Association of insulin resistance with the accumulation of saturated intramyocellular lipid: A comparison with other fat stores.

It has been shown using proton magnetic resonance spectroscopy (1 H MRS) that, in a group of females, whole-body insulin resistance was more closely related to accumulation of saturated intramyocellular lipid (IMCL) than to IMCL concentration alone. This has not been investigated in males. We investigated whether age- and body mass index-matched healthy males differ from the previously reported females in IMCL composition (measured as CH2 :CH3 ) and IMCL concentration (measured as CH3 ), and in their associations with insulin resistance. We ask whether saturated IMCL accumulation is more strongly associated with insulin resistance than other ectopic and adipose tissue lipid pools and remains a significant predictor when these other pools are taken into account. In this group of males, who had similar overall insulin sensitivity to the females, IMCL was similar between sexes. The males demonstrated similar and even stronger associations of IMCL with insulin resistance, supporting the idea that a marker reflecting the accumulation of saturated IMCL is more strongly associated with whole-body insulin resistance than IMCL concentration alone. However, this marker ceased to be a significant predictor of whole-body insulin resistance after consideration of other lipid pools, which implies that this measure carries no more information in practice than the other predictors we found, such as intrahepatic lipid and visceral adipose tissue. As the marker of saturated IMCL accumulation appears to be related to these two predictors and has a much smaller dynamic range, this finding does not rule out a role for it in the pathogenesis of insulin resistance.

Patient experience of telehealth appointments in head and neck cancer services during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic resulted in rapid changes to head and neck cancer (HNC) services. Multidisciplinary team (MDT) face-to-face appointments were converted to telehealth appointments (telephone and video-call) to reduce the risk of COVID-19 transmission. The literature exploring HNC patient experience of these appointment types is limited. AIMS: To explore patient experience of telehealth appointments at one UK centre during the COVID-19 pandemic, as well as the variables that may influence patient preference for virtual or face-to-face appointments. METHODS & PROCEDURES: A survey-based study design was used, with closed questions and open text options to capture the views of the participants. Quantitative data were analysed using descriptive statistics. Open text data was used to add depth to the findings. OUTCOMES & RESULTS: A total of 23 participant surveys were returned. Six categories were identified: Usability; Information receiving & giving; Satisfaction; Emotions and comfort; Rapport; and Travel time and cost. Overall, participants gave positive responses to each category and indicated that telehealth appointments met their needs. Areas for clinical consideration are highlighted. Variables such as age, travel distance from hospital site, fear of COVID-19 and information technology (IT) access did not appear to influence patient preference for appointment type. CONCLUSIONS & IMPLICATIONS: Going forward, telehealth may be considered for use in combination with face-to-face appointments in the HNC pathway. Areas for further development include a 'telehealth screening tool' that may help to identify those patients most appropriate for these appointment types, or who require support to access them. WHAT THIS PAPER ADDS: What is already known on this subject The COVID-19 pandemic resulted in major disruption to HNC centres across the world. Services adapted to meet the needs of patients with many implementing telehealth into pathways. Studies exploring telehealth in speech and language therapy (SLT) services with the HNC population indicate positive results. It is clear telehealth has a role in modern healthcare and should not be viewed as a temporary solution to the pandemic. It is, however, recognized that embedding telehealth into pathways is not straightforward and requires ongoing review and evaluation, which includes patient and clinician perceptions. What this study adds to the existing knowledge The service evaluation gives insight into HNC patient experience of telehealth appointments for MDT clinics (led by SLT, dietician and clinical nurse specialist) during the COVID-19 pandemic. Overall, patients report a positive experience of telehealth in the HNC pathway and are willing to accept this platform into their healthcare. Areas for clinical consideration are highlighted. What are the actual and clinical implications of this work? This findings of this service evaluation can be used to support the co-design of HNC pathways which embed telehealth as an option for patients. Areas that were important to the participants are highlighted; this includes the timing of telehealth appointments in the pathway, the need to meet the MDT face to face and the positive benefit of cost savings. The authors suggest a telehealth appointment screening tool as an area for future development.

Fibromyalgia status and depressive symptoms are linked to body mass index and physical performance in mid to late life.

