Canalization and plasticity in psychopathology.

This theoretical article revives a classical bridging construct, canalization, to describe a new model of a general factor of psychopathology. To achieve this, we have distinguished between two types of plasticity, an early one that we call 'TEMP' for 'Temperature or Entropy Mediated Plasticity', and another, we call 'canalization', which is close to Hebbian plasticity. These two forms of plasticity can be most easily distinguished by their relationship to 'precision' or inverse variance; TEMP relates to increased model variance or decreased precision, whereas the opposite is true for canalization. TEMP also subsumes increased learning rate, (Ising) temperature and entropy. Dictionary definitions of 'plasticity' describe it as the property of being easily shaped or molded; TEMP is the better match for this. Importantly, we propose that 'pathological' phenotypes develop via mechanisms of canalization or increased model precision, as a defensive response to adversity and associated distress or dysphoria. Our model states that canalization entrenches in psychopathology, narrowing the phenotypic state-space as the agent develops expertise in their pathology. We suggest that TEMP - combined with gently guiding psychological support - can counter canalization. We address questions of whether and when canalization is adaptive versus maladaptive, furnish our model with references to basic and human neuroscience, and offer concrete experiments and measures to test its main hypotheses and implications. This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series".

Psychedelic Communitas: Intersubjective Experience During Psychedelic Group Sessions Predicts Enduring Changes in Psychological Wellbeing and Social Connectedness.

Background: Recent years have seen a resurgence of research on the potential of psychedelic substances to treat addictive and mood disorders. Historically and contemporarily, psychedelic studies have emphasized the importance of contextual elements ('set and setting') in modulating acute drug effects, and ultimately, influencing long-term outcomes. Nevertheless, current small-scale clinical and laboratory studies have tended to bypass a ubiquitous contextual feature of naturalistic psychedelic use: its social dimension. This study introduces and psychometrically validates an adapted Communitas Scale, assessing acute relational experiences of perceived togetherness and shared humanity, in order to investigate psychosocial mechanisms pertinent to psychedelic ceremonies and retreats. Methods: In this observational, web-based survey study, participants (N = 886) were measured across five successive time-points: 2 weeks before, hours before, and the day after a psychedelic ceremony; as well as the day after, and 4 weeks after leaving the ceremony location. Demographics, psychological traits and state variables were assessed pre-ceremony, in addition to changes in psychological wellbeing and social connectedness from before to after the retreat, as primary outcomes. Using correlational and multiple regression (path) analyses, predictive relationships between psychosocial 'set and setting' variables, communitas, and long-term outcomes were explored. Results: The adapted Communitas Scale demonstrated substantial internal consistency (Cronbach's alpha = 0.92) and construct validity in comparison with validated measures of intra-subjective (visual, mystical, challenging experiences questionnaires) and inter-subjective (perceived emotional synchrony, identity fusion) experiences. Furthermore, communitas during ceremony was significantly correlated with increases in psychological wellbeing (r = 0.22), social connectedness (r = 0.25), and other salient mental health outcomes. Path analyses revealed that the effect of ceremony-communitas on long-term outcomes was fully mediated by communitas experienced in reference to the retreat overall, and that the extent of personal sharing or 'self-disclosure' contributed to this process. A positive relationship between participants and facilitators, and the perceived impact of emotional support, facilitated the emergence of communitas. Conclusion: Highlighting the importance of intersubjective experience, rapport, and emotional support for long-term outcomes of psychedelic use, this first quantitative examination of psychosocial factors in guided psychedelic settings is a significant step toward evidence-based benefit-maximization guidelines for collective psychedelic use.

Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing.

