β1-Integrin-Mediated Uptake of Chondrocyte Extracellular Vesicles Regulates Chondrocyte Homeostasis.

Osteoarthritis (OA) is the most prevalent age-related degenerative disorder, which severely reduces the quality of life of those affected. Whilst management strategies exist, no cures are currently available. Virtually all joint resident cells generate extracellular vesicles (EVs), and alterations in chondrocyte EVs during OA have previously been reported. Herein, we investigated factors influencing chondrocyte EV release and the functional role that these EVs exhibit. Both 2D and 3D models of culturing C28I/2 chondrocytes were used for generating chondrocyte EVs. We assessed the effect of these EVs on chondrogenic gene expression as well as their uptake by chondrocytes. Collectively, the data demonstrated that chondrocyte EVs are sequestered within the cartilage ECM and that a bi-directional relationship exists between chondrocyte EV release and changes in chondrogenic differentiation. Finally, we demonstrated that the uptake of chondrocyte EVs is at least partially dependent on β1-integrin. These results indicate that chondrocyte EVs have an autocrine homeostatic role that maintains chondrocyte phenotype. How this role is perturbed under OA conditions remains the subject of future work

Exposure to multiple childhood social risk factors and adult body mass index trajectories from ages 20 to 64 years

Background: While childhood social risk factors appear to be associated with adult obesity, it is unclear whether exposure to multiple childhood social risk factors is associated with accelerated weight gain during adulthood. / Methods: We used the Medical Research Council National Survey of Health and Development, a British population-based birth cohort study of participants born in 1946, height and weight were measured by nurses at ages 36, 43, 53 and 60–64 and self-reported at 20 and 26 years. The 9 childhood socioeconomic risk factors and 8 binary childhood psychosocial risk factors were measured, with 13 prospectively measured at age 4 years (or at 7 or 11 years if missing) and 3 were recalled when participants were age 43. Multilevel modelling was used to examine the association between the number of childhood social risk factors and changes in body mass index (BMI) with age. / Results: Increasing exposure to a higher number of childhood socioeconomic risk factors was associated with higher mean BMI across adulthood for both sexes and with a faster increase in BMI from 20 to 64 years, among women but not men. Associations remained after adjustment for adult social class. There was no evidence of an association between exposure to childhood psychosocial risk factors and mean BMI in either sex at any age. / Conclusions: Strategies for the prevention and management of weight gain across adulthood may need to tailor interventions in consideration of past exposure to multiple socioeconomic disadvantages experienced during childhood

Socioeconomic inequalities in resilience and vulnerability among older adults: a population-based birth cohort analysis

BACKGROUND: Aging is associated with declines in physical capability; however, some individuals demonstrate high well-being despite this decline, i.e. they are “resilient.” We examined socioeconomic position (SEP) and resilience and the influence of potentially modifiable behavioral resources, i.e. social support and leisure time physical activity (LTPA), on these relationships. METHODS: Data came from the Medical Research Council National Survey of Health and Development, a nationally-representative birth cohort study. Resilience–vulnerability at age 60–64 years (n = 1,756) was operationalized as the difference between observed and expected levels of well-being, captured by the Warwick–Edinburgh Mental Well-being Scale (WEMWBS), given the level of performance-based physical capability. SEP was assessed by father's and own social class, parental education, and intergenerational social mobility. PA and structural/functional social support were reported at ages 53 years and 60–64 years. Path analysis was used to examine mediation of SEP and resilience–vulnerability through LTPA and social support. RESULTS: Participants in the highest social class had scores on the resilience to vulnerability continuum that were an average of 2.3 units (β = 0.46, 95% CI 0.17, 0.75) higher than those in the lowest social class. Greater LTPA (β = 0.58, 95% CI 0.31, 0.85) and social support (β = 3.27, 95% CI 2.90, 3.63) were associated with greater resilience; LTPA partly mediated participant social class and resilience (23.4% of variance). CONCLUSIONS: Adult socioeconomic advantage was associated with greater resilience. Initiatives to increase LTPA may contribute to reducing socioeconomic inequalities in this form of resilience in later life

Evidence for a fractional quantum Hall state with anisotropic longitudinal transport

