Cognitive preoccupation with drinking and behavioral effects of alcohol as predictors of current consumption patterns.

BACKGROUND: Acute alcohol responses such as tolerance to alcohol-induced motor impairment and heightened sensitivity to alcohol-induced disinhibition are associated with heavier drinking. Additionally, certain cognitive characteristics may also indicate problem-drinking. For example, cognitive and emotional preoccupation (CEP) with alcohol is associated with heavier drinking. However, it is not clear if cognitive markers have value as predicators of heavier drinking beyond that of well-established alcohol response markers. The current study sought to test the predictive potential of CEP in the context of two well-documented alcohol response markers of heavy drinking. METHODS: Data aggregated from three studies comprised a sample of 94 young adult drinkers with no history of alcohol use disorder. Participants' motor coordination (grooved pegboard) and behavioral disinhibition (cued go/no-go) were assessed following consumption of 0.65g/kg alcohol and a placebo. CEP was measured via the Temptation and Restraint Inventory (TRI). RESULTS: Drinkers who expressed both alcohol response markers reported drinking higher doses regardless of their level of CEP. Among drinkers who expressed low sensitivity to both disinhibition and motor impairment, higher CEP was associated with higher typical quantities. Low sensitivity to motor impairment functioned as a standalone marker of heavier drinking. CONCLUSIONS: The findings suggest that a combination of tolerance to motor impairment and high alcohol-induced disinhibition may be sufficient to promote heavier consumption even in the absence of cognitive markers associated with problem drinking. Results also suggest that cognitive characteristics may drive early drinking and contribute to the development of tolerance to acute alcohol effects.

Heightened motor impairment as a protective factor against heavy drinking in individuals with high alcohol-induced disinhibition.

BACKGROUND: Behavioral disinhibition and motor impairment are both acutely elevated following alcohol consumption, and individual differences in sensitivity to alcohol-induced increases in these effects are associated with drinking habits. Specifically, high alcohol-induced disinhibition and low motor impairment have been identified as separate markers for alcohol-related problems. This study tested the degree to which alcohol-induced disinhibition and motor impairment jointly predict heavy drinking. We hypothesized that heavier drinkers would exhibit a combination of high sensitivity to alcohol-induced disinhibition and low sensitivity to its motor impairing effect. METHODS: Data from three studies were aggregated to comprise a sample of 96 young adults. Participants' motor coordination (grooved pegboard) and behavioral disinhibition (cued go/no-go) were assessed following consumption of 0.65 g/kg alcohol and a placebo during separate sessions. RESULTS: As BAC was ascending, alcohol increased motor impairment and disinhibition compared to placebo. Combined effects at this time of alcohol on motor impairment and disinhibition predicted typical drinking habits. Specifically, a combination of high sensitivity to alcohol's disinhibiting effect and low sensitivity to its motor impairing effect was associated with heavy drinking. As BAC was descending, only reduced sensitivity to motor impairment remained as a predictor of heavy drinking. CONCLUSIONS: The findings suggest that although motor impairment following alcohol consumption is associated with certain negative outcomes (e.g., increased risk for physical injury and motor vehicle accidents), such heightened motor impairment from alcohol may actually serve as a protective factor against the excessive drinking that can accompany the disinhibiting effect of alcohol.

"Sensitivity to the disinhibiting effect of alcohol: The role of trait impulsivity and sex differences": Clarification.

