The changing outlook of psychedelic drugs: The importance of risk assessment and occupational exposure limits

Serotonergic psychedelics, such as lysergic acid diethylamide (LSD), psilocybin, dimethyltryptamine (DMT), and 5‐methoxy‐ N , N ‐dimethyltryptamine (5‐MeO‐DMT), are currently being investigated for the treatment of psychiatric disorders such as depression and anxiety. Clinical trials with psilocybin and LSD have shown improvement in emotional and psychological scores. Although these drugs are reported to be safe in a controlled environment (such as clinical trials), exposure to low doses of these drugs can result in psychedelic effects, and therefore, occupational safety is an important consideration to prevent adverse effects in the workplace from low daily exposure. This article will discuss the factors involved in the derivation of occupational exposure limits (OELs) and risk assessment of these psychedelic drugs. To support the OEL derivations of psychedelic drugs, information regarding their mechanism of action, adverse effect profiles, pharmacokinetics, clinical effects, and nonclinical toxicity were considered. Additionally, psilocybin and LSD, which are the most extensively researched psychedelic substances, are employed as illustrative examples in case studies. The OELs derived for psilocybin and for LSD are 0.05 and 0.002 μg/m 3 , respectively, which indicates that these are highly hazardous compounds, and it is important to take into account suitable safety measures and risk‐management strategies in order to minimize workplace exposure.

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The cover image is based on the Research Article The changing outlook of psychedelic drugs: The importance of risk assessment and occupational exposure limits by Natália Bernardi Videira et al., https://doi.org/10.1002/jat.4533 .

Effects of glass–ceramic produced by the sol–gel route in macrophages recruitment and polarization into bone tissue regeneration

Abstract Effective bone substitute biomaterials remain an important challenge in patients with large bone defects. Glass ceramics produced by different synthesis routes may result in changes in the material physicochemical properties and consequently affect the success or failure of the bone healing response. To investigate the differences in the orchestration of the inflammatory and healing process in bone grafting and repair using different glass–ceramic routes production. Thirty male Wistar rats underwent surgical unilateral parietal defects filled with silicate glass–ceramic produced by distinct routes: BS – particulate glass–ceramic produced via the fusion/solidification route, and BG – particulate glass–ceramic produced via the sol–gel route. After 7, 14, and 21 days from biomaterial grafting, parietal bones were removed to be analyzed under H&E and Massons' Trichome staining, and immunohistochemistry for CD206, iNOS, and TGF‐β. Our findings demonstrated that the density of lymphocytes and plasma cells was significantly higher in the BS group at 45, and 7 days compared to the BG group, respectively. Furthermore, a significant increase of foreign body giant cells (FBGCs) in the BG group at day 7, compared to BS was found, demonstrating early efficient recruitment of FBGCs against sol–gel‐derived glass–ceramic particulate (BS group). According to macrophage profiles, CD206 + macrophages enhanced at the final periods of both groups, being significantly higher at 45 days of BS compared to the BG group. On the other hand, the density of transformation growth factor beta (TGF‐β) positive cells on 21 days were the highest in BG, and the lowest in the BS group, demonstrating a differential synergy among groups. Noteworthy, TGF‐β + cells were significantly higher at 21 days of BG compared to the BS group. Glass–ceramic biomaterials can act differently in the biological process of bone remodeling due to their route production, being the sol–gel route more efficient to activate M2 macrophages and specific FBGCs compared to the traditional route. Altogether, these features lead to a better understanding of the effectiveness of inflammatory response for biomaterial degradation and provide new insights for further preclinical and clinical studies involved in bone healing.

