Unlocking Therapeutic Potential: The Role of Theta Burst Stimulation in Multiple Sclerosis Management.

Objective: Current therapies for multiple sclerosis (MS) often have limited efficacy and side effects, necessitating alternative approaches. Noninvasive brain stimulation (NIBS), such as transcranial direct current stimulation and transcranial magnetic stimulation (TMS), offers potential solutions. Among NIBS techniques, theta burst stimulation (TBS) is notable for its ability to modulate cortical activity. The objective of this systematic review is to assess the impact of TBS on MS symptoms.Data Sources: The study conducted rigorous systematic searches in PubMed, Google Scholar, and Scopus databases up to June 2023, using specific Medical Subject Headings terms related to NIBS and MS, such as TMS and TBS, in conjunction with terms like MS or demyelinating disease. Additionally, the bibliographic references of included studies, book chapters, and original articles were manually reviewed.Study Selection: The study selection process involved a 2-tiered screening mechanism, beginning with an evaluation of titles and abstracts, followed by a full-text review of selected articles. Inclusion criteria incorporated randomized controlled trials (RCTs) focusing on TBS with MS patients. Exclusion criteria included non-qualitative, non-MS, and non-TBS studies. Risk of bias assessment was conducted using the 2008 Cochrane Risk of Bias 2 Scale for RCTs.Data Extraction: Data extraction was conducted by thoroughly reviewing each research article and systematically recording the relevant information using a standardized data extraction form, ensuring consistency and accuracy throughout the process.Results: In a systematic review encompassing 5 randomized controlled trials involving 117 individuals with relapsing-remitting or secondary progressive MS across Italy, France, and Russia, various forms of TBS were applied. These interventions ranged from intermittent TBS (iTBS) to continuous intermittent TBS (c-iTBS) that demonstrated favorable outcomes. Notably, TBS interventions led to significant reductions in spasticity, fatigue, and pain, with c-iTBS combined with vestibular rehabilitation showing additional improvements in vestibular-ocular reflexes, gait, and balance. While specific protocols varied among the studies, collectively, the results suggest promise for TBS approaches in alleviating MS-related symptoms.Conclusions: The findings of this review suggest that TBS may hold promise in addressing specific MS symptoms, notably fatigue and spasticity. Future research should include a more diverse participant pool to explore TBS effects across different MS subtypes and aim for larger sample sizes to enhance statistical power and result reliability.Prim Care Companion CNS Disord 2024;26(2):23r03645. Author affiliations are listed at the end of this article.

Modern Psychedelic Microdosing Research on Mental Health: A Systematic Review.

Objective: To investigate the relationship between psychedelic microdosing and its effects on mental health, aiming to understand if microdosing can improve mental well-being.Data Sources: PubMed and Scopus were searched on December 25, 2022, using search terms related to psychedelics, microdosing, and mental health. The inclusion criteria focused on studies published between January 1, 2012, and November 30, 2022. There were no language restrictions for the initial search; however, for the study selection, only articles in English were considered.Study Selection: A total of 45 articles were initially identified. After removing duplicates, 27 unique articles were screened based on their titles and abstracts, resulting in 19 articles included in the final review. The studies were selected based on their relevance to the relationship between mental health and psychedelic microdosing.Data Extraction: The extracted data from the selected studies included sample sizes, demographics, survey designs, and qualitative and quantitative analyses related to the outcomes of individuals with mental health issues who also engaged in psychedelic microdosing. The QualSyst Quality Assessment Checklist was used to assess the methodological rigor and quality of each study. The data extraction process involved systematically reviewing each article and summarizing key findings related to the impact of microdosing on mental health.Results: The review revealed that microdosing psychedelics, such as lysergic acid diethylamide and psilocybin, showed potential benefits on mental health. Users reported positive effects, including improved mood, increased focus, and better daily function. However, there were also challenges reported, such as physiologic discomfort and increased anxiety. Some studies observed that positive expectations about microdosing led to positive outcomes. The studies varied in design, with some being observational, others placebo-controlled, and some relying on self-reported data.Conclusions: There is a growing body of evidence suggesting a positive correlation between psychedelic microdosing and improved mental well-being. However, due to the limited number of controlled studies and the small sample sizes in some of the studies, the causal relationship between microdosing and mental health improvement remains uncertain. The review calls for further research with double-blind experiments, control groups, and larger sample sizes that represent the general population to better understand the potential benefits and risks of psychedelic microdosing on mental health.Prim Care Companion CNS Disord 2024;26(1):23r03581.Author affiliations are listed at the end of this article.