Reports a clarification to "Sensitivity to the disinhibiting effect of alcohol: The role of trait impulsivity and sex differences" by Holley C. Allen, Michael J. Wesley, Jessica Weafer and Mark T. Fillmore (Psychology of Addictive Behaviors, Advanced Online Publication, May 05, 2022, np). In the original article, simultaneous linear regression analyses examined the role of sex and trait impulsivity differences in participants' unintoxicated level of behavioral impulsivity and sensitivity to alcohol-induced increases in disinhibition. High levels of trait impulsivity were associated with higher unintoxicated disinhibition; however, no sex difference in this relationship was obtained. Similarly, high attention impulsivity was associated with elevated unintoxicated disinhibition, but no sex difference in this relationship was obtained. It is likely that the inclusion of participants with ADHD in the original analyses disproportionately accounted for the sex differences initially obtained. This reanalysis suggests that behavioral disinhibition serves as a broad indicator of trait impulsivity in both men and women. (The following abstract of the original article appeared in record 2022-58551-001). OBJECTIVE: Higher trait impulsivity is associated with more impulsive responding on certain behavioral measures of disinhibition. Additionally, behavioral disinhibition is acutely elevated following alcohol consumption. The present study examined the possibility that trait impulsivity may predict individual differences in sensitivity to the disinhibiting effect of alcohol. Specifically, the present study tested the hypothesis that those with elevated trait impulsivity also experience heightened sensitivity to the disinhibiting effect of alcohol, which might further compound their tendency toward impulsive action. METHOD: To test this hypothesis, data from six studies were aggregated to comprise a sample of 190 young adults. Participants completed the Barratt Impulsiveness Scale-11 (BIS-11), and behavioral disinhibition was assessed using a cued go/no-go task following consumption of 0.65 g/kg alcohol and a placebo. RESULTS: Alcohol increased disinhibition overall, but higher impulsivity did not predict increased sensitivity to alcohol-induced disinhibition. In men, higher levels of trait impulsivity predicted heightened disinhibition in the unintoxicated state following placebo, but this relationship was not present in women. CONCLUSIONS: These findings suggest significant sex differences in the relationship between trait impulsivity and disinhibition. This sex difference may explain inconsistent research findings in studies assessing links between trait and behavioral measures of impulsivity. The data also point to trait impulsivity and sensitivity to alcohol-induced disinhibition as independent constructs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Sensitivity to the disinhibiting effect of alcohol: The role of trait impulsivity and sex differences.

[Clarification Notice: A clarification for this article was reported online in Psychology of Addictive Behaviors on Aug 18 2022 (see record 2022-92429-001). In the original article, simultaneous linear regression analyses examined the role of sex and trait impulsivity differences in participants' unintoxicated level of behavioral impulsivity and sensitivity to alcohol-induced increases in disinhibition. High levels of trait impulsivity were associated with higher unintoxicated disinhibition; however, no sex difference in this relationship was obtained. Similarly, high attention impulsivity was associated with elevated unintoxicated disinhibition, but no sex difference in this relationship was obtained. It is likely that the inclusion of participants with ADHD in the original analyses disproportionately accounted for the sex differences initially obtained. This reanalysis suggests that behavioral disinhibition serves as a broad indicator of trait impulsivity in both men and women.] Objective: Higher trait impulsivity is associated with more impulsive responding on certain behavioral measures of disinhibition. Additionally, behavioral disinhibition is acutely elevated following alcohol consumption. The present study examined the possibility that trait impulsivity may predict individual differences in sensitivity to the disinhibiting effect of alcohol. Specifically, the present study tested the hypothesis that those with elevated trait impulsivity also experience heightened sensitivity to the disinhibiting effect of alcohol, which might further compound their tendency toward impulsive action. METHOD: To test this hypothesis, data from six studies were aggregated to comprise a sample of 190 young adults. Participants completed the Barratt Impulsiveness Scale-11 (BIS-11), and behavioral disinhibition was assessed using a cued go/no-go task following consumption of 0.65 g/kg alcohol and a placebo. RESULTS: Alcohol increased disinhibition overall, but higher impulsivity did not predict increased sensitivity to alcohol-induced disinhibition. In men, higher levels of trait impulsivity predicted heightened disinhibition in the unintoxicated state following placebo, but this relationship was not present in women. CONCLUSIONS: These findings suggest significant sex differences in the relationship between trait impulsivity and disinhibition. This sex difference may explain inconsistent research findings in studies assessing links between trait and behavioral measures of impulsivity. The data also point to trait impulsivity and sensitivity to alcohol-induced disinhibition as independent constructs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Acute rewarding and disinhibiting effects of alcohol as indicators of drinking habits.

RATIONALE: Laboratory studies have reliably shown that heightened sensitivity to the rewarding effects of alcohol is associated with heavier drinking patterns. More recently, there has been research to suggest that heightened sensitivity to the disinhibiting effects of alcohol might also contribute to drinking habits. Most research on the acute effects of alcohol has focused on drinking magnitudes averaged across participants with little attention paid to how individual differences influence alcohol abuse potential. In large part, this is due to limited sample sizes in previous laboratory studies. OBJECTIVES: This study overcomes previous limitations by testing the degree to which individual differences in acute sensitivity and tolerance to the rewarding and disinhibiting effects of alcohol relate to drinking behavior in a large sample size. METHODS: Data from six laboratory studies were aggregated to comprise a sample of 181 adults. Participants' level of "liking" (the effects of alcohol) and disinhibition were assessed following 0.65 g/kg alcohol once during the ascending limb of the blood alcohol concentration (BAC) curve and again at the same BAC during the descending limb of the curve. The measures were also assessed following placebo. RESULTS: Alcohol increased ratings of liking and behavioral disinhibition. Heavier drinking was associated with heightened sensitivity to liking on the ascending limb. Additionally, those who showed reduced acute tolerance to both disinhibition and liking were also heavier drinkers. CONCLUSIONS: These data suggest that individual variability in liking the effects of alcohol and persistent disinhibition are key indicators of drinking habits.

