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Midlife vascular disease increases risk for dementia and effects of vascular dysfunction on brain health differ between men and women. Elevated pulse pressure, a surrogate for arterial stiffness, contributes to cerebrovascular pathology and white matter damage that may advance cognitive aging; however, it remains unclear how associations between pulse pressure and neural integrity differ by sex and age. This study used restriction spectrum imaging to examine associations between pulse pressure and brain microstructure in community-dwelling women (N=88) and men (N=55), aged 56 to 97 (mean, 76.3) years. Restricted isotropic (presumed intracellular), hindered isotropic (presumed extracellular), neurite density, and free water diffusion were computed in white matter tracts and subcortical regions. After adjustment for age and sex, higher pulse pressure correlated with lower restricted isotropic diffusion in global white matter, with more pronounced associations in parahippocampal cingulum, as well as in thalamus and hippocampus. Subgroup analyses demonstrated stronger correlations between pulse pressure and restricted isotropic diffusion in association fibers for participants ≤75 years than for older participants, with stronger effects for women than men of this age group. Microstructure in parahippocampal cingulum and thalamus differed by pulse pressure level regardless of antihypertensive treatment. Increased pulse pressure may lead to widespread injury to white matter and subcortical structures, with greatest vulnerability for women in late middle to early older age. Restriction spectrum imaging could be useful for monitoring microstructural changes indicative of neuronal loss or shrinkage, demyelination, or inflammation that accompany age-related cerebrovascular dysfunction.

Chronic diffuse body pain is unequivocally highly prevalent in Veterans who served in the 1990–91 Persian Gulf War and diagnosed with Gulf War Illness (GWI). Diminished motor cortical excitability, as a measurement of increased resting motor threshold (RMT) with transcranial magnetic stimulation (TMS), is known to be associated with chronic pain conditions. This study compared RMT in Veterans with GWI related diffuse body pain including headache, muscle and joint pain with their military counterparts without GWI related diffuse body pain. Single pulse TMS was administered over the left motor cortex, using anatomical scans of each subject to guide the TMS coil, starting at 25% of maximum stimulator output (MSO) and increasing in steps of 2% until a motor response with a 50 µV peak to peak amplitude, defined as the RMT, was evoked at the contralateral flexor pollicis brevis muscle. RMT was then analyzed using Repeated Measures Analysis of Variance (RM-ANOVA). Veterans with GWI related chronic headaches and body pain (N = 20, all males) had a significantly (P Trial registration: This study was registered on January 25, 2017, on ClinicalTrials.gov with the identifier: NCT03030794. Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT03030794.

Background When patients present to emergency departments (EDs) with symptoms suspicious for ventriculoperitoneal shunt malfunction, evaluation often includes imaging of the shunt with both computed tomography (CT) of the head without contrast and a plain radiograph “shunt series” (SS). Recent literature has called into question the diagnostic value of the SS for the detection of ventriculoperitoneal shunt complications, suggesting that the plain radiographs provide redundant information and unnecessary exposure to radiation. Objective The aim of our study was to assess the frequency of abnormal SS plain radiography and head CT in the evaluation of shunt malfunction in all adult ED patients and to measure the association of abnormalities on CT and SS with surgical intervention. Methods We performed a retrospective chart review of all emergency department encounters at an urban level I trauma center between August 1, 2013 and October 3, 2018 in which an SS and head CT examination were performed within 24 h of each other. We described the results of imaging studies qualitatively and descriptive statistics were performed. Results Positive findings on CT were significantly associated with the decision to proceed to surgery. Positive findings on SS, however, were not significantly associated with the decision to proceed to surgery. Conclusions The potential information gained from SS and convenience of ordering simultaneously with head CT does not appear to outweigh the risk of increased radiation exposure to the patient, the additional costs of the study, and the potential delay in time to head CT. These findings support the initial use of head CT in evaluation of shunt malfunction.

Lyme disease (also known as Lyme borreliosis) is the most common vector-borne disease in the United States with an estimated 476,000 cases per year. While historically, the long-term impact of Lyme disease on patients has been controversial, mounting evidence supports the idea that a substantial number of patients experience persistent symptoms following treatment. The research community has largely lacked the necessary funding to properly advance the scientific and clinical understanding of the disease, or to develop and evaluate innovative approaches for prevention, diagnosis, and treatment. Given the many outstanding questions raised into the diagnosis, clinical presentation and treatment of Lyme disease, and the underlying molecular mechanisms that trigger persistent disease, there is an urgent need for more support. This review article summarizes progress over the past 5 years in our understanding of Lyme and tick-borne diseases in the United States and highlights remaining challenges.

Combat-related mild traumatic brain injury (mTBI) is a leading cause of sustained impairments in military service members and veterans. Recent animal studies show that GABA-ergic parvalbumin-positive interneurons are susceptible to brain injury, with damage causing abnormal increases in spontaneous gamma-band (30–80 Hz) activity. We investigated spontaneous gamma activity in individuals with mTBI using high-resolution resting-state magnetoencephalography source imaging. Participants included 25 symptomatic individuals with chronic combat-related blast mTBI and 35 healthy controls with similar combat experiences. Compared with controls, gamma activity was markedly elevated in mTBI participants throughout frontal, parietal, temporal, and occipital cortices, whereas gamma activity was reduced in ventromedial prefrontal cortex. Across groups, greater gamma activity correlated with poorer performances on tests of executive functioning and visuospatial processing. Many neurocognitive associations, however, were partly driven by the higher incidence of mTBI participants with both higher gamma activity and poorer cognition, suggesting that expansive upregulation of gamma has negative repercussions for cognition particularly in mTBI. This is the first human study to demonstrate abnormal resting-state gamma activity in mTBI. These novel findings suggest the possibility that abnormal gamma activities may be a proxy for GABA-ergic interneuron dysfunction and a promising neuroimaging marker of insidious mild head injuries.

