Death ideation in cancer patients: contributing factors

Advances in cancer research and therapy have improved prognosis and the quality of life of many patients. However, previous epidemiological studies in oncologic patients have shown an increased risk of suicide. Suicidal thoughts, relatively well known in those terminally ill, may be just as important for cancer patients who are survivors or are living with the disease. Nonetheless, there is a relative paucity of data about suicidality in this setting. The authors conducted a prospective observational study to identify death thoughts and to explore the factors associated with suicidal ideation in cancer patients. A sample of 130 patients referred for psychiatric consultation was obtained following informed consent and authorization from the local ethics committee. A semistructured interview assessed sociodemographic data, psychosocial support, and information regarding the cancer process and its treatment. Psychometric instruments were used to evaluate psychopathology, namely the Hospital Anxiety and Depression Scale, the Beck Hopelessness Scale, and the Beck Scale for Suicide Ideation. Psychiatric diagnoses were obtained through the application of the Mini International Neuropsychiatric Interview. Death ideation was identified in 34.6% of patients, yet only 10% had active suicidal thoughts. Risk of suicide was associated with female gender, a psychiatric diagnosis (major depressive disorder, panic disorder, or dysthymia), difficult interpersonal relationships, associated pain, high hopelessness, and depressive and anxiety symptoms. Although suicidal thoughts are frequent in cancer patients at different stages of disease, most are transitory. Risk factors for suicidal ideation have been identified, such as depression, hopelessness, uncontrolled pain, and difficult interpersonal relationships. Further assessment is necessary to identify those at higher risk of attempting suicide, and underlying psychiatric disorders should be vigorously treated

Characterization of virus-like particles associated with the human faecal and caecal microbiota

This work represents an investigation into the presence, abundance and diversity of virus-like particles (VLPs) associated with human faecal and caecal samples. Various methodologies for the recovery of VLPs from faeces were tested and optimized, including successful down-stream processing of such samples for the purpose of an in-depth electron microscopic analysis, pulsed-field gel electrophoresis and efficient DNA recovery. The applicability of the developed VLP characterization method beyond the use of faecal samples was then verified using samples obtained from human caecal fluid

Viral population estimation using pyrosequencing

The diversity of virus populations within single infected hosts presents a major difficulty for the natural immune response as well as for vaccine design and antiviral drug therapy. Recently developed pyrophosphate based sequencing technologies (pyrosequencing) can be used for quantifying this diversity by ultra-deep sequencing of virus samples. We present computational methods for the analysis of such sequence data and apply these techniques to pyrosequencing data obtained from HIV populations within patients harboring drug resistant virus strains. Our main result is the estimation of the population structure of the sample from the pyrosequencing reads. This inference is based on a statistical approach to error correction, followed by a combinatorial algorithm for constructing a minimal set of haplotypes that explain the data. Using this set of explaining haplotypes, we apply a statistical model to infer the frequencies of the haplotypes in the population via an EM algorithm. We demonstrate that pyrosequencing reads allow for effective population reconstruction by extensive simulations and by comparison to 165 sequences obtained directly from clonal sequencing of four independent, diverse HIV populations. Thus, pyrosequencing can be used for cost-effective estimation of the structure of virus populations, promising new insights into viral evolutionary dynamics and disease control strategies.Comment: 23 pages, 13 figure

Human oral viruses are personal, persistent and gender-consistent.

Viruses are the most abundant members of the human oral microbiome, yet relatively little is known about their biodiversity in humans. To improve our understanding of the DNA viruses that inhabit the human oral cavity, we examined saliva from a cohort of eight unrelated subjects over a 60-day period. Each subject was examined at 11 time points to characterize longitudinal differences in human oral viruses. Our primary goals were to determine whether oral viruses were specific to individuals and whether viral genotypes persisted over time. We found a subset of homologous viral genotypes across all subjects and time points studied, suggesting that certain genotypes may be ubiquitous among healthy human subjects. We also found significant associations between viral genotypes and individual subjects, indicating that viruses are a highly personalized feature of the healthy human oral microbiome. Many of these oral viruses were not transient members of the oral ecosystem, as demonstrated by the persistence of certain viruses throughout the entire 60-day study period. As has previously been demonstrated for bacteria and fungi, membership in the oral viral community was significantly associated with the sex of each subject. Similar characteristics of personalized, sex-specific microflora could not be identified for oral bacterial communities based on 16S rRNA. Our findings that many viruses are stable and individual-specific members of the oral ecosystem suggest that viruses have an important role in the human oral ecosystem

