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This research introduces ways of preparing the community to play a direct role in reducing the risk of earthquake and tsunami disasters. Nagari Matobe is a village located in South Sipora. This location is in an earthquake tsunami-prone area. The regional government has prepared Matobe village to be a disaster-resilient village. A previous survey from 2019-2020 showed that the community of Matobe village lacked knowledge of earthquakes, tsunamis, and disaster mitigation systems. This research aimed to improve preparation for earthquake and tsunami disasters by making the people of Matobe village resilient to disasters. The steps taken to improve community preparedness were: 1. An initial survey on community conditions, buildings, soil characteristics, and the community’s preparedness to face earthquakes and tsunamis; 2. The creation of a topographic map; 3. Education and training for elementary school students, with simulations, on the mechanism of earthquakes and tsunamis, on how to evacuate and prepare for evacuation, through stories using Doraemon, Nobita, and Dorami, comic characters from Japan; 4. Providing education and training on building materials under the 2002 Indonesian building planning standards and plans for earthquake-safe buildings following the 2016 earthquake-safe building structure standards; 5. Education and training to strengthen existing buildings; and 6. A proposal for a tsunami evacuation map and the location of evacuation signs. The community in Nagari Matobe was very cooperative and took an active role during the implementation of this research. The evaluation questionnaire distributed to elementary school students showed that the students were delighted and, on average, thought that the education and training in preparedness were beneficial. This education and training became an important reference for the community and government in developing Matobe village to become a disaster-resilient village.

This research introduces ways of preparing the community to play a direct role in reducing the risk of earthquake and tsunami disasters. Nagari Matobe is a village located in South Sipora. This location is in an earthquake tsunami-prone area. The regional government has prepared Matobe village to be a disaster-resilient village. A previous survey from 2019-2020 showed that the community of Matobe village lacked knowledge of earthquakes, tsunamis, and disaster mitigation systems. This research aimed to improve preparation for earthquake and tsunami disasters by making the people of Matobe village resilient to disasters. The steps taken to improve community preparedness were: 1. An initial survey on community conditions, buildings, soil characteristics, and the community's preparedness to face earthquakes and tsunamis; 2. The creation of a topographic map; 3. Education and training for elementary school students, with simulations, on the mechanism of earthquakes and tsunamis, on how to evacuate and prepare for evacuation, through stories using Doraemon, Nobita, and Dorami, comic characters from Japan; 4.Providing education and training on building materials under the 2002 Indonesian building planning standards and plans for earthquake-safe buildings following the 2016 earthquake-safe building structure standards; 5. Education and training to strengthen existing buildings; and 6. A proposal for a tsunami evacuation map and the location of evacuation signs. The community in Nagari Matobe was very cooperative and took an active role during the implementation of this research. The evaluation questionnaire distributed to elementary school students showed that the students were delighted and, on average, thought that the education and training in preparedness were beneficial. This education and training became an important reference for the community and government in developing Matobe village to become a disaster-resilient village. [ABSTRACT FROM AUTHOR]