Combat‐related mild traumatic brain injury (cmTBI) is a leading cause of sustained physical, cognitive, emotional, and behavioral disabilities in Veterans and active‐duty military personnel. Accurate diagnosis of cmTBI is challenging since the symptom spectrum is broad and conventional neuroimaging techniques are insensitive to the underlying neuropathology. The present study developed a novel deep‐learning neural network method, 3D‐MEGNET, and applied it to resting‐state magnetoencephalography (rs‐MEG) source‐magnitude imaging data from 59 symptomatic cmTBI individuals and 42 combat‐deployed healthy controls (HCs). Analytic models of individual frequency bands and all bands together were tested. The All‐frequency model, which combined delta‐theta (1–7 Hz), alpha (8–12 Hz), beta (15–30 Hz), and gamma (30–80 Hz) frequency bands, outperformed models based on individual bands. The optimized 3D‐MEGNET method distinguished cmTBI individuals from HCs with excellent sensitivity (99.9 ± 0.38%) and specificity (98.9 ± 1.54%). Receiver‐operator‐characteristic curve analysis showed that diagnostic accuracy was 0.99. The gamma and delta‐theta band models outperformed alpha and beta band models. Among cmTBI individuals, but not controls, hyper delta‐theta and gamma‐band activity correlated with lower performance on neuropsychological tests, whereas hypo alpha and beta‐band activity also correlated with lower neuropsychological test performance. This study provides an integrated framework for condensing large source‐imaging variable sets into optimal combinations of regions and frequencies with high diagnostic accuracy and cognitive relevance in cmTBI. The all‐frequency model offered more discriminative power than each frequency‐band model alone. This approach offers an effective path for optimal characterization of behaviorally relevant neuroimaging features in neurological and psychiatric disorders., This study developed a novel resting‐state magnetoencephalography (rs‐MEG) source‐magnitude imaging method, 3D‐MEGNET, using deep learning. The optimized 3D‐MEGNET method combining rs‐MEG data from all frequency bands distinguished individuals with combat‐related mild traumatic brain injury (cmTBI) from combat‐deployed healthy controls with high sensitivity, specificity, and diagnostic accuracy. This study provides an integrated framework for condensing large source‐imaging variable sets into optimal combinations of regions and frequencies with high diagnostic accuracy and cognitive relevance in cmTBI.

This study was designed to identify trends in the top-cited classic psychedelic publications. The top 50 publications on classic psychedelics with the greatest total of number of citations and annual citation rate were identified and pooled. Unique articles (n = 76) were dichotomized by median year of publication (2010.5); the differential distribution of study characteristics between the "Recent Cohort" (n = 38) and "Older Cohort" (n = 38) were documented. The Recent Cohort had a greater annual citation rate (median 76.0, IQR 38.5 to 101.5) compared to the Older Cohort (median10.0, IQR 5.2 to 19.3, p < .001). The Recent Cohort included a greater number of clinical studies (n = 26 [68.4%] vs. n = 9 [23.7%]) while the Older Cohort included more basic science and preclinical studies (n = 21 [55.3%] vs. n = 2 [5.3%], p < .001). Psilocybin was the predominant psychedelic studied in the Recent Cohort (n = 25 [65.8%] vs. n = 9 [23.7%]) while lysergic acid diethylamide (LSD) was predominantly studied in the Older Cohort (n = 25 [65.8%] vs. n = 18 [47.4%], p = .013). The Recent Cohort included more studies examining affective disorders (n = 15 [39.5%] vs. n = 3 [7.9%]) and substance use disorders (n = 6 [15.8%] vs. n = 0 [0.0%]), while the Older Cohort included a greater number of pharmacological outcomes (n = 29 [76.3%] vs. n = 6 [15.8%], p < .001). This study identified and documented trends in the top-cited classic psychedelic publications. The field is continuing to form a foundational understanding of the pharmacological effects of psychedelics and is now advancing with the identification of therapeutic uses within clinical populations.

Background: Diminished motor cortical excitability, as a measurement of increased resting motor threshold with transcranial magnetic stimulation (TMS), is known to be associated with chronic pain conditions. Over 175,000 veterans who were deployed to the Persian Gulf in 1990-91 suffer from an unexplained multisymptom illness termed Gulf War Illness (GWI) with chronic headaches and diffuse body pain as the most commonly reported symptoms. This study hypothesized that veterans with Gulf War Illness related pain exhibit diminished corticomotor excitability associated with chronic pain states and aimed to assess the resting motor threshold (RMT) at the primary motor cortex (M1) in veterans with GWI.Methods: Single pulse TMS was administered over the left motor cortex, using anatomical scans of each subject to guide the TMS coil, starting at 25% of maximum stimulator output (MSO) and increasing in steps of 2% until a motor response with a 50 µV peak to peak amplitude, defined as the RMT, was evoked at the flexor pollicis brevis muscle. RMT was then analyzed using Repeated Measures Analysis of Variance (RM-ANOVA).Results: Gulf War Veterans (GWV) with chronic headaches and body pain (N=20) had a significantly (P

Psilocybin is a classic psychedelic compound that may have efficacy for the treatment of mood and substance use disorders. Acute psilocybin effects include reduced negative mood, increased positive mood, and reduced amygdala response to negative affective stimuli. However, no study has investigated the long-term, enduring impact of psilocybin on negative affect and associated brain function. Twelve healthy volunteers (7F/5M) completed an open-label pilot study including assessments 1-day before, 1-week after, and 1-month after receiving a 25 mg/70 kg dose of psilocybin to test the hypothesis that psilocybin administration leads to enduring changes in affect and neural correlates of affect. One-week post-psilocybin, negative affect and amygdala response to facial affect stimuli were reduced, whereas positive affect and dorsal lateral prefrontal and medial orbitofrontal cortex responses to emotionally-conflicting stimuli were increased. One-month post-psilocybin, negative affective and amygdala response to facial affect stimuli returned to baseline levels while positive affect remained elevated, and trait anxiety was reduced. Finally, the number of significant resting-state functional connections across the brain increased from baseline to 1-week and 1-month post-psilocybin. These preliminary findings suggest that psilocybin may increase emotional and brain plasticity, and the reported findings support the hypothesis that negative affect may be a therapeutic target for psilocybin.

ObjectiveThoracic aortic disease (TAD) may have substantial impact on health-related quality of life (HRQOL). We described HRQOL in patients with TAD, cardiovascular screening participants and their partners; identified factors associated with HRQOL; and explored lived experiences and feelings of anxiety or depression using a mixed methods design.MethodsFor this cross-sectional study, all consecutive patients visiting the TAD outpatient clinic (2017–2019) at our centre were asked to complete three questionnaires: the Short Form 36 (SF-36), the Hospital Anxiety and Depression Scale (HADS) and the Rotterdam Disease Specific Questionnaire (RDSQ). A subsample was invited for in-depth interviews.ResultsIn total, 261 participants were included: 147 patients with TAD (thoracic aortic diameter ≥40 mm; 54 females, 36.7%), 114 screening participants (cardiovascular family screening; 71 females, 62.3%) and 66 partners. Compared with the general population, patients with TAD showed markedly lower HRQOL, whereas screening participants’ HRQOL was less impaired. Female and younger participants scored significantly lower on the SF-36 and HADS compared with male and older participants. Smaller aortic diameter was associated with better RDSQ score, and previous aortic surgery was associated with higher HADS depression scores. Furthermore, partners scored significantly lower on 2/8 SF-36 subdomains when compared with the general population. From 11 interviewees, determinants of psychological distress included coping strategies, impact on social and professional life, disease-related knowledge, state of aortic diameters and physical symptoms.ConclusionsHealthcare professionals must be aware of HRQOL impairments in patients with TAD, particularly in younger females. Moreover, attention for partners is needed. Coping strategies and communication within the family were found to be important factors influencing psychological distress, and might be valuable leads for counselling and HRQOL improvement in this population.