Fibromyalgia (FM) is a chronic pain condition that is frequently accompanied by comorbid conditions, including depression. Depression is associated with reduced physical functioning and health, disproportionately affecting middle-aged and older adults with FM. This study examined associations between FM status and depressive symptoms with body mass index (BMI) and several physical performance indicators among middle-aged and older adults. Participants included 239 community-dwelling middle-aged and older adults with or without FM. Depressive symptoms were measured using the Beck Depression Inventory-II (BDI-II), BMI was objectively assessed, and physical performance was measured using the Fullerton Advanced Balance scale, 6-minute walk test, 30-second chair stand, and 8-foot up and go test. A path model using structural equation modeling yielded good fit and revealed that, compared to pain-free adult controls, participants with FM reported more depressive symptoms, which were in turn associated with reduced physical performance across all indicators except BMI, after adjusting for age and symptom severity. Findings suggest that individuals with FM demonstrate disproportionately higher depressive symptoms compared to non-FM controls, which may diminish physical performance after accounting for age and symptom severity. This study supports FM status and depressive symptoms as important considerations when evaluating the health and disability risk of aging adults.

Multimodal Biomarkers Quantify Recovery in Autoimmune Autonomic Ganglionopathy.

OBJECTIVE: The objective of this study was to evaluate patients with ganglionic acetylcholine receptor antibody (gAChR-Ab) positive autoimmune autonomic ganglionopathy using a multimodal testing protocol to characterize their full clinical phenotype and explore biomarkers to quantify immunotherapy response. METHODS: We conducted a cohort study of 13 individuals (7 women, 21-69 years of age) with autonomic failure and gAChR-Ab >100 pM identified between 2005 and 2019. From 2018, all patients were longitudinally assessed with cardiovascular, pupillary, urinary, sudomotor, lacrimal and salivary testing, and Composite Autonomic Symptom Score (COMPASS-31) autonomic symptom questionnaires. The orthostatic intolerance ratio was calculated by dividing change in systolic blood pressure over time tolerated on head-up tilt. Eleven patients received immunotherapy. RESULTS: At first assessment, all 13 patients had cardiovascular and pupillary impairments, 7 of 8 had postganglionic sudomotor dysfunction, 9 of 11 had urinary retention and xeropthalmia, and 6 of 8 had xerostomia. After immunotherapy, there were significant improvements in orthostatic intolerance ratio (33.3 [17.8-61.3] to 5.2 [1.4-8.2], p = 0.007), heart rate response to deep breathing (1.5 [0.0-3.3] to 4.5 [3.0-6.3], p = 0.02), pupillary constriction to light (12.0 [5.5-18.0] to 19.0 [10.6-23.8]%, p = 0.02), saliva production (0.01 [0.01-0.05] to 0.08 [0.02-0.20] g/min, p = 0.03), and COMPASS-31 scores (52 to 17, p = 0.03). Orthostatic intolerance ratio correlated with autonomic symptoms at baseline (r = 0.841, p = 0.01) and following immunotherapy (r = 0.889, p = 0.02). Immunofluorescence analyses of skin samples from a patient 32 years after disease onset showed loss of nerve fibers supplying the dermal autonomic adnexa and epidermis, with clear improvements following immunotherapy. INTERPRETATION: Patients with autoimmune autonomic ganglionopathy demonstrated objective evidence of widespread sympathetic and parasympathetic autonomic failure, with significant improvements after immunotherapy. Quantitative autonomic biomarkers should be used to define initial deficits, guide therapeutic decisions, and document treatment response. ANN NEUROL 2021;89:753-768.

Associations between markers of social functioning and depression and quality of life in survivors of head and neck cancer: Findings from the Head and Neck Cancer 5000 study.