Psychedelic microdosing describes the ingestion of near-threshold perceptible doses of classic psychedelic substances. Anecdotal reports and observational studies suggest that microdosing may promote positive mood and well-being, but recent placebo-controlled studies failed to find compelling evidence for this. The present study collected web-based mental health and related data using a prospective (before, during and after) design. Individuals planning a weekly microdosing regimen completed surveys at strategic timepoints, spanning a core four-week test period. Eighty-one participants completed the primary study endpoint. Results revealed increased self-reported psychological well-being, emotional stability and reductions in state anxiety and depressive symptoms at the four-week primary endpoint, plus increases in psychological resilience, social connectedness, agreeableness, nature relatedness and aspects of psychological flexibility. However, positive expectancy scores at baseline predicted subsequent improvements in well-being, suggestive of a significant placebo response. This study highlights a role for positive expectancy in predicting positive outcomes following psychedelic microdosing and cautions against zealous inferences on its putative therapeutic value.

Severity of COVID-19 at elevated exposure to perfluorinated alkylates.

Background: The course of coronavirus disease 2019 (COVID-19) seems to be aggravated by air pollution, and some industrial chemicals, such as the perfluorinated alkylate substances (PFASs), are immunotoxic and may contribute as well. Methods: From Danish biobanks, we obtained plasma samples from 323 subjects aged 30-70 years with known SARS-CoV-2 infection. The PFAS concentrations measured at the background exposures included five PFASs known to be immunotoxic. Register data was obtained to classify disease status, other health information, and demographic variables. We used ordinal and ordered logistic regression analyses to determine associations between PFAS concentrations and disease outcome. Results: Plasma-PFAS concentrations were higher in males, in subjects with Western European background, and tended to increase with age, but were not associated with the presence of chronic disease. Of the study population, 108 (33%) had not been hospitalized, and of those hospitalized, 53 (16%) had been in intensive care or were deceased. Among the five PFASs considered, perfluorobutanoic acid (PFBA) showed an odds ratio (OR) of 2.19 (95% confidence interval, CI, 1.39-3.46) for increasing severities of the disease, although the OR decreased to 1.77 (95% CI, 1.09, 2.87) after adjustment for age, sex, sampling site and interval between blood sampling and diagnosis. Conclusions: Measures of individual exposures to immunotoxic PFASs included PFBA that accumulates in the lungs. Elevated plasma-PFBA concentrations were associated with an increased risk of more severe course of CIVID-19. Given the low background exposure levels in this study, the role of PFAS exposure in COVID-19 needs to be ascertained in populations with elevated exposures.

Ten minutes of ischemia is superior to shorter intervals for the remote ischemic conditioning of human microcirculation.

BACKGROUND: Surgical flaps have become reliable tools in the microsurgical armamentarium, but are still faced with tissue loss due to impaired perfusion which can lead to complete flap failure. Remote Ischemic Conditioning (RIC) has been demonstrated to be an effective way to improve microcirculation in surgical flaps in humans. However, little is known about the optimal amount and length of RIC cycles. OBJECTIVE: Determination of a superior protocol for RIC of cutaneous microcirculation in humans. METHODS: 60 healthy volunteers were randomized into different groups and received a RIC protocol, consisting of three cycles of either 1 second, 1, 5, or 10 minutes of ischemia followed by ten minutes of reperfusion. RIC was applied with a inflatable tourniquet placed on the upper arm. Changes in microcirculation were assessed via combined laser doppler/spectroscopy (O2C device) at the anterior lateral thigh. Relative increase at the end of conditioning vs. baseline measurements was calculated and compared between groups. RESULTS: RIC caused significant changes in cutaneous microcirculation (p < 0.05) which were more pronounced in groups with longer ischemia intervals. The ten minutes group was significantly superior. CONCLUSION: A conditioning protocol containing three cycles of ten minutes of ischemia is superior to protocols with shorter ischemia intervals for RIC of cutaneous microcirculation.

Cancer patients and positive sensory impressions in the hospital environment--a qualitative interview study.