At high magnetic fields, where the Fermi level lies in the N=0 lowest Landau level (LL), a clean two-dimensional electron system (2DES) exhibits numerous incompressible liquid phases which display the fractional quantized Hall effect (FQHE) (Das Sarma and Pinczuk, 1997). These liquid phases do not break rotational symmetry, exhibiting resistivities which are isotropic in the plane. In contrast, at lower fields, when the Fermi level lies in the $N\ge2$ third and several higher LLs, the 2DES displays a distinctly different class of collective states. In particular, near half filling of these high LLs the 2DES exhibits a strongly anisotropic longitudinal resistance at low temperatures (Lilly et al., 1999; Du et al., 1999). These "stripe" phases, which do not exhibit the quantized Hall effect, resemble nematic liquid crystals, possessing broken rotational symmetry and orientational order (Koulakov et al., 1996; Fogler et al., 1996; Moessner and Chalker, 1996; Fradkin and Kivelson, 1999; Fradkin et al, 2010). Here we report a surprising new observation: An electronic configuration in the N=1 second LL whose resistivity tensor simultaneously displays a robust fractionally quantized Hall plateau and a strongly anisotropic longitudinal resistance resembling that of the stripe phases.Comment: Nature Physics, (2011

Lifetime trajectories of socio-economic adversity and their associations with psychosocial factors and attitudes towards social class

© Authors 2020. Scientific understanding of the associations between socio-economic adversity and other domains such as health and psychosocial functioning may be improved by employing extensive, prospective life course data to model inter-individual heterogeneity in socio-economic trajectories. This study applied Latent Class Growth Analysis to derive a typology of trajectories of socio-economic adversity, and compared the psychosocial profiles of the groups based on this typology. Data were used from 2,950 men and women participating in the MRC National Survey of Health and Development in Great Britain, ascertained prospectively since birth in 1946 until age 53. Trajectories of socio-economic adversity were based on indicators of occupational class, overcrowding, housing tenure, household amenities and financial hardship at ages 4, 11, 15, 36, 43 and 53, and education at age 26. Psychosocial factors included parental interest in education, self-management, neuroticism and attitudes towards social class and social mobility. Seven distinct trajectories were identified: persistent high; persistent low; strongly declining; gradually declining; increasing; early childhood; and relapsing high adversity. Key findings include that those with increasing adversity had high parental interest in education but low self-management and high neuroticism; that those with only early childhood adversity had a less favourable psychosocial profile than those with persistent low exposure; and that groups with declining adversity had relatively favourable attitudes towards education. Findings emphasise the need to consider socio-economic and personality mechanisms in the context of one another in order to better understand later life inequality

Primary leptomeningeal oligodendrogliomatosis

Primary leptomeningeal oligodendrogliomas (PLOs) are rare intracranial malignancies where tumors grow in the subarachnoid space without an obvious connection to the brain or spinal cord parenchyma. Adding to the three previously reported cases of PLO with no parenchymal involvement we report a fourth case of the same in this paper in a 50-year-old woman presenting with unrelenting headaches. CT scan of her head revealed hydrocephalus and MRI revealed diffuse enhancement of her leptomeninges throughout her brain and spine, prominent over the basilar region. Biopsy obtained using a frameless stereotactic biopsy showed sharply defined cell borders, clear cytoplasm, and rounded nuclei consistent with an oligodendroglioma. Our case suggests that PLO can mimic diffuse forms of granulomatous meningitis and should be suspected in patients that clinically and radiographically present like granulomatous meningitis but without blood or CSF markers for the same

Expressing one’s feelings and listening to others increases emotional intelligence: a pilot study of Asian medical students

<p>Background: There has been considerable interest in Emotional Intelligence (EI) in undergraduate medical education, with respect to student selection and admissions, health and well-being and academic performance. EI is a significant component of the physician-patient relationship. The emotional well-being of the physician is, therefore, a significant component in patient care. The aim is to examine the measurement of TEIQue-SF in Asian medical students and to explore how the practice of listening to the feelings of others and expressing one’s own feelings influences an individual’s EI, set in the context of the emotional well-being of a medical practitioner.</p> <p>Methods: A group of 183 international undergraduate medical students attended a half-day workshop (WS) about mental-health and well-being. They completed a self-reported measure of EI on three occasions, pre- and post-workshop, and a 1-year follow-up.</p> <p>Result: The reliability of TEIQue-SF was high and the reliabilities of its four factors were acceptable. There were strong correlations between the TEIQue-SF and personality traits. A paired t-test indicated significant positive changes after the WS for all students (n=181, p= .014), male students (n=78, p= .015) and non-Japanese students (n=112, p= .007), but a repeated measures analysis showed that one year post-workshop there were significant positive changes for all students (n=55, p= .034), female students (n=31, p= .007), especially Japanese female students (n=13, p= .023). Moreover, 80% of the students reported that they were more attentive listeners, and 60% agreed that they were more confident in dealing with emotional issues, both within themselves and in others, as a result of the workshop.</p> <p>Conclusion: This study found the measurement of TEIQue-SF is appropriate and reliable to use for Asian medical students. The mental health workshop was helpful to develop medical students’ EI but showed different results for gender and nationality. The immediate impact on the emotional awareness of individuals was particularly significant for male students and the non-Japanese group. The impact over the long term was notable for the significant increase in EI for females and Japanese. Japanese female students were more conscious about emotionality. Emotion-driven communication exercises might strongly influence the development of students’ EI over a year.</p&gt

