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Background: Sex differences in emotion processing may play a role in women's increased risk for Major Depressive Disorder (MDD). However, studies of sex differences in brain mechanisms involved in emotion processing in MDD (or interactions of sex and diagnosis) are sparse.Methods: We conducted an event-related fMRI study examining the interactive and distinct effects of sex and MDD on neural activity during a facial emotion perception task. To minimize effects of current affective state and cumulative disease burden, we studied participants with remitted MDD (rMDD) who were early in the course of the illness. In total, 88 individuals aged 18-23 participated, including 48 with rMDD (32 female) and 40 healthy controls (HC; 25 female).Results: fMRI revealed an interaction between sex and diagnosis for sad and neutral facial expressions in the superior frontal gyrus and left middle temporal gyrus. Results also revealed an interaction of sex with diagnosis in the amygdala.Limitations: Data was from two sites, which might increase variability, but it also increases power to examine sex by diagnosis interactions.Conclusions: This study demonstrates the importance of taking sex differences into account when examining potential trait (or scar) mechanisms that could be useful in identifying individuals at-risk for MDD as well as for evaluating potential therapeutic innovations. [ABSTRACT FROM AUTHOR]

Background Following the Health and Social Care Act in England, public health teams were formally transferred from the NHS to local authorities in April 2013. Methods Online survey of Directors of Public Health (DsPH) in local authorities in England (n = 152) to investigate their experience within local government 1 year on. Tests of association were used to explore relationships between the perceived integration and influence of public health, and changes in how the public health budget was being spent. Results The organization of and managerial arrangements for public health within councils varied. Most DsPH felt that good relationships had been established within the council, and the move had made them more able to influence priorities for health improvement, even though most felt their influence was limited. Changes in commissioning using the public health budget were already widespread and included the de-commissioning of services. Conclusions There was a widespread feeling amongst DsPH that they had greater influence since the reforms, and that this went across the local authority and beyond. Public health's influence was most apparent when the transfer of staff to local government had gone well, when collaborative working relationships had developed, and when local partnership groups were seen as being effective. [ABSTRACT FROM AUTHOR]

To investigate the hypothesis that increasing alcohol consumption is accompanied by increasing use of acute, but decreasing use of preventative, medical services among the general population. Health and life-style survey of 41,000 randomly-sampled adults in SE England who self-completed a validated questionnaire covering socio-demographics, alcohol and tobacco usage and use of acute (A&E department and general practitioner) and preventative (dental, optician, mammography and cervical cytology) services: the response rate was 60%. Comparative use of acute and preventative health care services by patients with varying consumption of alcoholic beverages. This was estimated by the odds ratio for service use, after correcting for the following confounding variables; age, social class, ethnic group, employment status, whether lives with children or with other adults, whether is a career, limiting long-term illness, depression status, smoking habit and use of private health insurance. There was increased use of accident and emergency services by the harmful and intermediate drinking groups compared with the safe drinking group. Male abstainers attended their A&E departments more frequently than 'safe limit' drinkers. With respect to preventative services, both male and female abstainers and harmful drinkers used dental services less than safe limit drinkers. For females, mammography and cervical cytology services were less frequently used by abstainers and by harmful drinkers. This study supports the generally held view that heavy alcohol consumers are disproportionate users of acute medical services but they are relative under-users of preventative medical care services. Alcohol abstainers are also over-users of acute services, but under-users of preventative services. These latter observations are relevant to the claims that moderate alcohol consumers have lower apparent morbidity and mortality rates compared to abstainers. [ABSTRACT FROM AUTHOR]

