Not all smokers are alike: the hidden cost of sustained attention during nicotine abstinence

Nicotine Withdrawal Syndrome (NWS)-associated cognitive deficits are notably heterogeneous, suggesting underlying endophenotypic variance. However, parsing this variance in smokers has remained challenging. In this study, we identified smoker subgroups based on response accuracy during a Parametric Flanker Task (PFT) and then characterized distinct neuroimaging endophenotypes using a nicotine state manipulation. Smokers completed the PFT in two fMRI sessions (nicotine sated, abstinent). Based on response accuracy in the stressful, high cognitive demand PFT condition, smokers split into high (HTP, n = 21) and low task performer (LTP, n = 24) subgroups. Behaviorally, HTPs showed greater response accuracy (88.68% ± 5.19 SD) vs. LTPs (51.04% ± 4.72 SD), independent of nicotine state, and greater vulnerability to abstinence-induced errors of omission (EOm, p = 0.01). Neurobiologically, HTPs showed greater BOLD responses in attentional control brain regions, including bilateral insula, dorsal ACC, and frontoparietal Cx for the [correct responses (–) errors of commission] PFT contrast in both states. A whole-brain functional connectivity (FC) analysis with these subgroup-derived regions as seeds identified two circuits: Precentral Cx↔Insula and Insula↔Occipital Cx, with abstinence-induced FC strength increases seen only in HTPs. Finally, abstinence-induced FC and behavior (EOm) differences were positively correlated for HTPs in a Precentral Cx↔Orbitofrontal cortical circuit. In sum, only the HTP subgroup demonstrated sustained attention deficits following 48-hr nicotine abstinence, a stressor in dependent smokers. Unpacking underlying smoker heterogeneity with this ‘dual (task and abstinence) stressor’ approach revealed discrete smoker subgroups with differential attentional deficits to withdrawal that could be novel pharmacological/behavioral targets for therapeutic interventions to improve cessation outcomes.Subject terms: Attention, Addiction     

Mucosal melanomas of the head and neck

Only 3 per cent of all melanomas arise in the mucosa of the head and neck region. Melanomas of mucosal origin in this series differed from their cutaneous counterpart in that size of the primary lesion did not influence prognosis. Regional lymph node metastases were infrequent and did not seem to influence prognosis. Nearly all the primary lesions on microscopic review showed the presence of intralesional lymphatic and blood vessel invasion. Local recurrence at the primary site was the most common cause of treatment failure, in spite of seemingly adequate surgical resection. Surgical treatment offers long-term cure to only a limited number of patients.     

Needle electromyography and histopathologic correlation in myopathies

Introduction: The molecular mechanism of immune-mediated necrotizing myopathy (IMNM) remains unknown. Autophagy impairment, described in autoimmune diseases, is a key process in myofiber protein degradation flux and muscle integrity and has not been studied in IMNM. Methods: Muscle biopsies from patients with IMNM (n = 40), dermatomyositis (DM; 24), polymyositis (PM; 8), polymyositis with mitochondrial pathology (4), sporadic inclusion body myositis (8), and controls (6) were compared by immunohistochemistry. Results: The proportions of myofibers containing autophagy markers LC3b and p62 were higher in IMNM than in DM or PM and correlated with creatine kinase levels. In IMNM, compartmentalized LC3b puncta were located in regenerating and degenerating myofibers surrounded by major histocompatibility complex type II⁺ inflammatory cells. Several IMNM myofibers accumulated ubiquitin and misfolded protein. Discussion: The detection of LC3b⁺ or p62⁺ myofibers could be used in differentiating IMNM from PM. The identification of autophagy-modifying molecules potentially could improve patients’ outcomes. Muscle Nerve, 2019     

α4β1 and α5β1 Control Cell Migration on Fibronectin by Differentially Regulating Cell Speed and Motile Cell Phenotype

Computer-aided time lapse fluorescence videomicroscopy was used to study single cell migration behavior of human aortic endothelial cells on fibronectin coated substrates of varying protein surface density. The role of receptors _₅ _₁, __v _₃, and ₄₁ in mediating cell adhesion and migration on fibronectin was characterized using integrin specific monoclonal antibodies. Matrix density had a direct effect on controlling the proportion of migrating cells and the directional persistence of cell movement (p < 0.01). While there was relatively little influence of fibronectin surface density on absolute migration speed, the ability of endothelial cells to disperse over a surface, as measured by the dispersion coefficient, was biphasic with respect to the surface density of this matrix protein (p < 0.005). Both cell speed and the proportion of migrating cells was controlled by ₄₁ (p < 0.01). However, ₅₁ selectively regulated the transformation of stationary cells to those exhibiting motile behavior (p <0.05). Migratory responses on fibronectin were not influenced by blockade of the _v3 receptor. It is noteworthy that cell surface adhesive receptors which control commitment to a motile phenotype are not necessarily the same as those that control migration speed. © 1998 Biomedical Engineering Society. PAC98: 8722-q     

