The melatonin metabolite N1‐acetyl‐5‐methoxykynuramine facilitates long‐term object memory in young and aging mice

Melatonin (MEL) has been reported to enhance cognitive processes, making it a potential treatment for cognitive decline. However, the role of MEL’s metabolites, N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine (AFMK) and N1‐acetyl‐5‐methoxykynuramine (AMK), in these effects are unknown. The current study directly investigated the acute effects of systemic MEL, AFMK, and AMK on novel object recognition. We also analyzed MEL, AFMK, and AMK levels in hippocampus and temporal lobe containing the perirhinal cortex following systemic MEL and AMK treatment. AMK administered post‐training had a more potent effect on object memory than MEL and AFMK. AMK was also able to rescue age‐associated declines in memory impairments when object memory was tested up to 4 days following training. Results from administering AMK at varying times around the training trial and the metabolism time course in brain tissue suggest that AMK’s memory‐enhancing effects reflect memory consolidation. Furthermore, inhibiting the MEL‐to‐AMK metabolic pathway disrupted object memory at 24 hours post‐training, suggesting that endogenous AMK might play an important role in long‐term memory formation. This is the first study to report that AMK facilitates long‐term object memory performance in mice, and that MEL crosses the blood‐brain barrier and is immediately converted to AMK in brain tissue. Overall, these results support AMK as a potential therapeutic agent to improve or prevent memory decline.     

Prediction of the length of the femur from its fragments in a Sri Lankan population

ABSTRACT

In many forensic circumstances, the femur is fragmented due to decomposition and mutilation, thus necessitating development and application of regression equations to estimate the length of the femur from its fragments. In this study, regression equations were derived for the prediction of the femoral length, utilizing 11 standard femoral measurements (maximum length of femur, epicondylar breadth, vertical head diameter, transverse head diameter, vertical neck diameter, transverse neck diameter, neck length, subtrochanteric anterior–posterior diameter, subtrochanteric transverse diameter, mid-shaft anterior–posterior diameter and mid-shaft transverse diameter) obtained from 86 femora belonging to a contemporary Sri Lankan population. Univariate regression equations with moderate to high correlations (0.226 to 0.714) were formulated for the estimation of the maximum femoral length from the measurements of fragments of the femur. Of the single variables, the transverse neck diameter emerged as the best predictor (r = 0.714, SEE = 18.6596) of the maximum length of the femur. The multiple regression equations using a combination of variables yielded higher correlations (0.774–0.857) with lower error estimates (14.18–16.96). The regression equations presented in this study can be used to estimate the length of the femur of unknown, mutilated and dismembered human skeletal remains with considerable accuracy.     

Recent progress on the diagnosis of 2019 Novel Coronavirus

Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has become a global pandemic. Therefore, convenient, timely and accurate detection of SARS‐CoV‐2 is urgently needed. Here, we review the types, characteristics and shortcomings of various detection methods, as well as perspectives for the SARS‐CoV‐2 diagnosis. Clinically, nucleic acid‐based methods are sensitive but prone to false‐positive. The antibody‐based method has slightly lower sensitivity but higher accuracy. Therefore, it is suggested to combine the two methods to improve the detection accuracy of COVID‐19.     

A comparative study of short‐ and long‐TE 1H MRS at 3 T for in vivo detection of 2‐hydroxyglutarate in brain tumors

2‐Hydroxyglutarate (2HG) is produced in gliomas with mutations of isocitrate dehydrogenase (IDH) 1 and 2. The ¹H resonances of the J‐coupled spins of 2HG are extensively overlapped with signals from other metabolites. Here, we report a comparative study at 3 T of the utility of the point‐resolved spectroscopy sequence with a standard short TE (35 ms) and a long TE (97 ms), which had been theoretically designed for the detection of the 2HG 2.25‐ppm resonance. The performance of the methods is evaluated using data from phantoms, seven healthy volunteers and 22 subjects with IDH‐mutated gliomas. The results indicate that TE = 97 ms provides higher detectability of 2HG than TE = 35 ms, and that this improved capability is gained when data are analyzed with basis spectra that include the effects of the volume localizing radiofrequency and gradient pulses. Copyright © 2013 John Wiley & Sons, Ltd.     

