Adverse childhood experiences and alcohol related negative consequence among college student drinkers.

OBJECTIVE: Despite increasing college campus prevention efforts, and identification of effective strategies to reduce drinking, reducing alcohol related negative consequences (ARNC, e.g., regrets, blackouts, self- and other- injury, law enforcement exposure, sexual assault, and considering suicide) continues to be a challenge. While college students with a history of adverse childhood experiences (ACE) are at greater risk for alcohol misuse, research regarding the association between ACE and ARNC remains limited. METHODS: Data are responses of currently drinking students on the American College Health Association-National College Health Assessment (ACHA-NCHA II) and College Student Health Survey (CSHS), administered in 2018 to students in California and Minnesota (N = 6,667). RESULTS: On average, students reported one ARNC (SD = 1.30) although 13 % experienced three or more different types of ARNC in the past year. Every ACE was associated with a 19 % to 41 % increase in the IRR of ARNC. Students with 1-3 ACE experienced significantly more types of ARNC events (IRR 1.55, 95 % CI: 1.44-1.67) than students with no ACE and students with ≥ 4 ACE experienced statistically significantly more types of ARNC events (IRR 2.04, 95 % CI: 1.82-2.31) than their peers with 1-3 or no ACE. The ACE-ARNC relationship did not vary by drinking frequency or binge drinking. CONCLUSIONS: The consistent ACE - ARNC relationship across drinking behaviors suggests alcohol consumption does not fully explain the association between ACE and ARNC and that early adversity heightens vulnerability for ARNC. Implications for future prevention and intervention efforts are discussed.

Why does the UK need a Human Taphonomy Facility?

Human Taphonomy Facilities (HTFs) are outdoor laboratories where scientific research is carried out on donated human cadavers in order to understand how human decomposition progresses in a variety of conditions. There are currently eight such facilities in the USA, one in Australia and one on mainland Europe. Forensic scientists in the UK have started to ask the question 'Does the UK need a Human Taphonomy Facility?'. A review of the literature produced by the existing HTFs, as well as published opinion and commentaries about these facilities and the feasibility of one in the UK has been undertaken. The existing arguments for and against the establishment of a Human Taphonomy Facility in the UK have been examined. Given recent media interest in the possibility of the establishment of a Human Taphonomy Facility in the UK, and the surrounding controversy, it is important to evaluate the potential benefit or harm of the creation of such a facility to Society and the scientific community.

Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) α1.

OBJECTIVE: Development of brown-like/beige adipocytes in white adipose tissue (WAT) helps to reduce obesity. Thus we investigated the effects of resveratrol, a dietary polyphenol capable of preventing obesity and related complications in humans and animal models, on brown-like adipocyte formation in inguinal WAT (iWAT). METHODS: CD1 female mice (5-month old) were fed a high-fat diet with/without 0.1% resveratrol. In addition, primary stromal vascular cells separated from iWAT were subjected to resveratrol treatment. Markers of brown-like (beige) adipogenesis were measured and the involvement of AMP-activated protein kinase (AMPK) α1 was assessed using conditional knockout. RESULTS: Resveratrol significantly increased mRNA and/or protein expression of brown adipocyte markers, including uncoupling protein 1 (UCP1), PR domain-containing 16, cell death-inducing DFFA-like effector A, elongation of very long-chain fatty acids protein 3, peroxisome proliferator-activated receptor-γ coactivator 1α, cytochrome c and pyruvate dehydrogenase, in differentiated iWAT stromal vascular cells (SVCs), suggesting that resveratrol induced brown-like adipocyte formation in vitro. Concomitantly, resveratrol markedly enhanced AMPKα1 phosphorylation and differentiated SVC oxygen consumption. Such changes were absent in cells lacking AMPKα1, showing that AMPKα1 is a critical mediator of resveratrol action. Resveratrol also induced beige adipogenesis in vivo along with the appearance of multiocular adipocytes, increased UCP1 expression and enhanced fatty acid oxidation. CONCLUSIONS: Resveratrol induces brown-like adipocyte formation in iWAT via AMPKα1 activation and suggest that its beneficial antiobesity effects may be partly due to the browning of WAT and, as a consequence, increased oxygen consumption.

