Mindfulness-based interventions in epilepsy: a systematic review

Mindfulness based interventions (MBIs) are increasingly used to help patients cope with physical and mental long-term conditions (LTCs). Epilepsy is associated with a range of mental and physical comorbidities that have a detrimental effect on quality of life (QOL), but it is not clear whether MBIs can help. We systematically reviewed the literature to determine the effectiveness of MBIs in people with epilepsy. Medline, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Allied and Complimentary Medicine Database, and PsychInfo were searched in March 2016. These databases were searched using a combination of subject headings where available and keywords in the title and abstracts. We also searched the reference lists of related reviews. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Three randomised controlled trials (RCTs) with a total of 231 participants were included. The interventions were tested in the USA (n = 171) and China (Hong Kong) (n = 60). Significant improvements were reported in depression symptoms, quality of life, anxiety, and depression knowledge and skills. Two of the included studies were assessed as being at unclear/high risk of bias - with randomisation and allocation procedures, as well as adverse events and reasons for drop-outs poorly reported. There was no reporting on intervention costs/benefits or how they affected health service utilisation. This systematic review found limited evidence for the effectiveness of MBIs in epilepsy, however preliminary evidence suggests it may lead to some improvement in anxiety, depression and quality of life. Further trials with larger sample sizes, active control groups and longer follow-ups are needed before the evidence for MBIs in epilepsy can be conclusively determined

Clustering of antibiotic resistance of E. coli in couples: suggestion for a major role of conjugal transmission

BACKGROUND: Spread of antibiotic resistance in hospitals is a well-known problem, but studies investigating the importance of factors potentially related to the spread of resistant bacteria in outpatients are sparse. METHODS: Stool samples were obtained from 206 healthy couples in a community setting in Southern Germany in 2002–2003. E. coli was cultured and minimal inhibition concentrations were tested. Prevalences of E. coli resistance to commonly prescribed antibiotics according to potential risk factors were ascertained. RESULTS: Prevalences of ampicillin resistance were 15.7% and 19.4% for women and men, respectively. About ten percent and 15% of all isolates were resistant to cotrimoxazole and doxycycline, respectively. A partner carrying resistance was the main risk factor for being colonized with resistant E. coli. Odds ratios (95% CI) for ampicillin and cotrimoxazole resistance given carriage of resistant isolates by the partner were 6.9 (3.1–15.5) and 3.3 (1.5–18.0), respectively. CONCLUSION: Our data suggest that conjugal transmission may be more important for the spread of antibiotic resistance in the community setting than commonly suspected risk factors such as previous antibiotic intake or hospital contacts

Ab initio alpha-alpha scattering

Processes involving alpha particles and alpha-like nuclei comprise a major part of stellar nucleosynthesis and hypothesized mechanisms for thermonuclear supernovae. In an effort towards understanding alpha processes from first principles, we describe in this letter the first ab initio calculation of alpha-alpha scattering. We use lattice effective field theory to describe the low-energy interactions of nucleons and apply a technique called the adiabatic projection method to reduce the eight-body system to an effective two-cluster system. We find good agreement between lattice results and experimental phase shifts for S-wave and D-wave scattering. The computational scaling with particle number suggests that alpha processes involving heavier nuclei are also within reach in the near future.Comment: 6 pages, 6 figure

Nuclear receptor NR2F6 inhibition potentiates responses to PD-L1/PD-1 cancer immune checkpoint blockade

Immune checkpoints blockade (ICB) is a viable anti-cancer strategy. Here the authors show that nuclear receptor NR2F6 acts as an immune checkpoint in T cells and, using mouse models and human T cells, they show NR2F6 inhibition might improve current ICB therapy or work as an alternative therapeutic strategy

In vitro studies on the modification of low-dose hyper-radiosensitivity in prostate cancer cells by incubation with genistein and estradiol