Fetal development of the urinary tract of Cuniculus paca

Abstract The species Cuniculus paca is highly subject to predation, whether natural or anthropogenic, and the ability of species to withstand different levels of depredation depends directly on their reproductive dynamics. However, there is little literature on the developmental biology of this species, and so the aim of this paper was to describe the fetal development of the urinary tract of C. paca through morphological analysis. Twelve specimens with estimated gestational ages of between 75 and 157 days were used, divided into 3 groups. We found the urinary tract in pelvic‐abdominal topography with macroscopic differentiation between the organs already present in the first ages studied; in addition, the microscopic structural pattern changed little between the groups. This evidence reinforces the precocial development of these individuals. Research Highlights With the results obtained for development of urinary tract in Cuniculus paca reinforces the precocial development of these individuals. The urinary tract had pelvic‐abdominal topography with macroscopic differentiation between the organs already present in the first ages studied. The microscopic structural pattern changed little between the groups. At all analyzed fetal ages, the cortical region of kidney was characterized by the presence of glomeruli arranged throughout the region, formed by capillary plexuses surrounded by a glomerular capsule. In addition, the cortical region also presented convoluted tubules with cubic epithelial tissue cells and a brush border. The presence of a developed macula densa was observed next to the glomeruli, suggesting the initial formation of the fetal juxtaglomerular apparatus.

Medial opening low tibial osteotomy shifts the load laterally not only at the ankle joint but also at the knee joint

Abstract Purpose The purpose of this study was to determine the effects of medial opening low tibial osteotomy (LTO) on lower limb alignment, including the knee joint, 1 year after low tibial osteotomy. Methods This study included 20 legs of 20 patients (mean age, 66.8 ± 5.4 years) who underwent LTO for medial ankle osteoarthritis and evaluated the changes in the hip–knee–ankle angle (HKA), percentage hip‐to‐ankle line (%HA), percentage hip‐to‐calcaneal line (%HC), medial proximal tibial angle (MPTA), knee joint line convergence angle (K‐JLCA), tibio‐calcaneal angle (TCA), tibial anterior surface angle (TAS), tibio‐plafond inclination (TPI), talar inclination (TI), ankle joint line convergence angle (A‐JLCA), mechanical ankle joint axis point (MAJAP) on radiographs and the Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot scale before and 1 year after low tibial osteotomy. Results The mean preoperative/postoperative measured values showed the following: HKA (degrees) of 1.0 ± 3.7/−0.8 ± 3.7; %HC of 38.8 ± 10.0/53.8 ± 16.1; MPTA (degrees) of 85.6 ± 2.4/87.6 ± 2.1; and A‐JLCA (degrees) of 4.2 ± 2.9/1.1 ± 2.3 respectively. Including other measurements, a significant increase in the %HA, %HC, MPTA, TCA, TAS, MAJAP and JSSF ankle/hindfoot scale was observed postoperatively, whereas a significant decrease in the HKA, TPA, TI and A‐JLCA was observed postoperatively ( p  < 0.05). With the numbers available, no significant differences were observed between the preoperative and postoperative values of K‐JLCA (n.s.). Conclusion After LTO, the entire lower limb alignment became valgus, and the loading points of the knee and ankle joints shifted laterally. These changes must be considered when performing LTO, especially in patients with lateral knee OA. Level of Evidence Ⅳ

Identification of atypical hypoglycemia via continuous glucose monitoring in a patient presenting with hot flashes

Identification of risk groups for advanced liver fibrosis in the general population using the Fibrosis‐3 index

Background and Aim We conducted a study using the Fibrosis‐3 (FIB‐3) index, which is the established age‐independent index of fibrosis in nonviral liver disease and addresses the limitations of the FIB‐4 index in older age group, to assess the liver fibrosis risk among diverse demographic groups in the general population. Methods We analyzed 31 327 individuals who underwent health examinations between 2013 and 2020 and investigated the distribution of the FIB‐3 index by age group. In addition, we examined the age distribution of the FIB‐3 index stratified by background factors, such as sex, body mass index (BMI), alcohol consumption habits, and the presence or absence of fatty liver. Results In terms of age‐specific distribution, the FIB‐3 index remained below 1.5 in >90% of cases until the age of 50 years but exceeded 1.5 beyond the age of 50 years, in approximately 30% among those aged 70 years. Notably, the FIB‐3 index above 31 years old was significantly higher in men than in women. Among the different BMI categories, individuals with BMI < 18.5 exhibited the highest prevalence of fibrosis. Habitual drinkers had a higher proportion with FIB‐3. index ≥1.5, and some had FIB‐3 index ≥2.5, raising the suspicion of advanced hepatic fibrosis. No distinct association was identified between the FIB‐3 index and the presence of fatty liver. Conclusions The FIB‐3 index was useful for identifying cases of advancing hepatic fibrosis in a health checkup population. Liver fibrosis progresses with age in the general population, especially among men, those with low BMI, and habitual drinkers.