OBJECTIVE: To investigate associations between markers of social functioning (trouble with social eating and social contact), depression and health-related quality of life (QOL) among head and neck cancer survivors. METHODS: This cross-sectional analysis included individuals with oral cavity, oropharynx, larynx, salivary gland and thyroid cancers from Head and Neck 5000 alive at 12 months. Trouble with social eating and social contact were measured using items from EORTC QLQ-H&N35 and QOL using EORTC QLQ-C30; responses were converted into a score of 0-100, with a higher score equalling more trouble or better QOL. A HADS subscale score of ≥8 was considered significant depression. Associations between tertiles of trouble with social eating and social contact and depression and QoL were assessed using multivariable logistic and linear regression (with robust errors), respectively. RESULTS: Of 2561 survivors, 23% reported significant depression. The median QOL score was 75.0 (interquartile range 58.3-83.3). For trouble with social eating, after confounder adjustment, those in the intermediate and highest tertiles had higher odds of depression (intermediate: OR = 4.5, 95% CI 3.19-6.45; high: OR = 21.8, 15.17-31.18) and lower QOL (intermediate:ß = -8.7, 95% CI -10.35 to -7.14; high: ß = -24.8, -26.91 to -22.77). Results were similar for trouble with social contact. CONCLUSION: We found strong clinically important associations between markers of social functioning and depression and QOL. More effective interventions addressing social eating and contact are required. These may help survivors regain their independence, reduce levels of isolation and loneliness, and depression, and improve QOL outcomes generally.

Patient experience of the acute post-surgical period following total laryngectomy during the COVID-19 era.

BACKGROUND: Total laryngectomy (TL) results in permanent functional changes requiring rapid development of complex new skills. A significant portion of this learning happens in the acute post-surgical stage. There is increasing interest in enhanced recovery after surgery (ERAS) protocols in TL; however, implementation has been difficult. COVID-19 has placed significant pressures on acute services, requiring rapid service changes for TL patients. AIMS: To understand the acute patient experience of having a TL both before and during COVID-19. METHODS & PROCEDURES: Semi-structured interviews using a pre-designed topic guide were conducted with 10 people who had undergone a TL within the last 2 years. Participants were recruited by their speech and language therapists using purposive sampling. Braun and Clarke's iterative approach to data collection and thematic analysis was used to generate key themes from the data. OUTCOMES & RESULTS: Thematic analysis identified four main themes: (1) pre-operative information-giving: 'it was just words'; (2) decision-making influences: 'I just wanted them to get it all out and get it over with'; (3) coping with adjustment to the new normal: 'this is part of me now'; and (4) the importance of relationship-building: 'when you've had something like this, you need some care and understanding'. CONCLUSIONS & IMPLICATIONS: The need for an individualized approach to TL intervention which incorporates medical and psycho-social approaches from pre-treatment to acute discharge is vital. ERAS models should be reviewed to shift beyond the medical model alone. Rapid service changes due to COVID-19 did not contribute any major changes to the acute patient-reported experience. WHAT THIS PAPER ADDS: What is already known on the subject We know that ERAS protocols have the potential to improve patient outcomes following TL. However, the research does not consider anything other than the early oral feeding debate and it has therefore been difficult to implement ERAS protocols in current service models. COVID19 required head and neck cancer services to make quick changes to surgical pathways, with the potential that some ERAS protocols had been adopted inadvertently. In order to understand the impact of this, we need to understand the patient experience following TL both before and during COVID19. What this paper adds to existing knowledge This paper used qualitative interviews to understand the acute patient experience following TL both during and before COVID19. Findings from these interviews highlighted that people were on the most part, well prepared for the functional changes they would experience after surgery. However, people felt there were gaps in service delivery at the pre-treatment and early discharge home period. Overall, the gaps identified were from a more psycho-social need suggesting that future ERAS models of care should consider both medical and psycho-social principles to enhance patient experience and outcome. What are the potential or actual clinical implications of this work? Pre-treatment services provided to people who have a TL could be reviewed to help maximize long-term adjustment to life. Areas which could be reviewed include the method and mode of information delivery. Further work needs to be done in partnership with community services to improve the immediate discharge home experience.

The Importance of Hydration in Body Composition Assessment in Children Aged 6-16 Years.

