Talin-KANK1 interaction controls the recruitment of cortical microtubule stabilizing complexes to focal adhesions

The cross-talk between dynamic microtubules and integrin-based adhesions to the extracellular matrix plays a crucial role in cell polarity and migration. Microtubules regulate the turnover of adhesion sites, and, in turn, focal adhesions promote cortical microtubule capture and stabilization in their vicinity, but the underlying mechanism is unknown. Here, we show that cortical microtubule stabilization sites containing CLASPs, KIF21A, LL5 beta and liprins are recruited to focal adhesions by the adaptor protein KANK1, which directly interacts with the major adhesion component, talin. Structural studies showed that the conserved KN domain in KANK1 binds to the talin rod domain R7. Perturbation of this interaction, including a single point mutation in talin, which disrupts KANK1 binding but not the talin function in adhesion, abrogates the association of microtubule- stabilizing complexes with focal adhesions. We propose that the talin-KANK1 interaction links the two macromolecular assemblies that control cortical attachment of actin fibers and microtubules

Whole breast and regional nodal irradiation in prone versus supine position in left sided breast cancer

Background: Prone whole breast irradiation (WBI) leads to reduced heart and lung doses in breast cancer patients receiving adjuvant radiotherapy. In this feasibility trial, we investigated the prone position for whole breast + lymph node irradiation (WB + LNI). Methods: A new support device was developed for optimal target coverage, on which patients are positioned in a position resembling a phase from the crawl swimming technique (prone crawl position). Five left sided breast cancer patients were included and simulated in supine and prone position. For each patient, a treatment plan was made in prone and supine position for WB + LNI to the whole axilla and the unoperated part of the axilla. Patients served as their own controls for comparing dosimetry of target volumes and organs at risk (OAR) in prone versus in supine position. Results: Target volume coverage differed only slightly between prone and supine position. Doses were significantly reduced (P < 0.05) in prone position for ipsilateral lung (Dmean, D2, V5, V10, V20, V30), contralateral lung (Dmean, D2), contralateral breast (Dmean, D2 and for total axillary WB + LNI also V5), thyroid (Dmean, D2, V5, V10, V20, V30), oesophagus (Dmean and for partial axillary WB + LNI also D2 and V5), skin (D2 and for partial axillary WB + LNI V105 and V107). There were no significant differences for heart and humeral head doses. Conclusions: Prone crawl position in WB + LNI allows for good breast and nodal target coverage with better sparing of ipsilateral lung, thyroid, contralateral breast, contralateral lung and oesophagus when compared to supine position. There is no difference in heart and humeral head doses

Influence of Efforts of Employer and Employee on Return-to-Work Process and Outcomes

Background Research on disability and RTW outcome has led to significant advances in understanding these outcomes, however, limited studies focus on measuring the RTW process. After a prolonged period of sickness absence, the assessment of the RTW process by investigating RTW Effort Sufficiency (RTW-ES) is essential. However, little is known about factors influencing RTW-ES. Also, the correspondence in factors determining RTW-ES and RTW is unknown. The purpose of this study was to investigate 1) the strength and relevance of factors related to RTW-ES and RTW (no/partial RTW), and 2) the comparability of factors associated with RTW-ES and with RTW. Methods During 4 months, all assessments of RTW-ES and RTW (no/partial RTW) among employees applying for disability benefits after 2 years of sickness absence, performed by labor experts at 3 Dutch Social Insurance Institute locations, were investigated by means of a questionnaire. Results Questionnaires concerning 415 cases were available. Using multiple logistic regression analysis, the only factor related to RTW-ES is a good employer-employee relationship. Factors related to RTW (no/partial RTW) were found to be high education, no previous periods of complete disability and a good employer-employee relationship. Conclusions Different factors are relevant to RTW-ES and RTW, but the employer-employee relationship is relevant for both. Considering the importance of the assessment of RTW-ES after a prolonged period of sickness absence among employees who are not fully disabled, this knowledge is essential for the assessment of RTW-ES and the RTW process itself

