Summary Background Surprisingly little is known about how skin scars affect patients' lives, though specialist clinical impressions suggest their impact is related to both their physical and ...psychosocial effects. Facial scars have been shown to cause high levels of anxiety and self-consciousness, but further work has been neglected. We aimed to explore the influence of skin scars on patients' quality of life (QoL) and identify potential implications for clinical practice. Methods We adopted a needs-based approach to QoL and conducted semi-structured interviews with scar patients at a specialist clinic. Transcribed data underwent interpretative phenomenological analysis to identify common themes in individuals' personal experiences. Results Thirty-four scar patients (24 women; aged 14–70 years, mean = 35.7 years, SD = 17.9 years) with a wide range of scar type, severity and onset were recruited. Five hundred and seventy-three statements were identified from interview transcripts relating to need impairment by skin scars. These were subsequently classified into 44 themes covering five main areas: physical comfort and functioning; acceptability to self and others; social functioning; confidence in the nature and management of the condition; emotional well-being. The majority of respondents were unhappy with their scar's appearance due to their perceived stigma and psychological associations, and thus adopted different coping behaviours to hide or compensate for them. Often this made them unsociable and interfered with their communication skills, personal relationships, work life and leisure activities. Concerns about the diagnosis and persistent nature of scars were common, whilst unempathic management by general physicians and frustrations of current treatment compounded distress. Conclusions There are five main areas of impact on the needs of scar patients that should be addressed in their management, which are greater and more complex than previously considered. Support services should be made available, along with clinician and public education to improve management and help reduce patient distress. A need for a carefully designed measure of scar-related QoL is also indicated, for use in clinical settings and trials.
Human telomerase RNA (hTR) contains several guanine tracts at its 5'-end that can form a G4-quadruplex structure. Previous evidence suggests that a G4-quadruplex within this region disrupts the ...formation of an important structure within hTR known as the P1 helix, a critical element in defining the template boundary for reverse transcription. RNA associated with AU-rich element (RHAU) is an RNA helicase that has specificity for DNA and RNA G4-quadruplexes. Two recent studies identify a specific interaction between hTR and RHAU. Herein, we confirm this interaction and identify the minimally interacting RNA fragments. We demonstrate the existence of multiple quadruplex structures within the 5' region of hTR and find that these regions parallel the minimal sequences capable of RHAU interaction. We confirm the importance of the RHAU-specific motif in the interaction with hTR and demonstrate that the helicase activity of RHAU is sufficient to unwind the quadruplex and promote an interaction with 25 internal nucleotides to form a stable P1 helix. Furthermore, we have found that a 5'-terminal quadruplex persists following P1 helix formation that retains affinity for RHAU. Finally, we have investigated the functional implications of this interaction and demonstrated a reduction in average telomere length following RHAU knockdown by small interfering RNA (siRNA).
Background: Patient reported outcome measures used in studies of psoriatic arthritis (PsA) have been found to be inadequate for determining the impact of the disease from the patient’s perspective. ...Objective: To produce the PsAQoL, a PsA-specific quality of life (QoL) instrument, employing the needs based model of QoL that would be relevant and acceptable to respondents, valid, and reliable. Methods: Content was derived from qualitative interviews conducted with patients with PsA. Face and content validity were assessed by field test interviews with a new sample of patients with PsA. A postal survey was conducted to improve the scaling properties of the new measure. Finally, a test-retest postal survey was used to identify the final measure and to test its scaling properties, reliability, internal consistency, and validity. Results: Analysis of the qualitative interview transcripts identified a 51 item questionnaire. Field test interviews confirmed the acceptability and relevance of the measure. Analysis of data from the first postal survey (n = 94) reduced the questionnaire to 35 items. Rasch analysis of data from the test-retest survey (n = 286) identified a 20 item version of the PsAQoL with good item fit. This version had excellent internal consistency (α = 0.91), test-retest reliability (0.89), and validity. Conclusions: The PsAQoL is a valuable tool for assessing the impact of interventions for PsA in clinical studies and trials. It is well accepted by patients, taking about three minutes to complete, is easy to administer, and has excellent scaling and psychometric properties.
The field of cyber security is faced with ever‐expanding amounts of data and a constant barrage of cyber attacks. Within this space, we have designed BubbleNet as a cyber security dashboard to help ...network analysts identify and summarize patterns within the data. This design study faced a range of interesting constraints from limited time with various expert users and working with users beyond the network analyst, such as network managers. To overcome these constraints, the design study employed a user‐centered design process and a variety of methods to incorporate user feedback throughout the design of BubbleNet. This approach resulted in a successfully evaluated dashboard with users and further deployments of these ideas in both research and operational environments. By explaining these methods and the process, it can benefit future visualization designers to help overcome similar challenges in cyber security or alternative domains.