Sourcing HIV-1 infection HIV-1 has a multitude of strain variants, but sexual transmission of HIV-1 is assumed to result from productive infection by only one virus particle. Knowing the genetics of the virus strains that are transmitted could be crucial for developing successful vaccine strategies. Using epidemiological and genetic data from 112 pairs of sexual partners, Villabona-Arenas et al. found that individuals with acute infections are more likely to transmit multiple founder virus strains. In a phylodynamic approach that integrated phylogenetic analysis of sequence data with simulation of a transmission chain, the authors showed that multiple variant transmission is doubled during the first 3 months of infection irrespective of whether transmission was heterosexual or by men who have sex with men. Science , this issue p. 103

Background The infant mortality rate (IMR), a key indicator of the quality of a healthcare system, has remained at approximately 3.5‰ for the past 10 years in Germany. Generic quality indicators (QIs), as used in Germany since 2010, greatly help in ensuring such a good value but do not seem to be able to further reduce the IMR. The neonatal mortality rate (NMR) contributes to 65–70% of the IMR. We therefore propose single-case analysis of neonatal deaths as an additional method and show an efficient way to implement this approach. Methods We used the Nordic-Baltic classification (NBC) to detect avoidable neonatal deaths. We applied this classification to a sample of 1968 neonatal death records, which represent over 90% of all neonatal deaths in East Berlin from 1973 to 1989. All cases were analyzed as to their preventability based on the complete perinatal and clinical data by a special commission of different experts. The NBC was automatically applied through natural language processing and an ontology-based terminology server. Results The NBC was used to select the group of cases that had a high potential of avoidance. The selected group represented 6.0% of all cases, and 60.4% of the cases within that group were judged avoidable or conditionally avoidable. The automatic detection of malformations showed an F1 score of 0.94. Conclusion The results show that our method can be applied automatically and is a powerful and highly specific tool for selecting potentially avoidable neonatal deaths and thus for supporting efficient single-case analysis.

Background: Humans and animals with type 2 diabetes mellitus (T2DM) exhibit low skeletal muscle oxidative capacity and impaired glucose metabolism. The aim of the present study was to investigate the effects of exposure to mild hyperbaric oxygen on these changes in obese rats with T2DM. Methods: Five-week-old non-diabetic Long-Evans Tokushima Otsuka (LETO) and diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats were divided into normobaric (LETO-NB and OLETF-NB) and mild hyperbaric oxygen (LETO-MHO and OLETF-MHO) groups. The LETO-MHO and OLETF-MHO groups received 1266 hPa with 36% oxygen for 3 h daily for 22 weeks. Results: Fasting and non-fasting blood glucose, HbA1c, and triglyceride levels were lower in the OLETF-MHO group than in the OLETF-NB group (P < 0.05). In the soleus muscle, peroxisome proliferator-activated receptor δ/β (Pparδ/β), Pparγ, and PPARγ coactivator-1α (Pgc-1α) mRNA levels were lower in the OLETF-NB group than in all other groups (P < 0.05), whereas myogenin (Myog) and myogenic factor 5 (Myf5) mRNA levels were higher in the OLETF-MHO group than in the LETO-NB and OLETF-NB groups (P < 0.05). The soleus muscles in the OLETF-NB group contained only low-oxidative Type I fibers, whereas those in all other groups contained high-oxidative Type IIA and Type IIC fibers in addition to Type I fibers. Conclusions: Exposure to mild hyperbaric oxygen inhibits the decline in skeletal muscle oxidative capacity and prevents the hyperglycemia associated with T2DM. Pgc-1α, Myog, and Myf5 mRNA levels appear to be closely associated with skeletal muscle oxidative capacity in rats with T2DM.

Combining alcohol and caffeine is associated with increased alcohol consumption, but no prospective experimental studies have examined whether added caffeine increases alcohol consumption.This study examined how caffeine alters alcohol self-administration and subjective reinforcing effects in healthy adults.Thirty-one participants completed six double-blind alcohol self-administration sessions: three sessions with alcohol only (e.g., beverage A) and three sessions with alcohol and caffeine (e.g., beverage B). Participants chose which beverage to consume on a subsequent session (e.g., beverage A or B). The effects of caffeine on overall beverage choice, number of self-administered drinks, subjective ratings (e.g., Biphasic Alcohol Effects Scale), and psychomotor performance were examined.A majority of participants (65%) chose to drink the alcohol beverage containing caffeine on their final self-administration session. Caffeine did not increase the number of self-administered drinks. Caffeine significantly increased stimulant effects, decreased sedative effects, and attenuated decreases in psychomotor performance attributable to alcohol. Relative to nonchoosers, caffeine choosers reported overall lower stimulant ratings and reported greater drinking behavior prior to the study.Although caffeine did not increase the number of self-administered drinks, most participants chose the alcohol beverage containing caffeine. Given the differences in subjective ratings and pre-existing differences in self-reported alcohol consumption for caffeine choosers and nonchoosers, these data suggest that decreased stimulant effects of alcohol and heavier self-reported drinking may predict subsequent choice of combined caffeine and alcohol beverages. These predictors may identify individuals who would benefit from efforts to reduce risk behaviors associated with combining alcohol and caffeine.

Background Observational data and preliminary studies suggest serotonin 2A agonist psychedelics may hold potential in treating a variety of substance use disorders (SUDs), including opioid use disorder (OUD). Aims The study aim was to describe and analyze self-reported cases in which naturalistic psychedelic use was followed by cessation or reduction in other substance use. Methods An anonymous online survey of individuals reporting cessation or reduction in cannabis, opioid, or stimulant use following psychedelic use in non-clinical settings. Results Four hundred forty-four respondents, mostly in the USA (67%) completed the survey. Participants reported 4.5 years of problematic substance use on average before the psychedelic experience to which they attributed a reduction in drug consumption, with 79% meeting retrospective criteria for severe SUD. Most reported taking a moderate or high dose of LSD (43%) or psilocybin-containing mushrooms (29%), followed by significant reduction in drug consumption. Before the psychedelic experience 96% met SUD criteria, whereas only 27% met SUD criteria afterward. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced substance misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with greater reduction in drug consumption. Conclusions While these cross-sectional and self-report methods cannot determine whether psychedelics caused changes in drug use, results suggest the potential that psychedelics cause reductions in problematic substance use, and support additional clinical research on psychedelic-assisted treatment for SUD.

