Search

In brief, we report an Iranian family with a history of both azoospermia and premature ovarian insufficiency with the same heterozygote mutation in the NR5A1 gene that can be transmitted. As far as we know, this is the first observation that a common mutation in NR5A1 can cause these above-mentioned phenotypes in a family. [ABSTRACT FROM AUTHOR]

A modified pulsed-field gel electrophoresis (PFGE) protocol was developed and applied to clinical isolates of Mycobacterium tuberculosis complex to reduce the cost of using lyticase. This protocol reduces the expense of PFGE typing of Mycobacterium tuberculosis complex as it removes the use of lyticase during the spheroplast formation from these bacteria. [ABSTRACT FROM AUTHOR]

Background: The possible role of the insulinemic potential of diet in the etiology of type 2 diabetes (T2D) has recently received significant attention in observational studies. This meta-analysis aimed to synthesize available evidence and quantify the potential association between the empirical dietary index for hyperinsulinemia (EDIH) score and T2D risk., Methods: Various electronic databases, including Scopus, PubMed, and Web of Science, were comprehensively searched up to January 2024 using related keywords to identify relevant studies. The hazard ratios (HR) or odds ratios were extracted from eligible cohort studies, and a random-effects model with an inverse variance weighting method was used to calculate the pooled effect size, which was expressed as HR., Results: The analysis included six cohort studies (four publications), with sample sizes ranging from 3,732 to 90,786 individuals aged 20 to 79 years. During follow-up periods of 5 to over 20 years, 31,284 T2D incidents were identified. The pooled results showed that a higher EDIH score was associated with an increased risk of T2D incidence (HR: 1.47; 95%CI 1.21-1.77; I 2  = 91.3%). Significant publication bias was observed in the present meta-analysis (P = 0.020). Geographical region and follow-up period can be as sources of heterogeneity (P heterogeneity <0.001)., Conclusion: Our meta-analysis of observational studies suggested that a diet with a higher EDIH score may be associated with an increased risk of incidence of T2D., (© 2024. The Author(s).)

Multiple sclerosis (MS) is a neurological disorder characterized by immune dysregulation. It begins with a first clinical manifestation, a clinically isolated syndrome (CIS), which evolves to definite MS in case of further clinical and/or neuroradiological episodes. Here we evaluated the diagnostic value of transcriptional alterations in MS and CIS blood by machine learning (ML). Deep sequencing of more than 200 blood RNA samples comprising CIS, MS and healthy subjects, generated transcriptomes that were analyzed by the binary classification workflow to distinguish MS from healthy subjects and the Time-To-Event pipeline to predict CIS conversion to MS along time. To identify optimal classifiers, we performed algorithm benchmarking by nested cross-validation with the train set in both pipelines and then tested models generated with the train set on an independent dataset for final validation. The binary classification model identified a blood transcriptional signature classifying definite MS from healthy subjects with 97% accuracy, indicating that MS is associated with a clear predictive transcriptional signature in blood cells. When analyzing CIS data with ML survival models, prediction power of CIS conversion to MS was about 72% when using paraclinical data and 74.3% when using blood transcriptomes, indicating that blood-based classifiers obtained at the first clinical event can efficiently predict risk of developing MS. Coupling blood transcriptomics with ML approaches enables retrieval of predictive signatures of CIS conversion and MS state, thus introducing early non-invasive approaches to MS diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to examine the efficacy of whole genome sequencing (WGS) in accurately predicting susceptibility profiles, potentially eliminating the need for conventional phenotypic drug susceptibility testing (pDST) for first-line antituberculosis drugs in routine tuberculosis diagnosis., Methods: Over the period of 2017 to 2020, 1114 Mycobacterium tuberculosis complex isolates were collected with drug susceptibility testing conducted using the MGIT960 system and WGS performed for predicting drug resistance profiles. In addition, we implemented a new algorithm with an updated WGS workflow, omitting pan-susceptible strains from pDST., Results: Results showed that out of 1075 analysed isolates, WGS-based genotypic sensitivity predictions for isoniazid, rifampicin, ethambutol, and pyrazinamide were 100% (95% CI, 99.6-100%), 100% (95% CI, 99.62-100%), 99.8% (95% CI, 99.26-99.94%), and 100% (95% CI, 99.63-100%), respectively. In contrast, the WGS-based genotypic resistance prediction, was 98.85% (95% CI, 93.77-99.79%) for isoniazid, 94.74% (95% CI, 82.71-98.54%) for rifampicin, 86.96% (95% CI, 67.87-95.46%) for ethambutol, and 75.7% (95% CI, 59.9-86.63%) for pyrazinamide. Moreover, WGS enabled the implementation of a new testing algorithm that made it unnecessary to perform pDST in 954 of all 1075 samples (88.7%) and in 890 of 901 pan-susceptible samples (98.8%)., Discussion: Integrating WGS into tuberculosis management offers significant potential to replace phenotypic drug susceptibility testing, especially for problematic drugs like pyrazinamide and ethambutol, potentially improving treatment outcomes., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Generalized anxiety disorder (GAD) is a prevalent anxiety disorder characterized by uncontrollable worry, trouble sleeping, muscle tension, and irritability. Cognitive behavioural therapy (CBT) is one of the first-line treatments that has demonstrated high efficacy in reducing symptoms of anxiety. Electronically delivered CBT (e-CBT) has been a promising adaptation of in-person treatment, showing comparable efficacy with increased accessibility and scalability. Finding further scalable interventions that can offer benefits to patients requiring less intensive interventions can allow for better resource allocation. Some studies have indicated that weekly check-ins can also lead to improvements in GAD symptoms. However, there is a lack of research exploring the potential benefits of online check-ins for patients with GAD., Objective: This study aims to investigate the effects of weekly online asynchronous check-ins on patients diagnosed with GAD and compare it with a group receiving e-CBT., Methods: Participants ( n e-CBT = 45; n check-in = 51) with GAD were randomized into either an e-CBT or a mental health check-in program for 12 weeks. Participants in the e-CBT program completed pre-designed modules and homework assignments through a secure online delivery platform where they received personalized feedback from a trained care provider. Participants in the mental health check-in condition had weekly asynchronous messaging communication with a care provider where they were asked structured questions with a different weekly theme to encourage conversation., Results: Both treatments demonstrated statistically significant reductions in GAD-7-item questionnaire (GAD-7) scores over time, but when comparing the groups there was no significant difference between the treatments. The number of participants who dropped out and baseline scores on all questionnaires were comparable for both groups., Conclusions: The findings support the effectiveness of e-CBT and mental health check-ins for the treatment of GAD., Plain Language Summary Title: Comparing the Effectiveness of Electronically Delivered Therapy (e-CBT) to Weekly Online Mental Health Check-ins for Generalized Anxiety Disorder-A Randomized Controlled Trial., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: NA and MO co-founded OPTT and NA, MO, and AS have ownership stakes in OPTT Inc.

