RÉSUMÉ
To determine if ivacaftor (Kalydeco) influences non-CF human CFTR function in vivo, we measured CFTR-dependent (C-sweat) and CFTR-independent (M-sweat) rates from multiple identified sweat glands in 8 non-CF adults. The two types of sweating were stimulated sequentially with intradermal injections of appropriate reagents; each gland served as its own control via alternating off-on drug tests on both arms, given at weekly intervals with 3 off and 3 on tests per subject. We compared drug effects on C-sweating stimulated by either high or low concentrations of ß-adrenergic cocktail, and on methacholine-stimulated M-sweating. For each subject we measured ~700 sweat volumes from ~75 glands per arm (maximum 12 readings per gland), and sweat volumes were log-transformed for statistical analysis. T-tests derived from linear mixed models (LMMs) were more conservative than the familiar paired sample t-tests, and show that ivacaftor significantly increased C-sweating stimulated by both levels of agonist, with a larger effect in the low cocktail condition; ivacaftor did not increase M-sweat. Concurrent sweat chloride tests detected no effect of ivacaftor. We conclude that ivacaftor in vivo increases the open channel probability (PO) of WT CFTR, provided it is not already maximally stimulated.
Sujet(s)
Aminophénols/administration et posologie , Agonistes de canaux chlorure/administration et posologie , Protéine CFTR/métabolisme , Quinolinone/administration et posologie , Glandes sudoripares/effets des médicaments et des substances chimiques , Sudation/effets des médicaments et des substances chimiques , Adulte , Chlorures/analyse , Protéine CFTR/agonistes , Relation dose-effet des médicaments , Femelle , Humains , Mâle , Sueur/composition chimique , Glandes sudoripares/métabolismeRÉSUMÉ
Previous research has shown that American culture places a premium on excitement, enthusiasm, and other high-arousal positive states (HAP) compared with various East Asian cultures. In two studies, we tested the prediction that valuing HAP would be associated with less positive personal views of old age (i.e., fewer things people looked forward to and more things they dreaded about old age) in samples of European American, Chinese American, and Hong Kong Chinese younger, middle-aged, and older adults. In Study 1 (N = 849), participants rated how much they ideally wanted to feel HAP during a typical week and described their personal views of old age. As predicted, European American middle and older adults valued HAP more than did their Chinese American and Hong Kong Chinese peers, and these differences in ideal HAP were related to less positive personal views of old age. In Study 2 (N = 164), we experimentally manipulated how much individuals valued HAP and then assessed their personal views of old age: Across cultures, participants in the "value HAP" condition had less positive personal views of old age than did those in the control condition. These effects did not emerge for societal views of old age (i.e., what people associated with "someone" old vs. young). Together, these findings suggest that people's personal views of their own old age are due, in part, to how much excitement they ideally want to feel. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Sujet(s)
Émotions/physiologie , Plaisir/physiologie , Adolescent , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Vieillissement , Femelle , Humains , Mâle , Adulte d'âge moyen , Jeune adulteRÉSUMÉ
Creole languages are formed in conditions where speakers from distinct languages are brought together without a shared first language, typically under the domination of speakers from one of the languages and particularly in the context of the transatlantic slave trade and European colonialism. One such Creole in Suriname, Sranan, developed around the mid-seventeenth century, primarily out of contact between varieties of English from England, spoken by the dominant group, and multiple West African languages. The vast majority of the basic words in Sranan come from the language of the dominant group, English. Here, we compare linguistic features of modern-day Sranan with those of English as spoken in 313 localities across England. By way of testing proposed hypotheses for the origin of English words in Sranan, we find that 80% of the studied features of Sranan can be explained by similarity to regional dialect features at two distinct input locations within England, a cluster of locations near the port of Bristol and another cluster near Essex in eastern England. Our new hypothesis is supported by the geographical distribution of specific regional dialect features, such as post-vocalic rhoticity and word-initial 'h', and by phylogenetic analysis of these features, which shows evidence favouring input from at least two English dialects in the formation of Sranan. In addition to explicating the dialect features most prominent in the linguistic evolution of Sranan, our historical analyses also provide supporting evidence for two distinct hypotheses about the likely geographical origins of the English speakers whose language was an input to Sranan. The emergence as a likely input to Sranan of the speech forms of a cluster near Bristol is consistent with historical records, indicating that most of the indentured servants going to the Americas between 1654 and 1666 were from Bristol and nearby counties, and that of the cluster near Essex is consistent with documents showing that many of the governors and important planters came from the southeast of England (including London) (Smith 1987 The Genesis of the Creole Languages of Surinam; Smith 2009 In The handbook of pidgin and creole studies, pp. 98-129).This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.
