Serum keratin 19 (CYFRA21-1) is a prognostic biomarker in severe alcoholic hepatitis.

BACKGROUND AND AIMS: Up to 30% of patients with severe alcoholic hepatitis (sAH) die within 3 months of presentation. The degree of ductular reaction, characterized by accumulation of biliary and liver progenitor cells, confers a poor prognosis. Keratin fragments are established serological surrogates of liver injury and keratin 19 (K19) is a histological marker of the ductular reaction. We assessed the relationship between serum K19 levels (viz. CYFRA21-1), histology and outcome in patients with sAH. METHODS: Serum CYFRA21-1 was quantified in pre-treatment serum samples from 824 patients enrolled in the STOPAH trial. The cohort was randomly divided into two groups to test mortality associations; histological analyses were performed using the 87 cases with suitable samples. RESULTS: CYFRA21-1 levels were elevated in sAH and strongly predicted alcoholic steatohepatitis (ASH) on biopsy (area under the receiver operated characteristic [AUROC] 0.785 [95% Confidence Interval 0.602-0.967]) and 90-day survival (AUROC 0.684/0.693). The predictive ability of CYFRA21-1 was comparable with the model of end-stage liver disease (MELD) score and was independently associated with survival in multivariable analysis. CYFRA21-1 moderately correlated with hepatocellular injury markers M30/M65 but displayed a more robust predictive ability. A combination of MELD and CYFRA21-1 conferred a modest improvement in the AUROC value (0.731/0.743). CONCLUSIONS: In sAH serum, CYFRA21-1 levels associate with the presence of ASH on biopsy and independently predict 90-day survival. As a single marker performance is comparable to established scoring systems. Therefore, CYFRA21-1, which is available in many clinical laboratories, may become a useful component of prognostic models.

An enzymatic tandem reaction to produce odor-active fatty aldehydes.

Aldehydes represent a versatile and favored class of flavoring substances. A biocatalytic access to odor-active aldehydes was developed by conversion of fatty acids with two enzymes of the α-dioxygenase pathway. The recombinant enzymes α-dioxygenase (α-DOX) originating from Crocosphaera subtropica and fatty aldehyde dehydrogenase (FALDH) from Vibrio harveyi were heterologously expressed in E. coli, purified, and applied in a coupled (tandem) repetitive reaction. The concept was optimized in terms of number of reaction cycles and production yields. Up to five cycles and aldehyde yields of up to 26% were achieved. Afterward, the approach was applied to sea buckthorn pulp oil as raw material for the enzyme catalyzed production of flavoring/fragrance ingredients based on complex aldehyde mixtures. The most abundant fatty acids in sea buckthorn pulp oil, namely palmitic, palmitoleic, oleic, and linoleic acid, were used as substrates for further biotransformation experiments. Various aldehydes were identified, semi-quantified, and sensorially characterized by means of headspace-solid phase microextraction-gas chromatography-mass spectrometry-olfactometry (HS-SPME-GC-MS-O). Structural validation of unsaturated aldehydes in terms of double-bond positions was performed by multidimensional high-resolution mass spectrometry experiments of their Paternò-Büchi (PB) photoproducts. Retention indices and odor impressions of inter alia (Z,Z)-5,8-tetradecadienal (Z,Z)-6,9-pentadecadienal, (Z)-8-pentadecenal, (Z)-4-tridecenal, (Z)-6-pentadecenal, and (Z)-8-heptadecenal were determined for the first time. KEY POINTS: • Coupled reaction of Csα-DOX and VhFALDH yields chain-shortened fatty aldehydes. • Odors of several Z-unsaturated fatty aldehydes are described for the first time. • Potential for industrial production of aldehyde-based odorants from natural sources.

The chemical induction of synaesthesia.