Body composition is associated with many noncommunicable diseases. The accuracy of many simple techniques used for the assessment of body composition is influenced by the fact that they do not take into account tissue hydration and this can be particularly problematic in paediatric populations. The aims of this study were: (1) to assess the agreement of two dual energy X-ray absorptiometry (DXA) systems for determining total and regional (arms, legs, trunk) fat, lean, and bone mass and (2) to compare lean soft tissue (LST) hydration correction methods in children. One hundred and twenty four healthy children aged between 6 and 16 years old underwent DXA scans using 2 GE healthcare Lunar systems (iDXA and Prodigy). Tissue hydration was either calculated by dividing total body water (TBW), by 4-component model derived fat free mass (HFFMTBW) or by using the age and sex specific coefficients of Lohman, 1986 (HFFMLohman) and used to correct LST. Regression analysis was performed to develop cross-calibration equations between DXA systems and a paired samples t-test was conducted to assess the difference between LST hydration correction methods. iDXA resulted in significantly lower estimates of total and regional fat and lean mass, compared to Prodigy. HFFMTBW showed a much larger age/sex related variability than HFFMLohman. A 2.0 % difference in LST was observed in the boys (34.5 kg vs 33.8 kg respectively, p < 0.05) and a 2.5% difference in the girls (28.2 kg vs 27.5 kg respectively, p < 0.05) when corrected using either HFFMTBW or HFFMLohman. Care needs to be exercised when combining data from iDXA and Prodigy, as total and regional estimates of body composition can differ significantly. Furthermore, tissue hydration should be taken into account when assessing body composition as it can vary considerably within a healthy paediatric population even within specific age and/or sex groups.

Impact of Affect Balance on Cognitive and Physical Function in Adults With and Without Fibromyalgia.

OBJECTIVE: To identify the potential benefits of heightened levels of affect balance in older adults with and without chronic pain on various cognitive domains, physical performance, and perceived cognitive and physical health. METHOD: Ninety-one older adults, some with and some without fibromyalgia (FM) participated. Objective tests included cognitive (immediate and delayed recall, delayed recognition-CERAD 10-item word list) and physical measures (Fullerton Advanced Balance Scale; lower body strength-30-s chair stand; gait velocity-30-ft. walk). Self-report measures were problems with forgetting, activities of daily living (perceived function), and affect (Positive and Negative Affect Scale [PANAS]). Affect balance was calculated as positive minus negative affect from the PANAS. RESULTS: Hierarchical regression analyses revealed that-regardless of FM status-higher affect balance was associated with better episodic memory performance (immediate recall, delayed recognition), better balance, enhanced lower body strength (more chair stands), and healthier gait (30-ft. walk), as well as less forgetfulness and better perceived functional health. CONCLUSION: Increased affect balance was associated with better objective and subjective health in older adults both without and with chronic pain. Positive psychology treatments which increase affect balance are easy to administer, cost effective, and may add an important, additional treatment modality for maintaining health in normal aging adults as well as those with chronic pain. CLINICAL RELEVANCE: In order to help patients with healthy aging, nurses need to be aware of the potential long-term effect of emotional state on overall function and be able to counsel patients regarding potential treatments to enhance positive global emotions such as resilience.

Development and reliability of the revised Patterson Edema Scale.

OBJECTIVE: The Patterson Edema scale was developed in 2007 to address the lack of a reliable, sensitive scale to measure laryngeal and pharyngeal oedema in patients with head and neck cancer. The objective of this study was to revise the existing Patterson scale to improve its reliability and utility. DESIGN: Prospective investigation. SETTING: Academic medical center. PARTICIPANTS: Speech-Language Pathologists, Otolaryngologists, and Radiation Oncologists. MAIN OUTCOME MEASURES: Ratings using the Revised Patterson Edema Scale. METHODS: A consensus group reviewed existing literature regarding the performance of the original Patterson scale and revised the existing scale in regard to items to be included and descriptors for each severity level. The scale was then utilised by 18 speech language pathologists from the US and UK with >2 years-experience working with dysphagia and dysphonia with endoscopy. Each SLP rated a total of eight parameters (epiglottis, vallecula, pharyngoepiglottic folds, aryepiglottic folds, arytenoids, false vocal folds, true vocal folds and pyriform sinuses) using the Revised Patterson Edema Scale. Feedback was solicited from raters regarding areas where clarity was lacking for further scale revision. Scale revisions were completed and additional ratings were completed by otolaryngologists, radiation oncologists and less experienced SLP providers to establish reliability across disciplines. Quadratic weighted Kappa values were obtained to establish interrater reliability. RESULTS: Feedback received from raters included suggestions for clarification of how to rate unilateral oedema, use of a standard task battery to visualise and rate structures consistently, and clarification of true vocal fold oedema rating parameters. Overall interrater reliability was established using quadratic weighted Kappa with good agreement noted for the epiglottis, vallecula, arytenoids and false vocal folds; moderate agreement noted for aryepiglottic folds, pharyngoepiglottic folds and pyriform sinuses; and fair agreement noted for true vocal folds. CONCLUSIONS: The Revised Patterson Edema Scale demonstrates moderate-substantial interrater reliability for most parameters across multiple disciplines and experience levels, with the exception of the true vocal folds where agreement was fair. We believe the Revised Patterson Oedema Scale provides a reliable tool for clinicians and researchers to rate oedema in the supraglottic larynx and pharynx following treatment for head and neck cancer.