This study explores how cancer patients experience the meaning of positive sensory impressions in the hospital environment such as architecture, decoration and the interior. Data were obtained at a general hospital in Denmark by interviewing six cancer patients at two different wards. The analysis process was guided by the hermeneutical-phenomenological theory of interpretation as presented by the French philosopher Paul Ricoeur. Two main themes were identified: to preserve identity and positive thoughts and feelings. The participants experienced that positive sensory impressions in the hospital environment had a significant impact on their mood, generating positive thoughts and feelings. A view to nature also helped them to forget their negative thoughts for a while. The possibility of having a view helped some cancer patients to connect with good memories and personal life stories that enabled them to recall some of their feelings of identity. This paper adds knowledge about how cancer patients experience sensory impressions in the hospital environment. An environment that provides homeliness and offers a view to nature seems to help some patients to preserve their identity. Furthermore, positive sensory impressions and the opportunity for recreation through environmental facilities strengthen the patient's positive thoughts and feelings.

Constitutional medicine, neoromanticism, and the politics of antimechanism in interwar Germany.

One of the defining features of interwar medical debates in German-speaking countries was the remarkable popularity of holistic concepts among both experts and the lay public. Attacks on the allegedly too-mechanistic outlook of modern medicine were frequent and were often associated with calls to research and treat the constitution of patients rather than isolated causes of disease. This paper traces the rise of the new constitutional medicine, locating its roots in nineteenth-century medical science. The essay attempts to explain the increasingly antimechanistic outlook of promoters of constitutional medicine by relating it to the larger context of the politics of health in Weimar Germany, to concerns of medical practitioners over the rise of the welfare state and the popularity of nonlicensed healers, culminating in the widespread notion of a "crisis of medicine." Drawing on case studies of, among others, the Danzig surgeon Erwin Liek and the Vienna gynecologist Bernhard Aschner, the article distinguishes between rationalist and neoromantic constitutionalists and aims to demonstrate that antimechanism in constitutional medicine was related to neoromantic tendencies in art and other realms of society, while rationalists were concerned with making German men and women fit for war and the requirements of modern industry.

Control of mechanical viroid transmission by the disinfection of tables and tools.

Viroids are of practical importance as the cause of several economically significant infectious diseases. Potato spindle tuber viroid (PSTVd) causes severe yield losses in several crops, because the pathogen spreads fast within the culture. Viroids are small molecules, a few hundred nucleotides long, with a high degree of secondary structure. They do not code for any polypeptides and replicate independently of any associated plant virus. Viroids are readily transmitted by contaminated tools and tables. Furthermore PSTVd is transmitted through the pollen and true seed and can remain its infectious activity in seed for long periods. Vector transmission of PSTVd was reported to occur at low frequency. However, the mechanical transmission is the predominant factor and in this case we discuss the efficient disinfection of tools and tables as a main prophylactic trail to avoid viroid transmission. In previous studies we have tested the efficiency of several disinfectants to eliminate virus contamination. This paper demonstrates the efficient disinfection of MENNO-Florades (Menno-Chemie-GmbH, Norderstedt, Germany. A selection of different concentrations of the disinfectant and various times of incubation were applied in regard to practical use. The tests were confirmed by biological assays using suitable indicator plants, tissue print hybridization, gel electrophoresis and by nucleic acid hybridization. It was shown that PSTVd was eliminated when using the determined combination: 2% of the disinfectant while incubating for one minute or alternative 3%, 30 seconds. The possibility of viroid inactivation by a chemical method of disinfection--while plants are not affected--opens a new perspective to control viroid transmission via tools and tables.

Rationalizing 'folk medicine' in interwar Germany: faith, business, and science at "Dr. Madaus & Co.'.

The relationship between orthodox or mainstream medicine and heterodox or alternative practices has often been expressed in terms of dichotomies, such as science versus anti-science or rationality versus irrationality. By studying the history of a company producing herbal medicines and homoepathic remedies in Germany in the 1920s and 1930s, this paper attempts to create a more differentiated picture. 'Dr. Madaus & Co.' was founded in 1919 by the three sons of a free church minister and his wife, who practised as a non-licensed healer herself. The company not only sold medicines, it also produced journals and books promoting heterodox healing methods and contributing to ongoing health political debates, for example over compulsory vaccination programmes, human experimentation, quackery, and a general 'crisis of medicine'. Gerhard Madaus, a medical doctor and one of the three founders, published in 1938 a three-volume Textbook of Biological Healing Methods, turning folk medicine into science. The essay follows the rise of the Madaus family firm and interprets the story of 'Dr. Madaus & Co.' as an example of social rationalization, emphasizing the role of commercial operations in twentieth-century alternative medicine in Germany.