Maternal obesity downregulates microRNA let-7g expression, a possible mechanism for enhanced adipogenesis during ovine fetal skeletal muscle development.

BACKGROUND: Obesity in women of childbearing age is increasing at an alarming rate. Growing evidence shows that maternal obesity induces detrimental effects on offspring health, including pre-disposition to obesity. We have shown that maternal obesity increases fetal intramuscular adipogenesis at mid-gestation. However, the mechanisms are poorly understood. MicroRNAs (miRNAs) regulate mRNA stability. We hypothesized that maternal obesity alters fetal muscle miRNA expression, thereby influencing intramuscular adipogenesis. METHODS: Non-pregnant ewes received a control diet (Con, fed 100% of National Research Council (NRC) recommendations, n=6) or obesogenic diet (OB; 150% NRC recommendations, n=6) from 60 days before to 75 days after conception when the fetal longissimus dorsi (LD) muscle was sampled and miRNA expression analyzed by miRNA microarray. One of miRNAs with differential expression between Con and OB fetal muscle, let-7g, was further tested for its role in adipogenesis and cell proliferation in C3H10T1/2 cells. RESULTS: A total of 155 miRNAs were found with a signal above 500, among which, three miRNAs, hsa-miR-381, hsa-let-7g and bta-miR-376d, were differentially expressed between Con and OB fetuses, and confirmed by quantitative real-time PCR (QRT-PCR) analyses. Reduced expression of miRNA let-7g, an abundantly expressed miRNA, in OB fetal muscle was correlated with higher expression of its target genes. Overexpression of let-7g in C3H10T1/2 cells reduced their proliferation rate. Expression of adipogenic markers decreased in cells overexpressing let-7g, and the formation of adipocytes was also reduced. Overexpression of let-7g decreased expression of inflammatory cytokines. CONCLUSION: Fetal muscle miRNA expression was altered due to maternal obesity, and let-7g downregulation may enhance intramuscular adipogenesis during fetal muscle development in the setting of maternal obesity.

Treatment of pseudofolliculitis barbae using the Q-switched Nd:YAG laser with topical carbon suspension.

BACKGROUND: Pseudofolliculitis barbae (PFB) is a condition caused by ingrown hairs of the face. No treatment to date has shown long-term effectiveness without risk of side effects or ease of treatment. OBJECTIVE: The goal of this pilot study was to evaluate the use of the topical suspension-assisted Q-switched Nd:YAG laser in the treatment of PFB. METHODS: Nine patients were given two treatments 1 month apart and assessed by objective papule/pustule counts at 1 and 2 months after final treatment. Treatment sites were 9 cm2 regions on the mandible and neck, with contralateral controls. Patients also performed subjective evaluations. RESULTS: Reduction in the quantity of papules and pustules when compared with baseline was statistically significant for treatment of the mandibular region and combined sites at 1- and 2-month evaluations, as well as the neck region at the 2-month evaluation. CONCLUSION: Use of the Q-switched Nd:YAG laser with topical carbon suspension is an effective means of treating PFB, with results persisting at least 2 months after treatment.

Hair removal using topical suspension-assisted Q-switched Nd:YAG and long-pulsed alexandrite lasers: A comparative study.

BACKGROUND: The use of lasers for removal of unwanted hair has been shown to be effective in temporarily controlling hair growth. Several lasers are currently utilized for this purpose. OBJECTIVE: This study evaluates the short-term effectiveness and discomfort levels of the long-pulsed alexandrite laser and the topical suspension-assisted Q-switched Nd:YAG laser in a side-by-side comparison. METHODS: Fifteen subjects were treated in the bilateral hair-bearing axilla, using one treatment with the alexandrite laser for the right and two treatments with the topical suspension-assisted Nd:YAG laser for the left. Reduction in hair regrowth was measured at 2 and 3 months following the first treatment by comparing the terminal hair count to the baseline values. Patients rated their pain on a scale of 0-10 immediately following the first treatment at each site. RESULTS: The mean percentage reduction in hair regrowth 2 months following alexandrite laser treatment was 55% and 73% for the Nd:YAG laser-treated regions. After 3 months, alexandrite laser-treated patients showed a reduction of 19%, while Nd:YAG laser-treated patients showed a 27% reduction. Patients reported average pain values of 8 and 4 for the long-pulsed alexandrite and Nd:YAG laser sites, respectively. All differences were significant. CONCLUSION: While the design of this study makes it difficult to compare the relative effectiveness of the lasers, both systems evaluated were shown to delay hair growth and provide patients with a satisfactory treatment.