Racism as a Preventable Harm.

Since 1619, racism has been a preexisting condition placing Black people at higher risk of death in America. Generational harm done to the Black community has eroded trust in the health care system. Racial biases, largely unconscious, held by health care professionals can directly result in morbidity and mortality. These biases are amenable to intervention, and thus, these events are preventable. Health care institutions must choose to view racism as a preventable harm and address it with the same fervency devoted to other preventable harms that have been prioritized for decades. Prior attempts to address racism in health care institutions have not resulted in sustained cultural change because unconscious racial biases have not been addressed. Antiracism bundle elements are proposed as evidence-based, conscious tools for subverting unconscious racial biases held by health care providers, thus empowering leaders and staff to prevent further trauma to Black patients and families, with the goal of decreasing racialized health disparities.

Accumulation of saturated intramyocellular lipid is associated with insulin resistance.

Intramyocellular lipid (IMCL) accumulation has been linked to both insulin-resistant and insulin-sensitive (athletes) states. Biochemical analysis of intramuscular triglyceride composition is confounded by extramyocellular triglycerides in biopsy samples, and hence the specific composition of IMCLs is unknown in these states. 1H magnetic resonance spectroscopy (MRS) can be used to overcome this problem. Thus, we used a recently validated 1H MRS method to compare the compositional saturation index (CH2:CH3) and concentration independent of the composition (CH3) of IMCLs in the soleus and tibialis anterior muscles of 16 female insulin-resistant lipodystrophic subjects with that of age- and gender-matched athletes (n = 14) and healthy controls (n = 41). The IMCL CH2:CH3 ratio was significantly higher in both muscles of the lipodystrophic subjects compared with controls but was similar in athletes and controls. IMCL CH2:CH3 was dependent on the IMCL concentration in the controls and, after adjusting the compositional index for quantity (CH2:CH3adj), could distinguish lipodystrophics from athletes. This CH2:CH3adj marker had a stronger relationship with insulin resistance than IMCL concentration alone and was inversely related to VO2max The association of insulin resistance with the accumulation of saturated IMCLs is consistent with a potential pathogenic role for saturated fat and the reported benefits of exercise and diet in insulin-resistant states.

An Investigation Into the Differences in Bone Density and Body Composition Measurements Between 2 GE Lunar Densitometers and Their Comparison to a 4-Component Model.

We describe a study to assess the precision of the GE Lunar iDXA and the agreement between the iDXA and GE Lunar Prodigy densitometers for the measurement of regional- and total-body bone and body composition in normal to obese healthy adults. We compare the whole-body fat mass by dual-energy X-ray absorptiometry (DXA) to measurements by a 4-component (4-C) model. Sixty-nine participants, aged 37 ± 12 yr, with a body mass index of 26.2 ± 5.1 kg/cm2, were measured once on the Prodigy and twice on the iDXA. The 4-C model estimated fat mass from body mass, total body water by deuterium dilution, body volume by air displacement plethysmography, and bone mass by DXA. Agreements between measurements made on the 2 instruments and by the 4-C model were analyzed by Bland-Altman and linear regression analyses. Where appropriate, translational cross-calibration equations were derived. Differences between DXA software versions were investigated. iDXA precision was less than 2% of the measured value for all regional- and whole-body bone and body composition measurements with the exception of arm fat mass (2.28%). We found significant differences between iDXA and Prodigy (p < 0.05) whole-body and regional bone, fat mass (FM), and lean mass, with the exception of hip bone mass, area and density, and spine area. Compared to iDXA, Prodigy overestimated FM and underestimated lean mass. However, compared to 4-C, iDXA showed a smaller bias and narrower limits of agreement than Prodigy. No significant differences between software versions in FM estimations existed. Our results demonstrate excellent iDXA precision. However, significant differences exist between the 2 GE Lunar instruments, Prodigy and iDXA measurement values. A divergence from the reference 4-C observations remains in FM estimations made by DXA even following the recent advances in technology. Further studies are particularly warranted in individuals with large FM contents.