OBJECTIVE: Preliminary research suggests that experiences resembling synaesthesia are frequently reported under the influence of a diverse range of chemical substances although the incidence, chemical specificity, and characteristics of these effects are poorly understood. METHODS: Here we surveyed recreational drug users and self-reported developmental synaesthetes regarding their use of 28 psychoactive drugs from 12 different drug classes and whether they had experienced synaesthesia under the influence of these substances. RESULTS: The drug class of tryptamines exhibited the highest incidence rates of drug-induced synaesthesia in controls and induction rates of novel forms of synaesthesia in developmental synaesthetes. Induction incidence rates in controls were strongly correlated with the corresponding induction and enhancement rates in developmental synaesthetes. In addition, the use of lysergic acid diethylamide (LSD) was the strongest predictor of drug-induced synaesthesia in both controls and developmental synaesthetes. Clear evidence was observed for a clustering of synaesthesia-induction rates as a function of drug class in both groups, denoting non-random incidence rates within drug classes. Sound-colour synaesthesia was the most commonly observed type of induced synaesthesia. Further analyses suggest the presence of synaesthesia-prone individuals, who were more likely to experience drug-induced synaesthesia with multiple drugs. CONCLUSIONS: These data corroborate the hypothesized link between drug-induced synaesthesia and serotoninergic activity, but also suggest the possibility of alternative neurochemical pathways involved in the induction of synaesthesia. They further imply that the induction and modulation of synaesthesia in controls and developmental synaesthetes share overlapping mechanisms and that certain individuals may be more susceptible to experiencing induced synaesthesia with different drugs.

Managing behavioural and developmental paediatric conditions in rural outpatient clinics: An insight to the challenge ahead.

AIM: The aim of this study is to characterise the nature and caseload of general paediatric outpatient clinics in rural Queensland and to compare the findings with national data. METHODS: A retrospective clinical audit of medical records in paediatric clinics at two rural hospitals was undertaken over a 6-month period. Data extracted included demographics, diagnostic category and onward referral outcomes. The same diagnostic categories were used as the national Children Attending Paediatricians Study (CAPS) to facilitate comparison. RESULTS: A total of 346 records were reviewed, 56 (16.2%) documented Aboriginal and Torres Strait Islander descent. Compared to national data, significantly more children with behavioural/developmental diagnoses were seen in the rural clinics (CAPS 33.8%; rural 59.2%; P < 0.001). In contrast, children presenting with medical conditions (CAPS 48.2%; rural 28.6%; P < 0.001) and mixed medical/developmental conditions (CAPS 17.9%; rural 12.1%; P = 0.006) were seen less frequently in the rural clinics. Referral rates from the rural sites were lower than the rates reported by CAPS for children with behavioural/developmental diagnoses (CAPS 35.9%, rural 24.9%; P = 0.002) and mixed diagnoses (CAPS 40.6%, rural 19.0%; P = 0.005), while there was no difference in referral rates for children with medical diagnoses (CAPS 16.1%, rural 18.2%; P = 0.575). CONCLUSIONS: Rural paediatricians' caseloads are dominated by developmental/behavioural conditions, however children with these conditions are less likely to be referred to allied health and psychology services. The reasons for lower referral rates and specific pressures upon rural health services need to be investigated in future studies to provide better health services for rural children.

The variable spectrum of anterior mitral valve leaflet restriction in rheumatic heart disease screening.

INTRODUCTION: The World Heart Federation (WHF) screening criteria do not incorporate a strict, reproducible definition of anterior mitral valve leaflet (AMVL) restriction. Using a novel definition, we have identified two distinct AMVL restriction configurations. The first, called "distal tip" AMVL restriction is associated with additional morphological features of rheumatic heart disease (RHD), while the second, "gradual bowing" AMVL restriction is not. This "arch-like" leaflet configuration involves the base to tip of the medial MV in isolation. We hypothesize that this configuration is a normal variant. METHODOLOGY: The prevalence and associated leaflet configurations of AMVL restriction were assessed in schoolchildren with an established "very low" (VLP), "high" (HP), and "very high" prevalence (VHP) of RHD. RESULTS: 936 studies were evaluated (HP 577 cases; VLP 359 cases). Sixty-five cases of "gradual bowing" AMVL restriction were identified in the HP cohort (11.3%, 95% CI 8.9-14.1) and 35 cases (9.7%, 95% CI 7-13.2) in the VLP cohort (P = .47). In the second analyses, an enriched cohort of 43 studies with proven definite RHD were evaluated. "Distal tip" AMVL restriction was identified in all 43 VHP cases (100%) and affected the central portion of the AMVL in all cases. CONCLUSION: "Gradual bowing" AMVL restriction appears to be a normal, benign variant of the MV, not associated with RHD risk nor with any other morphological features of RHD. Conversely, "Distal tip" AMVL restriction was present in all cases in the VHP cohort with no cases exhibiting a straight, nonrestricted central portion of the AMVL. This novel finding requires further investigation as a potential RHD rule-out test of the MV.