Acute stress impairs NK cell adhesion and cytotoxicity through CD2, but not LFA-1.

Using a nonhuman primate model, we examined the mechanisms by which acute social stress inhibits the ability of NK cells to form conjugates with, and lyse target cells. We examined the expression and role of the primary NK cell adhesion molecules, CD2 and LFA-1, in mediating conjugation to target cells. Acute stress induced a decrease in NK cell expression of CD2 (17+/-3%); and to a lesser degree induced a decrease in expression of LFA-1 (CD11a: 8+/-3%; CD18: 7+/-3%). Antibody blocking studies indicated that anti-LFA-1 significantly inhibited NK cell conjugate formation and cytotoxicity in both control (approximately 40% and approximately 50%, respectively) and stressed (approximately 20% and approximately 45%, respectively) conditions. However, anti-CD2 blocked conjugation and cytotoxicity in the control condition by approximately 50%, but had no capacity to further affect the inhibition of conjugation or cytotoxicity of NK cells induced by acute stress. These data indicate that there are differential effects of acute stress on the expression and function of LFA-1 and CD2, and that the stress-induced inhibition of NK cell adhesion and cytotoxicity is dependent upon modulation of adhesion and/or signalling through CD2.

Cimetidine therapy for recalcitrant warts in adults: is it any better than placebo?

Three open-label, uncontrolled studies have documented successful treatment of warts with cimetidine, whereas two placebo-controlled, double-blind studies and two open-label comparative trials have failed to demonstrate efficacy. This double-blind, placebo-controlled study was designed with stringent enrollment and outcome criteria to minimize the confounding issue of spontaneous remission. Efficacy was not statistically superior to that of placebo, but a trend toward efficacy was suggested for younger subjects.

Selective reduction in CD2 expression on CD2bright/CD8+ lymphocytes from cynomolgus monkeys (Macaca fascicularis) in response to acute stress.

Numerous reports have demonstrated a link between stressful stimuli and immune suppression. However, the cellular mechanisms by which stress impairs immune function are largely unknown. We have examined the effects of an acute stressor on the T cell population, specifically, the number and phenotype of T cells in a nonhuman primate model. In nonstressed adult monkeys, we found differences in the level of expression of CD2 on T cells, revealing two distinct subsets of T cells, CD2dim and CD2bright cells, with CD2bright cells predominately coexpressing CD8. In response to acute stress, we observed a significant loss in the number and percent of CD2bright/CD8+ cells, with percent of CD2bright cells returning to pre-stress values within 24 h.

Spontaneous bladder perforation in paraplegia as a late complication of augmentation enterocystoplasty: case report.

The management of spinal cord injured (SCI) patients with small capacity, noncompliant bladders has focused on the preservation of renal function and social continence. When conservative management is unsuccessful, surgical intervention may prove beneficial. Augmentation enterocystoplasty is a reliable method of achieving increased bladder capacity while decreasing intravesical filling pressure. Spontaneous bladder rupture is a rare complication of augmentation enterocystoplasty. Because the urine is often colonized with bacteria, bladder rupture may result in chemical and bacterial peritonitis, which is associated with a 25% mortality rate. SCI patients may not present with the classic signs of an acute abdomen. Early diagnosis is critical so that aggressive management may be instituted. The case of late spontaneous perforation of an augmentation enterocystoplasty in a 33-year-old man with T7 complete paraplegia is presented, and the literature discussing the etiology, diagnosis, management, and prevention of augmented bladder perforation is reviewed.

Cystic fibrosis carrier screening in two New South Wales country towns.

