Genetic variation in serotonin transporter alters resting brain function in healthy individuals.

BACKGROUND: Perfusion functional magnetic resonance imaging (fMRI) was used to investigate the effect of genetic variation of the human serotonin transporter (5-HTT) gene (5-HTTLPR, SLC6A4) on resting brain function of healthy individuals. METHODS: Twenty-six healthy subjects, half homozygous for the 5-HTTLPR short allele (s/s group) and half homozygous for the long allele (l/l group), underwent perfusion functional and structural magnetic resonance imaging during a resting state. The two genotype groups had no psychiatric illness and were similar in age, gender, and personality scores. RESULTS: Compared with the l/l group, the s/s group showed significantly increased resting cerebral blood flow (CBF) in the amygdala and decreased CBF in the ventromedial prefrontal cortex. The effect of functional modulation in these regions by 5-HTTLPR genotype cannot be accounted for by variations in brain anatomy, personality, or self-reported mood. CONCLUSIONS: The 5-HTTLPR genotype alters resting brain function in emotion-related regions in healthy individuals, including the amygdala and ventromedial prefrontal cortex. Such alterations suggest a broad role of the 5-HTT gene in brain function that may be associated with the genetic susceptibility for mood disorders such as depression.     

Refining the Baveno VI elastography criteria for the definition of compensated advanced chronic liver disease

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Neurologic syndrome in 25 workers from an aluminum smelting plant.

BACKGROUND--This article expands on an earlier series of three patients with a neurologic syndrome, who had all worked in an aluminum smelting plant. METHODS--Twenty-five symptomatic workers from the same plant were referred for a standardized evaluation, including completion of a health questionnaire, neurologic examination, and neuropsychologic evaluation. An exposure index was calculated for each worker based on level and duration of exposure in the potroom, where exposures were the greatest. This index was correlated with symptoms, signs, and neuropsychologic test scores. RESULTS--Twenty-two (88%) of the patients reported frequent loss of balance, and 21 (84%) reported memory loss. Neurologic examination revealed signs of incoordination in 21 (84%) of the patients. Neuropsychologic test results showed preservation in certain spheres of functioning, such as verbal IQ, with substantial impairment in others, particularly memory functioning. On memory tests, 70% to 75% showed mild or greater impairment. The majority (17 of 19 tested, or 89%) showed depression on the Minnesota Multiphasic Personality Inventory. The exposure index was significantly correlated with signs and symptoms of incoordination. CONCLUSIONS--This study and others in humans and animals support the existence of a syndrome characterized by incoordination, poor memory, impairment in abstract reasoning, and depression. Aluminum exposure in the potroom seems the most likely cause.     

The Healthy Brains and Behavior Study: objectives,design, recruitment,and population coverage

Violence is increasingly viewed as a public health issue that may be ameliorated by health‐based interventions. The Healthy Brains and Behavior Study (HBBS) aims to identify environmental and biological risk factors for aggression in late childhood and to reduce aggression through psychological and nutritional treatments. Utilizing a cross‐disciplinary collaborative research approach, the HBBS has both human and animal components. The human component has two stages consisting of risk assessment followed by treatment. The risk assessment is based on 451 community‐residing children aged 11–12 years and their caregivers, during which genetic, brain imaging, neuroendocrine, psychophysiology, environment toxicology, neurocognitive, nutrition, psychological, social and demographic risk variables are collected. Children who met criteria (N = 219) for problematic aggressive behaviors were assigned to one of four treatment groups: cognitive‐behavior therapy (CBT) alone, nutritional supplements alone, both CBT and nutrition, or treatment‐as‐usual. Treatment duration was 12 weeks and all children whether in treatment or not were followed‐up at three, six, and 12 months. The animal component assessed the effects of dietary omega‐3 fatty acids on the development of aggression. This study contributes knowledge on how biological factors interact with social factors in shaping proactive and reactive aggression and assesses the efficacy of treatment approaches to reduce childhood aggression. Copyright © 2013 John Wiley & Sons, Ltd.     