[Primary extra-axial chondroid chordoma of the anterior nasal septum: case report of a rare chordoma with literature review]. / Primäres extraaxiales chondroides Chordom des anterioren Nasenseptums: Fallbericht eines seltenen Chordoms mit Literaturübersicht.

An 87-year-old patient reported a nodular, progressively enlarging mass of the anterior nasal septum leading to partial obstruction of the nostrils. The tumor showed no infiltration of the subcutis, bone, or paranasal sinuses in imaging or intraoperatively. Histological examination revealed a chondroid tumor with lobular growth and physaliferous cell morphology. Immunohistochemistry revealed a brachyury-positive tumor without EWSR1 rearrangement, leading to the diagnosis of a chondroid chordoma. The reported case demonstrates the differential diagnostic considerations pertaining to this rare tumor, which can also have an untypical and very rare extra-axial location. Review of the literature identified 34 primary extraosseous chordomas of the nose, nasopharynx, and paranasal sinuses, and allowed the nasal chordoma presented herein to be included in this group of extra-axial chordomas.

Examining the Anti-Tumor Activity of Dp44mT-Loaded Nanoparticles In Vitro.

We have recently reported encapsulating an antitumor iron chelator, Dp44mT (Di-2-pyridylketone-4,4dimethyl-3-thiosemicarbazone), in nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA). In this paper, we examine the effectiveness of this nano-formulation, referred to as Dp44mT-NPs, against several cancer cell lines in vitro; specifically, we evaluate the cytotoxicity of this formulation in glioma (U87, U251), breast (MCF7), and colorectal (HT29) cancer cell lines. Cell viability results from treatment of glioma cells with Dp44mT-NPs for 24-72 hrs revealed that these NPs were highly toxic towards these malignant cells with very low IC50 values (<100 nM). Although addition of a PEG (poly(ethylene glycol)) layer to the surface of NPs reduced their toxicity in glioma cells, they remained highly toxic towards these cells (IC50 of 135-210 nM). Dp44mT-NPs were also toxic towards breast MCF7 and colorectal HT29 cells, but at higher dosages (IC50 >1 µM) compared to glioma cells. Addition of PEG to these NPs, again lowered their toxicity in these cells. Varying the percentage of PEG on NPs resulted in changes in their cytotoxicity, highlighting the necessity of further optimization of this parameter. This study, overall, demonstrates the therapeutic potential of Dp44mT-NPs against different malignant cells, with particularly promising results in highly-aggressive glioma tumor cells.

Fabrication and Optimization of Dp44mT-Loaded Nanoparticles.

This paper describes the modulation of polymeric nanoparticle (NP) preparation to produce an optimal nanocarrier for delivery of the potent anti-tumor iron chelator, Di2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) towards application in cancer therapy. We have previously shown the potential of poly (lactic-co-glycolic acid) (PLGA) NPs as a nano-carrier for delivery of Dp44mT to malignant cells. The focus of this study is to alter the fabrication parameters to improve the characteristics of these NPs as a delivery vehicle for Dp44mT. To this end, PLGA NPs encapsulating Dp44mT are fabricated using the nanoprecipitation method with systematic variations in (i) the amount of surfactant poly (vinyl alcohol) (PVA) in aqueous phase, and (ii) the drug to polymer ratio in organic phase. The resultant NPs are characterized for size, surface potential, encapsulation efficiency, and drug release profile. Results of this study showed that increasing the PVA % (within the examined range of 0.5-4% w/v) and decreasing the Dp44mT to PLGA ratio (within the tested range of 0.0375-0.3: 1 mg/mL) both led to an increase in drug encapsulation efficiency. Focusing on the optimal PVA percentage, we found that the changes in drug to polymer ratio did not have a significant impact on the size distribution and surface potential of Dp44mT-NPs and these NPs remained in the desirable range of 80-120 nm. Lastly, the release of Dp44mT from NPs differed for different Dp44mT: PLGA ratios, providing a means to further optimize the NP formulation for future cancer treatment applications.