Introduction: Correctional workers (CWs) are frequently exposed to potentially traumatic events in the workplace, leading to an increased prevalence of mental health concerns. Online psychotherapy can address many of the barriers CWs face when seeking adequate mental health care. Despite their benefits, CWs' experience using digital mental health interventions is relatively unknown. This information could be valuable in developing enhanced care delivery to improve recruitment, retention, satisfaction, and treatment outcomes., Methods: This study investigated the experiences of a sample of CWs enrolled in a clinical trial evaluating the efficacy of the Online Psychotherapy Tool (OPTT) in this population. Participants were surveyed and interviewed to capture their opinions and feedback on the program. Survey analysis was conducted through Qualtrics statistical analysis software. The interview transcripts and open-ended survey questions were analyzed using thematic analysis methods in NVivo., Results: Participants (n=14) were cis-gender, predominantly white, with an average age of 38 years. While most respondents preferred in-person therapy, they also reported the benefits of the online psychotherapy program. Specifically, they expressed positive perceptions of the platform, the quality and interaction of their care provider, and the homework assignments and skills learned. Lack of motivation to complete weekly homework assignments was a frequently cited challenge. Unhelpful aspects of the therapy noted issues with the online format and frustration with certain program elements., Discussion: Participants expressed a positive outlook on the program, the platform, and treatment outcomes. A preference for in-person therapy was still indicated, demonstrating the need to focus on engagement in digital mental health interventions. In addition, the findings of this study shed light on the factors that can influence help-seeking in this population, including stigma in the work environment, demanding work schedules, workplace perceptions, and previous experiences accessing mental health services., Competing Interests: NA and MO co-founded the Online Psychotherapy Tool (OPTT) and have ownership stakes in OPTT Inc. The remaining authors declare that the research was conducted without commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor FN declared a shared parent affiliation with the Author AIFS at the time of review., (Copyright © 2024 Moghimi, Gutierrez, Stephenson, Gizzarelli, Jagayat, Holmes, Patel, Omrani, Simpson and Alavi.)