Cross-sectional study of female students reporting anabolic steroid use

OBJECTIVE: To determine the characteristics of female US high school students reporting anabolic steroid use. DESIGN: Cross-sectional assessment using the 2003 Centers for Disease Control and Prevention national school-based Youth Risk Behavior Survey database. SETTING: Nationally representative sample of US high schools. PARTICIPANTS: Female students in grades 9 through 12 (n = 7544). MAIN OUTCOME MEASURES: Participants' self-reported anabolic steroid use was compared with other health-related behaviors and with sports participation. RESULTS: Prior or ongoing anabolic steroid use was reported by 5.3% of female high school students. Those adolescent girls had a marked increase in other health-compromising behaviors, including past 30-day use of alcohol (odds ratio [OR], 8.83; 95% confidence interval [CI], 5.49-14.20]), cigarettes (OR, 5.14; 95% CI, 3.14-8.42), marijuana (OR, 7.91; 95% CI, 5.20-12.04), cocaine (OR, 10.78; 95% CI, 6.18-18.81), and diet pills (OR, 4.86; 95% CI, 2.98-7.93). They were more likely to carry a weapon (OR, 7.54; 95% CI, 4.83-11.76), have had sexual intercourse before age 13 years (OR, 2.90; 95% CI, 1.58-5.33), and have had feelings of sadness or hopelessness almost every day for at least 2 consecutive weeks (OR, 4.13; 95% CI, 2.57-7.22). They were less likely to play school-sponsored team sports (OR, 0.52; 95% CI 0.34-0.80). Steroid users participating in sports shared the same problem behaviors as steroid users not participating in team athletics. CONCLUSION: Self-reported anabolic steroid use is not confined to adolescent girls in competitive athletics and is an indicator of adolescent girls with a marked increase in a cluster of other health-harming behaviors.     

The use of positron emission tomography for early detection of recurrent head and neck squamous cell carcinoma in postradiotherapy patients

Positron emission tomography (PET) has recently proved to be highly sensitive in detecting known extracranial head and neck squamous cell carcinomas when compared to computed tomography and magnetic resonance imaging (MRI). The ability of PET to detect early subclinical recurrent squamous cell malignancies in patients who received primary radiotherapy was evaluated. A new PET-MRI coregistration technique was used to determine precise anatomic tumor location, enabling directed biopsies to confirm the presence of malignancy, and to plan additional therapeutic strategies. Ten patients underwent PET evaluation with intravenous [¹⁸F]-fluorodeoxyglucose and received postradiotherapy MRI scans. In all cases, PET accurately detected the presence of recurrent disease despite negative or equivocal MRI scans and indeterminate clinical examinations. PET appears to be highly effective in detecting early recurrent head and neck squamous cell malignancies in postirradiated patients.     

Inhaled Albuterol, but Not Intravenous Lidocaine, Protects Against Intubation-induced Bronchoconstriction in Asthma

Background: The ability of intravenous lidocaine to prevent intubation-induced bronchospasm is unclear. The authors performed a prospective, randomized, double-blind, placebo-controlled trial to test the ability of intravenous lidocaine and inhaled albuterol to attenuate airway reactivity after tracheal intubation in asthmatic patients undergoing general anesthesia.

Methods: Sixty patients were randomized to receive either 1.5 mg/kg intravenous lidocaine or saline, 3 min before tracheal intubation. An additional 50 patients were randomized to receive 4 puffs of inhaled albuterol or placebo 15-20 min before tracheal intubation. Anesthesia was induced with propofol. Immediately after intubation and at 5-min intervals, transpulmonary pressure and airflow were recorded, and lower pulmonary resistance (RL) was calculated. Isoflurane was administered after the initial two measurements to assess reversibility of bronchoconstriction. A bronchoconstrictor response to intubation was defined as RL greater than or equal to 5 cm H2O [middle dot] l-1 [middle dot] s-1 in the first two measurements after intubation and RL subsequently decreasing by 50% or more after isoflurane.

Results: The lidocaine and placebo groups were not different in the peak RL before administration of isoflurane (8.2 cm H2O [middle dot] l-1 [middle dot] s-1vs. 7.6 cm H2O [middle dot] l-1 [middle dot] s-1) or frequency of airway response to intubation (lidocaine 6 of 30 vs. placebo 5 of 27). In contrast, the albuterol group had lower peak RL (5.3 cm H2O [middle dot] l-1 [middle dot] s-1vs. 8.9 cm H2O [middle dot] l-1 [middle dot] s-1;P < 0.05) and a lower frequency of airway response (1 of 25 vs. 8 of 23;P < 0.05) than the placebo group.