The Rewarding Nature of Provocation-Focused Rumination in Women with Borderline Personality Disorder: A Preliminary fMRI Investigation

Background: Understanding why individuals with borderline personality disorder (BPD) ruminate on prior provocations, despite its negative outcomes, is crucial to improving interventions. Provocation-focused rumination may be rewarding in the short term by amplifying anger and producing feelings of justification, validation, and increased energy, while reducing self-directed negative affect. If provocation-focused rumination is utilized regularly as a rewarding emotion regulation strategy, it could result in increased activation in reward-related neural regions. The present pilot study examined neural correlates of provocation-focused rumination, relative to other forms of thought, in BPD. Method: Functional magnetic resonance imaging (fMRI) was utilized to examine this theory in a pilot study of women diagnosed with BPD (n = 13) and healthy controls (n = 16). All participants received highly critical feedback on a previously written essay in the scanner, followed by prompts to engage in provocation-focused, self-focused, and neutral thought. Results: Whole-brain analyses showed that in response to the provocation, participants with BPD (compared to controls) demonstrated increased activation in the ventrolateral prefrontal cortex (PFC). BPD participants also showed greater activation in the dorsomedial PFC during provocation-focused rumination (relative to neutral-focus). Subsequent ROI analyses revealed that provocation-focused rumination (compared to neutral-focus) increased activation in the nucleus accumbens for the BPD group only. Conclusions: These findings, while preliminary due to the small sample size and limitations of the protocol, provide initial data consistent with the proposed neurobiological mechanism promoting provocation-focused rumination in BPD. Directions for further research are discussed

Isolation of Phosphatidylethanolamine as a Solitary Cofactor for Prion Formation in the Absence of Nucleic Acids

Infectious prions containing the pathogenic conformer of the mammalian prion protein (PrP(Sc)) can be produced de novo from a mixture of the normal conformer (PrP(C)) with RNA and lipid molecules. Recent reconstitution studies indicate that nucleic acids are not required for the propagation of mouse prions in vitro, suggesting the existence of an alternative prion propagation cofactor in brain tissue. However, the identity and functional properties of this unique cofactor are unknown. Here, we show by purification and reconstitution that the molecule responsible for the nuclease-resistant cofactor activity in brain is endogenous phosphatidylethanolamine (PE). Synthetic PE alone facilitates conversion of purified recombinant (rec)PrP substrate into infectious recPrP(Sc) molecules. Other phospholipids, including phosphatidylcholine, phosphatidylserine, phosphatidylinositol, and phosphatidylglycerol, were unable to facilitate recPrP(Sc) formation in the absence of RNA. PE facilitated the propagation of PrP(Sc) molecules derived from all four different animal species tested including mouse, suggesting that unlike RNA, PE is a promiscuous cofactor for PrP(Sc) formation in vitro. Phospholipase treatment abolished the ability of brain homogenate to reconstitute the propagation of both mouse and hamster PrP(Sc) molecules. Our results identify a single endogenous cofactor able to facilitate the formation of prions from multiple species in the absence of nucleic acids or other polyanions

The rewarding nature of provocation-focused rumination in women with borderline personality disorder: a preliminary fMRI investigation

Abstract Background Understanding why individuals with borderline personality disorder (BPD) ruminate on prior provocations, despite its negative outcomes, is crucial to improving interventions. Provocation-focused rumination may be rewarding in the short term by amplifying anger and producing feelings of justification, validation, and increased energy, while reducing self-directed negative affect. If provocation-focused rumination is utilized regularly as a rewarding emotion regulation strategy, it could result in increased activation in reward-related neural regions. The present pilot study examined neural correlates of provocation-focused rumination, relative to other forms of thought, in BPD. Method Functional magnetic resonance imaging (fMRI) was utilized to examine this theory in a pilot study of women diagnosed with BPD (n = 13) and healthy controls (n = 16). All participants received highly critical feedback on a previously written essay in the scanner, followed by prompts to engage in provocation-focused, self-focused, and neutral thought. Results Whole-brain analyses showed that in response to the provocation, participants with BPD (compared to controls) demonstrated increased activation in the ventrolateral prefrontal cortex (PFC). BPD participants also showed greater activation in the dorsomedial PFC during provocation-focused rumination (relative to neutral-focus). Subsequent ROI analyses revealed that provocation-focused rumination (compared to neutral-focus) increased activation in the nucleus accumbens for the BPD group only. Conclusions These findings, while preliminary due to the small sample size and limitations of the protocol, provide initial data consistent with the proposed neurobiological mechanism promoting provocation-focused rumination in BPD. Directions for further research are discussed

Sequential multiple assignment randomised trial to develop an adaptive mobile health intervention to increase physical activity in people poststroke in the community setting in Ireland: TAPAS trial protocol

INTRODUCTION: Stroke is the second-leading cause of death and disability globally. Participation in physical activity (PA) is a cornerstone of secondary prevention in stroke care. Given the heterogeneous nature of stroke, PA interventions that are adaptive to individual performance are recommended. Mobile health (mHealth) has been identified as a potential approach to supporting PA poststroke. To this end, we aim to use a Sequential Multiple Assignment Randomised Trial (SMART) design to develop an adaptive, user-informed mHealth intervention to improve PA poststroke. METHODS AND ANALYSIS: The components included in the 12-week intervention are based on empirical evidence and behavioural change theory and will include treatments to increase participation in Structured Exercise and Lifestyle or a combination of both. 117 participants will be randomly assigned to one of the two treatment components. At 6 weeks postinitial randomisation, participants will be classified as responders or non-responders based on participants' change in step count. Non-responders to the initial treatment will be randomly assigned to a different treatment allocation. The primary outcome will be PA (steps/day), feasibility and secondary clinical and cost outcomes will also be included. A SMART design will be used to evaluate the optimum adaptive PA intervention among community-dwelling, ambulatory people poststroke. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Health Service Executive Mid-Western Ethics Committee (REC Ref: 026/2022). The findings will be submitted for publication and presented at relevant national and international academic conferences.</p

Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber

The Leo IV dwarf spheroidal galaxy: color-magnitude diagram and pulsating stars

We present the first V, B-V color-magnitude diagram of the Leo IV dwarf spheroidal galaxy, a faint Milky Way satellite recently discovered by the Sloan Digital Sky Survey. We have obtained B,V time-series photometry reaching about half a magnitude below the Leo IV turnoff, which we detect at V= 24.7 mag, and have performed the first study of the variable star population. We have identified three RR Lyrae stars (all fundamental-mode pulsators, RRab) and one SX Phoenicis variable in the galaxy. In the period-amplitude diagram the Leo IV RR Lyrae stars are located close to the loci of Oosterhoff type I systems and the evolved fundamental-mode RR Lyrae stars in the Galactic globular cluster M3. However, their mean pulsation period, $$=0.655 days, would suggest an Oosterhoff type II classification for this galaxy. The RR Lyrae stars trace very well the galaxy's horizontal branch, setting its average magnitude at $= 21.48 \pm 0.03$ mag (standard deviation of the mean). This leads to a distance modulus of $\mu_{0}=20.94 \pm 0.07$ mag, corresponding to a distance of $154 \pm 5$ kpc, by adopting for the Leo IV dSph a reddening $E(B-V) = 0.04 \pm 0.01$ mag and a metallicity of [Fe/H] = -2.31 $\pm$ 0.10.Comment: 14 pages, 4 figures, accepted for publication on The Astrophysical Journal Letter

Antibacterial activity of some selected medicinal plants of Pakistan

<p>Abstract</p> <p>Background</p> <p>Screening of the ethnobotenical plants is a pre-requisite to evaluate their therapeutic potential and it can lead to the isolation of new bioactive compounds.</p> <p>Methods</p> <p>The crude extracts and fractions of six medicinal important plants (<it>Arisaema flavum</it>, <it>Debregeasia salicifolia</it>, <it>Carissa opaca</it>, <it>Pistacia integerrima</it>, <it>Aesculus indica</it>, and <it>Toona ciliata</it>) were tested against three Gram positive and two Gram negative ATCC bacterial species using the agar well diffusion method.</p> <p>Results</p> <p>The crude extract of <it>P. integerrima </it>and <it>A. indica </it>were active against all tested bacterial strains (12-23 mm zone of inhibition). Other four plant's crude extracts (<it>Arisaema flavum</it>, <it>Debregeasia salicifolia</it>, <it>Carissa opaca</it>, and <it>Toona ciliata</it>) were active against different bacterial strains. The crude extracts showed varying level of bactericidal activity. The aqueous fractions of <it>A. indica </it>and <it>P. integerrima </it>crude extract showed maximum activity (19.66 and 16 mm, respectively) against <it>B. subtilis</it>, while the chloroform fractions of <it>T. ciliata </it>and <it>D. salicifolia </it>presented good antibacterial activities (13-17 mm zone of inhibition) against all the bacterial cultures tested.</p> <p>Conclusion</p> <p>The methanol fraction of <it>Pistacia integerrima</it>, chloroform fractions of <it>Debregeasia salicifolia </it>&<it>Toona ciliata </it>and aqueous fraction of <it>Aesculus indica </it>are suitable candidates for the development of novel antibacterial compounds.</p

The Structure of the Homunculus: I. Shape and Latitude Dependence from H2 and [Fe II] Velocity Maps of Eta Carinae

High resolution long-slit spectra obtained with the Phoenix spectrograph on Gemini South provide our most accurate probe of the three dimensional structure of the Homunculus around eta Car. The new near-infrared spectra dramatically confirm the double-shell structure inferred previously from thermal dust emission, resolving the nebula into a very thin outer shell seen in H2 21218, and a warmer, thicker inner layer seen in [Fe II] 16435. The thin H2 skin hints that the most important mass loss during the 19th century eruption had a very short duration of less than 5 yr. H2 emission traces the majority of the mass in the nebula, and has an average density of order 10^6.5 cm-3. This emission, in turn, yields our first definitive picture of the exact shape of the nebula, plus a distance of 2350pm50 pc and an inclination angle of 41deg (the polar axis is tilted 49deg from the plane of the sky). The distribution of the H2 emission provides the first measure of the latitude dependence of the speed, mass loss, and kinetic energy associated with eta Car's 19th century explosion. Almost 75 percent of the total mass and more than 90 percent of the kinetic energy in the ejecta were released at high latitudes. This rules out a model for the bipolar shape wherein an otherwise spherical explosion was pinched at the waist by a circumstellar torus. Also, the ejecta could not have been deflected toward polar trajectories by a companion star, since the kinetic energy of the polar ejecta is greater than the binding energy of the putative binary system. Instead, most of the mass appears to have been directed poleward by the explosion itself. [abridged]Comment: 25 pages, figs 2 and 3 in color. Accepted by Ap