Background: While most thyroid nodules are benign, 7-15% are malignant. Patients with indeterminate thyroid nodules (specifically Bethesda IV/Thy3f) often undergo diagnostic hemithyroidectomy to reach a diagnosis on final histology. The aim of this study was to assess the feasibility of circulating large extracellular vesicles as diagnostic biomarkers in patients presenting with Thy3f thyroid nodules., Methods: This was a two-gate diagnostic accuracy study; patients with Thy3f thyroid nodules were age, sex and body mass index matched to healthy individuals. Final histology confirmed benign and malignant diagnoses. Plasma large extracellular vesicle counts were quantified using flow cytometry. Large extracellular vesicle microRNA and protein profiles were identified using next generation sequencing and mass spectrometry, respectively., Results: A total of 42 patients with Thy3f nodules (22 with cancer, 20 with non-cancer diagnosis) and 16 healthy controls were included. Total large extracellular vesicle concentrations and the concentrations of extracellular vesicles expressing epithelial cell adhesion molecule and the cancer markers atypical chemokine receptor type 7, extracellular matrix metalloproteinase inducer and syndecan-4 were significantly higher in patients with Thy3f nodules (cancer and non-cancer) compared with healthy individuals. In patients with cancerous versus non-cancer Thy3f nodules, one microRNA was upregulated: mir-195-3p (P < 0.001). Five were downregulated: mir-3176 (P < 0.001), mir-205-5p (P < 0.001), novel-hsa-mir-208-3p (P < 0.001), mir-3529-3p (P = 0.01) and let-7i-3p (P = 0.02). Furthermore, three large extracellular vesicle proteins (kallikrein-related peptidase11 (KLK11) (P = 0.001), alpha-1-acid glycoprotein 2 (A1AG2) (P <0.001) and small integral membrane protein 1 (SMIM1) (P = 0.04)) were significantly upregulated, while 20 large extracellular vesicle proteins were significantly downregulated (most downregulated: chemokine (C-X-C motif) ligand 7 (CXCL7), tubulin beta chain 1 (TBB1), binding immunoglobulin protein (BIP) and actinin alpha 1 (ACTN1) (P < 0.001)) in cancerous compared with non-cancer Thy3f nodules., Conclusion: Circulating large extracellular vesicle miRNA and protein profiles have a high diagnostic value to discriminate between benign and malignant nodules for patients with Thy3f cytology. Further validation for clinical performance will be needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Posttraumatic stress disorder (PTSD) is characterised by dysregulated hypothalamic-pituitary-adrenal axis activity and altered glucocorticoid receptor sensitivity. Early treatment with glucocorticoids may reduce PTSD risk, although the effect of such treatment on the aetiologically critical step of traumatic-memory-formation remains unclear. Here we examine the effects of exogenous cortisol (hydrocortisone) in a preclinical model of PTSD, using a factorial (Drug × Sex), randomised-controlled, double-blind design. Healthy men and women (n = 120) were randomised to receive 30 mg oral hydrocortisone or matched placebo immediately after watching a stressful film. Effects on film-related intrusions were assessed acutely in the lab, and ecologically using daily memory diaries for one week. We found that participants receiving hydrocortisone showed a faster reduction in daily intrusion frequency. Voluntary memory was assessed once, at the end of the week, but was unaffected by hydrocortisone. Exploratory analyses indicated sex-dependent associations between intrusions and baseline estradiol and progesterone levels. In men receiving hydrocortisone, higher baseline estradiol levels were associated with fewer intrusions, whereas women exhibited the opposite pattern. By contrast, progesterone levels were positively associated with intrusions only in men treated with hydrocortisone. The findings suggest that hydrocortisone promotes an accelerated degradation of sensory-perceptual representations underlying traumatic intrusive memories. In addition, while sex alone was not an important moderator, the combination of sex and sex-hormone levels (especially estradiol) influenced hydrocortisone's effects on involuntary aversive memories. Future well-powered experimental studies may provide a basis for a precision-psychiatry approach to optimising early post-traumatic glucocorticoid treatments that target intrusive memories, based on individual endocrinological profiles., (© 2022. The Author(s).)

Rationale: A significant obstacle to an improved understanding of pathological dissociative and psychosis-like states is the lack of readily implemented pharmacological models of these experiences. Ketamine has dissociative and psychotomimetic effects but can be difficult to use outside of medical and clinical-research facilities. Alternatively, nitrous oxide (N 2 O) - like ketamine, a dissociative anaesthetic and NMDAR antagonist - has numerous properties that make it an attractive alternative for modelling dissociation and psychosis. However, development and testing of such pharmacological models relies on well-characterized measurement instruments., Objectives: To examine the factor structures of the Clinician Administered Dissociative States Scale (CADSS) and Psychotomimetic States Inventory (PSI) administered during N 2 O inhalation in healthy volunteers., Methods: Secondary analyses of data pooled from three previous N 2 O studies with healthy volunteers., Results: Effect sizes for N 2 O-induced dissociation and psychotomimesis were comparable to effects reported in experimental studies with sub-anaesthetic ketamine in healthy volunteers. Although, like ketamine, a three-factor representation of N 2 O-induced dissociation was confirmed, and a more parsimonious two-factor model might be more appropriate. Bayesian exploratory factor analysis suggested that N 2 O-induced psychosis-like symptoms were adequately represented by two negative and two positive symptom factors. Hierarchical cluster analysis indicated minimal item overlap between the CADSS and PSI., Conclusion: N 2 O and ketamine produce psychometrically similar dissociative states, although parallels in their psychosis-like effects remain to be determined. The CADSS and PSI tap largely non-overlapping experiences under N 2 O and we propose the use of both measures (or similar instruments) to comprehensively assess anomalous subjective states produced by dissociative NMDAR antagonists., (© 2022. The Author(s).)