A single-center, retrospective study of COVID-19 features in children: a descriptive investigation.

BACKGROUND: Compared to adults, there are relatively few studies on COVID-19 infection in children, and even less focusing on the unique features of COVID-19 in children in terms of laboratory findings, locations of computerized tomography (CT) lesions, and the role of CT in evaluating clinical recovery. The objective of this study is to report the results from patients at Wuhan Children's Hospital, located within the initial center of the outbreak. METHODS: Clinical, imaging, and laboratory data of 76 children were collected retrospectively and analyzed with the Fisher exact test and Cox regression statistical methods. RESULTS: Among 50 children with a positive COVID-19 real-time reverse-transcriptase polymerase chain reaction (PCR), five had negative PCR results initially but showed positive results in subsequent tests. Eight (16%) patients had lymphopenia, seven (14%) with thrombocytopenia, four (8%) with lymphocytosis, two (4%) with thrombocytosis, ten (20%) with elevated C-reactive protein, four (8%) with hemoglobin above, and six (12%) with below standard reference values. Seven (14%) of the 50 had no radiologic evidence of disease on chest CT. For the 43 patients who had abnormal CT findings, in addition to previously reported patterns of ground-glass opacity (67%), local patchy shadowing (37%), local bilateral patchy shadowing (21%), and lesion location of lower lobes (65%), other CT features include that an overwhelming number of pediatric patients had lesions in the subpleural area (95%) and 22 of the 28 lower lobe lesions were in the posterior segment (78%). Lesions in most of the 15 patients (67%) who received chest CT at discharge were not completely absorbed, and 26% of these pediatric patients had CT lesions that were either unchanged or worse. CONCLUSIONS: There were a few differences between COVID-19 children and COVID-19 adults in terms of laboratory findings and CT characteristics. CT is a powerful tool to detect and characterize COVID-19 pneumonia but has little utility in evaluating clinical recovery for children. These results oppose current COVID-19 hospital discharge criteria in China, as one requirement is that pulmonary imaging must show significant lesion absorption prior to discharge. These differences between pediatric and adult cases of COVID-19 may necessitate pediatric-specific discharge criteria.

Telavancin hospital-acquired pneumonia trials: impact of Gram-negative infections and inadequate Gram-negative coverage on clinical efficacy and all-cause mortality.

BACKGROUND: When hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP) is caused by gram-positive and gram-negative pathogens or both (mixed infections), the adequacy of gram-negative coverage (GNC) can confound the assessment of a gram-positive agent under study. This analysis examines the influence of gram-negative infections and the adequacy of GNC on clinical efficacy and all-cause mortality in the telavancin HABP/VABP phase 3 ATTAIN trials (Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia). METHODS: This post hoc analysis evaluated 3 patient groups from ATTAIN: (1) gram-positive-only infections, (2) gram-positive-only and mixed infections-adequate GNC, and (3) gram-negative-only infections and mixed infections with inadequate GNC. For each, clinical efficacy at test of cure and all-cause mortality at day 28 were compared for telavancin and vancomycin. RESULTS/CONCLUSIONS: In the ATTAIN safety population there were 16 more deaths in the telavancin arms than in the vancomycin arms. Of these, 13 were in patients with gram-negative-only infections (n = 9) or with mixed infections and inadequate GNC (n = 4) and all had estimated baseline creatinine clearances of <30ml/min. Based on this analysis, clinical response and all-cause mortality could be confounded because there were more patients with gram-negative pathogens at baseline and more patients received inadequate treatment of these gram-negative infections in the telavancin groups.