Background: The war in Ukraine has led to significant migration to neighboring countries, raising public health concerns. Notable tuberculosis (TB) incidence rates in Ukraine emphasize the immediate requirement to prioritize approaches that interrupt the spread and prevent new infections., Methods: We conducted a prospective genomic surveillance study to assess migration's impact on TB epidemiology in the Czech Republic and Slovakia. Mycobacterium tuberculosis isolates from Ukrainian war refugees and migrants, collected from September 2021 to December 2022 were analyzed alongside 1574 isolates obtained from Ukraine, the Czech Republic, and Slovakia., Results: Our study revealed alarming results, with historically the highest number of Ukrainian tuberculosis patients detected in the host countries. The increasing number of cases of multidrug-resistant TB, significantly linked with Beijing lineage 2.2.1 (p < 0.0001), also presents substantial obstacles to control endeavors. The genomic analysis identified the three highly related genomic clusters, indicating the recent TB transmission among migrant populations. The largest clusters comprised war refugees diagnosed in the Czech Republic, TB patients from various regions of Ukraine, and incarcerated individuals diagnosed with pulmonary TB specialized facility in the Kharkiv region, Ukraine, pointing to a national transmission sequence that has persisted for over 14 years., Conclusions: The data showed that most infections were likely the result of reactivation of latent disease or exposure to TB before migration rather than recent transmission occurring within the host country. However, close monitoring, appropriate treatment, careful surveillance, and social support are crucial in mitigating future risks, though there is currently no evidence of local transmission in EU countries., (© 2023. The Author(s).)

Extracellular vesicles (EVs) secreted by various cells offer great potential for use in the diagnosis and treatment of disease. EVs are heterogeneous membranous vesicles. Exosomes are a subtype of EVs, 40-150 nm spherical vesicles with a lipid layer derived from endosomes. Exosomes, which are involved in signal transduction and maintain homeostasis, are released from almost all cells, tissues, and body fluids. Although several methods exist to isolate and characterize EVs and exosomes, each technique has significant drawbacks and limitations that prevent progress in the field. New approaches in the biology of EVs show great potential for isolating and characterizing EVs, which will help us better understand their biological function. The strengths and limitations of conventional strategies and novel methods (microfluidic) for EV isolation are outlined in this review. We also present various exosome isolation techniques and kits that are commercially available and assess the global market demand for exosome assays., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Depression is a hidden burden, yet it is a leading cause of disability worldwide. Despite the adverse effects of depression, fewer than one-third of patients receive care. Internet-based cognitive behavioral therapy (i-CBT) is an effective treatment for depression, and combining i-CBT with supervised care could make the therapy scalable and effective. A stepped care model is a framework for beginning treatment with an effective and low-intensity intervention while adapting care based on the patient's needs., Objective: This study investigated the efficacy of a stepped care i-CBT model for depression based on changes in self-reported depressive symptoms., Methods: In this single-blinded, randomized controlled trial, participants were allocated to either the i-CBT-only group (28/56, 50%) or the i-CBT with stepped care group (28/56, 50%). Both groups received a 13-week i-CBT program tailored for depression. The i-CBT program was provided through a secure, online mental health clinic called the Online Psychotherapy Tool. Participants read through the sessions and completed the assignments related to each session. Participants in the stepped care group received additional interventions from their care provider based on standard questionnaire scores (ie, Patient Health Questionnaire-9 [PHQ-9], Quick Inventory of Depressive Symptomatology [QIDS], and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form) and their assignment responses. From lowest to highest intensity, the additional interventions included SMS text messages, phone calls, video calls, or a video call with a psychiatrist., Results: For this study, 56 participants were recruited to complete an i-CBT program (n=28, 50%; mean age 37.9; SD 13.08 y; 7/28, 27% were men) or an i-CBT with stepped care program (n=28, 50%; mean age 40.6; SD 14.28 y; 11/28, 42% were men). The results of this study indicate that the i-CBT program was effective in significantly reducing depressive symptoms, as measured by the PHQ-9 (F 4,80 =9.95; P<.001) and QIDS (F 2,28 =5.73; P=.008); however, there were no significant differences in the reduction of depressive symptoms between the 2 groups (PHQ-9: F 4,80 =0.43; P=.78; QIDS: F 2,28 =3.05; P=.06). The stepped care group was not significantly better in reducing depressive symptoms than the i-CBT group (PHQ-9, P=.79; QIDS, P=.06). Although there were no significant differences observed between the number of participants who completed the program between the groups (χ 2 1 =2.6; P=.10), participants in the stepped care group, on average, participated in more sessions than those who prematurely terminated participation in the i-CBT group (t 55 =-2; P=.03; 95% CI -4.83 to -0.002)., Conclusions: Implementing a stepped care approach in i-CBT is an effective treatment for depression, and the stepped care model can assist patients to complete more sessions in their treatment., Trial Registration: Clinicaltrials.gov NCT04747873; https://clinicaltrials.gov/study/NCT04747873., (©Jasleen Kaur Jagayat, Anchan Kumar, Yijia Shao, Amrita Pannu, Charmy Patel, Amirhossein Shirazi, Mohsen Omrani, Nazanin Alavi. Originally published in JMIR Mental Health (https://mental.jmir.org), 09.02.2024.)