Sujet(s)
Évolution culturelle , Langage , Linguistique , Angleterre , Humains , Phylogenèse , SurinameRÉSUMÉ
BACKGROUND: Growing evidence indicates that major depressive disorder (MDD) is characterized by accelerated biological aging, including greater age-related changes in physiological functioning. The disorder is also associated with abnormal neural reward circuitry, particularly in the basal ganglia (BG). Here we assessed age-related changes in BG volume in both patients with MDD and healthy control participants. METHODS: We obtained whole-brain T1-weighted images from patients with MDD and healthy controls. We estimated grey matter volumes of the BG, including the nucleus accumbens, caudate, pallidum and putamen. Volumes were assessed using multivariate analysis of covariance (MANCOVA) with age as a covariate, followed by appropriate post hoc tests. RESULTS: We included 232 individuals (116 patients with MDD) in our analysis. The MANCOVA yielded a significant group × age interaction (p = 0.043). Analyses for each region yielded a significant group × age interaction in the putamen (univariate test, p = 0.005; permutation test, p = 0.004); this effect was not significant in the other regions. The negative association between age and putamen volume was twice as large in the MDD than in the control group (-35.2 v. -16.7 mm3/yr), indicating greater age-related volumetric decreases in the putamen in individuals with MDD than in controls. LIMITATIONS: These findings are cross-sectional; future studies should assess the longitudinal impact of accelerated aging on anhedonia and neural indices of reward processing. CONCLUSION: Our results indicate that putamen aging is accelerated in patients with MDD. Thus, the putamen may uniquely contribute to the adverse long-term effects of depressive psychopathology and may be a useful target for the treatment of MDD across the lifespan.
Sujet(s)
Trouble dépressif majeur/imagerie diagnostique , Putamen/imagerie diagnostique , Adolescent , Adulte , Vieillissement/anatomopathologie , Antidépresseurs/usage thérapeutique , Anxiété/complications , Anxiété/imagerie diagnostique , Comorbidité , Études transversales , Trouble dépressif majeur/complications , Trouble dépressif majeur/traitement médicamenteux , Femelle , Substance grise/imagerie diagnostique , Humains , Imagerie tridimensionnelle , Modèles linéaires , Imagerie par résonance magnétique , Mâle , Adulte d'âge moyen , Analyse multifactorielle , Taille d'organe , Jeune adulteRÉSUMÉ
African-American Vernacular English (AAVE) is systematic, rooted in history, and important as an identity marker and expressive resource for its speakers. In these respects, it resembles other vernacular or nonstandard varieties, like Cockney or Appalachian English. But like them, AAVE can trigger discrimination in the workplace, housing market, and schools. Understanding what shapes the relative use of AAVE vs. Standard American English (SAE) is important for policy and scientific reasons. This work presents, to our knowledge, the first experimental estimates of the effects of moving into lower-poverty neighborhoods on AAVE use. We use data on non-Hispanic African-American youth (n = 629) from a large-scale, randomized residential mobility experiment called Moving to Opportunity (MTO), which enrolled a sample of mostly minority families originally living in distressed public housing. Audio recordings of the youth were transcribed and coded for the use of five grammatical and five phonological AAVE features to construct a measure of the proportion of possible instances, or tokens, in which speakers use AAVE rather than SAE speech features. Random assignment to receive a housing voucher to move into a lower-poverty area (the intention-to-treat effect) led youth to live in neighborhoods (census tracts) with an 11 percentage point lower poverty rate on average over the next 10-15 y and reduced the share of AAVE tokens by â¼3 percentage points compared with the MTO control group youth. The MTO effect on AAVE use equals approximately half of the difference in AAVE frequency observed between youth whose parents have a high school diploma and those whose parents do not.
