Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia

We performed a meta-analysis of 3 genome-wide association studies to identify additional common variants influencing chronic lymphocytic leukemia (CLL) risk. The discovery phase was composed of genome-wide association study data from 1121 cases and 3745 controls. Replication analysis was performed in 861 cases and 2033 controls. We identified a novel CLL risk locus at 6p21.33 (rs210142; intronic to the BAK1 gene, BCL2 antagonist killer 1; P = 9.47 × 10(-16)). A strong relationship between risk genotype and reduced BAK1 expression was shown in lymphoblastoid cell lines. This finding provides additional support for polygenic inheritance to CLL and provides further insight into the biologic basis of disease development.     

Glycogen Synthase Kinase-3 Inhibitors as Potent Therapeutic Agents for the Treatment of Parkinson Disease.

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The role of mutual in-feeding in maintaining problematic self-narratives: Exploring one path to therapeutic failure

Abstract

According to the author's narrative model of change, clients may maintain a problematic self-stability across therapy, leading to therapeutic failure, by a mutual in-feeding process, which involves a cyclical movement between two opposing parts of the self. During innovative moments (IMs) in the therapy dialogue, clients’ dominant self-narrative is interrupted by exceptions to that self-narrative, but subsequently the dominant self-narrative returns. The authors identified return-to-the-problem markers (RPMs), which are empirical indicators of the mutual in-feeding process, in passages containing IMs in 10 cases of narrative therapy (five good-outcome cases and five poor-outcome cases) with females who were victims of intimate violence. The poor-outcome group had a significantly higher percentage of IMs with RPMs than the good-outcome group. The results suggest that therapeutic failures may reflect a systematic return to a dominant self-narrative after the emergence of novelties (IMs).     

Age protects from harmful effects produced by chronic intermittent hypoxia

Obstructive sleep apnoea (OSA) affects an estimated 3–7% of the adult population, the frequency doubling at ages >60–65 years. As it evolves, OSA becomes frequently associated with cardiovascular, metabolic and neuropsychiatric pathologies defining OSA syndrome (OSAS). Exposing experimental animals to chronic intermittent hypoxia (CIH) can be used as a model of the recurrent hypoxic and O₂ desaturation patterns observed in OSA patients. CIH is an important OSA event triggering associated pathologies; CIH induces carotid body (CB)‐driven exaggerated sympathetic tone and overproduction of reactive oxygen species, related to the pathogenic mechanisms of associated pathologies observed in OSAS. Aiming to discover why OSAS is clinically less conspicuous in aged patients, the present study compares CIH effects in young (3–4 months) and aged (22–24 months) rats. To define potential distinctive patterns of these pathogenic mechanisms, mean arterial blood pressure as the final CIH outcome was measured. In young rats, CIH augmented CB sensory responses to hypoxia, decreased hypoxic ventilation and augmented sympathetic activity (plasma catecholamine levels and renal artery content and synthesis rate). An increased brainstem integration of CB sensory input as a trigger of sympathetic activity is suggested. CIH also caused an oxidative status decreasing aconitase/fumarase ratio and superoxide dismutase activity. In aged animals, CIH minimally affected CB responses, ventilation and sympathetic‐related parameters leaving redox status unaltered. In young animals, CIH caused hypertension and in aged animals, whose baseline blood pressure was augmented, CIH did not augment it further. Plausible mechanisms of the differences and potential significance of these findings for the diagnosis and therapy of OSAS are discussed.