Ebony and Ivory? Interracial dating intentions and behaviors of disadvantaged African American women in Kentucky.

Using data from 595 predominantly disadvantaged African American women in Kentucky, this study examines perceptions about racial/ethnic partner availability, cultural mistrust, and racism as correlates of interracial dating intentions and behaviors with both white and Hispanic men. Participants reported levels of dating intentions and behaviors were significantly higher with whites than Hispanics. The multivariate models indicate less cultural mistrust and believing it is easier to find a man of that racial/ethnic category were associated with higher interracial dating intentions. Women were more likely to have dated a white man if they believed it was easier to find a white man and had interracial dating intentions; however, interracial dating intentions was the only significant correlate of having dated a Hispanic man. Findings suggest a shrinking social distance between racial groups, broadening the MMPI for African American women; yet, the low levels of interracial relationships are likely driven by preferences of men.

The ownership that wasn't meant to be: Yearworth and property rights in human tissue.

This paper is concerned with the English Court of Appeal's decision in Yearworth v North Bristol NHS Trust that six men had, for the purposes of their claims against the trust, ownership of the sperm they had produced. The case has been discussed by many commentators and most, if not all, of those who have discussed the case have claimed or assumed that the court held that the claimants had property rights in the sperm they had produced. In this paper, I advance an interpretation of the case that does not regard the court as deciding that the men had property rights (in the narrow sense of that term) in the sperm they had produced. On this view, the 'ownership' that the Court of Appeal purported to vest in each of the men was not a right in rem, a right 'binding the world'. If this is so, it is perhaps unsurprising that some scholars, evaluating the success of the court's reasoning as a justification for vesting the claimants with property rights, have found it to be unsatisfactory.

On-field instrumented mouthguard coupling.

Instrumented mouthguard (iMG) sensors have been developed to measure sports head acceleration events (HAE) in brain injury research. Laboratory validation studies show that effective coupling of iMGs with the human skull is crucial for accurate head kinematics measurements. However, iMG-skull coupling has not been investigated in on-field sports settings. The objective of this study was to assess on-field iMG coupling using infrared proximity sensing and to investigate coupling effects on kinematics signal characteristics. Forty-two university-level men's ice hockey (n = 21) and women's rugby (n = 21) athletes participated in the study, wearing iMGs during 6-7 month in-season periods. Proximity data classified video-verified HAE recordings into four main iMG coupling categories: coupled (on-teeth), decoupling (on-teeth to off-teeth), recoupling (off-teeth to on-teeth) and decoupled (off-teeth). Poorly-coupled HAEs showed significantly higher peak angular acceleration amplitudes and greater signal power in medium-high frequency bands compared with well-coupled HAEs, indicating potential iMG movements independent of the skull. Further, even video-verified true positives included poorly-coupled HAEs, and iMG coupling patterns varied between the men's hockey and women's rugby teams. Our findings show the potential of using proximity sensing in iMGs to identify poorly-coupled HAEs. Utilizing this data screening process in conjunction with video review may mitigate a key source of sensor noise and enhance the overall quality of on-field sports HAE datasets.

On-field Head Acceleration Exposure Measurements Using Instrumented Mouthguards: Multi-stage Screening to Optimize Data Quality.

Instrumented mouthguards (iMGs) are widely applied to measure head acceleration event (HAE) exposure in sports. Despite laboratory validation, on-field factors including potential sensor skull-decoupling and spurious recordings limit data accuracy. Video analysis can provide complementary information to verify sensor data but lacks quantitative kinematics reference information and suffers from subjectivity. The purpose of this study was to develop a rigorous multi-stage screening procedure, combining iMG and video as independent measurements, aimed at improving the quality of on-field HAE exposure measurements. We deployed iMGs and gathered video recordings in a complete university men's ice hockey varsity season. We developed a four-stage process that involves independent video and sensor data collection (Stage I), general screening (Stage II), cross verification (Stage III), and coupling verification (Stage IV). Stage I yielded 24,596 iMG acceleration events (AEs) and 17,098 potential video HAEs from all games. Approximately 2.5% of iMG AEs were categorized as cross-verified and coupled iMG HAEs after Stage IV, and less than 1/5 of confirmed or probable video HAEs were cross-verified with iMG data during stage III. From Stage I to IV, we observed lower peak kinematics (median peak linear acceleration from 36.0 to 10.9 g; median peak angular acceleration from 3922 to 942 rad/s2) and reduced high-frequency signals, indicative of potential reduction in kinematic noise. Our study proposes a rigorous process for on-field data screening and provides quantitative evidence of data quality improvements using this process. Ensuring data quality is critical in further investigation of potential brain injury risk using HAE exposure data.