Exploratory analysis of the cervix tumoral HPV antigen-specific T-cell repertoire during chemoradiation and after brachytherapy.

BACKGROUND: Chemoradiation (CRT) may modulate the immune milieu as an in-situ vaccine. Rapid dose delivery of brachytherapy has unclear impact on T-cell repertoires. HPV-associated cancers express viral oncoproteins E6/E7, which enable tracking antigen/tumor-specific immunity during CRT. METHODS: Thirteen cervical cancer patients on a multi-institutional prospective protocol from 1/2020-1/2023 underwent standard-of-care CRT with pulsed-dose-rate brachytherapy boost (2 fractions). Cervix swabs at various timepoints underwent multiplex DNA deep sequencing of the TCR-ß/CDR3 region with immunoSEQ. Separately, HPV-responsive T-cell clones were also expanded ex vivo. Statistical analysis was via Mann-Whitney-U. RESULTS: TCR productive clonality, templates, frequency, or rearrangements increased post-brachytherapy in 8 patients. Seven patients had E6/E7-responsive evolution over CRT with increased productive templates (ranges: 1.2-50.2 fold-increase from baseline), frequency (1.2-1.7), rearrangements (1.2-40.2), and clonality (1.2-15.4). Five patients had HPV-responsive clonal expansion post-brachytherapy, without changes in HPV non-responsive clones. Epitope mapping revealed VDJ rearrangements targeting cervical cancer-associated antigens in 5 patients. The only two patients with disease recurrence lacked response in all metrics. A lack of global TCR remodeling correlated with worse recurrence-free survival, p = 0.04. CONCLUSION: CRT and brachytherapy alters the cervical cancer microenvironment to facilitate the expansion of specific T-cell populations, which may contribute to treatment efficacy.

The role of diabetes distress in Diabulimia.

IMPORTANCE: Diabulimia is a disordered eating behavior in which a person with type 1 diabetes withholds insulin injections to lose weight. It is thought that the psychosocial stress of managing this chronic disease, which is termed diabetes distress, may contribute to developing diabulimia. OBJECTIVE: This paper explores links between diabetes distress and diabulimia and their relevance to the diagnosis and treatment of diabulimia by assessing whether people with diabulimia report measurable evidence of diabetes distress. EVIDENCE REVIEW: We evaluated studies examining the qualitative experiences of people with disordered eating behaviors in the setting of type 1 diabetes for themes of diabetes distress by identifying aspects of the patients' stories that matched the criteria in the Diabetes Distress Scale. Selected studies recorded primary data, analyzed qualitative data, examined lived experiences of individuals with diabulimia, and were made available in English-language peer-reviewed journals between January 1, 2000 and August 31, 2022. Exclusion criteria included partial articles, editorials, reviews, and abstracts along with studies of patients with type 2 diabetes. FINDINGS: Over forty individual participants across twelve studies were found to have aspects of their experiences that met one or more criteria from the Diabetes Distress Scale. Participants reported experiences that matched criteria items from each of the seven subscales of the Diabetes Distress Scale. Participants in the twelve studies included 185 individuals with type 1 diabetes experiencing diabulimia, including 164 females (88.6%), 20 males (10.8%), and 1 non-reported gender (0.54%). CONCLUSION: We believe this discovery warrants further research probing the prevalence of diabetes distress among people with diabulimia as well as other links between the two conditions. We advocate for a diabetes distress-informed approach to diabulimia treatment and for diabetes distress screening in every patient with type 1 diabetes.

Route of administration significantly affects particle deposition and cellular recruitment.

Lung exposures to dusts, pollutants, and other aerosol particulates are known to be associated with pulmonary diseases such as asthma and Chronic Obstructive Pulmonary Disease. These health impacts are attributed to the ability of aerosol components to induce pulmonary inflammation, which promotes tissue remodeling, including fibrosis, tissue degradation, and smooth muscle proliferation. Consequently, the distribution of these effects can have a significant impact on the physiologic function of the lung. In order to study the impact of distribution of inhaled particulates on lung pathogenesis, we compared the effect of different methods of particle delivery. By comparing intranasal versus aerosol delivery of fluorescent microspheres, we observed strikingly distinct patterns of particle deposition; intranasal delivery provided focused deposition concentrated on larger airways, while aerosol delivery showed unform deposition throughout the lung parenchyma. Recognizing that the impacts of inflammatory cells are contingent upon their recruitment and behavior, we postulate that these variations in distribution patterns can result in significant alterations in biological responses. To elucidate the relevance of these findings in terms of biological representation, we subsequently conducted an investigation into the responses elicited by the administration of endotoxin (bacterial Lipopolysaccharide, or LPS) in a transgenic neutrophil reporter mouse model. As with the microsphere results, patterns of recruited neutrophil inflammatory responses matched the delivery method; that is, despite the active migratory behavior of neutrophils, inflammatory histopathology patterns were either focused on large airways (intranasal administration) or diffusely throughout the parenchyma (aerosol). These results demonstrate the importance of modes of aerosol delivery as different patterns of inflammation and tissue remodeling will have distinct impacts on lung physiology.

