pain and quality of life after primary surgery and before adjuvant treatment.

BACKGROUND: Breast cancer affects one in eight UK women during their lifetime: many of these women now receive adjuvant chemotherapy and hormone therapy. Joint and muscle pains, aches, and stiffness are common but the natural history, aetiology and impact of these symptoms are unknown. A cohort study of newly diagnosed women with primary breast cancer was established to explore this. In this paper we present study methods and sample characteristics, describe participants' experience of musculoskeletal pain at baseline interview, and explore its impact on quality of life. METHODS: Women with non-metastatic breast cancer were recruited following primary surgery into a multi-centre cohort study. They received questionnaires by post five times (baseline, 3, 6 , 9 and 12 months) to investigate prevalence, severity, location and correlates of musculoskeletal pain, and impact on quality-of-life. Pain was measured by the Nordic musculoskeletal questionnaire, the Brief Pain Inventory, and MSK-specific questions, and quality of life by the SF-36 and FACIT scales. RESULTS: 543 women (mean age 57 years, range 28-87, 64% postmenopausal) were recruited following surgery for primary breast cancer from breast cancer clinics in eight hospitals. Fifteen per cent of the eligible cohort was missed; 28% declined to participate. Joint or muscle aches, pains or stiffness were reported by 69% women with 28% specifically reporting joint pain/aches/stiffness. Quality of life, as measured by the FACT-B and adjusted for age, depression, surgery and analgesic use, is significantly worse in all domains in those with musculoskeletal problems than those without. CONCLUSIONS: Our findings highlights the importance of a better understanding of these symptoms and their impact on the lives of women with primary breast cancer so that healthcare professionals are better equipped to support patients and to provide accurate information to inform treatment decisions. Further papers from this study will address these issues.

Development and initial validation of a new outcome measure for hospice and palliative care: the St Christopher's Index of Patient Priorities (SKIPP).

OBJECTIVE: To develop and conduct a preliminary psychometric analysis of a hospice and palliative care patient-reported outcome measure to detect patients' perceptions of change in quality of life (QoL) and issues of concern, and views of service benefit. METHODS: Following pilot testing and cognitive interviewing, St Christopher's Index of Patient Priorities (SKIPP) was administered twice to hospice inpatients and homecare patients. QoL was rated 'now', and retrospectively 'before starting hospice care' or 'at the time of the first interview'. Patients nominated and rated progress with main concerns, rated the difference the service was making, and completed palliative care outcome scale. Patients completed SKIPP again within 24 h to measure test-retest reliability. RESULTS: QoL scores 'now' differed significantly from retrospective scores made at same time: QoL increased with hospice care when patients 'looked back' on previous QoL. Four-fifths reported that their first concern had got 'a little'/ 'much' better since initial service contact: this declined subsequently. Four-fifths at both time points said the hospice had made 'a lot of difference' to them. No significant differences were noted between time points on palliative care outcome scale items. Test-retest analyses were prevented by low numbers. CONCLUSIONS: SKIPP can detect patients' perception of change in QoL and main concerns, and the difference patients think the service has made to them. Its design with current and retrospective components addresses response shift and means it can be used for quality improvement or clinical purposes with only one administration, an advantage in frail populations. It is therefore a useful addition to hospice and palliative care patient-reported outcome measures.