Alcohol dependence is a complex disorder that initiates with episodes of excessive alcohol drinking known as binge drinking. It has a 50-60% risk contribution from inherited susceptibility genes; ...however, their exact identity and function are still poorly understood. We report that alcohol-preferring P rats have innately elevated levels of Toll-like receptor 4 (TLR4) and monocyte chemotactic protein-1 (MCP-1) that colocalize in neurons from the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA). To examine the potential role of a TLR4/MCP-1 signal, we used Herpes Simplex Virus (HSV) vectors (amplicons) that retain in vivo neurotropism. Infusion of amplicons for TLR4 or MCP-1 siRNA into the CeA or VTA from the P rats inhibited target gene expression and blunted binge drinking. A similarly delivered amplicon for scrambled siRNA did not inhibit TLR4 or MCP-1 expression nor reduce binge drinking, identifying a neuronal TLR4/MCP-1 signal that regulates the initiation of voluntary alcohol self-administration. The signal was sustained during alcohol drinking by increased expression of corticotropin-releasing factor and its feedback regulation of TLR4 expression, likely contributing to the transition to alcohol dependence.
•Increased cannabis use predict shorter sleep onset latency in young adults.•Higher levels of cannabis use predict lower sleep efficiency.•The associations of cannabis use levels with sleep were ...independent of depression.
The present study sought to determine the relationship between self-reported cannabis use dosage in grams per day with (1) objective sleep outcomes: sleep efficiency (SE), sleep onset latency SOL and number of night-time awakenings (NWAK) (2) if objective and subjective sleep measures, using the PSQI, differed between cannabis users and non-cannabis users.
Our sample included 178 participants, aged 18–35 years. We collected demographic information, cannabis use in dosage per day and frequency of use, depressive symptoms through the CESD, and subjective sleep reports using the PSQI. After the survey assessment, we monitored sleep using the Phillips Actiwatch Spectrum watch for a minimum of 5 nights.
The amount of cannabis consumed per day was inversely related to SOL and SE, and positively related to NWAK. After controlling for covariates, regression models were statistically significant for predicting SOL (β = -0.369, p <.001), SE (β = -0.232, p <.05) and NWAK, (β = -0.318, p <.001), indicating cannabis dosage per day is the strongest predictor for the sleep parameters. Subjective sleep measures did not differ from cannabis users versus non-cannabis users.
Recreational cannabis use is beneficial for SOL but may be detrimental to SE as those who reported increased cannabis use also had more NWAK. Cannabis may be useful for sleep onset, results suggest that increased use does not aid in sleep maintenance.
Heightened autonomic nervous system (ANS) arousal is a well-established contributor to the effect of stress on adverse cardiovascular health outcomes which disproportionately affect African ...Americans. ANS arousal is normally attenuated during sleep and compromise of this shift is associated with multiple adverse cardiovascular outcomes. Parasympathetic nervous system (PNS) dominance during sleep can be altered by stress. Racism has been recognized to have many negative health consequences in African Americans. Perceived racism has been linked to ANS activity, however, we are not aware of prior research on racism and nocturnal ANS balance. Objective: To examine relationships between perceived racism and nocturnal ANS activity indexed by heart rate variability (HRV) in healthy African American men and women age 18–35.
Fifty-four participants completed the Perceived Racism Scale and had 24-hour ambulatory electrocardiogram recordings in their homes. Power spectral analysis was used to derive normalized high frequency (nHF) to index PNS activity which was computed by 5-minute epochs during wake and sleep.
Endorsement of racism and negative emotional reactions during the past year were inversely related to nHF during time in bed. Multiple regression analysis indicated that negative emotional reactions were a significant predictor of nHF during the sleep period F(2,54) = 4.213, p = .020, R2 = 0.135 (adjusted R2 = 0.103). Relationships during wake were not statistically significant.
Findings suggest that perseverative thoughts triggered by negative emotional reactions to racism influencing nocturnal ANS activity may be a pathway by which perceived racism affects health.
Support: 3UL1TR001409-02S1 and R01HL087995 to Dr. Mellman.