Sujet(s)
, Langage , Caractéristiques de l'habitat , Adolescent , Enfant , Femelle , Humains , MâleRÉSUMÉ
To determine if oral dosing with the CFTR-potentiator ivacaftor (VX-770, Kalydeco) improves CFTR-dependent sweating in CF subjects carrying G551D or R117H-5T mutations, we optically measured sweat secretion from 32-143 individually identified glands in each of 8 CF subjects; 6 F508del/G551D, one G551D/R117H-5T, and one I507del/R117H-5T. Two subjects were tested only (-) ivacaftor, 3 only (+) ivacaftor and 3 (+/-) ivacaftor (1-5 tests per condition). The total number of gland measurements was 852 (-) ivacaftor and 906 (+) ivacaftor. A healthy control was tested 4 times (51 glands). For each gland we measured both CFTR-independent (M-sweat) and CFTR-dependent (C-sweat); C-sweat was stimulated with a ß-adrenergic cocktail that elevated [cAMP]i while blocking muscarinic receptors. Absent ivacaftor, almost all CF glands produced M-sweat on all tests, but only 1/593 glands produced C-sweat (10 tests, 5 subjects). By contrast, 6/6 subjects (113/342 glands) produced C-sweat in the (+) ivacaftor condition, but with large inter-subject differences; 3-74% of glands responded with C/M sweat ratios 0.04%-2.57% of the average WT ratio of 0.265. Sweat volume losses cause proportionally larger underestimates of CFTR function at lower sweat rates. The losses were reduced by measuring C/M ratios in 12 glands from each subject that had the highest M-sweat rates. Remaining losses were estimated from single channel data and used to correct the C/M ratios, giving estimates of CFTR function (+) ivacaftor â= 1.6%-7.7% of the WT average. These estimates are in accord with single channel data and transcript analysis, and suggest that significant clinical benefit can be produced by low levels of CFTR function.
Sujet(s)
Substitution d'acide aminé/génétique , Aminophénols/usage thérapeutique , Protéine CFTR/génétique , Mucoviscidose/traitement médicamenteux , Mucoviscidose/génétique , Quinolinone/usage thérapeutique , Sueur/métabolisme , Aminophénols/pharmacologie , Études cas-témoins , Femelle , Humains , Mâle , Quinolinone/pharmacologie , Sueur/effets des médicaments et des substances chimiques , Glandes sudoripares/effets des médicaments et des substances chimiques , Glandes sudoripares/métabolisme , Glandes sudoripares/anatomopathologieRÉSUMÉ
When given a choice, how do people decide which physician to select? Although significant research has demonstrated that how people actually feel (their "actual affect") influences their health care preferences, how people ideally want to feel (their "ideal affect") may play an even greater role. Specifically, we predicted that people trust physicians whose affective characteristics match their ideal affect, which leads people to prefer those physicians more. Consistent with this prediction, the more participants wanted to feel high arousal positive states on average (ideal HAP; e.g., excited), the more likely they were to select a HAP-focused physician. Similarly, the more people wanted to feel low arousal positive states on average (ideal LAP; e.g., calm), the more likely they were to select a LAP-focused physician. Also as predicted, these links were mediated by perceived physician trustworthiness. Notably, while participants' ideal affect predicted physician preference, actual affect (how much people actually felt HAP and LAP on average) did not. These findings suggest that people base serious decisions on how they want to feel, and highlight the importance of considering ideal affect in models of decision making preferences.
Sujet(s)
Affect , Prise de décision , Médecins , Éveil , Femelle , Humains , Mâle , Relations médecin-patient , Jeune adulteRÉSUMÉ
To assess CFTR function in vivo, we developed a bioassay that monitors and compares CFTR-dependent and CFTR-independent sweat secretion in parallel for multiple (~50) individual, identified glands in each subject. Sweating was stimulated by intradermally injected agonists and quantified by optically measuring spherical sweat bubbles in an oil-layer that contained dispersed, water soluble dye particles that partitioned into the sweat bubbles, making them highly visible. CFTR-independent secretion (M-sweat) was stimulated with methacholine, which binds to muscarinic receptors and elevates cytosolic calcium. CFTR-dependent secretion (C-sweat) was stimulated with a ß-adrenergic cocktail that elevates cytosolic cAMP while blocking muscarinic receptors. A C-sweat/M-sweat ratio was determined on a gland-by-gland basis to compensate for differences unrelated to CFTR function, such as gland size. The average ratio provides an approximately linear readout of CFTR function: the heterozygote ratio is ~0.5 the control ratio and for CF subjects the ratio is zero. During assay development, we measured C/M ratios in 6 healthy controls, 4 CF heterozygotes, 18 CF subjects and 4 subjects with 'CFTR-related' conditions. The assay discriminated all groups clearly. It also revealed consistent differences in the C/M ratio among subjects within groups. We hypothesize that these differences reflect, at least in part, levels of CFTR expression, which are known to vary widely. When C-sweat rates become very low the C/M ratio also tended to decrease; we hypothesize that this nonlinearity reflects ductal fluid absorption. We also discovered that M-sweating potentiates the subsequent C-sweat response. We then used potentiation as a surrogate for drugs that can increase CFTR-dependent secretion. This bioassay provides an additional method for assessing CFTR function in vivo, and is well suited for within-subject tests of systemic, CFTR-directed therapeutics.
