Relationships between impulsivity and subjective response in an IV ethanol paradigm

Rationale

Impulsivity and individual differences in subjective response to alcohol are risk factors for alcohol problems and possibly endophenotypes for alcohol dependence. Few prior studies have addressed relationships between the two constructs.

Objectives

To predict subjective responses to ethanol, we tested self-reported impulsiveness, ethanol dose condition (high dose, low dose, or placebo), and time (seven time points) along with interactions among these variables.

Methods

The present study is a secondary analysis of data from a within-subject, placebo-controlled, dose-ranging ethanol administration study using IV infusion with a clamping technique to maintain steady-state breath alcohol concentration. The sample consisted of healthy, non-alcohol dependent social alcohol drinkers between the ages of 21 and 30 (N?=?105). Participants at varying levels of impulsivity were compared with regard to stimulant and subjective responses to three ethanol dose conditions over time.

Results

Individuals with higher impulsivity reported elavated stimulant and dampened sedative response to alcohol, particularly at the higher dose. Higher impulsivity was associated with a steeper increase in stimulant effects during the first half of clamped ethanol infusion with the higher dose.

Conclusions

These results suggest that impulsive individuals may experience enhanced reinforcing, stimulant effects, and relatively muted aversive sedative effects from alcohol. These subjective responses may relate to enhanced risk of alcohol problems among more impulsive individuals.     

Effects of Δ9-tetrahydrocannabinol in individuals with a familial vulnerability to alcoholism

Background and aims

A family history (FH) of alcoholism accounts for approximately 50 % of the risk of developing alcohol problems. Several lines of preclinical evidence suggest that brain cannabinoid receptor (CB₁R) function may mediate the effects of alcohol and risk for developing alcoholism including the observations that reduced CB₁R function decreases alcohol-related behaviors and enhanced CB₁R function increases them. In this first human study, we probed CB₁R function in individuals vulnerable to alcoholism with the exogenous cannabinoid Δ⁹-tetrahydrocannabinol (Δ⁹-THC).

Design, setting, and participants

Healthy volunteers (n?=?30) participated in a three test day study during which they received 0.018 and 0.036 mg/kg of Δ⁹-THC, or placebo intravenously in a randomized, counterbalanced order under double-blind conditions.

Measurements

Primary outcome measures were subjective “high,” perceptual alterations, and memory impairment. Secondary outcome measures consisted of stimulatory and depressant subjective effects, attention, spatial memory, executive function, Δ⁹-THC and 11-hydroxy-THC blood levels, and other subjective effects. FH was calculated using the Family Pattern Density method and was used as a continuous variable.

Findings

Greater FH was correlated with greater “high” and perceptual alterations induced by Δ⁹-THC. This enhanced sensitivity with increasing FH was specific to Δ⁹-THC’s rewarding effects and persisted even when FH was calculated using an alternate method.

Conclusions

Enhanced sensitivity to the rewarding effects of Δ⁹-THC in high-FH volunteers suggests that alterations in CB₁R function might contribute to alcohol misuse vulnerability.     

延边地区肺结核病人归口转诊模式的探讨

目的　分析延边地区建立肺结核归口转诊模式对肺结核病人的转诊到位率的影响,探讨提高转诊到位率的方法。方法 对全州8个县(市)医院、中医医院、中心卫生院、大型厂矿企事业单位职工医院的执法检查考核资料进行评价。结果 1.建立归口转诊模式前期转诊率为48.3%,转诊到位率为29.0%,后期转诊率为89.0%,转诊到位率为72.4%,有明显提高;2.前期年平均涂阳病人新登记率为13.36/10万,后期为17.86/10万,实施归口转诊模式前期与实施后期的指标有显著性差异(P<0.01)。结论 延边地区实施的肺结核病人归口转诊模式,对提高肺结核病的转诊到位率十分有效,应不断完善并深入推广。     

The factor V B-domain provides two functions to facilitate thrombin cleavage and release of the light chain

Blood coagulation factors V and VIII are homologous proteins that have the domain organization A1-A2-B-A3-C1-C2. Upon thrombin activation, the B-domains of both molecules are released. Previous studies on factor VIII showed that the B-domain was not required for thrombin cleavage or activity. In contrast, deletion of the factor V B-domain (residues 709 to 1545) yielded a molecule with sevenfold reduced procoagulant activity that was not cleaved by thrombin. However, this factor V B- domain deletion molecule was activated by factor Xa, although the fold- activation was 85% that of wild-type factor V. Thrombin cleavage of factor V occurs initially after residue 709 and subsequently after residues 1018 and 1545. The requirement for thrombin cleavage within the B-domain at residue 1018 was evaluated by mutagenesis of Arg1018 to Ile. In the resultant R1018I mutant, the rate of thrombin activation and appearance of maximal cofactor activity was delayed and was consistent with delayed cleavage of the light chain at residue 1545. In contrast, the rate of factor Xa activation in the R1018I mutant was not altered. This finding suggests that thrombin cleavage at 1018 facilitates subsequent thrombin cleavage at 1545. Further mutagenesis was used to study the requirement for sequences within the factor V B- domain for thrombin cleavage at residue 1545. Whereas the factor V deletion molecule removing residues 709 to 1545 was not cleaved by thrombin, a smaller B-domain deletion molecule (residues 709 to 1476) containing an acidic amino acid-rich region (residues 1490 to 1520) was effectively cleaved by thrombin. These results show that residues 1476 to 1545, which contain an acidic amino acid-rich region, were required for thrombin cleavage of the light chain. Introduction of an acidic amino acid-rich region from factor VIII (residues 337 to 372) into the factor V 709 to 1545 deletion also restored thrombin cleavage of the light chain. In contrast, similar replacement with the acidic region from the factor VIII light chain (residues 1649 to 1689) was significantly less effective in promoting thrombin cleavage of the light chain. This finding suggests that the different acidic regions in factors V and VIII are not functionally equivalent in their interaction with thrombin.(ABSTRACT TRUNCATED AT 400 WORDS)     