Survival Data and Predictors of Functional Outcome an Average of 15 Years after the Fontan Procedure: The Pediatric Heart Network Fontan Cohort

ObjectiveMulticenter longitudinal outcome data for Fontan patients surviving into adulthood are lacking. The aim of this study was to better understand contemporary outcomes in Fontan survivors by collecting follow‐up data in a previously well‐characterized cohort.DesignBaseline data from the Fontan Cross‐Sectional Study (Fontan 1) were previously obtained in 546 Fontan survivors aged 11.9 ± 3.4 years. We assessed current transplant‐free survival status in all subjects 6.8 ± 0.4 years after the Fontan 1 study. Anatomic, clinical, and surgical data were collected along with socioeconomic status and access to health care.ResultsThirty subjects (5%) died or underwent transplantation since Fontan 1. Subjects with both an elevated (>21 pg/mL) brain natriuretic peptide and a low Child Health Questionnaire physical summary score (<44) measured at Fontan 1 were significantly more likely to die or undergo transplant than the remainder, with a hazard ratio of 6.2 (2.9–13.5). Among 516 Fontan survivors, 427 (83%) enrolled in this follow‐up study (Fontan 2) at 18.4 ± 3.4 years of age. Although mean scores on functional health status questionnaires were lower than the general population, individual scores were within the normal range in 78% and 88% of subjects for the Child Health Questionnaire physical and psychosocial summary score, and 97% and 91% for the SF‐36 physical and mental aggregate score, respectively. Since Fontan surgery, 119 (28%) had additional cardiac surgery; 55% of these (n = 66) in the interim between Fontan 1 and Fontan 2. A catheter intervention occurred in 242 (57%); 32% of these (n = 78) after Fontan 1. Arrhythmia requiring treatment developed in 118 (28%) after Fontan surgery; 58% of these (n = 68) since Fontan 1.ConclusionsWe found 95% interim transplant‐free survival for Fontan survivors over an average of 7 years of follow‐up. Continued longitudinal investigation into adulthood is necessary to better understand the determinants of long‐term outcomes and to improve functional health status.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110738/1/chd12193.pd

De novo mutations in histone modifying genes in congenital heart disease

Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births1. Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. By analysis of exome sequencing of parent-offspring trios, we compared the incidence of de novo mutations in 362 severe CHD cases and 264 controls. CHD cases showed a significant excess of protein-altering de novo mutations in genes expressed in the developing heart, with an odds ratio of 7.5 for damaging mutations. Similar odds ratios were seen across major classes of severe CHD. We found a marked excess of de novo mutations in genes involved in production, removal or reading of H3K4 methylation (H3K4me), or ubiquitination of H2BK120, which is required for H3K4 methylation2–4. There were also two de novo mutations in SMAD2; SMAD2 signaling in the embryonic left-right organizer induces demethylation of H3K27me5. H3K4me and H3K27me mark `poised' promoters and enhancers that regulate expression of key developmental genes6. These findings implicate de novo point mutations in several hundred genes that collectively contribute to ~10% of severe CHD

The broad spectrum of unbearable suffering in end of life cancer studied in dutch primary care