The impact of co-occurring opioid misuse and PTSD on response inhibition.

BACKGROUND: Posttraumatic Stress Disorder (PTSD) and opioid misuse are commonly co-occurring disorders. Both disorders are associated with deficits in response inhibition; however, these associations have not considered their comorbidity. Response inhibition has not been examined in a sample with comorbid PTSD and opioid misuse. The present study examined the effect of PTSD symptom severity on response inhibition in current and past opioid misusers. METHODS: Participants were currently (used within the last month) misusing opioids (56.6%) or in recovery (43.4%). All participants met DSM 5 criteria for PTSD. Response inhibition was measured with the stop signal task. RESULTS: Response inhibition was associated with increased PTSD symptom severity for those in recovery but not among current users. Additionally, across both groups, there were deficits in response inhibition when withholding automatic responses for a threatening stimulus compared to a neutral stimulus. CONCLUSIONS: PTSD Symptoms may exert a stronger effect on response inhibition among those in recovery as opposed to those who are actively using opioids.

The Moderating Effect of Childhood Maltreatment on the Relations Among PTSD Symptoms, Positive Urgency, and Negative Urgency.

Childhood maltreatment increases the risk for posttraumatic stress disorder (PTSD) and comorbid substance use disorder (SUD). One pathway by which this occurs is through impaired emotion regulation. Past research has shown that negative urgency, a deficit in the regulation of negative emotions, is strongly related to PTSD in those with comorbid SUD. However, there is minimal research on the relation between positive urgency and PTSD in those with comorbid SUD. The current study investigated the association between childhood maltreatment, positive urgency, negative urgency, and PTSD symptoms among those with SUD. Results suggested that PTSD was associated with negative urgency and positive urgency overall. Childhood maltreatment did not moderate the association between negative urgency and PTSD. Childhood emotional abuse, emotional neglect, and sexual abuse moderated the relation between positive urgency and PTSD (ΔR2 = .04 to .10). The association between PTSD and positive urgency was only significant at lower levels of emotional abuse and neglect. Future research should further examine the processing of positive emotions in those with PTSD and comorbid SUD. Findings might inform clinical interventions among populations exposed to childhood maltreatment to reduce or prevent the development of psychopathology.

The intervening role of urgency on the association between childhood maltreatment, PTSD, and substance-related problems.

A range of risk factors lead to opioid use and substance-related problems (SRP) including childhood maltreatment, elevated impulsivity, and psychopathology. These constructs are highly interrelated such that childhood maltreatment is associated with elevated impulsivity and trauma-related psychopathology such as posttraumatic stress disorder (PTSD), and impulsivity-particularly urgency-and PTSD are related. Prior work has examined the association between these constructs and substance-related problems independently and it is unclear how these multi-faceted constructs (i.e., maltreatment types and positive and negative urgency) are associated with one another and SRP. The current study used structural equation modeling (SEM) to examine the relations among childhood maltreatment, trait urgency, PTSD symptoms, and SRP in a sample of individuals with a history of opioid use. An initial model that included paths from each type of childhood maltreatment, positive and negative urgency, PTSD and SRP did not fit the data well. A pruned model with excellent fit was identified that suggested emotional abuse, positive urgency, and negative urgency were directly related to PTSD symptoms and only PTSD symptoms were directly related to SRP. Furthermore, significant indirect effects suggested that emotional abuse and negative urgency were related to SRP via PTSD symptom severity. These results suggest that PTSD plays an important role in the severity of SRP.

Investigating offering of vegetables by caregivers of preschool age children.

BACKGROUND: Research into the methods which caregivers use to encourage children to eat vegetables is limited, with minimal evidence about what the barriers are to offering these foods. Vegetable consumption in children is typically low, and so gaining information on these factors is vital in order to develop further caregiver-centred interventions to increase children's vegetable consumption. This study aimed to investigate the methods caregivers use to offer vegetables to preschool aged children, as well as the factors which influence whether and how caregivers present vegetables to their children. METHOD: Seventeen caregivers with a preschool aged child participated in focus groups to assess these questions. RESULTS: Thematic analysis indicated that caregivers use a range of methods to offer their children vegetables, with these methods falling into three broad categories: behavioural/active methods, passive methods and food manipulations. Influences on caregiver offering which emerged from the focus groups formed four categories: information, cost, parent factors and child factors. CONCLUSIONS: Together with large-scale quantitative data, this information can be used to shape future interventions aiming to increase children's vegetable intake as well as to tailor advice given to caregivers striving to achieve a healthful diet for their children.

