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An asymmetric index of community similarity, related to the Morisitaindex, was proposed in a recent paper by W. E. Kunin in Oikos. As the author reports, surprisingly, the index value can exceed the value one. I make some historical notes on the literature of asymmetric association measures used in different fields. These measures could be applied also to statistical ecology. I refer to a known index family, containing the Morisita index, which makes it possible to generalise the proposed asymmetric index. Making some notes on the numerical behaviour of the index family, I discuss conditions for obtaining an index value over one. [ABSTRACT FROM AUTHOR]

Overweight and obesity in children and adolescents may impact pharmacokinetics and drug exposure. The aim of the present study was to evaluate doses of antidepressants in relation to body weight in children. We used data from the BMI Epidemiology Study (BEST) Gothenburg cohort and the National Prescribed Drug Register and included children and adolescents with a prescription of fluoxetine (n = 347) or sertraline (n = 733) and a weight measurement. For fluoxetine, individuals with overweight or obesity received slightly lower doses at first prescriptions, but not in iterated prescriptions. The weight-normalized dose was lower in individuals with overweight or obesity in first and iterated prescriptions, compared with normal weight (p < 0.01). For sertraline, there were no significant dose differences between individuals with overweight or obesity, compared with normal weight. However, pronounced differences were seen in dose per kilogram body weight in both first and iterated prescriptions (p < 0.01). We conclude that the doses of fluoxetine and sertraline were essentially similar in individuals with overweight or obesity, but the weight-normalized doses were clearly lower. Given the ongoing obesity epidemic, larger studies addressing optimal dosing in individuals with elevated weight are warranted., Competing Interests: Competing interests None of the authors has any conflict of interest. E.E.K. and E.D. are employed by the Swedish Medical Products Agency. The views expressed in this study are the personal views of the authors and not necessarily the view of the government agency., (© 2024. The Author(s).)

Lithium salts are used as mood-balancing medication prescribed to patients suffering from neuropsychiatric disorders, such as bipolar disorder and major depressive disorder. Lithium salts cross the blood-brain barrier and reach the brain parenchyma within few hours after oral application, however, how lithium influences directly human neuronal function is unknown. We applied patch-clamp and microelectrode array technology on human induced pluripotent stem cell (iPSC)-derived cortical neurons acutely exposed to therapeutic (<1 mM) and overdose concentrations (>1 mM) of lithium chloride (LiCl) to assess how therapeutically effective and overdose concentrations of LiCl directly influence human neuronal electrophysiological function at the synapse, single-cell, and neuronal network level. We describe that human iPSC-cortical neurons exposed to lithium showed an increased neuronal activity under all tested concentrations. Furthermore, we reveal a lithium-induced, concentration-dependent, transition of regular synchronous neuronal network activity using therapeutically effective concentration (<1 mM LiCl) to epileptiform-like neuronal discharges using overdose concentration (>1 mM LiCl). The overdose concentration lithium-induced epileptiform-like activity was similar to the epileptiform-like activity caused by the GABA A -receptor antagonist. Patch-clamp recordings reveal that lithium reduces action potential threshold at all concentrations, however, only overdose concentration causes increased frequency of spontaneous AMPA-receptor mediated transmission. By applying the AMPA-receptor antagonist and anti-epileptic drug Perampanel, we demonstrate that Perampanel suppresses lithium-induced epileptiform-like activity in human cortical neurons. We provide insights in how therapeutically effective and overdose concentration of lithium directly influences human neuronal function at synapse, a single neuron, and neuronal network levels. Furthermore, we provide evidence that Perampanel suppresses pathological neuronal discharges caused by overdose concentrations of lithium in human neurons.