OBJECTIVE: To assess the feasibility of offering community testing for carrier status of delta F508, a gene mutation associated with cystic fibrosis (CF). DESIGN: Prospective pilot survey. SETTING: General practice, the two main high schools and workplaces in the country towns of Young and Harden (combined population, 14,940; with 7707 people aged 16-55 years) in New South Wales (NSW). PARTICIPANTS: Individuals aged 16 years and over. MAIN OUTCOME MEASURES: Number of delta F508 carriers, test uptake rates, mode of learning about the testing, motivation for testing, retention of knowledge about CF, and test results and emotional effects of knowledge about carrier status. RESULTS: We tested 610 people (8% of the population aged 16-55 years) and identified 47 carriers (20% of the expected number in the 7707 people aged 16-55 years). Testing in schools had the highest uptake. Retention of knowledge was high; all delta F508-positive individuals recalled their carrier status accurately. Anxiety was transient among carriers; over 90% of all respondents felt they had made the right decision to be tested. CONCLUSIONS: We recommend community testing for carrier detection and suggest targeting those with a family history of CF and girls aged over 16 in high schools.

The special/general education integration initiative for students with specific learning disabilities: a "snapshot" of program change.

As part of a broader investigation, this study sought to (a) provide a statewide "snapshot" of educators' views regarding the current status of and process associated with increased integration efforts for serving students with specific learning disabilities (SLD) in Virginia, and (b) document factors serving as the basis of or creating reluctance toward such efforts. Survey respondents included the population of special education supervisors and samples of general education supervisors, building principals, general secondary and elementary education teachers, and LD teachers (N = 788). Results suggest active efforts to increase the amount of time students with SLD spend in general classroom settings; however, limited program change-related guidelines or category-specific outcome-monitoring measures were reported. Across groups, participants expressed doubts regarding the adequacy of general education teachers' skills for making needed instructional adaptations. Over half of the respondents tended to disagree or disagreed that general education teachers were willing to make needed adaptations for students with SLD. Differences in the views expressed by the different respondent groups were examined.

Infection control in critically ill patients: effects of selective decontamination of the digestive tract.

The use of selective decontamination of the digestive tract (SDD) to control infection in the intensive care unit (ICU) is reviewed. There are three basic patterns of infection in the ICU: primary endogenous, secondary endogenous, and exogenous. In exogenous infection, no microbial carriage precedes colonization and infection. In endogenous infection, infection is preceded by oropharyngeal or GI carriage. A primary endogenous infection is caused by an organism carried by the patient on admission to the ICU, whereas a secondary endogenous infection is caused by organisms acquired in the ICU. The traditional approach to infection control in the ICU has included frequent hand washing, limiting the use of agents for prophylaxis of stress-ulcer bleeding, and limiting the use of injectable antimicrobials to the treatment of infection in order to prevent resistance. The recognition that hand washing only partially reduces endogenous infection led to the use of nonabsorbable antimicrobials to abolish oropharyngeal and gastrointestinal carriage of potentially pathogenic microorganisms. In addition, the use of an injectable antimicrobial during the first four days in the ICU to control primary endogenous infection was considered not to lead to resistance as long as it was combined with nonabsorbable antimicrobials. Of 41 fully reported clinical trials of SDD, 33 showed a significant reduction of infectious morbidity among patients who received SDD. Of the 32 trials in which carriage of potential pathogens was a measured endpoint, 31 showed a reduction in carriage. Of the 24 studies in which resistance was an endpoint, 22 showed no increase in resistance associated with SDD. Only 10 of 35 trials that examined death showed a significant decrease in mortality. SDD, used in conjunction with traditional infection-control measures, diminishes microbial carriage and infectious morbidity in the ICU without increasing antimicrobial resistance.

Benzodiazepine and beta-carboline regulation of single GABAA receptor channels of mouse spinal neurones in culture.