Intensive Short‐Term Dynamic Psychotherapy for generalized anxiety disorder: A pilot effectiveness and process‐outcome study

The objective of this study was to evaluate the clinical‐ and cost‐effectiveness of Intensive Short‐Term Dynamic Psychotherapy (ISTDP) for generalized anxiety disorder (GAD). We further aimed to examine if a key clinical process within the ISTDP framework, termed the level of mobilization of unprocessed complex emotions (MUCE), was related to outcome. The sample consisted of 215 adult patients (60.9% female) with GAD and comorbid conditions treated in a tertiary mental health outpatient setting. The patients were provided an average of 8.3 sessions of ISTDP delivered by 38 therapists. The level of MUCE in treatment was assessed from videotaped sessions by a rater blind to treatment outcome. Year‐by‐year healthcare costs were derived independently from government databases. Multilevel growth models indicated significant decreases in psychiatric symptoms and interpersonal problems during treatment. These gains were corroborated by reductions in healthcare costs that continued for 4 years post‐treatment reaching normal population means. Further, we found that the in‐treatment level of MUCE was associated with larger treatment effects, underlining the significance of emotional experiencing and processing in the treatment of GAD. We conclude that ISTDP appears to reduce symptoms and costs associated with GAD and that the ISTDP framework may be useful for understanding key therapeutic processes in this challenging clinical population. Controlled studies of ISTDP for GAD are warranted.     

Synthetic immunostimulatory oligonucleotides in experimental and clinical practice

BackgroundOligonucleotides belong to a class of macromolecules with great potential for research and various therapeutic applications. Their mechanisms of action are extremely diverse, although they are rather homogeneous in composition. Single-stranded oligodeoxynucleotides are not only inhibitors of gene expression, but their CpG sequence motifs may activate the innate immune response. Recent progress made in preclinical and clinical testing, as well as the case of the most recently discovered RNA interference technology, will help to overcome efficacy problems of the previous approaches of the ‘standard therapy’ of such diseases as tumors and various infections.MethodsThe aim of this article is to present various therapeutic aspects of oligonucleotides, and to review the most significant therapeutic applications of synthetic oligonucleotides. This paper presents a comprehensive review of current literature on various therapeutic properties of synthetic oligonucleotides.ConclusionsThe available results gathered from preclinical and clinical studies suggest that TLR9-targeted therapy of oligonucleotides can stimulate both innate and adaptive immunity. It also appears that CpG ODNs are generally safe, although moderate adverse effects, based on a backbone-related mechanism have been reported. The presented studies demonstrate that adjuvant CpG ODN can unify an immune response that leads to enhanced antigen-specific Ab formation. CpG ODN may therefore provide a unique approach to enhancing the efficacy of immunization, including the strengthening of antitumor immunity.     

Refining a personalized mHealth intervention to promote medication adherence among HIV+ methamphetamine users

Mobile health (mHealth) interventions to promote antiretroviral therapy (ART) adherence have shown promise; however, among persons living with HIV who abuse methamphetamine (MA), effective tailoring of content to match the expressed needs of this patient population may be necessary. This study aimed (1) to understand patient perspectives of barriers and facilitators of ART adherence among people with HIV who use MA, and (2) to obtain feedback on the thematic content of an mHealth intervention in order to tailor the intervention to this subgroup. Two separate focus groups, each with 10 HIV+/MA+ individuals, were conducted. Transcribed audio recordings were qualitatively analyzed to identify emergent themes. Inter-rater reliability of themes was high (mean Kappa = .97). Adherence barriers included MA use, misguided beliefs about ART adherence, memory and planning difficulties, social barriers and perceived stigma, and mental heath issues. Facilitators of effective ART adherence were cognitive compensatory strategies, promotion of well-being, health-care supports, adherence education, and social support. Additionally, the focus groups generated content for reminder text messages to be used in the medication adherence intervention. This qualitative study demonstrates the feasibility of using focus groups to derive patient-centered intervention content to address the health challenge at hand in targeted populations.