•The association of perceived racism and vagal activity during sleep was marginally significant•A model with perceived racism and negative emotional response was significant in predicting vagal tone during sleep•Effects of perceived racism and negative emotional response on vagal tone could be a pathway where racism influences health
is a plant pathogen from the
family and a causative agent of the devastating agricultural disease fire blight. Here we characterize eight lytic bacteriophages of
that we isolated from the Wasatch ...front (Utah, United States) that are highly similar to vB_EamM_Ea35-70 which was isolated in Ontario, Canada. With the genome size ranging from 271 to 275 kb, this is a novel jumbo family of bacteriophages. These jumbo bacteriophages were further characterized through genomic and proteomic comparison, mass spectrometry, host range and burst size. Their proteomes are highly unstudied, with over 200 putative proteins with no known homologs. The production of 27 of these putative proteins was confirmed by mass spectrometry analysis. These bacteriophages appear to be most similar to bacteriophages that infect
and
rather than
bacteria by protein similarity, however, we were only able to detect infection of
and the closely related strains of
.
Summary
Compromised sleep and increased sympathetic nervous system (SNS) activity are implicated in the pathogenesis of, and disparities in, cardiovascular disease. Parasympathetic dominance during ...sleep may be important for cardiovascular health. Sleep and autonomic balance influence immune activity, which impacts atherogenesis. We evaluated relationships between autonomic balance during sleep and morning levels of the immune activating cytokines, C‐reactive protein (CRP) and interleukin (IL)‐6. Ninety‐four (59 female) young adult African Americans without medical conditions and substance use disorders spent 2 consecutive nights in a clinical research unit for sleep recordings and blood drawing on awakening. Cardiac tracings from the second sleep recording were analysed for heart rate variability (HRV). Body mass index was the only non‐HRV measure correlated with cytokine levels. Indicators of SNS activity for the presleep, and first non‐rapid eye movement (REM) and REM sleep periods were correlated independently with morning IL‐6 levels. Altered autonomic balance during sleep may be a modifiable factor that influences immune activation.
We used Drosophila olfactory memory as a model to study the molecular basis of cognitive defects in Fragile X syndrome in vivo. We observed that fragile X protein was acutely required and interacted ...with argonaute1 and staufen in the formation of long-term memory. Occlusion of long-term memory formation in Fragile X mutants could be rescued by protein synthesis inhibitors, suggesting that excess baseline protein synthesis could negatively affect cognition.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Childhood stress and trauma are associated with substance use disorders in adulthood, but the neurological changes that confer increased vulnerability are largely unknown. In this study, maternal ...separation (MS) stress, restricted to the pre-weaning period, was used as a model to study mechanisms of protracted effects of childhood stress/traumatic experiences on binge drinking and impulsivity. Using an operant self-administration model of binge drinking and a delay discounting assay to measure impulsive-like behavior, we report that early life stress due to MS facilitated acquisition of binge drinking and impulsivity during adulthood in rats. Previous studies have shown heightened levels of corticotropin releasing factor (CRF) after MS, and here, we add that MS increased expression levels of GABA(A) α2 subunit in central stress circuits. To investigate the precise role of these circuits in regulating impulsivity and binge drinking, the CRF1 receptor antagonist antalarmin and the novel GABA(A) α2 subunit ligand 3-PBC were infused into the central amygdala (CeA) and medial prefrontal cortex (mPFC). Antalarmin and 3-PBC at each site markedly reduced impulsivity and produced profound reductions on binge-motivated alcohol drinking, without altering responding for sucrose. Furthermore, whole-cell patch-clamp studies showed that low concentrations of 3-PBC directly reversed the effect of relatively high concentrations of ethanol on α2β3γ2 GABA(A) receptors, by a benzodiazepine site-independent mechanism. Together, our data provide strong evidence that maternal separation, i.e. early life stress, is a risk factor for binge drinking, and is linked to impulsivity, another key risk factor for excessive alcohol drinking. We further show that pharmacological manipulation of CRF and GABA receptor signaling is effective to reverse binge drinking and impulsive-like behavior in MS rats. These results provide novel insights into the role of the brain stress systems in the development of impulsivity and excessive alcohol consumption.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To compare long-acting reversible contraceptive (LARC) uptake before and after the Affordable Care Act (ACA) contraceptive mandate among women undergoing a first trimester surgical abortion.
We ...conducted a retrospective chart review of 867 women undergoing a first trimester surgical abortion at an academic gynecology practice between December 2010 and December 2014 (excluding August to December 2012) to evaluate intrauterine device and contraceptive implant uptake before and after the ACA contraceptive mandate.