Abbreviations

24M

rats aged 22–24 months

24MCIH

rats aged 22–24 months exposed to chronic intermittent hypoxia

3M

rats aged 3–4 months

3MCIH

rats aged 3–4 months exposed to chronic intermittent hypoxia

A

adrenaline

AP

arterial pressure

CA

catecholamine

CB

carotid body

CI

confidence interval

CIH

chronic intermittent hypoxia

CRP

C‐reactive protein

CuZnSOD

cytoplasmic superoxide dismutase

DA

dopamine

E_GSH

glutathione redox potential

GPx

glutathione peroxidase

GSH

reduced glutathione

GSSG

oxidized glutathione

LPO

lipid peroxide

MnSOD

mitochondrial superoxide dismutase

MV

minute ventilation

NA

noradrenaline

NTS

nucleus of the tractus solitarius

OSA

obstructive sleep apnoea

OSAS

obstructive sleep apnoea syndrome

PaO₂

arterial oxygen pressure

RA

renal artery

ROS

reactive oxygen species

RVLM

rostroventrolateral medulla

SaO₂

arterial haemoglobin saturation

SOD

superoxide dismutase

SSA

5‐sulfosalicylic acid

TV

tidal volume

UA

upper airway

     

Effect of enamel matrix proteins on the treatment of intrabony defects: a split-mouth randomized controlled trial study

The objective of this split-mouth, double-blind, randomized controlled trial was to compare the clinical effect of treatment of 2- or 3-wall intrabony defects with open flap debridement (OFD) combined or not with enamel matrix proteins (EMP). Thirteen volunteers were selected with one pair of or more intrabony defects and probing pocket depth (PPD) > or = 5 mm. All individuals received instructions regarding oral hygiene and were submitted to scaling and root planing. Each participant received the two treatment modalities: test sites were treated with OFD and EMP, and control sites received only OFD. After 6 months, a significant reduction was observed in PPD for the EMP group (from 6.42 +/- 1.08 mm to 2.67 +/- 1.15 mm) and for the OFD group (from 6.08 +/- 1.00 mm to 2.00 +/- 0.95 mm) (p < 0.0001), but with no significant difference between groups (p = 0.13). A significant gain in relative attachment level (RAL) was observed in both groups (EMP: from 13.42 +/- 1.88 mm to 10.75 +/- 2.26 mm, p < 0.001; OFD: from 12.42 +/- 1.98 mm to 10.58 +/- 2.23 mm, p = 0.013), but with no significant difference between groups (p = 0.85). Gingival recession (GR) was higher in the EMP group (from 1.08 +/- 1.50 mm to 2.33 +/- 1.43 mm; p = 0.0009) than in the OFD group (from 0.66 +/- 1.15 mm to 1.16 +/- 1.33 mm; p = 0.16), but this difference was not significant (p = 0.06). In conclusion, the results showed that OFD combined with EMP was not able to improve treatment of intrabony defects compared to OFD alone.     

Disappearance of abnormal Q waves after aortocoronary bypass surgery

Sixty-one patients were selected from 100 consecutive patients undergoing aortocoronary artery bypass. The number of vessels diseased as defined by coronary arteriography and the number of bypass grafts were recorded. Review of the preoperative electrocardiograms showed an infarct pattern in 26 of the 61 patients and analysis of the postoperative electrocardiograms revealed loss of abnormal Q waves in 3 of the 26. The pre- and postoperative clinical course of these three patients is analyzed and the extent of their coronary artery disease and number of bypass grafts compared with those of the 23 patients who had persistence of the infarction pattern and the 17 patients who manifested new Q waves. Possible explanations for the disappearance of abnormal Q waves are discussed.     

Task difficulty in mental arithmetic affects microsaccadic rates and magnitudes

Microsaccades are involuntary, small‐magnitude saccadic eye movements that occur during attempted visual fixation. Recent research has found that attention can modulate microsaccade dynamics, but few studies have addressed the effects of task difficulty on microsaccade parameters, and those have obtained contradictory results. Further, no study to date has investigated the influence of task difficulty on microsaccade production during the performance of non‐visual tasks. Thus, the effects of task difficulty on microsaccades, isolated from sensory modality, remain unclear. Here we investigated the effects of task difficulty on microsaccades during the performance of a non‐visual, mental arithmetic task with two levels of complexity. We found that microsaccade rates decreased and microsaccade magnitudes increased with increased task difficulty. We propose that changes in microsaccade rates and magnitudes with task difficulty are mediated by the effects of varying attentional inputs on the rostral superior colliculus activity map.