Deficiency in peroxisome proliferator-activated receptor gamma coactivator 1-alpha. (PGC-1α) expression or function is implicated in numerous neurological and psychiatric disorders. PGC-1α is required for the expression of genes involved in synchronous neurotransmitter release, axonal integrity, and metabolism, especially in parvalbumin-positive interneurons. As a transcriptional coactivator, PGC-1α requires transcription factors to specify cell-type-specific gene programs; while much is known about these factors in peripheral tissues, it is unclear if PGC-1α utilizes these same factors in neurons. Here, we identified putative transcription factors controlling PGC-1α-dependent gene expression in the brain using bioinformatics and then validated the role of the top candidate in a knockout mouse model. We transcriptionally profiled cells overexpressing PGC-1α and searched for over-represented binding motifs in the promoters of upregulated genes. Binding sites of the estrogen-related receptor (ERR) family of transcription factors were enriched, and blockade of ERRα attenuated PGC-1α-mediated induction of mitochondrial and synaptic genes in cell culture. Localization in the mouse brain revealed enrichment of ERRα expression in parvalbumin-expressing neurons with tight correlation of expression with PGC-1α across brain regions. In ERRα null mice, PGC-1α-dependent genes were reduced in multiple regions, including neocortex, hippocampus, and cerebellum, though not to the extent observed in PGC-1α null mice. Behavioral assessment revealed ambulatory hyperactivity in response to amphetamine and impairments in sensorimotor gating without the overt motor impairment characteristic of PGC-1α null mice. These data suggest that ERRα is required for normal levels of expression of PGC-1α-dependent genes in neurons but that additional factors may be involved in their regulation., (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Sex differences in emotion processing may play a role in women's increased risk for Major Depressive Disorder (MDD). However, studies of sex differences in brain mechanisms involved in emotion processing in MDD (or interactions of sex and diagnosis) are sparse., Methods: We conducted an event-related fMRI study examining the interactive and distinct effects of sex and MDD on neural activity during a facial emotion perception task. To minimize effects of current affective state and cumulative disease burden, we studied participants with remitted MDD (rMDD) who were early in the course of the illness. In total, 88 individuals aged 18-23 participated, including 48 with rMDD (32 female) and 40 healthy controls (HC; 25 female)., Results: fMRI revealed an interaction between sex and diagnosis for sad and neutral facial expressions in the superior frontal gyrus and left middle temporal gyrus. Results also revealed an interaction of sex with diagnosis in the amygdala., Limitations: Data was from two sites, which might increase variability, but it also increases power to examine sex by diagnosis interactions., Conclusions: This study demonstrates the importance of taking sex differences into account when examining potential trait (or scar) mechanisms that could be useful in identifying individuals at-risk for MDD as well as for evaluating potential therapeutic innovations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Headache is the most common neurological symptom presenting to general practitioners (GPs). Identifying factors predicting outcome in patients consulting their GPs for headache may help GPs with prognosis and choose management strategies which would improve patient care. We followed up a cohort of patients receiving standard medical care, recruited from 18 general practices in the South Thames region of England, approximately 9 months after their initial participation in the study. Of the baseline sample (N=255), 134 provided both full baseline and follow-up data on measures of interest. We determined associations between patients' follow-up scores on the Headache Impact Test-6 and baseline characteristics (including headache impact and frequency scores, mood, attributions about psychological/medical causes of their headaches, satisfaction with GP care and illness perceptions). Greater impact and stronger beliefs about the negative consequences of headaches at baseline were the strongest predictors of poor outcome at follow-up., (© 2011 Taylor & Francis)

Much of the cell surface on the ciliate Tetrahymena thermophila is covered by a polarized lattice of cytoskeletal structures that are associated with basal bodies of the ciliary rows. Unique structural landmarks, including an oral apparatus and contractile vacuole pores, develop before cell division in localized domains located, respectively, posterior and anterior to the transverse fission zone. All of these structures can be visualized by specific monoclonal antibodies. A single-locus recessive mutation, disorganized-A (disA), primarily affects the striated rootlets of the ciliary-row basal bodies and brings about a severe disorganization in the positioning and orientation of these basal bodies and associated cytoskeletal elements. Nonetheless, the new oral apparatus, contractile vacuole pores, and other unique structures appeared at or near their normal sites along the anteroposterior axis of disA cells, indicating that the positioning of these localized structures is not dependent on the integrity of the ciliary rows. Abnormalities were present in the details of construction of some of the localized structures and in aspects of cell shape that may be influenced by these details. In the main, however, analysis of disA mutant cells indicates that intracellular domains near the cell poles develop independently of the vectorial polarity of the ciliary rows.