Association of Body Dysmorphic-Induced Anabolic-Androgenic Steroid Use With Mental Health Outcomes: A Systematic Review.

Objective: To explore the relationship between body dysmorphic disorder (BDD), anabolic-androgenic steroid use (AAS) use, and mental health outcomes and to identify potential interventions and treatments that may help mitigate these detrimental effects.Data Sources: PubMed, Scopus, CINAHL, Embase, and PsycINFO were searched from 1992 to 2022 with no language limits. Search terms included "AAS" AND "mental health outcomes" AND "body dysmorphia" and were expanded in PubMed to include "anabolic steroids induced depression," "anabolic steroids induced depression in athletes," "steroids," "mental health," and "performance-enhancing drugs."Study Selection: Forty-one articles were identified, and 37 remained after duplicates were removed. After full-text appraisal, 33 articles were included in the final review.Data Extraction: Two reviewers independently screened studies for inclusion criteria, extracted pertinent data, and assessed the quality of evidence.Results: Bodybuilders and fitness athletes may be more susceptible to developing muscle dysmorphia, having disordered eating habits, and using performance-enhancing drugs like AAS. The COVID-19 pandemic increased reliance on social media and online interactions, which was previously associated with disordered eating patterns and negative body image. Being a member of a sexual minority may increase one's risk of developing muscle dysmorphia and other types of BDD, as these individuals may experience additional stressors and difficulties due to stigma and discrimination, which may worsen one's sense of self and body image.Conclusion: The development and evaluation of interventions such as cognitive-behavioral therapy, mindfulness-based interventions, and peer support programs, should be prioritized to deter AAS use in people at risk.Prim Care Companion CNS Disord 2023;25(5):23r03532. Author affiliations are listed at the end of this article.

Tumor-resident Lactobacillus iners confer chemoradiation resistance through lactate-induced metabolic rewiring.

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other body sites are also significantly associated with survival in colorectal, lung, head and neck, and skin cancers. Our findings demonstrate that lactic acid bacteria in the tumor microenvironment can alter tumor metabolism and lactate signaling pathways, causing therapeutic resistance. Lactic acid bacteria could be promising therapeutic targets across cancer types.

Body mass index on perinatal depression: A critical viewpoint.

I am pleased to submit a viewpoint titled "Body mass index on perinatal depression: A critical viewpoint" in response to an article by Ventriglio et al. titled, "The impact of body mass index on the pregnancy outcomes and risk of perinatal depression: Findings from a multicenter Italian study" for consideration for publication in your journal.

Thymic mimetic cells function beyond self-tolerance.

Development of immunocompetent T cells in the thymus is required for effective defence against all types of pathogens, including viruses, bacteria and fungi. To this end, T cells undergo a very strict educational program in the thymus, during which both non-functional and self-reactive T cell clones are eliminated by means of positive and negative selection1.Thymic epithelial cells (TECs) have an indispensable role in these processes, and previous studies have shown the notable heterogeneity of these cells2-7. Here, using multiomic analysis, we provide further insights into the functional and developmental diversity of TECs in mice, and reveal a detailed atlas of the TEC compartment according to cell transcriptional states and chromatin landscapes. Our analysis highlights unconventional TEC subsets that are similar to functionally well-defined parenchymal populations, including endocrine cells, microfold cells and myocytes. By focusing on the endocrine and microfold TEC populations, we show that endocrine TECs require Insm1 for their development and are crucial to maintaining thymus cellularity in a ghrelin-dependent manner; by contrast, microfold TECs require Spib for their development and are essential for the generation of thymic IgA+ plasma cells. Collectively, our study reveals that medullary TECs have the potential to differentiate into various types of molecularly distinct and functionally defined cells, which not only contribute to the induction of central tolerance, but also regulate the homeostasis of other thymus-resident populations.