Background Kratom, a Southeast Asian plant with opioid-receptor mediated effects, has emerged as a potential substance of abuse, with limited data on its use and effects. This study characterized kratom user demographics, use patterns, and perceived drug effects. Methods A cross-sectional, anonymous online survey was conducted between January and December 2017. Results 2,798 kratom users – mean age 40 (SD = 12); predominantly White (90 %), female (61 %), and located in the US (97 %) – completed the survey. Kratom was primarily taken orally in doses of 1−3 g (49 %), with daily use (59 %) being most common. Kratom was used for pain (91 %), anxiety (67 %), and depression (65 %), with high ratings of effectiveness. 1,144 (41 %) used kratom to stop or reduce prescription or illicit opioid use, citing decreased opioid withdrawal and craving related to kratom use, with 411 reporting >1-year continuous abstinence from opioids attributed to kratom use. Roughly one-third of respondents reported adverse effects of kratom, largely rated as mild in severity and lasting ≤24 h. Seventeen participants (0.6 %) sought treatment for adverse effects. Fifty-six individuals (2 %) met DSM-5 criteria for a past-year moderate or severe kratom-related substance use disorder (SUD). When asked how troubled they felt regarding their kratom use, the mean (SD) rating was 3.2 (9.8) on a scale from 0 to 100. Conclusion Kratom is used among White, middle-aged Americans for symptoms of pain, anxiety, depression, and opioid withdrawal. Although regular use was typical, kratom-related SUD and serious adverse effects were uncommon. Additional research on kratom epidemiology and pharmacology is imperative in light of the present opioid epidemic.

BackgroundWomen with Turner syndrome (TS) are at increased risk of aortic dissection, which is related to ascending aortic diameter. However, the relation between aortic diameter and outcome is not well determined. This study evaluates the prevalence of aortic dilatation, the growth rate of the aorta and the risk of aortic complications in adults with TS.MethodsSingle centre, retrospective study of all women with TS followed with a strict protocol in an outpatient TS clinic. Aortic diameters were analysed using advanced imaging. The primary outcome was a combined endpoint of aortic-related mortality, aortic dissection and preventive aortic surgery. The secondary endpoint was aortic growth and prevalence of aortic dilatation, defined as an aortic size index >20 mm/m2 at baseline.ResultsAt least one cardiac MR/CT was available in 268 women with TS, having median age of 28.7 (IQR: 21.3–39.7) years. Aortic dilatation was present in 22%. Linear regression identified independent factors associated with larger aortic diameters: age (coefficient=0.23; pConclusionsAortic dilatation is common and known associations were confirmed in large adult TS cohort However, aortic dissection, related mortality and preventive aortic surgery are rare. Growth hormone treatment in childhood was associated with aortic dimensions.

This randomized clinical trial examines the efficacy of psilocybin as an adjunct to psychotherapy and other treatments for major depressive disorder., Key Points Question Is psilocybin-assisted therapy efficacious among patients with major depressive disorder? Findings In this randomized clinical trial of 24 participants with major depressive disorder, participants who received immediate psilocybin-assisted therapy compared with delayed treatment showed improvement in blinded clinician rater–assessed depression severity and in self-reported secondary outcomes through the 1-month follow-up. Meaning This randomized clinical trial found that psilocybin-assisted therapy was efficacious in producing large, rapid, and sustained antidepressant effects in patients with major depressive disorder., Importance Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression. Objective To investigate the effect of psilocybin therapy in patients with MDD. Design, Setting, and Participants This randomized, waiting list–controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland. Adults aged 21 to 75 years with an MDD diagnosis, not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were eligible to participate. Enrollment occurred between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. A total of 27 participants were randomized to an immediate treatment condition group (n = 15) or delayed treatment condition group (waiting list control condition; n = 12). Data analysis was conducted from July 1, 2019, to July 31, 2020, and included participants who completed the intervention (evaluable population). Interventions Two psilocybin sessions (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) were given (administered in opaque gelatin capsules with approximately 100 mL of water) in the context of supportive psychotherapy (approximately 11 hours). Participants were randomized to begin treatment immediately or after an 8-week delay. Main Outcomes and Measures The primary outcome, depression severity was assessed with the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline (score of ≥17 required for enrollment) and weeks 5 and 8 after enrollment for the delayed treatment group, which corresponded to weeks 1 and 4 after the intervention for the immediate treatment group. Secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR). Results Of the randomized participants, 24 of 27 (89%) completed the intervention and the week 1 and week 4 postsession assessments. This population had a mean (SD) age of 39.8 (12.2) years, was composed of 16 women (67%), and had a mean (SD) baseline GRID-HAMD score of 22.8 (3.9). The mean (SD) GRID-HAMD scores at weeks 1 and 4 (8.0 [7.1] and 8.5 [5.7]) in the immediate treatment group were statistically significantly lower than the scores at the comparable time points of weeks 5 and 8 (23.8 [5.4] and 23.5 [6.0]) in the delayed treatment group. The effect sizes were large at week 5 (Cohen d = 2.2; 95% CI, 1.4-3.0; P

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes. Trial Registration ClinicalTrials.gov identifier: NCT00465595

A recent open-label pilot study (N = 15) found that two to three moderate to high doses (20 and 30 mg/70 kg) of the serotonin 2A receptor agonist, psilocybin, in combination with cognitive behavioral therapy (CBT) for smoking cessation, resulted in substantially higher 6-month smoking abstinence rates than are typically observed with other medications or CBT alone.To assess long-term effects of a psilocybin-facilitated smoking cessation program at ≥12 months after psilocybin administration.The present report describes biologically verified smoking abstinence outcomes of the previous pilot study at ≥12 months, and related data on subjective effects of psilocybin.All 15 participants completed a 12-month follow-up, and 12 (80%) returned for a long-term (≥16 months) follow-up, with a mean interval of 30 months (range = 16-57 months) between target-quit date (i.e., first psilocybin session) and long-term follow-up. At 12-month follow-up, 10 participants (67%) were confirmed as smoking abstinent. At long-term follow-up, nine participants (60%) were confirmed as smoking abstinent. At 12-month follow-up 13 participants (86.7%) rated their psilocybin experiences among the five most personally meaningful and spiritually significant experiences of their lives.These results suggest that in the context of a structured treatment program, psilocybin holds considerable promise in promoting long-term smoking abstinence. The present study adds to recent and historical evidence suggesting high success rates when using classic psychedelics in the treatment of addiction. Further research investigating psilocybin-facilitated treatment of substance use disorders is warranted.

The effects of daily repeated bouts of concentric, isometric, or eccentric contractions induced by high frequency (kilohertz) transcutaneous electrical stimulation in ameliorating atrophy of the soleus muscle in hindlimb unloaded rats were determined. Five groups of male rats were studied: control, hindlimb unloaded for 2 weeks (HU), or HU plus two daily bouts of concentric, isometric, or eccentric high-frequency electrical stimulation-induced contractions of the calf musculature. Soleus mass and fiber size were smaller, the levels of phosphorylated Akt1 and FoxO3a lower, and atrogin-1 and ubiquitinated proteins higher in the HU, and the HU plus concentric or isometric contraction groups than in the control group. In contrast, daily bouts of eccentric contractions maintained these values at near control levels and all measures were significantly different from all other HU groups. These results indicate that daily bouts of eccentric contractions induced by high-frequency stimulation inhibited the ubiquitin-proteasome catabolic pathway and enhanced the Akt1/FoxO3a anabolic pathway that resulted in a prevention of the atrophic response of the soleus muscle to chronic unloading.

