Caenorhabditis elegans orthologs of human genes differentially expressed with age are enriched for determinants of longevity

We report a systematic RNAi longevity screen of 82 Caenorhabditis elegans genes selected based on orthology to human genes differentially expressed with age. We find substantial enrichment in genes for which knockdown increased lifespan. This enrichment is markedly higher than published genomewide longevity screens in C. elegans and similar to screens that preselected candidates based on longevity-correlated metrics (e.g., stress resistance). Of the 50 genes that affected lifespan, 46 were previously unreported. The five genes with the greatest impact on lifespan (>20% extension) encode the enzyme kynureninase (kynu-1), a neuronal leucine-rich repeat protein (iglr-1), a tetraspanin (tsp-3), a regulator of calcineurin (rcan-1), and a voltage-gated calcium channel subunit (unc-36). Knockdown of each gene extended healthspan without impairing reproduction. kynu-1(RNAi) alone delayed pathology in C. elegans models of Alzheimer's disease and Huntington's disease. Each gene displayed a distinct pattern of interaction with known aging pathways. In the context of published work, kynu-1, tsp-3, and rcan-1 are of particular interest for immediate follow-up. kynu-1 is an understudied member of the kynurenine metabolic pathway with a mechanistically distinct impact on lifespan. Our data suggest that tsp-3 is a novel modulator of hypoxic signaling and rcan-1 is a context-specific calcineurin regulator. Our results validate C. elegans as a comparative tool for prioritizing human candidate aging genes, confirm age-associated gene expression data as valuable source of novel longevity determinants, and prioritize select genes for mechanistic follow-up

Recovery from Posttraumatic Stress Symptoms: A Qualitative Study of Attributions in Survivors of War

This study was funded by a grant from the European Commission, contract number INCO-CT-2004-50917

Mechanisms of Psychological Distress following War in the Former Yugoslavia: The Role of Interpersonal Sensitivity

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This study was funded by a grant from the European Commission, contract number INCO-CT-2004-509176. AN was supported by a Clinical Early Career Research Fellowship (113295) and a Project Grant (104288

Understanding psychiatric institutionalization: a conceptual review

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Effects among healthy subjects of the duration of regularly practicing a guided imagery program

BACKGROUND: We examined a large number of healthy adults in the general community who had individually participated in a guided imagery (GI) program daily and for various durations, to examine the psychophysiological effects of a GI program within a healthy group. METHODS: We studied 176 subjects who had participated in sessions that were part of a guided imagery program, and who had practiced GI at home for 20 minutes once daily in a quiet place after mastering GI in the group sessions. The average duration of GI practiced at home was 6.88 ± 14.06 months (n = 138, range: 0 to 72). The Multiple Mood Scale (MMS), Betts (1909) Shortened Questionnaire on Mental Imagery (QMI), and a visual analog scale (VAS) of imagery vividness, salivary cortisol (C(S)) levels, general stress and general health were used in the sessions. RESULTS: We examined the relationship between the duration of daily GI practiced at home and MMS, QMI, C(S), general health, and general stress at baseline. The subjects who had practiced GI at home longer had lower negative mood scores at baseline and lower severity of stress, and higher positive mood at baseline (both at a session and at home), general health, and QMI scores at baseline. The MMS change during a session and the duration of daily GI practiced at home were not correlated. Repeated-measures analysis of covariance showed that the duration of daily GI practiced as the covariate was not associated with changes in the three C(S )levels. CONCLUSION: Although regularly practicing a GI program daily for 20 min did not affect the C(S )level or mood during a GI session for several hours, it kept a good condition of the general mental, physical well-being and their overall stress of the practitioners as they had practiced it for long duration. We postulate that subjects who have the high ability of imaging vividness showed the better mood, health status and less stress than those subjects who have the low ability of it did. The ability of image vividness of the long-term regular practitioners of GI was higher than its short-term or inexperienced practitioners, which allowed practitioners to produce more comfortable imagery. Consequently, the longer the duration that they had practiced GI program once a day regularly, the lower scores of their stress were and the higher scores of their health were. We suggest that the regular daily practice of a GI program might be connected to less stress and better health