Sleep deficits but no metabolic deficits in premanifest Huntington's disease.

OBJECTIVE: Huntington disease (HD) is a fatal autosomal dominant, neurodegenerative condition characterized by progressively worsening motor and nonmotor problems including cognitive and neuropsychiatric disturbances, along with sleep abnormalities and weight loss. However, it is not known whether sleep disturbances and metabolic abnormalities underlying the weight loss are present at a premanifest stage. METHODS: We performed a comprehensive sleep and metabolic study in 38 premanifest gene carrier individuals and 36 age- and sex-matched controls. The study consisted of 2 weeks of actigraphy at home, 2 nights of polysomnography and multiple sleep latency tests in the laboratory, and body composition assessment using dual energy x-ray absorptiometry scanning with energy expenditure measured over 10 days at home by doubly labeled water and for 36 hours in the laboratory by indirect calorimetry along with detailed cognitive and clinical assessments. We performed a principal component analyses across all measures within each studied domain. RESULTS: Compared to controls, premanifest gene carriers had more disrupted sleep, which was best characterized by a fragmented sleep profile. These abnormalities, as well as a theta power (4-7Hz) decrease in rapid eye movement sleep, were associated with disease burden score. Objectively measured sleep problems coincided with the development of cognitive, affective, and subtle motor deficits and were not associated with any metabolic alterations. INTERPRETATION: The results show that among the earliest abnormalities in premanifest HD is sleep disturbances. This raises questions as to where the pathology in HD begins and also whether it could drive some of the early features and even possibly the pathology.

Molecular phylogeny, biogeography, and habitat preference evolution of marsupials.

Marsupials exhibit great diversity in ecology and morphology. However, compared with their sister group, the placental mammals, our understanding of many aspects of marsupial evolution remains limited. We use 101 mitochondrial genomes and data from 26 nuclear loci to reconstruct a dated phylogeny including 97% of extant genera and 58% of modern marsupial species. This tree allows us to analyze the evolution of habitat preference and geographic distributions of marsupial species through time. We found a pattern of mesic-adapted lineages evolving to use more arid and open habitats, which is broadly consistent with regional climate and environmental change. However, contrary to the general trend, several lineages subsequently appear to have reverted from drier to more mesic habitats. Biogeographic reconstructions suggest that current views on the connectivity between Australia and New Guinea/Wallacea during the Miocene and Pliocene need to be revised. The antiquity of several endemic New Guinean clades strongly suggests a substantially older period of connection stretching back to the Middle Miocene and implies that New Guinea was colonized by multiple clades almost immediately after its principal formation.

Activation of Mouse Cumulus-Oocyte Complex Maturation In Vitro Through EGF-Like Activity of Versican.

In vitro maturation of oocytes is suboptimal to in vivo maturation with altered gene expression and compromised oocyte quality. The large proteoglycan versican is abundant in mouse cumulus-oocyte complexes (COCs) matured in vivo but is absent in cultured COCs. Versican is also positively correlated with human oocyte quality. Versican contains an epidermal growth factor (EGF) motif, and based on EGF-like activities in other systems we hypothesized that versican acts as an EGF-like signaling factor during COC maturation. Here, we purified recombinant versican and compared its function with that of EGF during in vitro maturation (IVM). Versican significantly increased cumulus expansion and induced cumulus-specific genes Ptgs2, Tnfaip6, and Has2, which was blocked by EGF receptor antagonist. Microarray analysis revealed that versican has overlapping function with EGF; however, a subset of genes was uniquely altered following 6 h of IVM with either treatment. Following 6 h of IVM, both Areg and Ereg were significantly increased by both treatments, whereas Egln3, Nr4a1, Nr4a2, Nr4a3, and Adamts5 were significantly higher following versican treatment compared with EGF. In contrast, Sprr1a and Aqp3 were increased after 6 h of EGF but not versican treatment. To determine whether there were temporal differences, COCs were cultured with EGF or versican for 0-12 h. Versican-induced expression occurred later but remained elevated for longer compared with EGF for Ptgs2, Ereg, and Nr4a3. The unique expression profiles of Aqp3 and Nr4a3 during IVM were similarly regulated in vivo. These data indicate that versican has EGF-like effects on COC gene expression, but with distinct temporal characteristics.