Two pathways of exocytosis of cytoplasmic granule contents and target cell killing by cytokine-induced CD3+ CD56+ killer cells

Cytokine-induced killer (CIK) cells are non-major histocompatibility complex-restricted cytotoxic cells generated by incubation of peripheral blood lymphocytes with anti-CD3 monoclonal antibody (MoAb), interleukin-2 (IL-2), IL-1, and interferon-gamma. Cells with the greatest effector function in CIK cultures coexpress CD3 and CD56 surface molecules. CIK cell cytotoxicity can be blocked by MoAbs directed against the cell surface protein leukocyte function associated antigen-1 but not by anti-CD3 MoAbs. CIK cells undergo release of cytoplasmic cytotoxic granule contents to the extracellular space upon stimulation with anti-CD3 MoAbs or susceptible target cells. Maximal granule release was observed from the CD3+ CD56+ subset of effector cells. The cytoplasmic granule contents are lytic to target cells. Treatment of the effector cells with a cell-permeable analog of cyclic adenosine monophosphate (cAMP) inhibited anti-CD3 MoAb and target cell- induced degranulation and cytotoxicity of CIK cells. The immunosuppressive drugs cyclosporin (CsA) and FK506 inhibited anti-CD3- mediated degranulation, but did not affect cytotoxicity of CIK cells against tumor target cells. In addition, degranulation induced by target cells was unaffected by CsA and FK506. Our results indicate that two mechanisms of cytoplasmic granule release are operative in the CD3+ CD56+ killer cells; however, cytotoxicity proceeds through a cAMP- sensitive, CsA- and FK506-insensitive pathway triggered by yet-to-be- identified target cell surface molecules.     

The prognostic value of post-exercise blood pressure reduction in patients with hypertensive response during exercise stress test

BACKGROUND: Hypertensive response at peak-exercise and during the recovery phase of exercise stress test (ET) is associated with poor cardiovascular prognosis. We investigated whether decrease in blood pressure (BP) from peak to post-exercise would identify a subgroup at higher cardiovascular risk. METHODS: Eighty-six non-hypertensive patients (0-4 cardiovascular risk factors) with hypertensive reaction at peak-ET (systolic>180 mm Hg and/or diastolic>100 mm Hg) were divided based on BP 5 min after exercise termination into two groups: Normal response (NrmR) (<160/90 mm Hg), Hypertensive response (HypR) (>/=160/90 mm Hg). Five years later the prevalence of cardiovascular risk factors and cardiovascular morbidity and mortality was assessed for each group. RESULTS: Both groups had similar pre- and peak-exercise BP. However the HypR group had higher post-exercise BP (systolic: 163+/-13 vs. 125+/-14 mm Hg, respectively, p<0.01, and diastolic: 74+/-6 vs. 75+/-4 mm Hg, respectively, p<0.01), smaller decrease in BP after exercise (Delta systolic: 46.9+/-3.1 vs. 73.9+/-3.6 mm Hg, respectively, p<0.01, Delta diastolic: 12.4+/-1.5 vs. 26.5+/-2.2 mm Hg, respectively, p<0.01), and higher post- than pre-exercise BP (Delta systolic: 24.5+/-3.5 vs. -6+/-4.1 mm Hg, respectively, p<0.01, A diastolic: 19+/-2.1 vs. -13+/-2.3 mm Hg, respectively, p<0.01). Five years later, HypR group had higher prevalence of abnormal cholesterol serum level (p<0.01), hypertension (p<0.01) and combined ischemic heart disease and cerebrovascular disease (RR 1.32, 95% CI=1.13-1.54, p<0.01). CONCLUSION: During ET evaluation, it is important to evaluate the BP at 5 min after exercise because reduced BP drop, at this routinely measured point, identifies a subgroup with higher cardiovascular risk.