Coming back together: a qualitative survey study of coping and support strategies used by people to cope with extended difficulties after the use of psychedelic drugs.

Introduction: A growing body of literature is investigating the difficulties that some individuals encounter after psychedelic experiences. Existing research has explored the nature and predictors of these difficulties; however, a research gap exists in understanding how individuals endeavour to cope with such difficulties. Methods: The current study collected data from an international cohort of 608 participants who reported experiencing difficulties that persisted for at least one day after a psychedelic experience. They provided written data on how they used coping strategies to alleviate these difficulties. The qualitative analysis of the written data on coping was conducted using Structured Tabular Thematic Analysis. Results: A wide range of individual and social coping strategies were employed that were found helpful. The most common individual strategies were meditation and prayer, followed by self-educational activities such as reading and journaling. The most prevalent forms of social coping involved seeking support from friends or family members, followed by obtaining assistance from a therapist or coach. Features of social coping that were reported to be helpful included feeling heard/accepted, a non-judgemental attitude and sharing similar experiences. Discussion: Our findings hold potential for informing the design of therapeutic interventions and educational resources aimed at enhancing positive outcomes for those experiencing extended difficulties after psychedelic use.

Multicentre, randomised, double-blind, placebo-controlled, proof of concept study of LSALT peptide as prevention of acute respiratory distress syndrome and acute kidney injury in patients infected with SARS-CoV-2 (COVID-19).

OBJECTIVE: Dipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19. DESIGN: Phase 2a randomised, placebo-controlled, double-blinded, trial. SETTING: Hospitals in Canada, Turkey and the USA. PARTICIPANTS: A total of 61 subjects with moderate-to-severe COVID-19. INTERVENTIONS: Randomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers. RESULTS: At 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O2 ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups. CONCLUSION: In a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19. TRIAL REGISTRATION NUMBER: NCT04402957.

Evaluation of intravenous voriconazole in patients with compromised renal function.

BACKGROUND: Incorporation of the solubilizing excipient, sulfobutylether-ß-cyclodextrin (SBECD), in the intravenous (IV) formulation of voriconazole has resulted in the recommendation that this formulation be used with caution in patients with creatinine clearances (Clcr) < 50 mL/min. This study evaluated the safety of IV voriconazole compared with two other IV antifungals not containing SBECD in patients with compromised renal function. METHODS: A total of 128 patients aged 11-93 years who had a baseline Clcr < 50 mL/min between January 1, 2007 and December 31, 2010 were identified from a database of a university-affiliated inpatient healthcare system; of these, 55 patients received caspofungin, 54 patients received fluconazole, and 19 patients received voriconazole. Changes in serum creatinine (Scr) and Clcr levels while on therapy were compared with baseline values and between groups. RESULTS: The groups had similar characteristics apart from the larger proportion of females that received fluconazole. Baseline Scr was higher in those receiving caspofungin, but maximal increases of Scr and decreases in Clcr were greatest for the fluconazole group. Acute kidney injury (AKI), assessed by RIFLE criteria, was more frequent in the fluconazole vs. the caspofungin group (p < 0.01); incidence of AKI in the voriconazole group was not significantly different than found in the other two groups. The infecting organism was a predictor of AKI and formulation with SBECD was not. CONCLUSIONS: Treatment of fungal infections in patients with compromised renal function with an SBECD-containing antifungal agent was not associated with AKI in clinical practice. Since the infecting organism was associated with AKI, decision on which antifungal to use should be determined by susceptibilities to the organism and not the incorporation of SBECD in the IV formulation.