Background: Lockdowns and social distancing resulting from the COVID-19 pandemic have worsened the population's mental health and made it more difficult for individuals to receive care. Electronic cognitive behavioral therapy (e-CBT) is a cost-effective and evidence-based treatment for anxiety and depression and can be accessed remotely., Objective: The objective of the study was to investigate the efficacy of online psychotherapy tailored to depression and anxiety symptoms during the pandemic., Methods: The pilot study used a pre-post design to evaluate the efficacy of a 9-week e-CBT program designed for individuals with depression and anxiety affected by the pandemic. Participants were adults (N=59) diagnosed with major depressive disorder and generalized anxiety disorder, whose mental health symptoms initiated or worsened during the COVID-19 pandemic. The online psychotherapy program focused on teaching coping, mindfulness, and problem-solving skills. Symptoms of anxiety and depression, resilience, and quality of life were assessed., Results: Participants demonstrated significant improvements in symptoms of anxiety (P=.02) and depression (P=.03) after the intervention. Similar trends were observed in the intention-to-treat analysis. No significant differences were observed in resilience and quality-of-life measures. The sample comprised mostly females, making it challenging to discern the benefits of the intervention in males. Although a pre-post design is less rigorous than a controlled trial, this design was selected to observe changes in scores during a critical period., Conclusions: e-CBT for COVID-19 is an effective and accessible treatment option. Improvements in clinical symptoms of anxiety and depression can be observed in individuals whose mental health is affected by the COVID-19 pandemic., Trial Registration: ClinicalTrials.gov NCT04476667; https://clinicaltrials.gov/study/NCT04476667., International Registered Report Identifier (irrid): RR2-10.2196/24913., (©Elnaz Moghimi, Callum Stephenson, Anika Agarwal, Niloofar Nikjoo, Niloufar Malakouti, Gina Layzell, Anne O'Riordan, Jasleen Jagayat, Amirhossein Shirazi, Gilmar Gutierrez, Ferwa Khan, Charmy Patel, Megan Yang, Mohsen Omrani, Nazanin Alavi. Originally published in JMIR Mental Health (https://mental.jmir.org), 25.12.2023.)

Introduction: Depression is a leading cause of disability worldwide, affecting up to 300 million people globally. Despite its high prevalence and debilitating effects, only one-third of patients newly diagnosed with depression initiate treatment. Electronic cognitive behavioural therapy (e-CBT) is an effective treatment for depression and is a feasible solution to make mental health care more accessible. Due to its online format, e-CBT can be combined with variable therapist engagement to address different care needs. Typically, a multi-professional care team determines which combination therapy most benefits the patient. However, this process can add to the costs of these programs. Artificial intelligence (AI) has been proposed to offset these costs., Methods: This study is a double-blinded randomized controlled trial recruiting individuals experiencing depression. The degree of care intensity a participant will receive will be randomly decided by either: (1) a machine learning algorithm, or (2) an assessment made by a group of healthcare professionals. Subsequently, participants will receive depression-specific e-CBT treatment through the secure online platform. There will be three available intensities of therapist interaction: (1) e-CBT; (2) e-CBT with a 15-20-min phone/video call; and (3) e-CBT with pharmacotherapy. This approach aims to accurately allocate care tailored to each patient's needs, allowing for more efficient use of resources., Discussion: Artificial intelligence and providing patients with varying intensities of care can increase the efficiency of mental health care services. This study aims to determine a cost-effective method to decrease depressive symptoms and increase treatment adherence to online psychotherapy by allocating the correct intensity of therapist care for individuals diagnosed with depression. This will be done by comparing a decision-making machine learning algorithm to a multi-professional care team. This approach aims to accurately allocate care tailored to each patient's needs, allowing for more efficient use of resources with the convergence of technologies and healthcare., Ethics: The study received ethics approval and began participant recruitment in December 2022. Participant recruitment has been conducted through targeted advertisements and physician referrals. Complete data collection and analysis are expected to conclude by August 2024., Clinical Trial Registration: ClinicalTrials.Gov, identifier NCT04747873., Competing Interests: NA and MO have co-founded the care delivery platform in use (i.e., OPTT) and have ownership stakes in OPTT Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Stephenson, Jagayat, Kumar, Khamooshi, Eadie, Pannu, Meartsi, Danaee, Gutierrez, Khan, Gizzarelli, Patel, Moghimi, Yang, Shirazi, Omrani, Patel and Alavi.)