Vitamin D Supplementation and Prevention of Type 2 Diabetes

BACKGROUND Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the risk of diabetes is unknown. METHODS We randomly assigned adults who met at least two of three glycemic criteria for prediabetes (fasting plasma glucose level, 100 to 125 mg per deciliter; plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter; and glycated hemoglobin level, 5.7 to 6.4%) and no diagnostic criteria for diabetes to receive 4000 IU per day of vitamin D3 or placebo, regardless of the baseline serum 25-hydroxyvitamin D level. The primary outcome in this time-to-event analysis was new-onset diabetes, and the trial design was event-driven, with a target number of diabetes events of 508. RESULTS A total of 2423 participants underwent randomization (1211 to the vitamin D group and 1212 to the placebo group). By month 24, the mean serum 25-hydroxyvitamin D level in the vitamin D group was 54.3 ng per milliliter (from 27.7 ng per milliliter at baseline), as compared with 28.8 ng per milliliter in the placebo group (from 28.2 ng per milliliter at baseline). After a median follow-up of 2.5 years, the primary outcome of diabetes occurred in 293 participants in the vitamin D group and 323 in the placebo group (9.39 and 10.66 events per 100 person-years, respectively). The hazard ratio for vitamin D as compared with placebo was 0.88 (95% confidence interval, 0.75 to 1.04; P = 0.12). The incidence of adverse events did not differ significantly between the two groups. CONCLUSIONS Among persons at high risk for type 2 diabetes not selected for vitamin D insufficiency, vitamin D3 supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; D2d ClinicalTrials.gov number, NCT01942694.

The contribution of embarrassment to phobic dental anxiety: a qualitative research study

BACKGROUND: Embarrassment is emphasized, yet scantily described as a factor in extreme dental anxiety or phobia. Present study aimed to describe details of social aspects of anxiety in dental situations, especially focusing on embarrassment phenomena. METHODS: Subjects (Ss) were consecutive specialist clinic patients, 16 men, 14 women, 20–65 yr, who avoided treatment mean 12.7 yr due to anxiety. Electronic patient records and transcribed initial assessment and exit interviews were analyzed using QSR"N4" software to aid in exploring contexts related to social aspects of dental anxiety and embarrassment phenomena. Qualitative findings were co-validated with tests of association between embarrassment intensity ratings, years of treatment avoidance, and mouth-hiding behavioral ratings. RESULTS: Embarrassment was a complaint in all but three cases. Chief complaints in the sample: 30% had fear of pain; 47% cited powerlessness in relation to dental social situations, some specific to embarrassment and 23% named co-morbid psychosocial dysfunction due to effects of sexual abuse, general anxiety, gagging, fainting or panic attacks. Intense embarrassment was manifested in both clinical and non-clinical situations due to poor dental status or perceived neglect, often (n = 9) with fear of negative social evaluation as chief complaint. These nine cases were qualitatively different from other cases with chief complaints of social powerlessness associated with conditioned distrust of dentists and their negative behaviors. The majority of embarrassed Ss to some degree inhibited smiling/laughing by hiding with lips, hands or changed head position. Secrecy, taboo-thinking, and mouth-hiding were associated with intense embarrassment. Especially after many years of avoidance, embarrassment phenomena lead to feelings of self-punishment, poor self-image/esteem and in some cases personality changes in a vicious circle of anxiety and avoidance. Embarrassment intensity ratings were positively correlated with years of avoidance and degree of mouth-hiding behaviors. CONCLUSIONS: Embarrassment is a complex dental anxiety manifestation with qualitative differences by complaint characteristics and perceived intensity. Some cases exhibited manifestations similar to psychiatric criteria for social anxiety disorder as chief complaint, while most manifested embarrassment as a side effect