Epigenetic alterations have been increasingly implicated in oncogenesis. Analysis of Drosophila mutants suggests that Polycomb and SWI/SNF complexes can serve antagonistic developmental roles. ...However, the relevance of this relationship to human disease is unclear. Here, we have investigated functional relationships between these epigenetic regulators in oncogenic transformation. Mechanistically, we show that loss of the SNF5 tumor suppressor leads to elevated expression of the Polycomb gene EZH2 and that Polycomb targets are broadly H3K27-trimethylated and repressed in SNF5-deficient fibroblasts and cancers. Further, we show antagonism between SNF5 and EZH2 in the regulation of stem cell-associated programs and that Snf5 loss activates those programs. Finally, using conditional mouse models, we show that inactivation of Ezh2 blocks tumor formation driven by Snf5 loss.
► The SNF5 tumor suppressor and EZH2 antagonistically regulate gene expression ► Polycomb-regulated genes are broadly repressed in SNF5-deficient tumors ► SNF5 and EZH2 modulate stem cell-associated programs, and SNF5 loss activates them ► Ezh2 is essential for tumor formation caused by Snf5 inactivation in vivo
Background: Although disease-specific health status measures are available for ankylosing spondylitis (AS), no instrument exists for assessing quality of life (QoL) in the condition. Objective: To ...produce an AS-specific QoL measure that would be relevant and acceptable to respondents, valid, and reliable. Methods: The ASQoL employs the needs-based model of QoL and was developed in parallel in the UK and the Netherlands (NL). Content was derived from interviews with patients in each country. Face and content validity were assessed through patient field test interviews (UK and NL). A postal survey in the UK produced a more efficient version of the ASQoL, which was tested for scaling properties, reliability, internal consistency, and validity in a further postal survey in each country. Results: A 41 item questionnaire was derived from interview transcripts. Field testing interviews confirmed acceptability. Rasch analysis of data from the first survey (n=121) produced a 26 item questionnaire. Rasch analysis of data from the second survey (UK: n=164; NL: n=154) showed some item misfit, but showed that items formed a hierarchical order and were stable over time. Problematic items were removed giving an 18 item scale. Both language versions had excellent internal consistency (α=0.89–0.91), test-retest reliability (rs=0.92 UK and rs=0.91 NL), and validity. Conclusions: The ASQoL provides a valuable tool for assessing the impact of interventions for AS and for evaluating models of service delivery. It is well accepted by patients, taking about four minutes to complete, and has excellent scaling and psychometric properties.
Oesophageal cancer incidence is increasing and survival rates remain extremely poor. Natural agents with potential for chemoprevention include the phytochemical curcumin (diferuloylmethane). We have ...examined the effects of curcumin on a panel of oesophageal cancer cell lines.
MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assays and propidium iodide staining were used to assess viability and DNA content, respectively. Mitotic catastrophe (MC), apoptosis and autophagy were defined by both morphological criteria and markers such as MPM-2, caspase 3 cleavage and monodansylcadaverine (MDC) staining. Cyclin B and poly-ubiquitinated proteins were assessed by western blotting.
Curcumin treatment reduces viability of all cell lines within 24 h of treatment in a 5-50 muM range. Cytotoxicity is associated with accumulation in G2/M cell-cycle phases and distinct chromatin morphology, consistent with MC. Caspase-3 activation was detected in two out of four cell lines, but was a minor event. The addition of a caspase inhibitor zVAD had a marginal or no effect on cell viability, indicating predominance of a non-apoptotic form of cell death. In two cell lines, features of both MC and autophagy were apparent. Curcumin-responsive cells were found to accumulate poly-ubiquitinated proteins and cyclin B, consistent with a disturbance of the ubiquitin-proteasome system. This effect on a key cell-cycle checkpoint regulator may be responsible for the mitotic disturbances and consequent cytotoxicity of this drug.
Curcumin can induce cell death by a mechanism that is not reliant on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of oesophageal cancer.
To examine measures of social support and associations with neurobehavioral, psychiatric, and cognitive symptoms in Veterans who underwent the Veterans Health Administration's Traumatic Brain Injury ...(TBI) Screening and Evaluation Program.
Nationally representative sample of U.S. Veterans enrolled in the Veterans Affairs Million Veteran Program.
Veterans (N = 9,837) were classified into the following three diagnostic groups based on results from the TBI Screening and Evaluation Program: (1) negative TBI screen (Screen–; n = 6,523), (2) positive TBI screen but no TBI diagnosis (Screen+/TBI-; n = 1,308), or (3) positive TBI screen and TBI diagnosis (Screen+/TBI+; n = 2,006).
Epidemiological cross-sectional study.
Medical Outcomes Study Social Support Survey Instrument (MOS-SSSI), with subscales representing emotional, tangible, and affectionate support and positive social interaction; Neurobehavioral Symptom Inventory (NSI); PTSD Checklist (PCL); Patient Health Questionnaire-4 (PHQ-4); and Medical Outcomes Study Cognitive Functioning-Revised Scale (MOS-Cog-R).