Background: Nitrous oxide (N2O) is an anesthetic gas with both therapeutic and abuse potential. Because N2O is an NMDA receptor (NMDAR) antagonist, its effects are expected to resemble those of the prototypical NMDAR antagonist, ketamine. In this study, we examined the subjective rewarding effects of N2O using measures previously employed in studies of ketamine. We also tested for moderation of these effects by bipolar phenotype, depressive symptoms, and impulsivity., Methods: Healthy volunteers were randomly assigned to either 50% N2O (n = 40) or medical air (n = 40). Self-reported rewarding (liking and wanting), and alcohol-like effects were assessed pre-, peri- and post inhalation., Results: Effect sizes for the various rewarding/alcohol-like effects of N2O were generally similar to those reported in studies of moderate-dose ketamine. Impulsivity moderated the subjective reinforcing (liking) effects of inhaled gas, while depressive symptoms moderated motivational (wanting [more]) effects. However, depression and impulsivity had opposite directional influences, such that higher impulsivity was associated with higher N2O liking, and higher depression, with lower N2O wanting., Conclusion: To the extent that static (versus longitudinal) subjective rewarding effects are a reliable indicator of future problematic drug use, our findings suggests that impulsivity and depression may predispose and protect, respectively, against N2O abuse. Future studies should examine if these moderators are relevant for other NMDAR antagonists, including ketamine, and novel ketamine-like therapeutic and recreational drugs. Similarities between moderate-dose N2O and moderate-dose ketamine in the intensity of certain subjective effects suggest that N2O may, at least to some extent, serve as substitute for ketamine as a safe and easily implemented experimental tool for probing reward-related NMDAR function and dysfunction in humans., (© The Author(s) 2021. Published by Oxford University Press on behalf of CINP.)

Background: Maladaptive learning linking environmental food cues to high-palatability food reward plays a central role in overconsumption in obesity and binge eating disorders. The process of memory reconsolidation offers a mechanism to weaken such learning, potentially ameliorating over-eating behaviour. Here we investigated whether putatively interfering with synaptic plasticity using the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, could weaken retrieved chocolate reward memories through blockade of reconsolidation., Methods: Seventy five healthy volunteers with a tendency to binge eat chocolate were randomised to retrieve chocolate reward memory under 10 mg rapamycin (RET + RAP, active condition), or placebo (RET + PBO), or they received 10 mg rapamycin without subsequent retrieval (NO RET + RAP). Indices of chocolate reward memory strength were assessed one week pre and post manipulation and at one month follow-up., Results: Contrary to hypotheses, the RET + RAP group did not show any greater reduction than control groups on indices of motivational salience of chocolate cues, motivation to consume chocolate or liking of chocolate. Mild evidence of improvement in the RET + RAP group was found, but this was limited to reduced chocolate binge episodes and improved healthy food choices., Conclusions: We did not find convincing evidence of comprehensive naturalistic chocolate reward memory reconsolidation blockade by rapamycin. The effects on chocolate bingeing and food choices may warrant further investigation. These limited positive findings may be attributable to insufficient interference with mTOR signalling with 10 mg rapamycin, or failure to destabilise chocolate memories during retrieval.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background: Pharmacological treatments targeting the neuroendocrine stress response may hold special promise in secondary prevention of posttraumatic stress disorder (PTSD). However, findings from clinical trials have been inconsistent and the efficacy of specific drugs, their temporal window of efficacy, effective doses and the characteristics of likely treatment responders remain unclear., Method: Using an experimental human model of distressing involuntary memory formation, we compare the effects of two drugs that have theoretical or empirical support as secondary preventive agents in PTSD. Eighty-eight healthy women (average age: 23.5 years) received oral propranolol (80 mg), hydrocortisone (30 mg), or matched placebo immediately after viewing a 'trauma film'. They then completed daily, time-stamped intrusion diaries for 1 week, at the end of which, voluntary memory was tested., Results: While neither drug affected voluntary memory for the trauma narrative, propranolol treatment was associated with 42% fewer, and hydrocortisone with 55% fewer intrusions across the week, relative to placebo. Additionally, propranolol reduced general trauma-like symptoms, and post-drug cortisol levels were negatively correlated with intrusion frequency in the hydrocortisone group., Conclusions: Overall, this study shows substantial reductions in intrusive memories and preserved voluntary narrative-declarative memory following either propranolol or hydrocortisone in an experimental model of psychological trauma. As such, despite some inconsistencies in clinical trials, our findings support continued investigation of propranolol and hydrocortisone as secondary preventive agents for re-experiencing symptoms of PTSD. The findings also suggest that it is critical for future research to identify the conditions governing the preventive efficacy of these drugs in PTSD.