<p>Abstract</p> <p>Background</p> <p>As the majority of prostate cancers (PC) express estrogen receptors, we evaluated the combination of radiation and estrogenic stimulation (estrogen and genistein) on the radiosensitivity of PC cells in vitro.</p> <p>Methods</p> <p>PC cells LNCaP (androgen-sensitive) and PC-3 (androgen-independent) were evaluated. Estrogen receptor (ER) expression was analyzed by means of immunostaining. Cells were incubated in FCS-free media with genistein 10 μM and estradiol 10 μM 24 h before irradiation and up to 24 h after irradiation. Clonogenic survival, cell cycle changes, and expression of p21 were assessed.</p> <p>Results</p> <p>LNCaP expressed both ER-α and ER-β, PC-3 did not. Incubation of LNCaP and PC-3 with genistein resulted in a significant reduction of clonogenic survival. Incubation with estradiol exhibited in low concentrations (0.01 μM) stimulatory effects, while higher concentrations did not influence survival. Both genistein 10 μM and estradiol 10 μM increased low-dose hyper-radiosensitivity [HRS] in LNCaP, while hormonal incubation abolished HRS in PC-3. In LNCaP cells hormonal stimulation inhibited p21 induction after irradiation with 4 Gy. In PC-3 cells, the proportion of cells in G2/M was increased after irradiation with 4 Gy.</p> <p>Conclusion</p> <p>We found an increased HRS to low irradiation doses after incubation with estradiol or genistein in ER-α and ER-β positive LNCaP cells. This is of high clinical interest, as this tumor model reflects a locally advanced, androgen dependent PC. In contrast, in ER-α and ER-β negative PC-3 cells we observed an abolishing of the HRS to low irradiation doses by hormonal stimulation. The effects of both tested compounds on survival were ER and p53 independent. Since genistein and estradiol effects in both cell lines were comparable, neither ER- nor p53-expression seemed to play a role in the linked signalling. Nevertheless both compounds targeted the same molecular switch. To identify the underlying molecular mechanisms, further studies are needed.</p

Visualizing early splenic memory CD8+ T cells reactivation against intracellular bacteria in the mouse

International audienceMemory CD8(+) T cells represent an important effector arm of the immune response in maintaining long-lived protective immunity against viruses and some intracellular bacteria such as Listeria monocytogenes (L.m). Memory CD8(+) T cells are endowed with enhanced antimicrobial effector functions that perfectly tail them to rapidly eradicate invading pathogens. It is largely accepted that these functions are sufficient to explain how memory CD8(+) T cells can mediate rapid protection. However, it is important to point out that such improved functional features would be useless if memory cells were unable to rapidly find the pathogen loaded/infected cells within the infected organ. Growing evidences suggest that the anatomy of secondary lymphoid organs (SLOs) fosters the cellular interactions required to initiate naive adaptive immune responses. However, very little is known on how the SLOs structures regulate memory immune responses. Using Listeria monocytogenes (L.m) as a murine infection model and imaging techniques, we have investigated if and how the architecture of the spleen plays a role in the reactivation of memory CD8(+) T cells and the subsequent control of L.m growth. We observed that in the mouse, memory CD8(+) T cells start to control L.m burden 6 hours after the challenge infection. At this very early time point, L.m-specific and non-specific memory CD8(+) T cells localize in the splenic red pulp and form clusters around L.m infected cells while naïve CD8(+) T cells remain in the white pulp. Within these clusters that only last few hours, memory CD8(+) T produce inflammatory cytokines such as IFN-gamma and CCL3 nearby infected myeloid cells known to be crucial for L.m killing. Altogether, we describe how memory CD8(+) T cells trafficking properties and the splenic micro-anatomy conjugate to create a spatio-temporal window during which memory CD8(+) T cells provide a local response by secreting effector molecules around infected cells