Background: Generalized anxiety disorder (GAD) is a debilitating mental health disorder with first-line treatments include cognitive behavioral therapy (CBT) and pharmacotherapy. CBT is costly, time-consuming, and inaccessible. Electronic delivery (e-CBT) is a promising solution to address these barriers. However, due to the novelty of this intervention, more research testing the e-CBT efficacy independently and in conjunction with other treatments is needed., Objective: This study investigated the efficacy of e-CBT compared to and in conjunction with pharmacotherapy for GAD., Methods: This study employed a quasi-experimental design where patients selected their preferred treatment modality. Patients with GAD were enrolled in either e-CBT, medication, or combination arms. The 12-week e-CBT program was delivered through a digital platform. The medications followed clinical guidelines. The efficacy of each arm was evaluated using questionnaires measuring depression, anxiety, and stress severity, as well as quality of life., Results: There were no significant differences between arms (N e-CBT = 41; N Medication = 41; N Combination = 33) in the number of weeks completed or baseline scores. All arms showed improvements in anxiety scores after treatment. The medication and combination arms improved depression scores. The e-CBT and Combination arms improved quality of life, and the combination arm improved stress scores. There were no differences between the groups in depression, anxiety, or stress scores post-treatment. However, the combination arm had a significantly larger improvement in quality of life. Gender and treatment arm were not predictors of dropout, whereas younger age was., Conclusion: Incorporating e-CBT on its own or in combination with pharmaceutical interventions is a viable option for treating GAD. Treating GAD with e-CBT or medication appears to offer significant improvements in symptoms, with no meaningful difference between the two. Combining the treatments also offer significant improvements, while not necessarily superior to either independently. The findings suggest that all options are viable. Taking the patient's preferred treatment route based on their lifestyle, personality, and beliefs into account when deciding on treatment should be a priority for care providers., Competing Interests: NA and MO have co-founded the care delivery platform in use (i.e., OPTT) and have ownership stakes in OPTT Inc. AS was employed by OPTT Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Stephenson, Moghimi, Shao, Kumar, Yee, Miller, Stefatos, Gholamzadehmir, Abbaspour, Jagayat, Shirazi, Gizzarelli, Gutierrez, Khan, Patel, Patel, Yang, Omrani and Alavi.)

Background: Generalized anxiety disorder (GAD) is a prevalent anxiety disorder, with cognitive behavioral therapy (CBT) being the gold standard treatment. However, it is inaccessible and costly to many, as the mental health industry is overwhelmed by the demand for treatment. This means effective, accessible, and time-saving strategies must be developed to combat these problems. Web-based interventions for mental health disorders are an innovative and promising way to address these barriers. While electronically delivered CBT (e-CBT) has already proved productive and scalable for treating anxiety, other less resource-intensive interventions can be innovated. Checking up on mental health face-to-face has been shown to provide similar benefits to patients with anxiety disorders previously, but more research is needed to evaluate the efficacy of web-based delivery of this intervention., Objective: This study will compare the efficacy of e-CBT and a web-based mental health check-in program to treat GAD. These programs will both be delivered through a secure, web-based care delivery platform., Methods: We will randomly allocate participants (N=100) who are 18 years or older with a confirmed diagnosis of GAD to either an e-CBT program or a mental health check-in program over 12 weeks to address their anxiety symptoms. Participants in the e-CBT arm will complete predesigned modules and homework assignments while receiving personalized feedback and asynchronous interaction with a therapist through the platform. Participants in the mental health check-in arm will be contacted weekly through the web-based platform's written chat feature (messaging system). Therapists will ask the participants a series of predesigned questions that revolve around a different theme each week to prompt conversation. Using clinically validated questionnaires, the efficacy of the e-CBT arm will be compared to the mental health check-in arm. These questionnaires will be completed at baseline, week 6, and week 12., Results: The study received ethics approval in April 2021, and participant recruitment began in May 2021. Participant recruitment has been conducted through targeted advertisements and physician referrals. Complete data collection and analysis are expected to conclude by August 2023. Linear and binomial regression (continuous and categorical outcomes, respectively) will be conducted., Conclusions: To the research team's knowledge, this will be the first study to date comparing the efficacy of e-CBT with a web-based mental health check-in program to treat GAD. The findings from this study can help progress the development of more scalable, accessible, and efficacious mental health treatments., Trial Registration: ClinicalTrials.gov NCT04754438; https://classic.clinicaltrials.gov/ct2/show/NCT04754438., International Registered Report Identifier (irrid): DERR1-10.2196/48899., (©Callum Stephenson, Anchan Kumar, Niloufar Malakouti, Niloofar Nikjoo, Jasleen Jagayat, Tessa Gizzarelli, Charmy Patel, Gilmar Gutierrez, Amirhossein Shirazi, Megan Yang, Mohsen Omrani, Nazanin Alavi. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 20.09.2023.)