Maladaptive reward memories (MRMs) are involved in the development and maintenance of acquired overconsumption disorders, such as harmful alcohol and drug use. The process of memory reconsolidation - where stored memories become briefly labile upon retrieval - may offer a means to disrupt MRMs and prevent relapse. However, reliable means for pharmacologically weakening MRMs in humans remain elusive. Here we demonstrate that the N-methyl D-aspartate (NMDA) antagonist ketamine is able to disrupt MRMs in hazardous drinkers when administered immediately after their retrieval. MRM retrieval + ketamine (RET + KET) effectively reduced the reinforcing effects of alcohol and long-term drinking levels, compared to ketamine or retrieval alone. Blood concentrations of ketamine and its metabolites during the critical 'reconsolidation window' predicted beneficial changes only following MRM reactivation. Pharmacological reconsolidation interference may provide a means to rapidly rewrite maladaptive memory and should be further pursued in alcohol and drug use disorders.

Objective: To study the effects of Cydonia oblonga Miller (COM) total flavonoids (TF) from leaves and fruit on the blood lipid and antioxidant potentials using hyperlipidaemic rat models., Methods: Hyperlipidaemic rat models were created with high-lipid emulsion. Rats were distributed into normal controls, hyperlipidaemic models, and daily high (160mg/kg), medium (80mg/kg) and low (40mg/kg) TF from leaves and fruit and simvastatin (5mg/kg) groups. After four weeks, serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), as well as hepatic superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured., Results: Compared with the hyperlipidaemic model group, TF significantly reduced serum TC, TG, LDL-C (P<0.01), ALT and AST (P<0.01 or P<0.05) and increased HDL-C (P<0.05 or P<0.01). TF also reduced MDA (P<0.01 or P<0.01)., Conclusion: COM total flavonoids can effectively regulate the metabolism of lipids, and remove oxygen free radicals. This confirms its potential value in the prevention and treatment of hyperlipidaemia., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Cydonia oblonga Mill. (COM) is used in traditional Uyghur medicine to treat or prevent cardiovascular disease. In a previous study COM leaf extracts were found to be active in renal hypertensive rats (RHR). The present study tests the dose-dependence of the effect of ethanol leaf extracts on hypertension and on biomarkers associated with blood pressure control, such as angiotensin-II (AII), plasma renin activity (PRA), apelin-12 (A), endothelin (ET) and nitric oxide (NO), compared to captopril., Methods: Two-kidney one-clip (2K1C) Goldblatt model rats were divided randomly into six groups: sham, model, captopril 25 mg/kg, COM leaf extract 80, 160 and 320 mg/kg (n=10 each). Drugs were administered orally daily for eight weeks. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured before treatment and every 2 weeks. Blood and kidney samples were collected after the last treatment to measure AII, PRA, A, ET and NO., Results: RHR had increased blood pressure, AII, A, PRA, ET and decreased NO. Treatment with captopril reduced blood pressure, AII, A, PRA, and ET, though not quite to normal values. COM leaf extracts significantly and dose-dependently reduced blood pressure, AII, A, RA and ET, whereas NO was increased. The highest dose of COM had the same effects as captopril., Conclusion: The effects of COM extracts on blood pressure and biomarkers were dose-dependent and at the highest dose similar to those of captopril. This suggests an action of COM on the renin-angiotensin system, which could explain its antihypertensive effect., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Quince, Cydonia oblonga Mill. (COM), is used in traditional Uyghur medicine to treat or prevent cardiovascular diseases. Uyghur people have greater longevity and lower blood pressure than other central Asian populations. We therefore tested COM fruit and leaf extracts on blood pressure and rheology in renal hypertensive rats (RHR)., Materials and Methods: Two-kidney, one-clip (2K1C) renal hypertensive rats were divided randomly into eleven groups: sham, model, and model treated with daily doses of 80 and 160mg/kg aqueous or ethanol extracts of COM fruit or leaves, or 25mg/kg captopril (n=10 per group), given orally once daily for 8 weeks. Blood pressure was measured before treatment and every 2 weeks thereafter. Blood rheology was tested after 8 weeks., Results: Model rats had higher blood pressure than sham 8 weeks after the procedure (systolic blood pressure 193±7 vs. 138±8mmHg, p<0.05). Those treated with captopril had decreased blood pressure within 2 weeks but that did not return to the level found in the sham group at 8 weeks (167±7, p<0.05 vs. model). With the COM extracts, the effect on blood pressure was notable after 4 weeks. At 8 weeks blood pressure was similar with captopril and with 160mg ethanol leaf extract (166±4, p<0.05 vs. model), the most effective of the extracts. Model rats had higher blood viscosity and lower erythrocyte deformability than sham. Captopril had little effect on blood rheology; whereas COM extracts reduced whole blood viscosity and improved erythrocyte deformability to levels approaching those found in sham., Conclusions: COM extracts have antihypertensive activity in renal hypertensive rats. The additional effect on rheology, compared to captopril, may convey added interest. Further studies of these effects in man appear warranted., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)