This is your brain on death: a comparative analysis of a near-death experience and subsequent 5-Methoxy-DMT experience.

Introduction: Much research has focused on the modeling of the near-death experience (NDE) by classical and atypical psychedelics; however, to date, no study has reported on the relationship between the NDE and the experience induced by the highly potent, endogenous psychedelic drug 5-Methoxy-DMT (5MeO-DMT). This article presents a case study of an individual who is popularly documented to have had a profound near-death experience while in a coma caused by bacterial meningoencephalitis. Additionally, the individual also subsequently underwent an experience with 5MeO-DMT. Methods: A semi-structured interview was conducted with the subject concerning his experiences with both the NDE and 5MeO-DMT. A basic thematic analysis was performed on both the original text describing the NDE as well as the interview itself, which mainly focused on the subject's experience with 5MeO-DMT. This analysis was organized to identify both the similar and different emergent themes between the two states, with a particular emphasis on the subject's perceptions of the similarities and differences between the experiences. Results: There is a very high level of comparability between the original NDE and psychedelic experiences in general, including shared characteristics such as entering other worlds, meeting menacing or benevolent entities, experiencing synesthesia, perinatal regression, and lucid dreamlike properties. Much comparability was also identified with the 5MeO-DMT experience, in particular the major mystical experiential domains, such as ego dissolution, but especially transcendence of time and space. However, there were also a few unique themes (life review, the deceased, and the threshold) that emerged in the NDE that were not present in the 5MeO-DMT experience or other psychedelic experience studies, suggesting that these themes may be more unique to the NDE. Discussion: Despite such similarities, the participant asserted that his NDE and psychedelic experiences were not similar enough to be attributed to endogenous psychedelics. In this study, we discussed several mechanisms that could potentially account for the NDE, including lucid dreams and perinatal regression. However, the study also explored the possibility that the unique etiology of the participant's NDE, bacterial meningoencephalitis affecting the neocortex, may have triggered similar downstream neural activity as that initiated by psychedelic agents through pyramidal neuronal activation. This hypothesis is presented with appropriate caveats and acknowledged as speculative.

An encounter with the self: A thematic and content analysis of the DMT experience from a naturalistic field study.

Introduction: N,N-Dimethyltryptamine (DMT) is an endogenous serotonergic psychedelic capable of producing radical shifts in an experience that have significant implications for consciousness and its neural correlates, especially given the "disconnected consciousness" suggested by the "breakthrough" DMT state. Its increasing usage and clinical trial indicate the growing importance of a thorough elucidation of the experience's qualitative content, over and above the phenomenological structure. This is particularly in light of the intensely pervasive effects of DMT occasions in all dimensions of the self, which are often ontologically challenging yet potentially transformative. Methods: This is the second report on the first naturalistic field study of DMT use exploring its qualitative analysis. Screened, healthy, anonymized, and experienced DMT users were observed during their non-clinical use of the drug at home (40-75-mg inhaled). In-depth semi-structured interviews, inspired by the micro-phenomenological technique, were employed immediately after their experience. This study reports on the thematic and content analysis of one major domain of the breakthrough experiences elicited, the "self"; where analyses of the "other" were previously reported. A total of 36 post-DMT experience interviews with mostly Caucasian (83%) men (eight women) of a mean of 37 years were predominantly inductively coded. Results: Invariably, profound and highly intense experiences occurred. The first overarching category comprised the onset of effects, encompassing super-ordinate themes including sensory, emotion and body, and space-time shifts; the second category comprised bodily effects, encompassing themes including pleasurable, neutral/both, and uncomfortable; the third category comprised the sensorial effects, encompassing open-eye, visual, and cross-modal and other; the fourth comprised the psychological effects, encompassing memory and language, awareness and sense of self, and time distortions; and the fifth comprised the emotional effects, encompassing positive, neither/both, and challenging experiences. Many further subthemes also illuminate the rich content of the DMT experience. Discussion: The present study provides a systematic and nuanced analysis of the content of the breakthrough DMT state pertaining to one's personal and self-referential experiences of the body, senses, psychology, and emotions. The resonances both with previous DMT studies and other types of extraordinary experiences, such as the alien abduction, shamanic and near-death experiences, are also elaborated upon. Putative neural mechanisms and their promise as a psychotherapeutic agent, especially owing to deep emotional impact, are discussed.