Background: Previous studies have shown that insulin directly affects the risk of type 2 diabetes mellitus (T2DM) but the relationship between insulinaemic potential of diet and lifestyle and the T2DM risk is still unknown. Accordingly, we aimed to investigate the relationship between the insulinaemic potential of diet and lifestyle based on indices including empirical dietary index for hyperinsulinaemia (EDIH), empirical lifestyle index for hyperinsulinaemia (ELIH), empirical dietary index for insulin resistance (EDIR) and empirical lifestyle index for insulin resistance (ELIR) and the T2DM risk in the Iranian adults., Methods: This study was performed on data of enrollment phase of the Yazd Health Study (YaHS) and TAghzieh Mardom-e-Yazd (Yazd Nutrition Study) (TaMYZ) on 5714 adults aged 20-70 years (mean: 36.29 years). A validated food frequency questionnaire and clinical tests were used to assess food intake and T2DM ascertainment, respectively. We used the Cox regression analysis for determining the relationship between the indices and T2DM risk., Results: After adjusting for confounding variables, our findings showed that diet with higher ELIH score is 2.28 times more likely for T2DM risk (RR 2.28 [95% CI 1.69-2.56]), but there was no significant relationship between the EDIH, ELIR and EDIR scores and T2DM risk in adults, in the entire study population., Conclusions: Our findings suggest that diets with higher ELIH score increases the T2DM risk, but there was no significant relationship between the EDIH, ELIR and EDIR scores and T2DM risk. Further epidemiological studies are needed to confirm our findings., (© 2023. The Author(s).)

Mobilized peripheral blood is increasingly used instead of bone marrow as a source of autologous hematopoietic stem/progenitor cells for ex vivo gene therapy. Here, we present an unplanned exploratory analysis evaluating the hematopoietic reconstitution kinetics, engraftment and clonality in 13 pediatric Wiskott-Aldrich syndrome patients treated with autologous lentiviral-vector transduced hematopoietic stem/progenitor cells derived from mobilized peripheral blood (n = 7), bone marrow (n = 5) or the combination of the two sources (n = 1). 8 out of 13 gene therapy patients were enrolled in an open-label, non-randomized, phase 1/2 clinical study (NCT01515462) and the remaining 5 patients were treated under expanded access programs. Although mobilized peripheral blood- and bone marrow- hematopoietic stem/progenitor cells display similar capability of being gene-corrected, maintaining the engineered grafts up to 3 years after gene therapy, mobilized peripheral blood-gene therapy group shows faster neutrophil and platelet recovery, higher number of engrafted clones and increased gene correction in the myeloid lineage which correlate with higher amount of primitive and myeloid progenitors contained in hematopoietic stem/progenitor cells derived from mobilized peripheral blood. In vitro differentiation and transplantation studies in mice confirm that primitive hematopoietic stem/progenitor cells from both sources have comparable engraftment and multilineage differentiation potential. Altogether, our analyses reveal that the differential behavior after gene therapy of hematopoietic stem/progenitor cells derived from either bone marrow or mobilized peripheral blood is mainly due to the distinct cell composition rather than functional differences of the infused cell products, providing new frames of references for clinical interpretation of hematopoietic stem/progenitor cell transplantation outcome., (© 2023. The Author(s).)

Background: Bipolar disorder (BD) is a highly prevalent psychiatric condition that can significantly impact every aspect of a person's life if left untreated. A subtype of BD, bipolar disorder type II (BD-II), is characterized by long depressive episodes and residual depression symptoms, with short-lived hypomanic episodes. Medication and psychotherapy, such as cognitive behavioral therapy (CBT), are the main treatment options for BD-II. CBT specific for BD-II involves the recognition of warning signs, potentially triggering stimuli, and the development of coping skills to increase euthymic periods and improve global functioning. However, access to in-person CBT may be limited by several barriers, including low availability, high costs, and geographical limitations. Thus, web-based adaptations of CBT (e-CBT) have become a promising solution to address these treatment barriers. Nevertheless, e-CBT for the treatment of BD-II remains understudied., Objective: The proposed study aims to establish the first e-CBT program specific for the treatment of BD-II with residual depressive symptoms. The primary objective of this study will be to determine the effect of e-CBT in managing BD symptomatology. The secondary objective will be to assess the effects of this e-CBT program on quality of life and resilience. The tertiary objective will involve gathering user feedback using a posttreatment survey to support the continuous improvement and optimization of the proposed program., Methods: Adult participants (N=170) with a confirmed diagnosis of BD-II experiencing residual depressive symptoms will be randomly assigned to either the e-CBT and treatment as usual (TAU; n=85) group or the TAU (n=85) control group. Participants in the control group will be able to participate in the web-based program after the first 13 weeks. The e-CBT program will consist of 13 weekly web-based modules designed following a validated CBT framework. Participants will complete module-related homework and receive asynchronous personalized feedback from a therapist. TAU will consist of standard treatment services conducted outside of this research study. Depression and manic symptoms, quality of life, and resiliency will be assessed using clinically validated symptomatology questionnaires at baseline, week 6, and week 13., Results: The study received ethics approval in March 2020, and participant recruitment is expected to begin in February 2023 through targeted advertisements and physician referrals. Data collection and analysis are expected to conclude by December 2024. Linear and binomial regression (continuous and categorical outcomes, respectively) will be conducted along with qualitative interpretive methods., Conclusions: The findings will be the first on the effectiveness of delivering e-CBT for patients with BD-II with residual depressive symptoms. This approach can provide an innovative method to address barriers to in-person psychotherapy by increasing accessibility and decreasing costs., Trial Registration: ClinicalTrials.gov NCT04664257; https://clinicaltrials.gov/ct2/show/NCT04664257., International Registered Report Identifier (irrid): PRR1-10.2196/46157., (©Gilmar Gutierrez, Callum Stephenson, Jazmin Eadie, Elnaz Moghimi, Mohsen Omrani, Dianne Groll, Claudio N Soares, Roumen Milev, Gustavo Vazquez, Megan Yang, Nazanin Alavi. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 19.05.2023.)