Postherpetic Neuralgia: Role of Gabapentin and Other Treatment Modalities

Postherpetic neuralgia (PHN) is a chronic and painful condition that may occur after a herpes zoster infection. The frequency of PHN after untreated zoster varies widely. Age is the most important risk factor for development of PHN. The condition occurs in an estimated 50% of patients older than 50 years. The pain of PHN can be severe and debilitating and is frequently associated with allodynia. Although in most patients pain remits within the first year, it may persist for a lifetime. Tricyclic antidepressants (TCAs), topical agents, opioids, and gabapentin, a structural Γ-amino butyric acid (GABA) analogue, are the only agents that have demonstrated efficacy in randomized clinical trials for treatment of both the shooting and the burning form of pain associated with PHN. TCAs are among the most commonly used classes of agents for treating PHN and are effective in a significant proportion of patients. However, various adverse events can limit treatment. These side effects tend to be more acute in the elderly, the population most likely to suffer from PHN. Topical agents have led to mild to moderate improvement in patients with PHN but are usually ineffective as monotherapy for this condition. Until recently, carbamazepine was the only antiepileptic drug evaluated for the treatment of PHN. Over the past few years, however, gabapentin has received increasing attention as a useful treatment for neuropathic pain. Gabapentin lacks significant drug-drug interactions and has a favorable safety profile, which makes it particularly useful for treatment of PHN.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65597/1/j.1528-1157.1999.tb00933.x.pd

Identifying factors relevant in the assessment of return-to-work efforts in employees on long-term sickness absence due to chronic low back pain: a focus group study

ABSTRACT: BACKGROUND: Efforts undertaken during the return to work (RTW) process need to be sufficient to prevent unnecessary applications for disability benefits. The purpose of this study was to identify factors relevant to RTW Effort Sufficiency (RTW-ES) in cases of sick-listed employees with chronic low back pain (CLBP). METHODS: Using focus groups consisting of Labor Experts (LE's) working at the Dutch Social Insurance Institute, arguments and underlying grounds relevant to the assessment of RTW-ES were investigated. Factors were collected and categorized using the International Classification of Functioning, Disability and Health (ICF model). RESULTS: Two focus groups yielded 19 factors, of which 12 are categorized in the ICF model under activities (e.g. functional capacity) and in the personal (e.g. age, tenure) and environmental domain (e.g. employer-employee relationship). The remaining 7 factors are categorized under intervention, job accommodation and measures. CONCLUSIONS: This focus group study shows that 19 factors may be relevant to RTW-ES in sick-listed employees with CLBP. Providing these results to professionals assessing RTW-ES might contribute to a more transparent and systematic approach. Considering the importance of the quality of the RTW process, optimizing the RTW-ES assessment is essential

A Hypothesis-Testing Framework for Studies Investigating Ontogenetic Niche Shifts Using Stable Isotope Ratios

Ontogenetic niche shifts occur across diverse taxonomic groups, and can have critical implications for population dynamics, community structure, and ecosystem function. In this study, we provide a hypothesis-testing framework combining univariate and multivariate analyses to examine ontogenetic niche shifts using stable isotope ratios. This framework is based on three distinct ontogenetic niche shift scenarios, i.e., (1) no niche shift, (2) niche expansion/reduction, and (3) discrete niche shift between size classes. We developed criteria for identifying each scenario, as based on three important resource use characteristics, i.e., niche width, niche position, and niche overlap. We provide an empirical example for each ontogenetic niche shift scenario, illustrating differences in resource use characteristics among different organisms. The present framework provides a foundation for future studies on ontogenetic niche shifts, and also can be applied to examine resource variability among other population sub-groupings (e.g., by sex or phenotype)

A Hypothesis-Testing Framework for Studies Investigating Ontogenetic Niche Shifts Using Stable Isotope Ratios