An ACT self-help intervention for adults with a visible difference in appearance: A pilot feasibility and acceptability randomized controlled study.

Individuals living with a visible difference in appearance experience high levels of social anxiety, yet self-help interventions for this heterogeneous population are not available. We conducted a pilot trial of a novel Acceptance and Commitment Therapy (ACT) based self-help intervention.Individuals with anxiety about having a visible difference in appearance (n = 284) were randomized to an ACT-based four-week intervention (n = 145) or a waitlist control condition (n = 139). We collected pre and follow-up (four-weeks after the completion of the intervention) data. Primary outcomes included social anxiety and impairments in functioning. Psychological flexibility (PF) was also examined. ANCOVAs, controlling for pre scores, indicated significant improvements in functioning by the intervention group. No significant differences were observed for anxiety and PF between conditions at follow-up. Drop out was 68% for the intervention and 41% for the control group, with no differences in the groups in age, origin, gender, or type of visible difference. Participants in the intervention group found the intervention almost equally, useful (77%) and helpful (73%). An ACT-based self-help intervention can alleviate distress related to visible difference in appearance. More sophisticated designs are needed now, to collect idiographic and longitudinal data and examine personalized changes across time in this population.

Extended difficulties following the use of psychedelic drugs: A mixed methods study.

Long-term adverse experiences following psychedelic use can persist for weeks, months, or even years, and are relatively unexplored in psychedelic research. Our convergent mixed-method study gained quantitative and qualitative data from 608 participants who reported extended difficulties following psychedelic experiences. Data was gathered on the context of use, the nature and duration of the challenges they experienced (including a written description of these), plus a range of possible risk factors and perceived causes. The most common forms of extended difficulty were feelings of anxiety and fear, existential struggle, social disconnection, depersonalization and derealization. For approximately one-third of the participants, problems persisted for over a year, and for a sixth, they endured for more than three years. It was found that a shorter duration of difficulties was predicted by knowledge of dose, drug type and lower levels of difficulty reported during the psychoactive experience, while a narrower range of difficulties was predicted by taking the drug in a guided setting. Implications for psychedelic harm reduction are discussed.

Among psychedelic-experienced users, only past use of psilocybin reliably predicts nature relatedness.

BACKGROUND: Past research reports a positive relationship between experience with classic serotonergic psychedelics and nature relatedness (NR). However, these studies typically do not distinguish between different psychedelic compounds, which have a unique psychopharmacology and may be used in specific contexts and with different intentions. Likewise, it is not clear whether these findings can be attributed to substance use per se or unrelated variables that differentiate psychedelic users from nonusers. AIMS: The present study was designed to determine the relative degree to which lifetime experience with different psychedelic substances is predictive of self-reported NR among psychedelic-experienced users. METHODS: We conducted a combined reanalysis of five independent datasets (N = 3817). Using standard and regularized regression analyses, we tested the relationship between degree of experience with various psychedelic substances (binary and continuous) and NR, both within a subsample of psychedelic-experienced participants as well as the complete sample including psychedelic-naïve participants. RESULTS/OUTCOMES: Among people experienced with psychedelics, only past use of psilocybin (versus LSD, mescaline, Salvia divinorum, ketamine, and ibogaine) was a reliable predictor of NR and its subdimensions. Weaker, less reliable results were obtained for the pharmacologically similar N,N-dimethyltryptamine (DMT). Results replicate when including psychedelic-naïve participants. In addition, among people exclusively experience with psilocybin, use frequency positively predicted NR. CONCLUSIONS/INTERPRETATION: Results suggest that experience with psilocybin is the only reliable (and strongest) predictor of NR. Future research should focus on psilocybin when investigating effects of psychedelic on NR and determine whether pharmacological attributes or differences in user expectations/use settings are responsible for this observation.