Ingeborg Syllm-Rapoport, the first Chair in neonatology in Europe, passed away on March 23. Her biography illustrates how medical and scientific work has been influenced by social, ideological, and economic frames and boundaries in the 20th century. Regarded as a “Half-Jew” by the Nazi racist laws, she was denied her medical doctorate. She went to the USA, where she trained in paediatrics and met her husband, the biochemist Samuel Mitja Rapoport. During the “McCarthy Era” both were persecuted as communists. They returned to Europe and became two of the most influential figures at the Charité Hospital in East Berlin. She had to wait until 2015 to finally undergo the doctoral examination at the age of 102 years, making her the oldest person in history to receive a doctorate. We describe Syllm-Rapoport's life and the challenges she had to face living in several countries under different political systems in the 20th century.

Background The thalamus has a demonstrated role in language, particularly through its connectivity to frontal language cortices. Case Description A 59-year-old man with transient mixed aphasia following resection of a left-sided thalamic cavernous malformation is reported. No operative complications were encountered, and there was no surgical contact with cortical language areas. The patient recovered full language function within a week postoperatively. Conclusions The role of thalamic nuclei in language processes and other reports of transient thalamic aphasia are reviewed.

The relationship between the extracellular signal-regulated kinase 1 and 2 (ERK1/2), one of the mitogen-activated protein kinases (MAPKs), and mammalian skeletal muscle fiber phenotype is unclear. We looked at this relationship in three in vivo conditions in male Wistar rats. First, the levels of phosphorylated (active) ERK1/2 protein were closely associated with the fiber type composition of sedentary rat hindlimb muscles: highest in the superficial portion of the gastrocnemius (100% fast fibers), lower in the plantaris (~ 80% fast fibers), and lowest in the soleus (~ 15% fast fibers). Second, during growth, there was a gradual decrease in the percentage of fast fibers from 40% at 3 weeks to 1.5% at 65 weeks and a concomitant gradual decrease in the levels of phosphorylated ERK1/2 in the soleus muscle. Third, sciatic nerve denervation induced a significant decrease in the weight of both the soleus and plantaris, but a slow-to-fast fiber type shift and increase in phosphorylated ERK1/2 protein were observed only in the soleus. Although only a few fast and fast + slow hybrid fibers of the denervated soleus muscle reacted positively to the anti-phosphorylated ERK1/2 antibody by immuno-histochemical analysis, our results suggest that the phosphorylated form of ERK1/2 seems to be closely related to the fast fiber phenotype program. Further evidence for this relationship was provided by the observation that several slow fiber phenotype-specific proteins, i.e., Hsp72, Hsp60, and PGC-1, changed in the opposite direction of the levels of phosphorylated ERK1/2 protein.

Classic psychedelics (serotonin 2A receptor agonists) and dissociative hallucinogens (NMDA receptor antagonists), though differing in pharmacology, may share neuropsychological effects. These drugs, however, have undergone limited direct comparison. This report presents data from a double-blind, placebo-controlled within-subjects study comparing the neuropsychological effects of multiple doses of the classic psychedelic psilocybin with the effects of a single high dose of the dissociative hallucinogen dextromethorphan (DXM). Twenty hallucinogen users (11 females) completed neurocognitive assessments during five blinded drug administration sessions (10, 20, and 30 mg/70 kg psilocybin; 400 mg/70 kg DXM; and placebo) in which participants and study staff were informed that a large range of possible drug conditions may have been administered. Global cognitive impairment, assessed using the Mini-Mental State Examination during peak drug effects, was not observed with psilocybin or DXM. Orderly and dose-dependent effects of psilocybin were observed on psychomotor performance, working memory, episodic memory, associative learning, and visual perception. Effects of DXM on psychomotor performance, visual perception, and associative learning were in the range of effects of a moderate to high dose (20 to 30 mg/70 kg) of psilocybin. This was the first study of the dose effects of psilocybin on a large battery of neurocognitive assessments. Evidence of delirium or global cognitive impairment was not observed with either psilocybin or DXM. Psilocybin had greater effects than DXM on working memory. DXM had greater effects than all psilocybin doses on balance, episodic memory, response inhibition, and executive control.

Background Caffeine Use Disorder was added to DSM-5 as a diagnosis for further research, but few studies have been conducted to identify effective treatments. This randomized, controlled clinical trial examined the efficacy of a manual-only treatment program for caffeine cessation and reduction among individuals seeking treatment for problematic caffeine use. Methods Individuals meeting at least two proposed DSM-5 diagnostic criteria for Caffeine Use Disorder were randomly assigned to receive either immediate treatment or treatment delayed by 7 weeks. The treatment consisted of a manual containing information about caffeine and instructions for gradually reducing caffeine consumption over a period of 6 weeks, with no counseling or additional support. Caffeine consumption and caffeine-related distress were assessed before treatment, 7 weeks after receiving the treatment manual (end-of-treatment), and 20 weeks post-treatment. Results The manual-only treatment resulted in significant reductions in participants’ self-reported caffeine consumption and caffeine-related distress at end-of-treatment that were sustained at 20-weeks post-treatment. Salivary caffeine levels and community observers corroborated the self-reported reductions in caffeine consumption. Comparisons between the immediate and delayed treatment groups suggest the reductions in caffeine consumption were attributable to the manualized treatment rather than spontaneous with the passage of time. Conclusions The present study provides evidence that a gradual caffeine reduction and cessation program may be successfully implemented using a manual-only approach. This time- and cost-effective intervention may be easily adopted by practitioners with limited time or experience with behavioral interventions who want to encourage their patients to reduce caffeine consumption.

Background: Recent pilot trials suggest feasibility and potential efficacy of psychedelic-facilitated addiction treatment interventions. Fifteen participants completed a psilocybin-facilitated smoking cessation pilot study between 2009 and 2015. Aims: The aims of this study were as follows: (1) to identify perceived mechanisms of change leading to smoking cessation in the pilot study; (2) to identify key themes in participant experiences and long-term outcomes to better understand the therapeutic process. Methods: Participants were invited to a retrospective follow-up interview an average of 30 months after initial psilocybin sessions. Semi-structured interviews were conducted with 12 of the 15 participants. Data were analysed using thematic analysis. Results: Participants reported gaining vivid insights into self-identity and reasons for smoking from their psilocybin sessions. Experiences of interconnectedness, awe, and curiosity persisted beyond the duration of acute drug effects. Participants emphasised that the content of psilocybin experiences overshadowed any short-term withdrawal symptoms. Preparatory counselling, strong rapport with the study team, and a sense of momentum once engaged in the study treatment were perceived as vital additional factors in achieving abstinence. In addition, participants reported a range of persisting positive changes beyond smoking cessation, including increased aesthetic appreciation, altruism, and pro-social behaviour. Conclusions: The findings highlight the value of qualitative research in the psychopharmacological investigation of psychedelics. They describe perceived connections between drug- and non-drug factors, and provide suggestions for future research trial design and clinical applications.