Identification of clinical‐biological features of newly diagnosed early relapse multiple myeloma patients eligible for autologous stem cell transplantation

Abstract A portion of multiple myeloma (MM) patients relapse early or do not respond to first line treatment. Identification of possible clinical and or biological features of these patients remains an unmet medical need. In this study we assesed the predictive markers for early relapse MM, defined as a progressive disease that occurred within 18 months, from autologoust stem cell transplantation (ASCT) in MM patients who did not have primary refractory disease. 74 consecutive MM patients were included in the study that received intensive therapy with ASCT. The study was able to identify the main features of newly diagnosed ER MM patients eligible for ASCT identifying the IgA isotype and the R2‐ISS score system as the main predictive prognostic factors for ER in this cohort of MM patients.

Development of a unit conversion tool for five quantitative anti‐spike assays and agreement analysis of three qualitative anti‐nucleocapsid assays for SARS‐CoV‐2

Abstract Commercially available assays for measuring severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) anti‐spike (S) or anti‐nucleocapsid (N) antibodies differ in units, making results comparisons challenging. This study aimed to develop conversion equations between five quantitative anti‐S antibody tests and to assess the agreement over time between three qualitative anti‐N antibody tests. Blood samples from 24 216 vaccinated healthcare workers in Hiroshima Prefecture, Japan, were analyzed for anti‐S antibodies using five quantitative tests (Abbott, Fujirebio, Ortho, Sysmex, Roche) and for anti‐N antibodies using three qualitative tests (Abbott, Sysmex, Roche). Geometric mean regression was performed to establish equations for converting measured values between the five quantitative tests. Fleiss κ statistic was used to assess the agreement between the three qualitative tests. A strong correlation (Pearson's coefficient r > 0.9) was found for each pair of the five quantitative tests measuring anti‐S antibodies, enabling the development of equations to convert values between each pair. Using these equations, which are based on the original output unit of each test, values obtained from one test can be transformed to be equivalent to the corresponding values in another test. For the three tests for anti‐N antibodies, the agreement was substantial in the total sample (Fleiss' κ , 0.74) and moderate among those with self‐reported past coronavirus disease 2019 (COVID‐19) infection (Fleiss' κ , 0.39). The agreement decreased with time after infection. Reduced agreement between anti‐N antibodies tests over time suggests caution in comparing seroepidemiological studies of COVID‐19 exposure based on anti‐N antibodies measurement. The findings could help improve antibody measurement systems and inform public health decision‐makers.

The cortical thickness of tricenarian cocaine users assembles features of an octogenarian brain

It has been suggested that substance use disorders could lead to accelerated biological aging, but only a few neuroimaging studies have investigated this hypothesis so far. In this cross‐sectional study, structural neuroimaging was performed to measure cortical thickness (CT) in tricenarian adults with cocaine use disorder (CUD, n 1  = 30) and their age‐paired controls (YC, n 1  = 30), and compare it with octogenarian elder controls (EC, n 1  = 20). We found that CT in the right fusiform gyrus was similar between CUD and EC, thinner than the expected values of YC. We also found that regarding CT of the right inferior temporal gyrus, right inferior parietal cortex, and left superior parietal cortex, the CUD group exhibited parameters that fell in between EC and YC groups. Finally, CT of the right pars triangularis bordering with orbitofrontal gyrus, right superior temporal gyrus, and right precentral gyrus were reduced in CUD when contrasted with YC, but those areas were unrelated to CT of EC. Despite the 50‐year age gap between our age groups, CT of tricenarian cocaine users assembles features of an octogenarian brain, reinforcing the accelerated aging hypothesis in CUD.