1. The effects of the benzodiazepine receptor agonist, diazepam (DZ), and the inverse agonist, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), on gamma-aminobutyric acid (GABAA) receptor single channel currents were characterized. Outside-out patches were obtained from somata of cultured mouse spinal cord neurones and voltage clamped at -75 mV (ECl = 0 mV). 2. GABA (2 microM) alone or with DZ (20-1000 nM) or DMCM (20-100 nM) was applied to patches by pressure ejection from blunt micropipettes. DZ enhanced GABAA receptor currents with an inverted U-shaped concentration-response curve. Mean steady-state currents were increased by low concentrations of DZ (20-50 nM). At higher concentrations of DZ, the enhancement was diminished. Mean steady-state currents were decreased by DMCM at all concentrations. 3. GABAA receptor channels opened most frequently to a 27 pS main conductance level and less frequently to a 19 pS subconductance level. Neither DZ nor DMCM altered the proportion of time spent at either of the conductance levels. The kinetic properties of the main conductance level were studied. 4. Neither DZ nor DMCM altered the mean GABAA receptor channel open or burst durations. Sums of three exponential functions were required to fit best open and burst duration-frequency histograms for GABA alone or with DZ or DMCM. No significant changes in the three time constants or areas of the three exponential functions for open or burst duration histograms were produced by DZ or DMCM. 5. With increasing concentrations of DZ up to 50 nM, GABA evoked an increased frequency of channel openings and bursts. With higher DZ concentrations, the magnitudes of the increase in channel opening and burst frequencies were reduced. At all concentrations of DMCM, GABA evoked a decreased frequency of channel openings and bursts. 6. Closed duration-frequency histograms for GABA alone or with DZ or DMCM were best fitted by sums of at least six exponential functions. The three shortest closed duration time constants were unchanged by DZ or DMCM. The three longest closed duration time constants were altered by DZ and DMCM, consistent with alterations in opening frequency. 7. DZ increased and DMCM decreased steady-state GABAA receptor current by increasing or decreasing channel opening frequency without altering mean channel open duration. We propose that DZ and DMCM alter GABAA receptor current by acting reciprocally to increase or decrease only, respectively, the apparent agonist association rate at the first of two proposed GABA binding steps without altering channel gating.(ABSTRACT TRUNCATED AT 400 WORDS)

Chronic ethanol treatment reduces inhibition in CA1 of the rat hippocampus.

The effect of chronic ethanol exposure on inhibition in the rat hippocampal slice was investigated using paired-pulse stimulation techniques with stimulation in stratum radiatum or stratum oriens of CA1. Experimental animals were fed ethanol in a liquid diet for 20 weeks and were withdrawn for at least 8 weeks prior to electrophysiological recording. Prior ethanol treatment had no effect on basic input-output relationships for the extracellular population spike. Ethanol treatment significantly reduced the recurrent inhibition produced by antidromic stimulation in a manner dependent upon stimulus intensity. In addition, with orthodromic paired-pulse stimulation of either stratum radiatum or oriens, a trend toward an augmentation of the facilitation of population spike amplitude was observed, suggesting that feedforward inhibition may also be reduced. These results are similar to those found with treatments that reduce inhibition. Therefore, we conclude that chronic ethanol exposure produces an enduring disruption of inhibitory neuronal function in the rat hippocampus.

Intraburst kinetic properties of the GABAA receptor main conductance state of mouse spinal cord neurones in culture.

1. The intraburst kinetic properties of the main conductance state of gamma-aminobutyric acidA (GABAA) receptor channels in excised outside-out patches obtained from somata of mouse spinal cord neurones in cell culture were investigated using the patch clamp single-channel recording technique. 2. At 2 microM-GABA, the burst duration distribution was fitted by four exponential functions with time constants of 0.5, 2.4, 8.3 and 31.8 ms. 3. At 0.5, 1 and 2 microM-GABA, frequency distribution histograms of the number of apparent openings per burst were best fitted by three geometric functions with similar mean numbers (1.1, 1.9 and 3.6) of openings per burst. The proportion of bursts with a mean of 1.1 openings per burst decreased with increased GABA concentration while the proportion of bursts with means of 1.9 and 3.6 openings per burst increased with GABA concentration. 4. Analyses of GABA receptor channel intraburst kinetics were performed at all three GABA concentrations. The results were similar for all concentrations, but detailed results are presented only for 2 microM-GABA. 5. The open time distribution for all intraburst openings was best fitted by three exponential functions with time constants of 0.6, 2.9 and 8.9 ms. 6. Intraburst open time and total open time distributions for bursts with one to five openings were fitted with two or three exponential functions or gamma distributions, respectively. The number of components, time constants and relative areas were similar for both distributions. 7. The distributions of open times for the nth opening within bursts of k openings were similar for bursts containing two to five openings. The distributions of open times for the nth opening of all bursts varied with position within the burst. The distributions shifted to longer openings as the opening number increased from one to five. 8. The distributions of all closings within all bursts or within bursts with two to five openings and of closings relative to position in all bursts could be fitted by two exponential functions with time constants of about 0.20 and 3.1 ms and relative proportions of 0.55 and 0.45 at all GABA concentrations. 9. The total closed time distributions for bursts containing two to four closings, however, were all best fitted with only a single gamma distribution with a time constant of 1.3 ms.(ABSTRACT TRUNCATED AT 400 WORDS)