Disease tolerance is a defense strategy against infections that aims at maintaining host health even at high pathogen replication or load. Tolerance mechanisms are currently intensively studied with the long-term goal of exploiting them therapeutically. Because tolerance-based treatment imposes less selective pressure on the pathogen it has been hypothesised to be “evolution-proof”. However, the primary public health goal is to reduce the incidence and mortality associated with a disease. From this perspective, tolerance-based treatment bears the risk of increasing the prevalence of the disease, which may lead to increased mortality. We assessed the promise of tolerance-based treatment strategies using mathematical models. Conventional treatment was implemented as an increased recovery rate, while tolerance-based treatment was assumed to reduce the disease-related mortality of infected hosts without affecting recovery. We investigated the endemic phase of two types of infections: acute and chronic. Additionally, we considered the effect of pathogen resistance against conventional treatment. We show that, for low coverage of tolerance-based treatment, chronic infections can cause even more deaths than without treatment. Overall, we found that conventional treatment always outperforms tolerance-based treatment, even when we allow the emergence of pathogen resistance. Our results cast doubt on the potential benefit of tolerance-based over conventional treatment. Any clinical application of tolerance-based treatment of infectious diseases has to consider the associated detrimental epidemiological feedback., PLoS Computational Biology, 14 (5), ISSN:1553-734X, ISSN:1553-7358

The MRI appearance of intraventricular neoplasms is often nonspecific, however knowledge of patient age and tumor location facilitates the formulation of a differential diagnosis. Imaging and pertinent clinical features of the following intraventricular neoplasms are reviewed: ependymoma, subependymoma, central neurocytoma, subependymal giant cell tumor, choroid plexus tumors, medulloblastoma, meningioma, chordoid glioma, rosette-forming glioneuronal tumor, central nervous system lymphoma, and metastasis.

Introduction Skeletal muscle oxidative capacity decreases and fatigability increases after spinal cord injury. Transcription factor peroxisome proliferator-activated receptor δ (PPARδ) promotes a more oxidative phenotype. Methods We asked whether PPARδ overexpression could ameliorate these deficits in the medial gastrocnemius of spinal cord transected (ST) adult mice. Results Time-to-peak tension and half-relaxation times were longer in PPARδ-Con and PPARδ-ST compared with littermate wild-type (WT) controls. Fatigue index was 50% higher in PPARδ-Con than WT-Con and 70% higher in the PPARδ-ST than WT-ST. There was an overall higher percent of darkly stained fibers for succinate dehydrogenase in both PPARδ groups. Conclusions The results indicate a conversion toward slower, more oxidative, and less fatigable muscle properties with overexpression of PPARδ. Importantly, the elevated fatigue resistance was maintained after ST, suggesting that enhanced PPARδ expression, and possibly small molecule agonists, could ameliorate the increased fatigability routinely observed in chronically paralyzed muscles.

Treadmill walking exercise is not always effective for prevention of detrimental effects on soleus muscle caused by gravitational unloading. Thus, the effects of walking speed and/or uphill inclination on the mobilization of leg muscles were studied to reconsider the optimum prescription for the countermeasure. The subjects performed barefoot walking exercise on a treadmill at 4 and 6 km/h and at a 0, 6, 10, and 15% uphill incline. The activity of electromyogram (EMG) was recorded in soleus, lateral portion of gastrocnemius, and tibialis anterior muscles. In addition, the total time spent for each step (step duration from landing to the next landing of the left foot) and the time soleus was active per step (EMG burst duration) during each step were determined. Furthermore, video was recorded to measure the ankle and knee joint angles in the front and back foot, when the front foot landed on the treadmill. Most of the subjects stepped down using the heel (rear-foot strike), but one subject stepped down using the fore-foot (fore-foot strike). The EMG activity of soleus in the rear-foot strikers was elevated with an increase in treadmill inclination and/or speed. In contrast, soleus EMG activity was decreased in the fore-foot striker under the same conditions, whereas the EMG activity of gastrocnemius was increased. These results indicate that individual differences in foot-strike patterns should be considered for the optimum prescription of walking as an exercise countermeasure and suggest that similar considerations may be warranted for other exercise countermeasures.

Mild traumatic brain injury (mTBI) is common in the United States, accounting for as many as 75–80% of all TBIs. It is recognized as a significant public health concern, but there are ongoing controversies regarding the etiology of persistent symptoms post-mTBI. This constellation of nonspecific symptoms is referred to as postconcussive syndrome (PCS). The present study combined results from magnetoencephalography (MEG) and cognitive assessment to examine group differences and relationships between brain activity and cognitive performance in 31 military and civilian individuals with a history of mTBI+PCS and 33 matched healthy control subjects. An operator-free analysis was used for MEG data to increase reliability of the technique. Subjects completed a comprehensive neuropsychological assessment, and measures of abnormal slow-wave activity from MEG were collected. Results demonstrated significant group differences on measures of executive functioning and processing speed. In addition, significant correlations between slow-wave activity on MEG and patterns of cognitive functioning were found in cortical areas, consistent with cognitive impairments on exams. Results provide more objective evidence that there may be subtle changes to the neurobiological integrity of the brain that can be detected by MEG. Further, these findings suggest that these abnormalities are associated with cognitive outcomes and may account, at least in part, for long-term PCS in those who have sustained an mTBI.

Introduction: We investigated heat-stress effects on the adult myosin heavy chain (MyHC) profile of soleus muscle fibers at an early stage of regeneration. Methods: Regenerating fibers in adult rats were analyzed 2, 4, or 6 days after bupivacaine injection. Rats were heat stressed by immersion in water (42 ± 1°C) for 30 minutes 24 hours after bupivacaine injection and every other day thereafter. Results: No adult MyHC isoforms were observed after 2 days, whereas some fibers expressed only fast MyHC after 4 days. Heat stress increased fast and slow MyHC in regenerating fibers after 6 days. Regenerating fibers expressing only slow MyHC were observed only in heat-stressed muscles. Bupivacaine injection increased the number of Pax7+ and MyoD+ satellite cells in regenerating fibers, more so in heat-stressed rats. Conclusion: The results indicate that heat stress accelerates fast-to-slow MyHC phenotype conversion in regenerating fibers via activation of satellite cells. Muscle Nerve, 2015