The Morphological Identity of Insect Dendrites

Dendrite morphology, a neuron's anatomical fingerprint, is a neuroscientist's asset in unveiling organizational principles in the brain. However, the genetic program encoding the morphological identity of a single dendrite remains a mystery. In order to obtain a formal understanding of dendritic branching, we studied distributions of morphological parameters in a group of four individually identifiable neurons of the fly visual system. We found that parameters relating to the branching topology were similar throughout all cells. Only parameters relating to the area covered by the dendrite were cell type specific. With these areas, artificial dendrites were grown based on optimization principles minimizing the amount of wiring and maximizing synaptic democracy. Although the same branching rule was used for all cells, this yielded dendritic structures virtually indistinguishable from their real counterparts. From these principles we derived a fully-automated model-based neuron reconstruction procedure validating the artificial branching rule. In conclusion, we suggest that the genetic program implementing neuronal branching could be constant in all cells whereas the one responsible for the dendrite spanning field should be cell specific

An investigation into the validity of cervical spine motion palpation using subjects with congenital block vertebrae as a 'gold standard'

BACKGROUND: Although the effectiveness of manipulative therapy for treating back and neck pain has been demonstrated, the validity of many of the procedures used to detect joint dysfunction has not been confirmed. Practitioners of manual medicine frequently employ motion palpation as a diagnostic tool, despite conflicting evidence regarding its utility and reliability. The introduction of various spinal models with artificially introduced 'fixations' as an attempt to introduce a 'gold standard' has met with frustration and frequent mechanical failure. Because direct comparison against a 'gold standard' allows the validity, specificity and sensitivity of a test to be calculated, the identification of a realistic 'gold standard' against which motion palpation can be evaluated is essential. The objective of this study was to introduce a new, realistic, 'gold standard', the congenital block vertebra (CBV) to assess the validity of motion palpation in detecting a true fixation. METHODS: Twenty fourth year chiropractic students examined the cervical spines of three subjects with single level congenital block vertebrae, using two commonly employed motion palpation tests. The examiners, who were blinded to the presence of congenital block vertebrae, were asked to identify the most hypomobile segment(s). The congenital block segments included two subjects with fusion at the C2–3 level and one with fusion at C5-6. Exclusion criteria included subjects who were frankly symptomatic, had moderate or severe degenerative changes in their cervical spines, or displayed signs of cervical instability. Spinal levels were marked on the subject's skin overlying the facet joints from C1 to C7 bilaterally and the motion segments were then marked alphabetically with 'A' corresponding to C1-2. Kappa coefficients (K) were calculated to determine the validity of motion palpation to detect the congenitally fused segments as the 'most hypomobile' segments. Sensitivity and specificity of the diagnostic procedure were also calculated. RESULTS: Kappa coefficients (K) showed substantial overall agreement for identification of the segment of greatest hypomobility (K = 0.65), with substantial (K = 0.76) and moderate (K = 0.46) agreement for hypomobility at C2-3 and C5-6 respectively. Sensitivity ranged from 55% at the C5-6 CBV to 78% at the C2-3 level. Specificity of the procedure was high (91 – 98%). CONCLUSION: This study indicates that relatively inexperienced examiners are capable of correctly identifying inter-segmental fixations (CBV) in the cervical spine using 2 commonly employed motion palpation tests. The use of a 'gold standard' (CBV) in this study and the substantial agreement achieved lends support to the validity of motion palpation in detecting major spinal fixations in the cervical spine

Inhibition of cholesterol recycling impairs cellular PrPSc propagation

The infectious agent in prion diseases consists of an aberrantly folded isoform of the cellular prion protein (PrPc), termed PrPSc, which accumulates in brains of affected individuals. Studies on prion-infected cultured cells indicate that cellular cholesterol homeostasis influences PrPSc propagation. Here, we demonstrate that the cellular PrPSc content decreases upon accumulation of cholesterol in late endosomes, as induced by NPC-1 knock-down or treatment with U18666A. PrPc trafficking, lipid raft association, and membrane turnover are not significantly altered by such treatments. Cellular PrPSc formation is not impaired, suggesting that PrPSc degradation is increased by intracellular cholesterol accumulation. Interestingly, PrPSc propagation in U18666A-treated cells was partially restored by overexpression of rab 9, which causes redistribution of cholesterol and possibly of PrPSc to the trans-Golgi network. Surprisingly, rab 9 overexpression itself reduced cellular PrPSc content, indicating that PrPSc production is highly sensitive to alterations in dynamics of vesicle trafficking