Background: Insomnia is one of the most prevalent sleep disorders characterized by an inability to fall or stay asleep. Available treatments include pharmacotherapy and cognitive behavioural therapy for insomnia (CBTi). Although CBTi is the first-line treatment, it has limited availability. Therapist-guided electronic delivery of CBT for insomnia (e-CBTi) offers scalable solutions to enhance access to CBTi. While e-CBTi produces comparable outcomes to in-person CBTi, there is a lack of comparison to active pharmacotherapies. Therefore, direct comparisons between e-CBTi and trazodone, one of the most frequently prescribed medications for insomnia, is essential in establishing the effectiveness of this novel digital therapy in the health care system., Objective: The aim of this study is to compare the effectiveness of a therapist-guided electronically-delivered cognitive behavioural therapy (e-CBTi) program to trazodone in patients with insomnia., Methods: Patients (n = 60) will be randomly assigned to two groups: treatment as usual (TAU) + trazodone and TAU + e-CBTi for seven weeks. Each weekly sleep module will be delivered through the Online Psychotherapy Tool (OPTT), a secure, online mental health care delivery platform. Changes in insomnia symptoms will be evaluated throughout the study using clinically validated symptomatology questionnaires, Fitbits, and other behavioural variables., Results: Participant recruitment began in November 2021. To date, 18 participants have been recruited. Data collection is expected to conclude by December 2022 and analyses are expected to be completed by January 2023., Conclusions: This comparative study will improve our understanding of the efficacy of therapist-guided e-CBTi in managing insomnia. These findings can be used to develop more accessible and effective treatment options and influence clinical practices for insomnia to further expand mental health care capacity in this population., Trial Registration: ClinicalTrials.gov (NCT05125146)., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: The principal investigator (NA) and collaborator (MO) have cofounded the care delivery platform in use (OPTT) and have ownership stakes in OPTT Inc., which is the platform used in the current study. Hence, NA and MO will not be involved in statistical analyses to mitigate potential conflicts of interest. The other authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The increased prevalence of major depressive disorder (MDD) amid the COVID-19 pandemic has resulted in substantial growth in online mental health care delivery. Compared to its in-person counterpart, online cognitive behavioral therapy (e-CBT) is a time-flexible and cost-effective method of improving MDD symptoms. However, how its efficacy compares to in-person CBT is yet to be explored. Therefore, the current study compared the efficacy of a therapist-supported, electronically delivered e-CBT program to in-person therapy in individuals diagnosed with MDD., Methods: Participants ( n  = 108) diagnosed with MDD selected either a 12 week in-person CBT or an asynchronous therapist-supported e-CBT program. E-CBT participants ( n  = 55) completed weekly interactive online modules delivered through a secure cloud-based online platform (Online Psychotherapy Tool; OPTT). These modules were followed by homework in which participants received personalized feedback from a trained therapist. Participants in the in-person CBT group ( n  = 53) discussed sessions and homework with their therapists during one-hour weekly meetings. Program efficacy was evaluated using clinically validated symptomatology and quality of life questionnaires., Results: Both treatments yielded significant improvements in depressive symptoms and quality of life from baseline to post-treatment. Participants who opted for in-person therapy presented significantly higher baseline symptomatology scores than the e-CBT group. However, both treatments demonstrated comparable significant improvements in depressive symptoms and quality of life from baseline to post-treatment. e-CBT seems to afford higher participant compliance as dropouts in the e-CBT group completed more sessions on average than those in the in-person CBT group., Conclusion: The findings support e-CBT with therapist guidance as a suitable option to treat MDD. Future studies should investigate how treatment accessibility is related to program completion rates in the e-CBT vs. in-person group., Clinical Trial Registration: ClinicalTrials.Gov Protocol Registration and Results System (NCT04478058); clinicaltrials.gov/ct2/show/NCT04478058., Competing Interests: NA and MO cofounded the care delivery platform in use (i.e., OPTT) and have ownership stakes in OPTT Inc. AmS was employed by OPTT Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alavi, Moghimi, Stephenson, Gutierrez, Jagayat, Kumar, Shao, Miller, Yee, Stefatos, Gholamzadehmir, Abbaspour, Shirazi, Gizzarelli, Khan, Patel, Patel, Yang and Omrani.)