Introduction: We determined the effects of low-intensity exercise on the three-dimensional capillary structure and associated angiogenic factors in the soleus muscle of Goto-Kakizaki (GK) diabetic rats. Methods: Four groups of male rats were studied: sedentary nondiabetic (Con), exercised nondiabetic control (Ex), sedentary GK, and exercised GK (GK+Ex). Rats in the Ex and GK+Ex groups were subjected to chronic low-intensity running on a treadmill (15 m/min, 60 min/session, 5 sessions/week for 3 weeks). Results: Although mean capillary volume and diameter were lower in the GK compared with all other groups, low-intensity exercise increased both of these measures in GK rats. Mitochondrial markers, i.e., SDH activity and PGC-1α expression, and the levels of angiogenic factors were higher in the GK+Ex than all other groups. Exercise increased vascular endothelial growth factor (VEGF) protein levels and the VEGF-to-TSP-1 ratio, an indicator of angiogenesis, in GK rats. Conclusions: Combined, the results indicate that low-intensity exercise reduces some of the microcirculatory complications in type 2 diabetic muscles. Muscle Nerve 51: 391–399, 2015

Mild traumatic brain injury (mTBI) is a leading cause of sustained impairments in military service members, Veterans, and civilians. However, few treatments are available for mTBI, partially because the mechanism of persistent mTBI deficits is not fully understood.We used magnetoencephalography (MEG) to investigate neuronal changes in individuals with mTBI following a passive neurofeedback-based treatment programme called IASIS. This programme involved applying low-intensity pulses using transcranial electrical stimulation (LIP-tES) with electroencephalography monitoring. Study participants included six individuals with mTBI and persistent post-concussive symptoms (PCS). MEG exams were performed at baseline and follow-up to evaluate the effect of IASIS on brain functioning.At the baseline MEG exam, all participants had abnormal slow-waves. In the follow-up MEG exam, the participants showed significantly reduced abnormal slow-waves with an average reduction of 53.6 ± 24.6% in slow-wave total score. The participants also showed significant reduction of PCS scores after IASIS treatment, with an average reduction of 52.76 ± 26.4% in PCS total score.The present study demonstrates, for the first time, the neuroimaging-based documentation of the effect of LIP-tES treatment on brain functioning in mTBI. The mechanisms of LIP-tES treatment are discussed, with an emphasis on LIP-tES's potentiation of the mTBI healing process.

RATIONALE: Although psilocybin and dextromethorphan (DXM) are hallucinogens, they have different receptor mechanisms of action and have not been directly compared. OBJECTIVE: This study compared subjective, behavioral and physiological effects of psilocybin and dextromethorphan under conditions that minimized expectancy effects. METHODS: Single, acute oral doses of psilocybin (10, 20, 30 mg/70kg), DXM (400 mg/70kg), and placebo were administered under double-blind conditions to 20 healthy participants with histories of hallucinogen use. Instructions to participants and staff minimized expectancy effects. Various subjective, behavioral, and physiological effects were assessed after drug administration. RESULTS: High doses of both drugs produced similar increases in participant ratings of peak overall drug effect strength, with similar times to maximal effect and time-course. Psilocybin produced orderly dose-related increases on most participant-rated subjective measures previously shown sensitive to hallucinogens. DXM produced increases on most of these same measures. However the high dose of psilocybin produced significantly greater and more diverse visual effects than DXM including greater movement and more frequent, brighter, distinctive, and complex (including textured and kaleidoscopic) images and visions. Compared to DXM, psilocybin also produced significantly greater mystical-type and psychologically insightful experiences, and greater absorption in music. In contrast, DXM produced larger effects than psilocybin on measures of disembodiment, nausea/emesis, and lightheadedness. Both drugs increased systolic blood pressure, heart rate, and pupil dilation, and decreased psychomotor performance and balance. CONCLUSIONS: Psilocybin and DXM produced similar profiles of subjective experiences, with psilocybin producing relatively greater visual, mystical-type, insightful, and musical experiences, and DXM producing greater disembodiment.

Our aim was to determine the effects of pre‐ and/or postconditioning with mild hyperbaric oxygen (1.25 atmospheric pressure, 36% oxygen for 3 h/day) on the properties of the soleus muscle that was atrophied by hindlimb suspension‐induced unloading. Twelve groups of 8‐week‐old rats were housed under normobaric conditions (1 atmospheric pressure, 20.9% oxygen) or exposed to mild hyperbaric oxygen for 2 weeks. Ten groups then were housed under normobaric conditions for 2 weeks with their hindlimbs either unloaded via suspension or not unloaded. Six groups subsequently were either housed under normobaric conditions or exposed to mild hyperbaric oxygen for 2 weeks: the suspended groups were allowed to recover under reloaded conditions (unrestricted normal cage activity). Muscle weights, cross‐sectional areas of all fiber types, oxidative capacity (muscle succinate dehydrogenase activity and fiber succinate dehydrogenase staining intensity) decreased, and a shift of fibers from type I to type IIA and type IIC was observed after hindlimb unloading. In addition, mRNA levels of peroxisome proliferator‐activated receptor γ coactivator‐1α decreased, whereas those of forkhead box‐containing protein O1 increased after hindlimb unloading. Muscle atrophy and decreased oxidative capacity were unaffected by either pre‐ or postconditioning with mild hyperbaric oxygen. In contrast, these changes were followed by a return to nearly normal levels after 2 weeks of reloading when pre‐ and postconditioning were combined. Therefore, a combination of pre‐ and postconditioning with mild hyperbaric oxygen can be effective against the atrophy and decreased oxidative capacity of skeletal muscles associated with hindlimb unloading.

Psilocybin and other 5-hydroxytryptamine2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research. Here, we review therapeutic research on psilocybin, the classic psychedelic that has been the focus of most recent research. For mood and anxiety disorders, three controlled trials have suggested that psilocybin may decrease symptoms of depression and anxiety in the context of cancer-related psychiatric distress for at least 6 months following a single acute administration. A small, open-label study in patients with treatment-resistant depression showed reductions in depression and anxiety symptoms 3 months after two acute doses. For addiction, small, open-label pilot studies have shown promising success rates for both tobacco and alcohol addiction. Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.

We present a new perspective on the concept of feed-forward compared to feedback mechanisms for motor control. We propose that conceptually all sensory information in real time provided to the brain and spinal cord can be viewed as a feed-forward phenomenon. We also propose that the spinal cord continually adapts to a broad array of ongoing sensory information that is used to adjust the probability of making timely and predictable decisions of selected networks that will execute a given response. One interpretation of the term feedback historically entails responses with short delays. We propose that feed-forward mechanisms, however, range in timeframes of milliseconds to an evolutionary perspective, that is, “evolutionary learning.” Continuously adapting events enable a high level of automaticity within the sensorimotor networks that mediate “planned” motor tasks. We emphasize that either a very small or a very large proportion of motor responses can be under some level of conscious vs automatic control. Furthermore, we make a case that a major component of automaticity of the neural control of movement in vertebrates is located within spinal cord networks. Even without brain input, the spinal cord routinely uses feed-forward processing of sensory information, particularly proprioceptive and cutaneous, to continuously make fundamental decisions that define motor responses. In effect, these spinal networks may be largely responsible for executing coordinated sensorimotor tasks, even those under normal “conscious” control.