Sujet(s)
Protéine CFTR/métabolisme , Mucoviscidose/métabolisme , Glandes sudoripares/métabolisme , Sueur/métabolisme , Agonistes bêta-adrénergiques/administration et posologie , Adulte , Aminophylline/administration et posologie , Atropine/administration et posologie , Mucoviscidose/génétique , Protéine CFTR/génétique , Relation dose-effet des médicaments , Femelle , Hétérozygote , Humains , Injections intradermiques , Isoprénaline/administration et posologie , Mâle , Chlorure de méthacholine/administration et posologie , Agonistes muscariniques , Antagonistes muscariniques/administration et posologie , Mutation , Antagonistes des récepteurs purinergiques P1/administration et posologie , Sueur/effets des médicaments et des substances chimiques , Glandes sudoripares/effets des médicaments et des substances chimiques , Facteurs tempsRÉSUMÉ
BACKGROUND: The women portrayed in the bijin-ga of the past, particularly those from the Meiji Period (18681912), tended not to show much resemblance to those of women portrayed in the more modern bijin-ga (from after World War II), and such an observation came across as a possible indication that Japanese standards of beauty have changed over the two eras. To examine whether the apparent discrepancy can be interpreted as an actual change in the standards or not, a study was designed with the aim of assigning numeric values to several aspects of the eyes and testing for the presence of a statistically significant difference in each of the aspects between the Meiji bijin-ga and the modern bijin-ga. METHODS: For this study, 29 Meiji bijin-ga and 36 modern bijin-ga were selected. The eye was chosen as the subject of comparison, and five aspects were categorized and measured: (1) presence or absence of a double fold, (2) eye width, (3) eye height, (4) eyebrow-to-upper lid distance, and (D) corneal diameter. The eye width, the eye height, and the eyebrow-to-upper lid distance were divided by the corneal diameter to derive standardized grounds for comparison. RESULTS: The difference in double-fold frequencies between the Meiji bijin-ga (24%) and the modern bijin-ga (36%) was not found to be statistically significant (p=0.298). There was no difference in the eye width-to-corneal diameter ratio between the Meiji bijin-ga (mean 2.57±0.6) and the modern bijin-ga (mean 2.61±0.85) (p=0.86). The eye height-to-corneal diameter ratio derived from the Meiji bijin-ga (mean 0.62±0.15) was significantly smaller than that derived from the modern bijin-ga (mean 0.82±0.18) (p=0.000). The eyebrow to upper lid distance-to-corneal diameter ratio derived from the Meiji bijin-ga (mean 2.21±0.83) was significantly greater than that derived from the modern bijin-ga (mean 1.36±0.78) (p=0.000). CONCLUSIONS: The results of the study support the notion that Westernization contributed to bringing about changes in the Japanese standards of beautiful eyes in the context of bijin-ga. However, the fact that the changeover has not occurred in all the categories in question does not indicate that the Occidental characteristics came to be emulated in their entirety. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at http://www.springer.com/00266.
Sujet(s)
Beauté , Oeil/anatomie et histologie , Portraits comme sujet , Femelle , Histoire du 19ème siècle , Histoire du 20ème siècle , Histoire du 21ème siècle , Humains , JaponRÉSUMÉ
Participants recruited from one Historically Black University (HBU) and two predominantly White higher-education institutions evaluated and decided simulated voting rights case summaries in which the plaintiff was either a racially-defined (African American) or a nonracially-defined (farmers) minority group. Contrary to social identity and social justice findings of an in-group bias, the present study showed greater support at all institutions for the voting rights of the African Americans than for the rural farmers, and the greatest support for both minority groups was found at the HBU. Perceived evidence strength was a better predictor of decisions than perceived unfairness, and both of these predictor variables completely mediated the effects of institution-type and involvement of a racially-defined group on decisions.