Antitumour 2-(4-aminophenyl)benzothiazoles generate DNA adducts in sensitive tumour cells in vitro and in vivo

2-(4-Aminophenyl)benzothiazoles represent a potent and highly selective class of antitumour agent. In vitro, sensitive carcinoma cells deplete 2-(4-aminophenyl)benzothiazoles from nutrient media; cytochrome P450 1A1 activity, critical for execution of antitumour activity, and protein expression are powerfully induced. 2-(4-Amino-3-methylphenyl)benzothiazole-derived covalent binding to cytochrome P450 1A1 is reduced by glutathione, suggesting 1A1-dependent production of a reactive electrophilic species. In vitro, 2-(4-aminophenyl)benzothiazole-generated DNA adducts form in sensitive tumour cells only. At concentrations >100 nM, adducts were detected in DNA of MCF-7 cells treated with 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203). 5F 203 (1 μM) led to the formation of one major and a number of minor adducts. However, treatment of cells with 10 μM 5F 203 resulted in the emergence of a new dominant adduct. Adducts accumulated steadily within DNA of MCF-7 cells exposed to 1 μM 5F 203 between 2 and 24 h. Concentrations of the lysylamide prodrug of 5F 203 (Phortress) ≥100 nM generated adducts in the DNA of sensitive MCF-7 and IGROV-1 ovarian cells. At 1 μM, one major Phortress-derived DNA adduct was detected in these two sensitive phenotypes; 10 μM Phortress led to the emergence of an additional major adduct detected in the DNA of MCF-7 cells. Inherently resistant MDA-MB-435 breast carcinoma cells incurred no DNA damage upon exposure to Phortress (⩽10 μM, 24 h). In vivo, DNA adducts accumulated within sensitive ovarian IGROV-1 and breast MCF-7 xenografts 24 h after treatment of mice with Phortress (20 mg kg−1). Moreover, Phortress-derived DNA adduct generation distinguished sensitive MCF-7 tumours from inherently resistant MDA-MB-435 xenografts implanted in opposite flanks of the same mouse

Perceived Discrimination and Adherence to Medical Care in a Racially Integrated Community

BACKGROUND: Past research indicates that access to health care and utilization of services varies by sociodemographic characteristics, but little is known about racial differences in health care utilization within racially integrated communities. OBJECTIVE: To determine whether perceived discrimination was associated with delays in seeking medical care and adherence to medical care recommendations among African Americans and whites living in a socioeconomically homogenous and racially integrated community. DESIGN: A cross-sectional analysis from the Exploring Health Disparities in Integrated Communities Study. PARTICIPANTS: Study participants include 1,408 African-American (59.3%) and white (40.7%) adults (≥18 years) in Baltimore, Md. MEASUREMENTS: An interviewer-administered questionnaire was used to assess the associations of perceived discrimination with help-seeking behavior for and adherence to medical care. RESULTS: For both African Americans and whites, a report of 1–2 and >2 discrimination experiences in one’s lifetime were associated with more medical care delays and nonadherence compared to those with no experiences after adjustment for need, enabling, and predisposing factors (odds ratio [OR] = 1.8, 2.6; OR = 2.2, 3.3, respectively; all P < .05). Results were similar for perceived discrimination occurring in the past year. CONCLUSIONS: Experiences with discrimination were associated with delays in seeking medical care and poor adherence to medical care recommendations INDEPENDENT OF NEED, ENABLING, AND PREDISPOSING FACTORS, INCLUDING MEDICAL MISTRUST; however, a prospective study is needed. Further research in this area should include exploration of other potential mechanisms for the association between perceived discrimination and health service utilization