Before the ACA contraceptive mandate, 79% of privately insured women (213 of 271) had full LARC coverage (no out-of-pocket costs) compared with 92% (298 of 324) after the mandate (p < .001). We found no difference in postabortal LARC uptake before and after the ACA in women with private insurance, Medicaid, or overall. Among all women, 46% chose a postabortal LARC method before the mandate as compared with 48% after the mandate (p = .63). Among privately insured women, 45% used a postabortal LARC method before the mandate as compared with 50% after the mandate (p = .25). One-half of privately insured women (268 of 534) with full or partial LARC coverage used a postabortal LARC method compared with 32% of privately insured women (18 of 56) with no LARC coverage after implementation of the ACA contraceptive mandate (p = .01).
Despite the significant increase in full coverage of LARC among privately insured women, there was no change in postabortal LARC use after the ACA. However, privately insured women with full or partial LARC coverage were more likely to use a postabortal LARC method compared with privately insured women with no LARC coverage after the implementation of the ACA contraceptive mandate.
Drosophila model for Angelman syndrome Wu, Yaning; Bolduc, Francois V; Bell, Kimberly ...
Proceedings of the National Academy of Sciences - PNAS,
08/2008, Letnik:
105, Številka:
34
Journal Article
Recenzirano
Odprti dostop
Angelman syndrome is a neurological disorder whose symptoms include severe mental retardation, loss of motor coordination, and sleep disturbances. The disease is caused by a loss of function of ...UBE3A, which encodes a HECT-domain ubiquitin ligase. Here, we generate a Drosophila model for the disease. The results of several experiments show that the functions of human UBE3A and its fly counterpart, dube3a, are similar. First, expression of Dube3a is enriched in the Drosophila nervous system, including mushroom bodies, the seat of learning and memory. Second, we have generated dube3a null mutants, and they appear normal externally, but display abnormal locomotive behavior and circadian rhythms, and defective long-term memory. Third, flies that overexpress Dube3a in the nervous system also display locomotion defects, dependent on the ubiquitin ligase activity. Finally, missense mutations in UBE3A alleles of Angelman syndrome patients alter amino acid residues conserved in the fly protein, and when introduced into dube3a, behave as loss-of-function mutations. The simplest model for Angelman syndrome is that in the absence of UBE3A, particular substrates fail to be ubiquitinated and proteasomally degraded, accumulate in the brain, and interfere with brain function. We have generated flies useful for genetic screens to identify Dube3a substrates. These flies overexpress Dube3a in the eye or wing and display morphological abnormalities, dependent on the critical catalytic cysteine. We conclude that dube3a mutants are a valid model for Angelman syndrome, with great potential for identifying the elusive UBE3A substrates relevant to the disease.
Background Controversy exists regarding the optimal technique of subscapularis mobilization during shoulder arthroplasty. The purpose of this study was to compare healing rates and subscapularis ...fatty infiltration in patients undergoing a lesser tuberosity osteotomy (LTO) versus subscapularis peel for exposure during shoulder arthroplasty. Materials and methods Eighty-seven patients, with a mean age of 67.8 ± 10.9 years, undergoing shoulder arthroplasty, were randomized to receive either an LTO (n = 43) or peel (n = 44). Computed tomography scans were conducted preoperatively and at 12 months postoperatively. Outcome variables included healing rates and subscapularis Goutallier fatty infiltration grade, as well as subscapularis strength and Western Ontario Osteoarthritis of the Shoulder Index and American Shoulder and Elbow Surgeons outcome scores. Results Computed tomography imaging was available in 91% (n = 79) of the cohort. The healing rates for the peel (100%) and for the LTO (95%) did not differ significantly ( P = .493). Preoperatively, the mean fatty infiltration grade for the peel (mean, 0.53) was not significantly different ( P = .925) from the LTO (mean, 0.54). Postoperatively, the Goutallier mean fatty infiltration grade for the peel (mean, 0.95) did not differ significantly ( P = .803) from the LTO (mean, 0.9). A significant increase in subscapularis fatty infiltration grade occurred postoperatively from the preoperative status (peel, P = .003; LTO, P = .0002). No statistically significant associations were observed between postoperative fatty infiltration grades and subscapularis strength, Western Ontario Osteoarthritis of the Shoulder Index scores, or American Shoulder and Elbow Surgeons scores. Discussion No statistically significant differences were observed in the healing rates or subscapularis fatty infiltration grades between the peel and the LTO. This trial does not show any clear difference in radiologic and clinical outcomes of one subscapularis management technique over the other.
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