<p>Abstract</p> <p>Background</p> <p>Unbearable suffering most frequently is reported in end-of-life cancer patients in primary care. However, research seldom addresses unbearable suffering. The aim of this study was to comprehensively investigate the various aspects of unbearable suffering in end-of-life cancer patients cared for in primary care.</p> <p>Methods</p> <p>Forty four general practitioners recruited end-of-life cancer patients with an estimated life expectancy of half a year or shorter. The inclusion period was three years, follow-up lasted one additional year. Practices were monitored bimonthly to identify new cases. Unbearable aspects in five domains and overall unbearable suffering were quantitatively assessed (5-point scale) through patient interviews every two months with a comprehensive instrument. Scores of 4 (serious) or 5 (hardly can be worse) were defined unbearable. The last interviews before death were analyzed. Sources providing strength to bear suffering were identified through additional open-ended questions.</p> <p>Results</p> <p>Seventy six out of 148 patients (51%) requested to participate consented; the attrition rate was 8%, while 8% were alive at the end of follow-up. Sixty four patients were followed up until death; in 60 patients interviews were complete. Overall unbearable suffering occurred in 28%. A mean of 18 unbearable aspects was present in patients with serious (score 4) overall unbearable suffering. Overall, half of the unbearable aspects involved the domain of traditional medical symptoms. The most frequent unbearable aspects were weakness, general discomfort, tiredness, pain, loss of appetite and not sleeping well (25%-57%). The other half of the unbearable aspects involved the domains of function, personhood, environment, and nature and prognosis of disease. The most frequent unbearable aspects were impaired activities, feeling dependent, help needed with housekeeping, not being able to do important things, trouble accepting the situation, being bedridden and loss of control (27%-55%). The combination of love and support was the most frequent source (67%) providing strength to bear suffering.</p> <p>Conclusions</p> <p>Overall unbearable suffering occurred in one in every four end-of-life cancer patients. Half of the unbearable aspects involved medical symptoms, the other half concerned psychological, social and existential dimensions. Physicians need to comprehensively assess suffering and provide psychosocial interventions alongside physical symptom management.</p

Novel phages of healthy skin metaviromes from South Africa

Recent skin metagenomic studies have investigated the harbored viral diversity and its possible influence on healthy skin microbial populations, and tried to establish global patterns of skin-phage evolution. However, the detail associated with the phages that potentially play a role in skin health has not been investigated. While skin metagenome and -metavirome studies have indicated that the skin virome is highly site specific and shows marked interpersonal variation, they have not assessed the presence/absence of individual phages. Here, we took a semi-culture independent approach (metaviromic) to better understand the composition of phage communities on skin from South African study participants. Our data set adds over 130 new phage species of the skin to existing databases. We demonstrated that identical phages were present on different individuals and in different body sites, and we conducted a detailed analysis of the structural organization of these phages. We further found that a bacteriophage related to the Staphylococcus capitis phage Stb20 may be a common skin commensal virus potentially regulating its host and its activities on the ski

Viruses in extreme environments

The original publication is available at www.springerlink.comInternational audienceThe tolerance limits of extremophiles in term of temperature, pH, salinity, desiccation, hydrostatic pressure, radiation, anaerobiosis far exceed what can support non-extremophilic organisms. Like all other organisms, extremophiles serve as hosts for viral replication. Many lines of evidence suggest that viruses could no more be regarded as simple infectious ‘‘fragments of life'' but on the contrary as one of the major components of the biosphere. The exploration of niches with seemingly harsh life conditions as hypersaline and soda lakes, Sahara desert, polar environments or hot acid springs and deep sea hydrothermal vents, permitted to track successfully the presence of viruses. Substantial populations of double-stranded DNA virus that can reach 109 particles per milliliter were recorded. All these viral communities, with genome size ranging from 14 kb to 80 kb, seem to be genetically distinct, suggesting specific niche adaptation. Nevertheless, at this stage of the knowledge, very little is known of their origin, activity, or importance to the in situ microbial dynamics. The continuous attempts to isolate and to study viruses that thrive in extreme environments will be needed to address such questions. However, this topic appears to open a new window on an unexplored part of the viral world

Plant Virus Biodiversity and Ecology

The Plant Virus Biodiversity and Ecology (PVBE) project has been initiated to survey the biodiversity of viruses affecting vascular plants