COVID-19: mobilising CT as a frontline management tool

As the COVID-19 pandemic has spread across the globe, questions have arisen about the approach healthcare systems should adopt in order to optimally manage patient influx. With a focus on the impact of COVID-19 on the NHS, we describe the frontline experience of a severely affected hospital in close proximity to London. We highlight a protocol-driven approach, incorporating the use of CT in the rapid triage, assessment and cohorting of patients, in an environment where there was a lack of readily available, onsite RT-PCR testing facilities. Furthermore, the effects of the protocol on the effective streamlining of patient flow within the hospital are discussed, as are the resultant improvements in clinical management decisions within the acute care service. This model may help other healthcare systems in managing this pandemic whilst assessing their own needs and resources.     

Routine Testing for Anaerobic Bacteria in Cerebrospinal Fluid Cultures Improves Recovery of Clinically Significant Pathogens

In North America, the widespread use of vaccines targeting Haemophilus influenzae type b and Streptococcus pneumoniae have dramatically altered the epidemiology of bacterial meningitis, while the methodology for culturing cerebrospinal fluid (CSF) specimens has remained largely unchanged. The aims of this study were 2-fold: to document the current epidemiology of bacterial meningitis at a tertiary care medical center and to assess the clinical utility of routinely querying for anaerobes in CSF cultures. To that end, we assessed CSF cultures submitted over a 2-year period. A brucella blood agar (BBA) plate, incubated anaerobically for 5 days, was included in the culture procedure for all CSF specimens during the second year of evaluation. In the pre- and postimplementation years, 2,353 and 2,302 CSF specimens were cultured, with 49 and 99 patients having positive culture results, respectively. The clinical and laboratory data for patients with positive cultures were reviewed. Anaerobic bacteria were isolated in the CSF samples from 33 patients post-BBA compared to two patients pre-BBA (P = 0.01). The anaerobic isolates included Bacteroides thetaiotaomicron (n = 1), Propionibacterium species (n = 15), and Propionibacterium acnes (n = 19) isolates; all of these isolates were recovered on the BBA. Eight of the 35 patients from whom anaerobic organisms were isolated received antimicrobial therapy. Although six of these patients had central nervous system hardware, two patients did not have a history of a neurosurgical procedure and had community-acquired anaerobic bacterial meningitis. This study demonstrates that the simple addition of an anaerobically incubated BBA to the culture of CSF specimens enhances the recovery of clinically significant anaerobic pathogens.     

Human Antibody Responses to the Polyclonal Dryvax Vaccine for Smallpox Prevention Can Be Distinguished from Responses to the Monoclonal Replacement Vaccine ACAM2000

Dryvax (Wyeth Laboratories, Inc., Marietta, PA) is representative of the vaccinia virus preparations that were previously used for preventing smallpox. While Dryvax was highly effective, the national supply stocks were depleted, and there were manufacturing concerns regarding sterility and the clonal heterogeneity of the vaccine. ACAM2000 (Acambis, Inc./Sanofi-Pasteur Biologics Co., Cambridge, MA), a single-plaque-purified vaccinia virus derivative of Dryvax, recently replaced the polyclonal smallpox vaccine for use in the United States. A substantial amount of sequence heterogeneity exists within the polyclonal proteome of Dryvax, including proteins that are missing from ACAM2000. Reasoning that a detailed comparison of antibody responses to the polyclonal and monoclonal vaccines may be useful for identifying unique properties of each antibody response, we utilized a protein microarray comprised of approximately 94% of the vaccinia poxvirus proteome (245 proteins) to measure protein-specific antibody responses of 71 individuals receiving a single vaccination with ACAM2000 or Dryvax. We observed robust antibody responses to 21 poxvirus proteins in vaccinated individuals, including 11 proteins that distinguished Dryvax responses from ACAM2000. Analysis of protein sequences from Dryvax clones revealed amino acid level differences in these 11 antigenic proteins and suggested that sequence variation and clonal heterogeneity may contribute to the observed differences between Dryvax and ACAM2000 antibody responses.     

Primary migration of a mini-implant under a functional orthodontic loading

Objectives

The objective of this study was to examine whether cortical bone thickness and bone mineral density (BMD) can explain the primary migration of a mini-implant under a functional orthodontic tangential loading at the early stage following implantation.

Materials and methods

Mini-implants were installed in human mandibular sections. A constant tangential load (2 N) was applied to the mini-implant under hydration. Creep, which is a time-dependent viscoelastic displacement in the bone surrounding the mini-implant, was assessed as the change in displacement during 2 h of loading. The total migration was measured as a maximum displacement that combined an initial elastic displacement and creep. After removal of the mini-implant, all specimens were scanned together by cone beam computed tomography. Cortical bone thickness and BMD were measured for the bone voxels surrounding the implant site.

Results

BMD had significant correlations with the displacement parameters (p?<?0.019), but the cortical bone thickness did not (p?>?0.272). Permanent bone deformation adjacent to the implant was observed to be resulting from substantial creep development under the orthodontic functional loading level.

Conclusions

BMD controls the primary migration of the mini-implant system in mandibular bone. Viscoelastic creep can develop at a small constant functional loading level, leading to migration of the mini-implant.

Clinical relevance

The current results indicated that mini-implant migration can develop under the small level of functional orthodontic load used in clinic. If the active bone remodeling around the mini-implant accelerates the migration, the risk of causing damage in vital organs next to the mini-implant increases.