Objectives: The objectives of the study were to determine the prevalence and socio-economic determinants of autism among children attending primary and secondary schools in South East, Nigeria. Methods: This was a cross-sectional study that assessed the prevalence and socio-economic pattern of childhood autism among children attending primary and secondary schools in Enugu and Ebonyi states, South East Nigeria. The questionnaire was adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR, 2000). The study was carried out between June and October, 2014. The schools were selected by listing all the mixed schools in the urban and semi- urban areas by simple random sampling. Results: A total of 721 subjects completed the questionnaire. The age of respondents ranged between 3 and 18 years, with mean age of 12.71 and standard deviation of 3.03 years. Twenty one children fulfilled the criteria for autism giving a prevalence of 2.9%. There is a significant association between age in categories (fishers exact test, p = 0.013) and social class (p=0.033). Conclusion: The prevalence of autism was 2.9%; and the socio-economic characteristics of childhood autism in South East Nigeria are similar to those in other parts of the world. Keywords: Childhood autism; primary and secondary schools; Nigeria

Data suggest psychedelics such as psilocybin and lysergic acid diethylamide (LSD) may hold therapeutic potential in the treatment of addictions, including tobacco dependence. This retrospective cross-sectional anonymous online survey characterized 358 individuals (52 females) who reported having quit or reduced smoking after ingesting a psychedelic in a non-laboratory setting ⩾1 year ago. On average, participants smoked 14 cigarettes/day for 8 years, and had five previous quit attempts before their psychedelic experience. Of the 358 participants, 38% reported continuous smoking cessation after psychedelic use (quitters). Among quitters, 74% reported >2 years’ abstinence. Of the 358 participants, 28% reported a persisting reduction in smoking (reducers), from a mode of 300 cigarettes/month before, to a mode of 1 cigarette/month after the experience. Among reducers, 62% reported >2 years of reduced smoking. Finally, 34% of the 358 participants (relapsers) reported a temporary smoking reduction before returning to baseline smoking levels, with a mode time range to relapse of 3–6 months. Relapsers rated their psychedelic experience significantly lower in personal meaning and spiritual significance than both other groups. Participants across all groups reported less severe affective withdrawal symptoms (e.g. depression, craving) after psychedelic use compared with previous quit attempts, suggesting a potential mechanism of action for psychedelic-associated smoking cessation/reduction. Changes in life priorities/values were endorsed as the most important psychological factor associated with smoking cessation/reduction. Results suggest psychedelics may hold promise in treating tobacco addiction as potentially mediated by spiritual experience, changed priorities/values, and improved emotional regulation.

We describe an instance in which complete paraplegia was evident immediately postoperatively after apparently uneventful lumbar epidural-general anesthesia in a patient with Morquio Type A syndrome (Morquio A) with moderate thoracic spinal stenosis.A 16-yr-old male with Morquio A received lumbar epidural-general anesthesia for bilateral distal femoral osteotomies. Preoperative imaging had revealed a stable cervical spine and moderate thoracic spinal stenosis with a mild degree of spinal cord compression. Systolic blood pressure (BP) was maintained within 20% of the pre-anesthetic baseline value. The patient sustained a severe thoracic spinal cord infarction. The epidural anesthetic contributed to considerable delay in the recognition of the diagnosis of paraplegia.This experience leads us to suggest that, in patients with Morquio A, it may be prudent to avoid the use of epidural anesthesia without very firm indication, to support BP at or near baseline levels in the presence of even moderate spinal stenosis, and to avoid flexion or extension of the spinal column in intraoperative positioning. If the spinal cord/column status is unknown or if the patient is known to have any degree of spinal stenosis, we suggest that the same rigorous BP support practices that are typically applied in other patients with severe spinal stenosis, especially stenosis with myelomalacia, should apply to patients with Morquio A and that spinal cord neurophysiological monitoring should be employed. In the event that cord imaging is not available, e.g., emergency procedures, it would be prudent to assume the presence of spinal stenosis.

Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-week smoking cessation treatment protocol. Participants were 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake. Biomarkers assessing smoking status, and self-report measures of smoking behavior demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up. The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacological therapies (typically

This study investigated the bidirectional relationship between the intensity of low back pain (LBP) and sleep disturbance. Further, the study aimed to determine whether any relationship is dependent on pain duration, symptoms of depression and anxiety, and the method of sleep assessment (subjective vs. objective).Eighty patients with LBP completed a sleep diary. A subgroup of 50 patients additionally wore an electronic device (Armband) to measure sleep for 7 consecutive days. Pain intensity was assessed twice daily using a sleep diary. Depression and anxiety symptoms were assessed at baseline using the Depression Anxiety Stress Scale questionnaire. Generalized estimating equations (GEE) with an exchangeable correlation structure were used to examine the relationship between day-time pain intensity and sleep.The GEE analysis showed that a night of poor sleep quality, difficulty falling sleep (assessed by the sleep diary), waking after sleep onset, and low sleep efficiency (assessed by the sleep diary and Armband) were followed by a day with higher pain intensity. Further, a day with higher pain intensity was associated with a decrease in the subsequent night's sleep quality, an increase in sleep latency (assessed by the sleep diary), waking after sleep onset (assessed by both measures), and low sleep efficiency (assessed by the Armband).The findings demonstrate that there is a bidirectional relationship between sleep and pain intensity in patients with LBP. The relationship is independent of pain duration and baseline symptoms of depression and anxiety and somewhat dependent on the method of sleep measurement (sleep diary or Armband). Future research is needed to determine whether targeting sleep improvement in patients with LBP contributes to pain reduction.

A chronic decrease in neuromuscular activity (activation and/or loading) results in muscle atrophy and capillary regression that are due, in part, to the overproduction of reactive oxygen species. We have reported that antioxidant treatment with astaxanthin attenuates the overexpression of reactive oxygen species in atrophied muscles that, in turn, ameliorates capillary regression in hindlimb-unloaded rats. Astaxanthin supplementation, however, had little effect on muscle mass and fibre cross-sectional area. In contrast, intermittent loading of the hindlimbs of hindlimb-unloaded rats ameliorates muscle atrophy. Therefore, we hypothesized that the combination of astaxanthin supplementation and intermittent loading would attenuate both muscle atrophy and capillary regression during hindlimb unloading. As expected, 2 weeks of hindlimb unloading resulted in atrophy, a decrease in capillary volume and a shift towards smaller-diameter capillaries in the soleus muscle. Intermittent loading alone (1 h of cage ambulation per day) attenuated atrophy of the soleus, while astaxanthin treatment alone maintained the capillary network to near control levels. The combination of intermittent loading and astaxanthin treatment, however, ameliorated atrophy of the soleus and maintained the capillary volume and luminal diameters and the superoxide dismutase-1 protein levels near control values. These results indicate that intermittent loading combined with astaxanthin supplementation could be an effective therapy for both the muscle atrophy and the capillary regression associated with a chronic decrease in neuromuscular activity.