Persistent neural stem cell (NSC) proliferation is, among others, a hallmark of immaturity in human induced pluripotent stem cell (hiPSC)-based neural models. TGF-β1 is known to regulate NSCs in vivo during embryonic development in rodents. Here we examined the role of TGF-β1 as a potential candidate to promote in vitro differentiation of hiPSCs-derived NSCs and maturation of neuronal progenies. We present that TGF-β1 is specifically present in early phases of human fetal brain development. We applied confocal imaging and electrophysiological assessment in hiPSC-NSC and 3D neural in vitro models and demonstrate that TGF-β1 is a signaling protein, which specifically suppresses proliferation, enhances neuronal and glial differentiation, without effecting neuronal maturation. Moreover, we demonstrate that TGF-β1 is equally efficient in enhancing neuronal differentiation of human NSCs as an artificial synthetic small molecule. The presented approach provides a proof-of-concept to replace artificial small molecules with more physiological signaling factors, which paves the way to improve the physiological relevance of human neural developmental in vitro models., (Copyright © 2020 Izsak, Vizlin-Hodzic, Iljin, Strandberg, Jadasz, Olsson Bontell, Theiss, Hanse, Ågren, Funa and Illes.)

Human induced pluripotent stem cell (hiPSC)-derived in vitro neural and organoid models resemble fetal, rather than adult brain properties, indicating that currently applied cultivation media and supplements are insufficient to achieve neural maturation beyond the fetal stage. In vivo, cerebrospinal fluid molecules are regulating the transition of the immature fetal human brain into a mature adult brain. By culturing hiPSC-3D neural aggregates in human cerebrospinal fluid (hCSF) obtained from healthy adult individuals, we demonstrate that hCSF rapidly triggers neurogenesis, gliogenesis, synapse formation, neurite outgrowth, suppresses proliferation of residing neural stem cells, and results in the formation of synchronously active neuronal circuits in vitro within 3 days. Thus, a physiologically relevant and adult brain-like milieu triggers maturation of hiPSC-3D neural aggregates into highly functional neuronal circuits in vitro. The approach presented here opens a new avenue to identify novel physiological factors for the improvement of hiPSC neural in vitro models., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Reproducibly generating human induced pluripotent stem cell-based functional neuronal circuits, solely obtained from single individuals, poses particular challenges to achieve personalized and patient specific functional neuronal in vitro models. A hallmark of functional neuronal assemblies, synchronous neuronal activity, can be non-invasively studied by microelectrode array (MEA) technology, reliably capturing physiological and pathophysiological aspects of human brain function. In our here presented manuscript, we demonstrate a procedure to generate 3D neural aggregates comprising astrocytes, oligodendroglial cells, and neurons obtained from the same human tissue sample. Moreover, we demonstrate the robust ability of those neurons to create a highly synchronously active neuronal network within 3 weeks in vitro , without additionally applied astrocytes. The fusion of MEA-technology with functional neuronal circuits solely obtained from one individual's cells represent isogenic person-specific human neuronal sensor chips that pave the way for specific personalized in vitro neuronal networks as well as neurological and neuropsychiatric disease modeling.

"We used diversity indices to quantify the dominance conditions of death cause frequencies [in England, Finland, Hungary, Japan, and Norway]. Plotting age-diversity values, the curves exhibit large changes in the death cause diversity/concentration by age.... The differences are mostly attributed to the site and value of the characteristic maximum. In both studied sections (Neoplasms and Circulatory Diseases) the Japan diversity curves differ considerably from corresponding curves of the European countries. Characteristic departures are observable between the diversity graphs of the male and female groups." (SUMMARY IN ITA), (excerpt)

Relationships between cold tolerance, serum levels of thyroxine (T4), thyronine (T3), and thyrotropine (TSH), and thyroid morphometry have been investigated in male CBA/Ca inbred mice at various ages through their life span. From the data obtained it appeared that there was an age-related decrease in cold tolerance up to 18 months of age which was followed by an increase, the age effect being most apparent in relation to cold resistance and cold tolerance during the recovery period following cold exposure. The age-related changes in cold tolerance appeared to be associated with changes in the serum concentrations of T3, T4, and TSH. In contrast to the T3 serum levels which showed a decrease at 36 months, the thyroxine contents showed a perceptible decrease from the age of 12-18 months onwards. A similar pattern was observed for the TSH levels, with a peak at 21 months, followed by a decline at 30 months. A relationship with age between serum T4 level and thyroid weight was indicated together with structural changes in the thyroid gland, particularly during senescence, for example the size and number of thyroid epithelial cells had become enlarged by 30 months of age.