In vitro study of an intra-aortic VAD: Effect of reverse-rotating mode on ventricular recovery.

Cardiac recovery has been observed in end-stage heart failure patients with mechanical circulatory support. An intra-aortic ventricular assist device (IntraVAD) is a novel rotary blood pump designed to operate in the ascending aorta behind the aortic valve, working in series with the compromised left ventricle (LV). Such a device requires optimal motion control in order to enhance the myocardial perfusion and thus promote cardiac recovery. Therefore, a reverse-rotating control (RRc) mode has been proposed to increase the mean arterial pressure (MAP) in diastole where the most coronary flow occurs. The RRc mode consists of two motions - forward rotating speed (FS) and reversely rotating speed (RS). The capability of cardiac recovery of three control modes, including `continuous', `on/off ' and `RRc' modes, was evaluated in vitro. Stroke work (SW), ventricular volume, coronary perfusion pressure (CPP), and arterial pulsatility index (API) were used to evaluate LV unloading, myocardial perfusion and arterial pulsatility. The results show that, all three modes increased the LV stroke work (0.98W vs 1.00W vs 1.01W for continuous, on/off and RRc, respectively; baseline 0.9W) and decreased both end-diastolic volume (EDV) and end-systolic volume (ESV). The "RRc" mode improved CPP significantly (78.4 mm Hg compared to 66.4 mmHg and 70.9 mm Hg for continuous and on/off modes; baseline 71 mm Hg). The arterial pulsatility was higher in `RRc' mode (0.84 compared to 0.43 and 0.59; baseline 0.48). In summary, the IntraVAD operating in the RRc mode can successfully unload the LV, enhance the myocardial perfusion, and restore the arterial pulsatility; therefore, it could be a promising therapeutic option to bridge heart failure patients to recovery.

A mock circulatory loop for designing and evaluating total artificial hearts.

A mock circulatory loop was constructed to facilitate total artificial heart development. The loop includes many novel features such as a pressure-regulated tank to simulate exercise conditions, controllable systemic and pulmonary vascular resistance to create left-right flow imbalances as seen in postural change and breathing, and a left atrial suction valve. Dual HeartMate II pumps and the BiVACOR® rotary total artificial heart were used to generate pressure and flow data characterizing the flow loop.

RoBo-1, a novel member of the urokinase plasminogen activator receptor/CD59/Ly-6/snake toxin family selectively expressed in rat bone and growth plate cartilage.

Using differential display polymerase chain reaction, we cloned a novel cDNA named RoBo-1 from rat tibia. RoBo-1 is abundantly expressed in bone, including the hypertrophic chondrocytes of the growth plate where cartilage is remodeled into bone. RoBo-1 mRNA expression increased in response to two modulators of bone metabolism, estradiol and intermittent mechanical loading, suggesting a role in bone homeostasis. The 1.6-kilobase cDNA encodes a 240-amino acid protein with a cysteine spacing pattern, suggesting that RoBo-1 is a novel member of the urokinase plasminogen activator receptor/CD59/Ly-6/snake toxin family. Furthermore, the C-terminal contains a glycosyl-phosphatidylinositol attachment site, suggesting that it is a cell surface protein similar to other mammalian members of this family. The strongest homology of RoBo-1 is to the snake serum-derived phospholipase A2 inhibitors, which uniquely contain two of the cysteine domains but are secreted proteins. Interestingly, RoBo-1 is likely the first membrane-anchored member of this family containing two cysteine domains. Thus, the tissue specificity, responsiveness to bone protective mediators, along with its relationship to the multifunctional urokinase plasminogen activator receptor/CD59/Ly-6/snake toxin family suggests that RoBo-1 may play a novel role in the growth or remodeling of bone.

Guidelines for treatment of malpractice claims reduces diversity.

Various accounting practices are used for the treatment of medical malpractice claims, related malpractice insurance, and trust funds. To decrease the diversity of accounting practices in these areas and provide more specific guidance to healthcare providers, the AICPA has issued several proposed guidelines concerning accounting treatment of asserted and unasserted medical malpractice claims, providers' claims-made insurance policies, retrospectively rated insurance premiums, captive insurance companies, and trust funds.