Ontogenetic niche shifts occur across diverse taxonomic groups, and can have critical implications for population dynamics, community structure, and ecosystem function. In this study, we provide a hypothesis-testing framework combining univariate and multivariate analyses to examine ontogenetic niche shifts using stable isotope ratios. This framework is based on three distinct ontogenetic niche shift scenarios, i.e., (1) no niche shift, (2) niche expansion/reduction, and (3) discrete niche shift between size classes. We developed criteria for identifying each scenario, as based on three important resource use characteristics, i.e., niche width, niche position, and niche overlap. We provide an empirical example for each ontogenetic niche shift scenario, illustrating differences in resource use characteristics among different organisms. The present framework provides a foundation for future studies on ontogenetic niche shifts, and also can be applied to examine resource variability among other population sub-groupings (e.g., by sex or phenotype)

Perspectives on advance directives in Japanese society: A population-based questionnaire survey

BACKGROUND: In Japan, discussion concerning advance directives (ADs) has been on the rise during the past decade. ADs are one method proposed to facilitate the process of communication among patients, families and health care providers regarding the plan of care of a patient who is no longer capable of communicating. In this paper, we report the results of the first in-depth survey on the general population concerning the preferences and use of ADs in Japan. METHOD: A self-administered questionnaire was sent via mail to a stratified random sampling of 560 residents listed in the residential registry of one district of Tokyo, Japan (n = 165,567). Association between correlating factors and specific preferences toward ADs was assessed using contingency table bivariate analysis and multivariate regression model to estimate independent contribution. RESULTS: Of the 560 questionnaires sent out, a total of 425 participants took part in the survey yielding a response rate of 75.9 %. The results of the present study indicate that: 1) the most important components to be addressed are the specifics of medical treatment at the end of life stage and disclosure of diagnosis and prognosis; 2) the majority of participants found it suitable to express their directives by word to family and/or physician and not by written documentation; 3) there is no strong need for legal measures in setting up an AD; 4) it is permissible for family and physician to loosely interpret one's directives; 5) the most suitable proxy is considered to be a family member, relative, or spouse. Multivariate analysis found the following five factors as significantly associated with preferences: 1) awareness regarding living wills, 2) experience with the use of ADs, 3) preferences for end-of-life treatment, 4) preferences for information disclosure, and 5) intentions of creating a will. CONCLUSIONS: Written ADs might be useful in the Japanese setting when the individual either wishes: 1) to not provide a lot of leeway to surrogates and/or caregivers, and/or 2) to ensure his or her directives in the cases of terminal illness, brain death, and pain treatment, as well as regarding information disclosure

Might Depression, Psychosocial Adversity, and Limited Social Assets Explain Vulnerability to and Resistance against Violent Radicalisation?

BACKGROUND: This study tests whether depression, psychosocial adversity, and limited social assets offer protection or suggest vulnerability to the process of radicalisation. METHODS: A population sample of 608 men and women of Pakistani or Bangladeshi origin, of Muslim heritage, and aged 18-45 were recruited by quota sampling. Radicalisation was measured by 16 questions asking about sympathies for violent protest and terrorism. Cluster analysis of the 16 items generated three groups: most sympathetic (or most vulnerable), most condemning (most resistant), and a large intermediary group that acted as a reference group. Associations were calculated with depression (PHQ9), anxiety (GAD7), poor health, and psychosocial adversity (adverse life events, perceived discrimination, unemployment). We also investigated protective factors such as the number social contacts, social capital (trust, satisfaction, feeling safe), political engagement and religiosity. RESULTS: Those showing the most sympathy for violent protest and terrorism were more likely to report depression (PHQ9 score of 5 or more; RR = 5.43, 1.35 to 21.84) and to report religion to be important (less often said religion was fairly rather than very important; RR = 0.08, 0.01 to 0.48). Resistance to radicalisation measured by condemnation of violent protest and terrorism was associated with larger number of social contacts (per contact: RR = 1.52, 1.26 to 1.83), less social capital (RR = 0.63, 0.50 to 0.80), unavailability for work due to housekeeping or disability (RR = 8.81, 1.06 to 37.46), and not being born in the UK (RR = 0.22, 0.08 to 0.65). CONCLUSIONS: Vulnerability to radicalisation is characterised by depression but resistance to radicalisation shows a different profile of health and psychosocial variables. The paradoxical role of social capital warrants further investigation