Barbiturate regulation of kinetic properties of the GABAA receptor channel of mouse spinal neurones in culture.

1. Barbiturate regulation of the kinetic properties of gamma-aminobutyric acidA (GABA) receptor channel chloride currents from somata of mouse spinal cord neurones were investigated using whole-cell and excised outside-out patch-clamp recording techniques. 2. GABA (2 microM), GABA (2 microM) plus phenobarbitone (PhB) (500 microM) and GABA (2 microM) plus pentobarbitone (PB) (50 microM), applied by pressure ejection from blunt perfusion micropipettes, evoked inward chloride currents when neurones or patches were voltage clamped at -75 mV and the chloride equilibrium potential was 0 mV. GABA receptor channel currents were increased by PhB and PB. 3. Single GABA receptor channel currents were recorded with a main conductance state of 27 pS and a less frequent subconductance state of 16.5 pS. The conductances of the two states were unchanged by the barbiturates. 4. The main conductance state kinetics were analysed. GABA alone or with the barbiturates gated the channel open singly and in groups of openings. 5. The barbiturates increased GABA receptor channel mean open time and shifted frequency histograms of channel open times to longer times. 6. Three exponential functions were required to fit the frequency histograms of GABA receptor channel open times, suggesting that the channel has at least three open states (O1, O2, O3). The time constants for the exponential functions (0.9, 2.7 and 7.8 ms, respectively) were unchanged by the barbiturates. The increases in mean open times and the shifts of the open-time frequency histograms by the barbiturates were due to a reduction in relative frequency of occurrence of the two short open states (O1 and O2) and to an increase in the relative frequency of occurrence of the longest open state (O3). 7. Frequency histograms of GABA receptor channel closed times were fitted with five exponential functions, suggesting that the channel has multiple closed states. None of the time constants nor areas of the exponential functions were significantly changed by the barbiturates. 8. For analysis, a burst was defined as openings surrounded by closures greater than a critical closed time, tc, of 5 ms. For GABA (2 microM), frequency histograms of GABA receptor channel bursts were fitted with three exponential functions, suggesting that the channel has three burst states (B1, B2, B3). The B1 burst state was probably a single opening to the O1 open state while the B2 and B3 burst states were probably composed of multiple openings to the O2 and O3 open states.(ABSTRACT TRUNCATED AT 400 WORDS)

Differential regulation of gamma-aminobutyric acid receptor channels by diazepam and phenobarbital.

The anticonvulsant activity of diazepam and phenobarbital may be mediated in part by enhancement of inhibition involving gamma-aminobutyric acid (GABA). While both diazepam and phenobarbital increase GABA receptor chloride current, they may have different mechanisms of action, since they bind to different sites on the GABA receptor-chloride channel complex. We used the patch clamp technique to compare the effects of diazepam and phenobarbital on single GABA receptor currents. Outside-out patches were obtained from mouse spinal cord neurons grown in cell culture for 2 to 4 weeks. GABA (2 microM) evoked single channel currents that occurred as single brief openings or in bursts of multiple openings. Diazepam (20 nM) and phenobarbital (500 microM) both increased the GABA receptor current by increasing mean open time without altering channel opening frequency. However, the temporal grouping of openings into bursts suggested that the enhancement occurred via different mechanisms. Diazepam increased the frequency of bursting GABA receptor currents with minimal effect on the duration of bursts. Phenobarbital increased the duration of bursting GABA receptor currents without altering the frequency of bursts. These results suggest that diazepam binds to a site that may enhance single channel burst frequency by increasing the affinity of GABA binding, while phenobarbital may stabilize the bursting open state of the channel by binding to a different modulatory site at or near the chloride channel.