Genetic and experiential influences on behavior: Twins reunited at seventy-eight years.

Twins living in different countries offer opportunities to explore associations between observed differences and experiential effects. This report compared the life histories, cognitive abilities, personality traits, psychomotor skills, medical characteristics, job satisfaction, social support and social relations of dizygotic (DZ) female twins reunited at 78, the world's longest separated set. The twins' advanced age also enabled a study of how co-twin differences in aging may be associated with current behavioral and social differences. Consistent with previous studies, these dizygotic reared apart (DZA) twins showed discordance across some, but not all, traits. Their different rearing situations and life histories may explain current differences in their responses to meeting their twin. This case highlights the importance of both genetic and rearing factors on behavior, but does not allow firm conclusions regarding the extent to which these sources explain individual developmental differences. However, such data contribute to the growing number of cross-culturally separated twins, generating novel hypotheses that may be assessed using larger samples.

Perceived Stress and Life Stressors in Adults with and without Fibromyalgia.

Chronic medical conditions (i.e., chronic widespread pain) may contribute to accelerated/accentuated aging, such that middle-aged individuals with comorbidities may actually show increased declines in physical, cognitive, and mental health compared to normal aging adults. We examined perceived stress, life stressors, and depression in adults with and without fibromyalgia, a chronic pain condition. Ninety-four participants (52% with fibromyalgia, 78% female) aged 50 to 93 were administered the Perceived Stress Scale, Social Readjustment Rating Scale, and Beck Depression Inventory. Hierarchical regression analyses were conducted: the predictor variables were age, gender, fibromyalgia status, depression, and fibromyalgia-depression interaction. The interaction term significantly predicted perceived stress, but not life stressors. Depression significantly predicted stress for Social Readjustment Rating Scale measures after controlling for covariates. Significant associations were found between perceived stress and life stressors in all participants. In addition, those with fibromyalgia were significantly more likely to report higher levels of stress above standardized scores on both the Perceived Stress Scale and the Social Readjustment Rating Scale. Finally, depressive symptoms played a more significant role than fibromyalgia status in predicting life stressors. Conclusions: These findings emphasize the importance of assessing different types of stress and stressors in individuals with chronic widespread pain and/or depression in mid-life and beyond to better treat individuals with these conditions.

Cancer-related pain in head and neck cancer survivors: longitudinal findings from the Head and Neck 5000 clinical cohort.

PURPOSE: Reports suggest pain is common in head and neck cancer (HNC). However, past studies are limited by small sample sizes and design and measurement heterogeneity. Using data from the Head and Neck 5000 longitudinal cohort, we investigated pain over a year post-diagnosis. We assessed: temporal trends; compared pain across HNC treatments, stages, sites and by HPV status; and identified subgroups of patients at increased risk of pain. METHODS: Sociodemographic and clinical data and patient-reported pain (measured by EORTC QLQ-C30 and QLQ-H&N35) were collected at baseline (pre-treatment), 4- and 12- months. Using mixed effects multivariable regression, we investigated time trends and identified associations between (i) clinically-important general pain and (ii) HN-specific pain and clinical, socio-economic, and demographic variables. RESULTS: 2,870 patients were included. At baseline, 40.9% had clinically-important general pain, rising to 47.6% at 4-months and declining to 35.5% at 12-months. HN-specific pain followed a similar pattern (mean score (sd): baseline 26.4 (25.10); 4-months. 28.9 (26.55); 12-months, 17.2 (19.83)). Across time, general and HN-specific pain levels were increased in: younger patients, smokers, and those with depression and comorbidities at baseline, and more advanced, oral cavity and HPV negative cancers. CONCLUSIONS: There is high prevalence of general pain in people living with HNC. We identified subgroups more often reporting general and HN-specific pain towards whom interventions could be targeted. IMPLICATIONS FOR CANCER SURVIVORS: Greater emphasis should be placed on identifying and treating pain in HNC. Systematic pain screening could help identify those who could benefit from an early pain management plan.

SMIM1 absence is associated with reduced energy expenditure and excess weight.

BACKGROUND: Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments. METHODS: We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1-/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan. FINDINGS: We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure. CONCLUSION: This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them. FUNDING: This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.