Introduction: In the last few years, online psychotherapy programs have burgeoned since they are a more accessible and scalable treatment option compared to in-person therapies. While these online programs are promising, understanding the user experience and perceptions of care is essential for program optimization., Methods: This study investigated the experiences of end-users who had previously received online psychotherapy through a web-based platform. A 35-item multiple-choice survey was developed by the research team and distributed to past users to capture their perceptions of the program., Results: The survey yielded 163 responses, with a 90 % completion rate. Participants were predominantly white and female, with an average age of 42 years. While most participants preferred in-person therapy, they also reported the benefits of the online psychotherapy program. Participants had positive perceptions of the platform, the quality and interaction of their therapist, and the homework assignments and skills covered. Lack of motivation to complete weekly homework assignments was cited as a common struggle., Discussion: The findings support online psychotherapy as a beneficial digital mental health tool and highlight some areas for improvement. Scalability and accessibility are key benefits of the platform. At the same time, improvements in participant engagement, including those from equity-seeking and equity-deserving groups, may enhance the efficacy of the programs offered., Competing Interests: NA and MO co-founded the Online Psychotherapy Tool (i.e., OPTT) and have ownership stakes in OPTT Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Published by Elsevier B.V.)

Background: Post-secondary students frequently experience high rates of mental health challenges. However, they present meagre rates of treatment-seeking behaviours. This elevated prevalence of mental health problems, particularly after the COVID-19 pandemic, can lead to distress, poor academic performance, and lower job prospects following the completion of education. To address the needs of this population, it is important to understand students' perceptions of mental health and the barriers preventing or limiting their access to care., Methods: A broad-scoping online survey was publicly distributed to post-secondary students, collecting demographic, sociocultural, economic, and educational information while assessing various components of mental health., Results: In total, 448 students across post-secondary institutions in Ontario, Canada, responded to the survey. Over a third (n = 170; 38.6%) of respondents reported a formal mental health diagnosis. Depression and generalized anxiety disorder were the most commonly reported diagnoses. Most respondents felt that post-secondary students did not have good mental health (n = 253; 60.5%) and had inadequate coping strategies (n = 261; 62.4%). The most frequently reported barriers to care were financial (n = 214; 50.5%), long wait times (n = 202; 47.6%), insufficient resources (n = 165; 38.9%), time constraints (n = 148; 34.9%), stigma (n = 133; 31.4%), cultural barriers (n = 108; 25.5%), and past negative experiences with mental health care (n = 86; 20.3%). The majority of students felt their post-secondary institution needed to increase awareness (n = 231; 56.5%) and mental health resources (n = 306; 73.2%). Most viewed in-person therapy and online care with a therapist as more helpful than self-guided online care. However, there was uncertainty about the helpfulness and accessibility of different forms of treatment, including online interventions. The qualitative findings highlighted the need for personal strategies, mental health education and awareness, and institutional support and services., Conclusions: Various barriers to care, perceived lack of resources, and low knowledge of available interventions may contribute to compromised mental health in post-secondary students. The survey findings indicate that upstream approaches such as integrating mental health education for students may address the varying needs of this critical population. Therapist-involved online mental health interventions may be a promising solution to address accessibility issues., (© 2023. The Author(s).)

Monitoring aflatoxin M1 (AFM1) in dairy products and milk-based foods is very important. The main purpose of this research was to investigate and determine the amount and human health risk assessment of aflatoxin M1 (AFM1) in the most famous and widely used brands of infant dried powder milk (IDPM) consumed in Iran. For this study, 45 imported IDPM (IM-IDPM) samples and 45 domestically produced IDPM (DO-IDPM) samples (a total of 90 samples) were selected randomly. All samples were analyzed for AFM1 using a competitive enzyme-linked immunosorbent assay (ELISA) technique. The mean level and the percentage of positive samples for AFM1 in DO-IDPM were 9.2 ± 5.4 ng/kg and 73.3%, and for IM-IDPM, they were 5.1 ± 3.8 ng/kg and 33.3%, respectively. The average level of AFM1 in all samples was lower than the EU and Iranian national standards (25 ng/kg). AFM1 intake through IDPM consumption by Iranian infants less than one-year-old was lower than the allowable level, but the hazard quotient for infants less than 6 months was higher than the allowable level. Although the concentration of AFM1 in IDPM consumed in Iran is not hazardous, since Iranian infants may be exposed to AFM1 through other sources, including baby food, breast milk, raw and pasteurized milk, continuous monitoring of IDMP quality in Iranian markets should be taken., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)