ANCOVAs showed significant associations between diagnostic group and all aspects of social support. Pairwise comparisons revealed that Veterans in the two Screen+ groups (Screen+/TBI+ and Screen+/TBI-) reported comparable levels of social support, but that both Screen+ groups reported significantly lower levels of social support compared to the Screen– group. Among the Screen+ groups, adjusted linear regression models controlling for age, sex, and race/ethnicity showed significant associations between social support indices and all symptom measures, such that lower levels of social support were associated with more severe neurobehavioral and psychiatric symptoms and worse cognitive functioning. Finally, mediation analyses showed that psychiatric symptoms mediated the association between TBI screen group and social support.
Our results are clinically informative and suggest (1) that the relationship between TBI screen status and social support is influenced by psychiatric symptoms and (2) that implementing distress reduction techniques before social support interventions may be most beneficial for Veterans screening positive for TBI.
•Lower levels of social support were reported by Veterans screening positive for TBI.•Social support was associated with more severe symptom distress.•Social support was also associated with worse subjective cognitive functioning.•Psychiatric symptoms mediated the association between TBI group and social support.
Objectives/Hypothesis
We investigated speech acoustics and self‐reported vocal symptoms in mask‐wearing healthcare professionals. We hypothesized that there would be an attenuation of spectral ...energies and increase in vocal effort during masked speech compared to unmasked speech.
Study Design
Within and between subject quasi‐experimental design.
Methods
We prospectively enrolled 21 healthcare providers (13 cisgender female, 8 cisgender male; M = 32.9 years; SD = 7.9 years) and assessed acoustics and perceptual measures with and without a face mask in place. Measurements included: 1) acoustic Vowel Articulation Index (VAI); 2) cepstral and spectral acoustic measures; 3) traditional vocal measures (e.g., fundamental frequency, intensity); 4) relative fundamental frequency (RFF); and 5) self‐reported ratings of vocal effort and dyspnea.
Results
During masked speech, there was a significant reduction in VAI, high‐frequency information (>4 kHz), and RFF offset 10, as well as a significant increase in cepstral peak prominence and perceived vocal effort. Further analysis showed that high‐frequency attenuation was more pronounced when wearing an N95 mask compared to a simple mask.
Conclusions
Face masks pose an additional barrier to effective communication that primarily impacts spectral characteristics, vowel space measures, and vocal effort. Future work should evaluate how long‐term mask use impacts vocal health and may contribute to vocal problems.
Level of Evidence
3 Laryngoscope, 132:391–397, 2022
In herds with typical moderate to low within-herd prevalence, testing for Mycobacterium avium ssp. paratuberculosis (MAP), the infectious agent of Johne's disease, will be more cost-effective if ...individual fecal samples are cultured in composite pools. However, sensitivity to classify a pool containing 1 or more positive individual samples as positive may depend on pool size and number of individual positive samples within a pool. Fecal samples collected from 994 dairy cows sampled at slaughter were cultured to detect MAP. Culturing was done both individually and as composite pooled samples using the TREK ESP Culture System II broth medium (Thermo Fisher Scientific, Trek Diagnostic Systems Inc., Cleveland, OH). Composite samples consisted of pools containing feces from 3, 5, 8, 10, or 15 cows. The number of individual fecal culture-positive cows within each pool ranged from 0 to 4. Culture of individual fecal samples detected MAP in 36 (3.6%) of the 994 cows. Individual samples that were detected within the first 50 d by TREK ESP Culture System II were more likely to lead to a positive pool result. In total, 840 pooled fecal samples were examined for presence of MAP, and of those, 272 pools actually contained feces from fecal culture-positive cows. The crude sensitivity (proportion of pools that contained at least 1 fecal-positive cow that tested positive) for pools of 3, 5, 8, 10, and 15 was 47, 67, 44, 59, and 39%, respectively. Across pools, an increase of the number of fecal culture-positive samples from 1 to 2 enhanced overall crude sensitivity from 44 to 71%. However, sensitivity did not further increase for pools with 3 or 4 fecal culture-positive samples (63 and 60%, respectively). Additionally, a simulation analysis assessing probability of pooled fecal samples being positive in herds of 50 and 100 cows was conducted. The simulation assumed that 1, 2, or 5 cows per herd were MAP fecal culture-positive and that pools of 5 and 10 were used. This low-prevalence herd simulation indicated that weighted mean herd probabilities of detecting a positive herd ranged between 52 and 99.3%, with the lowest probability for pools of 10 with 1 positive cow in the herd and the highest probability for pools of 5 with 5 positive cows in the herd. However, overall, pools of 5 and 10 had similar diagnostic capabilities, enabling cost savings by utilizing pools of 10.
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