[Meniscus injuries in dogs with rupture of the cruciate ligament]. / Zur Meniskusverletzung bei Hunden mit Kreuzbandriss.

In a period of 18 months, 132 stifle joints of 125 dogs with a partial or complete rupture of the cranial cruciate ligament were examined according to a systematic protocol at the Clinic for Small Animals of the School of Veterinary Medicine, Hannover, Germany. Surgery was performed with either an intraarticular or extraarticular surgical technique. In all cases a "cleaning up" was carried out. If the medial meniscus was damaged it was resected and the lesion was inspected macroscopically. After six months, 88 patients were examined clinically and radiologically according to the same protocol as half a year before. Injuries of the medial meniscus occurred in 77.3% of the 132 cases. Furthermore it could be shown that patients which had a lameness for more than six weeks before examination had a higher rate of lesions of the medial meniscus than patients that had been lame for a shorter period. A detachment of the caudal horn of the medial meniscus was the most common meniscal lesion. There was no difference in success of therapy between patients with a meniscal resection and those without resection.

[Maintenance of the cranial cruciate ligament rupture in the dog using an intra-articular ("over-the-top") and an extra-articular ("fascia-doubling") method]. / Versorgung des vorderen Kreuzbandrisses beim Hund mit einer intraartikulären (" Over-the-top ") und einer extraartikulären (" Fasziendopplungs "-) Methode.

The present study compares the results of an intraarticular ("over-the-top") and an extraarticular (fascia lata imbrication) surgical method to treat the rupture of the cranial cruciate ligament in dogs. In a period of 18 months, 132 stifle joints of 125 dogs with a partial or complete rupture of the cranial cruciate ligament were examined according to a systematic protocol at the Clinic for Small Animals of the Hannover School of Veterinary Medicine, Hannover, Germany. Surgery was performed with either one or the other of the two surgical techniques. In all cases a " cleaning up " was carried out. If the medial meniscus was damaged, it was resected and the lesion was investigated. The imbrication technique of the lateral aspect of the fascia lata was easier and faster to perform. Using the "over-the-top" method, there were difficulties to guide the fascial strip through the intercondylar notch. After six months 88 patients were re-examined clinically and radiologically according to the same protocol as mentioned above. In the present study it was demonstrated that patients treated with the extraarticular method showed a higher rate (76.5%) of normal limb function after six months and walked earlier without lameness compared with dogs operated with the "over-the-top" technique (41.5%). The same results were valid for patients of giant breeds. Patients operated with the imbrication technique showed more arthrosis of the patellar tip. After six months stability, evaluated with the cranial drawer test and the tibia compression test was satisfying with both techniques.

Handling optical cables: safety aspects.

We found that it is very dangerous to stare directly at thQ free end of an optical cable excited by a GaAlAs laser or by a high radiance LED. We determined the minimum tolerable distance between the human eye and the cable end. In the case of a cable with one multimode fiber, the typical safety zone should be 1 m when using a laser light source and 15 cm when using an LED. In the case of a single mode fiber the critical distance is approximately two to four times as large as in the multimode case; however, when taking into account typical values of the power level in single mode fibers, the critical distance is approximately 1 m as well. For N fibers within the cable the critical distance agrees with that of the single fiber, provided that the fibers are not too closely packaged.

Highly efficient light coupling from GaAlAs lasers into optical fibers.

A new technique is reported for highly efficient light coupling from GaAlAs lasers into step or graded index fibers. The cladding of the fiber is etched to reduce the fiber diameter to nearly the core diameter. Then the fiber end is cut and dipped in a low melting, transparent material to form a lens. This technique is reproducible and is applicable-contrary to a flame melting process-to all types of multimode fibers. We measured 80% coupling efficiency to a 20-m long, cabled graded index fiber (silica, NA = 0.13) with a glass lens on its etched end.