Vitamin D Supplementation and Prevention of Type 2 Diabetes

BACKGROUND Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the risk of diabetes is unknown. METHODS We randomly assigned adults who met at least two of three glycemic criteria for prediabetes (fasting plasma glucose level, 100 to 125 mg per deciliter; plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter; and glycated hemoglobin level, 5.7 to 6.4%) and no diagnostic criteria for diabetes to receive 4000 IU per day of vitamin D3 or placebo, regardless of the baseline serum 25-hydroxyvitamin D level. The primary outcome in this time-to-event analysis was new-onset diabetes, and the trial design was event-driven, with a target number of diabetes events of 508. RESULTS A total of 2423 participants underwent randomization (1211 to the vitamin D group and 1212 to the placebo group). By month 24, the mean serum 25-hydroxyvitamin D level in the vitamin D group was 54.3 ng per milliliter (from 27.7 ng per milliliter at baseline), as compared with 28.8 ng per milliliter in the placebo group (from 28.2 ng per milliliter at baseline). After a median follow-up of 2.5 years, the primary outcome of diabetes occurred in 293 participants in the vitamin D group and 323 in the placebo group (9.39 and 10.66 events per 100 person-years, respectively). The hazard ratio for vitamin D as compared with placebo was 0.88 (95% confidence interval, 0.75 to 1.04; P = 0.12). The incidence of adverse events did not differ significantly between the two groups. CONCLUSIONS Among persons at high risk for type 2 diabetes not selected for vitamin D insufficiency, vitamin D3 supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; D2d ClinicalTrials.gov number, NCT01942694.

Childhood adversity, mental ill-health and aggressive behavior in an African orphanage: Changes in response to trauma-focused therapy and the implementation of a new instructional system

<p>Abstract</p> <p>Background</p> <p>The number of orphans in Sub-Saharan Africa is constantly rising. While it is known that family or community care is preferable over institutional care of African orphans, little is known about the quality of care in orphanages and possibilities of improvement.</p> <p>Study 1</p> <p>Methods</p> <p>Exposure to traumatic stress, experiences of violence in the home, school and orphanage, as well as mental ill-health and aggression of 38 children (mean age of <it>M </it>= 8.64 years) living in an orphanage in rural Tanzania were assessed at two time points. The severity of post-traumatic stress disorder symptoms (PTSD), depressive symptoms, and internalizing and externalizing problems were used as indicators of mental ill-health.</p> <p>Results</p> <p>Violence experienced in the orphanage correlated more strongly with all indicators of mental ill-health than violence in the former home, school or neighborhood at time point 1. Additionally, violence experienced in the orphanage had a positive relationship with the aggressive behavior of the children at time point 2.</p> <p>Study 2</p> <p>Methods</p> <p>With the help of the pre-post assessment of Study 1, the implementation of a new instructional system and psychotherapeutic treatment (KIDNET) for trauma-related illness were evaluated.</p> <p>Results</p> <p>In response to both, a change in the instructional system and psychotherapeutic treatment of PTSD, a massive decline in experienced violence and in the severity of PTSD-symptoms was found, whereas depressive symptoms and internalizing and externalizing problems exhibited little change.</p> <p>Conclusions</p> <p>These studies show that violence, especially in the orphanage, can severely contribute to mental ill-health in orphans and that mental health can be improved by implementing a new instructional system and psychotherapeutic treatment in an orphanage. Moreover, the results indicate that the experience of violence in an orphanage also plays a crucial role in aggressive behavior of the orphans.</p

Writing Toward Readers\u27 Better Health: A Case Study Examining the Development of Online Health Information

Each year, more people search the Internet for health information. Through a case study conducted at a prominent health information company, I will show that technical communicators are well suited to contribute to the development of online health information. Like other technical communicators, online health information developers must make rhetorical choices based on audience needs, function within specific social contexts, and work through challenges of writing, editing, and project management