In Tetrahymena, two unique cell-surface structures, the oral apparatus and the cytoproct, are formed at opposite ends of one ciliary row, the reference meridian, which is propagated longitudinally during clonal growth. A third set of unique structures, the contractile vacuole pore(s) (CVP), is located at a nearly constant proportion of the cell circumference to the cell's right of the reference meridian. Three allelic recessive temperature-sensitive mutations, collectively named hypoangular (hpo), alter both the geometry of propagation of the reference meridian and the location of the CVPs. In mutant cells, the reference meridian typically undergoes a steady rightward shift in successive cell generations ("cortical slippage"); concomitantly, CVP sets come to lie closer to the reference meridian. Although CVP location is still proportional to the cell circumference, the constant of proportionality (the "CVP angle") is reduced. Another effect is an alteration in the widths of morphogenetic domains within the cortex. As the temperature is raised (made more restrictive), these effects are accentuated and the CVP angle becomes reduced further. At the extreme, the CVP angle collapses to zero and less, i.e., there is a topological switch such that CVPs come to lie to the left of the reference meridian, and the direction of cortical slippage reverses from rightward to leftward. These observations are hard to reconcile with existing formal models of pattern specification in this system and suggest that the hpo locus might specify a key component of the intracellular positional system.

The oral apparatus (OA) of the ciliated protozoan Tetrahymena thermophila consists of four ordered arrays of ciliary units. In wild-type cells, these arrays are constant in spatial organization and vary little in size except during extreme starvation. Recessive mutations at five gene loci are known to increase the size of the OA. They do this by increasing the length of the ciliary arrays, without affecting their width and often without increasing their number beyond the usual four. Comparison of the oral arrays over a large range of sizes has revealed: (1) that the lengths of the anterior two of three parallel arrays (membranelles) are rather tightly coordinated; (2) that the specific basal body configurations resulting from remodelling of the membranelles are only slightly affected by large changes in lengths of membranelles; and (3) that the third membranelle is restricted to a nearly constant length, except in the very largest OAs in which the structure is lengthened but interrupted by a gap in the middle. This gap may reveal the spatial extent of a putative zone of basal body regression. These phenomena are not specific to any of the genotypes utilized in this investigation; the effect of the mutations is to loosen quantitative restrictions and thus reveal underlying associations and constraints.

Ciliates exhibit an asymmetry in arrangement of surface structures around the cell which could be termed handedness. If the usual order of placement of structures defines a 'right-handed' (RH) cell, then a cell with this order reversed would be 'left-handed' (LH). Such LH forms appear to be produced in Tetrahymena thermophila through aberrant reorganization of homopolar doublets back to the singlet condition. Four clones of LH forms were selected and subjected to genetic analysis to test whether this drastic phenotypic alteration resulted from a nuclear genetic change. The results of this analysis indicate that the change in handedness is not due to a genetic change in either the micronucleus or macronucleus. The LH form can, under certain circumstances, revert to the RH form, but typically it propagates itself across both vegetative and sexual generations with similar fidelity. While this analysis does not formally rule out certain possibilities of nuclear genic control involving regulatory elements transmitted through the cytoplasm, when the circumstances of origin and propagation of the LH condition are taken into account direct cortical perpetuation seems far more likely. Here we outline a conceptual framework centred on the idea of longitudinally propagated positional information; the positive evidence supporting this idea as well as further application of the idea itself are presented in the accompanying paper.

The ciliary arrays of the oral apparatus of the ciliated protozoan Tetrahymena thermophila each have their own unique 'pattern signature', which varies little so long as the number of arrays remains the same. In this study, we analyse the consequence of increases in the number of these arrays (membranelles) brought about by certain mutations. In oral apparatuses of mutant cells, the addition of a membranelle is associated with specific alterations in at least one of the other membranelles. The features that are altered include the relative lengths of membranelles, the state of ciliation of basal bodies located at specific positions within these membranelles, and the spatial configurations resulting from displacement of ciliary units during late oral development. The final organization of each membranelle depends upon its relative position along the length of the oral apparatus. This indicates that the membranelles are not individually 'named' by the organism, and suggests that the unit of pattern organization is the membranelle field as a whole. In the Discussion, we consider means for testing whether the same underlying idea might also apply to multicellular systems, such as the vertebrate limb, in which spatially ordered differences appear to be superimposed upon a fundamental repeating pattern.